The Pathobiology of Vascular Dementia
Open accessAbstract
Vascular cognitive impairment defines alterations in cognition, ranging from subtle deficits to full-blown dementia, attributable to cerebrovascular causes. Often coexisting with Alzheimer's disease, mixed vascular and neurodegenerative dementia has emerged as the leading cause of age-related cognitive impairment. Central to the disease mechanism is the crucial role that cerebral blood vessels play in brain health, not only for the delivery of oxygen and nutrients, but also for the trophic signaling that inextricably links the well-being of neurons and glia to that of cerebrovascular cells. This review will examine how vascular damage disrupts these vital homeostatic interactions, focusing on the hemispheric white matter, a region at heightened risk for vascular damage, and on the interplay between vascular factors and Alzheimer's disease. Finally, preventative and therapeutic prospects will be examined, highlighting the importance of midlife vascular risk factor control in the prevention of late-life dementia.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
0 of 273 cited sources checked · 0 supported · 0 flagged
- Premisecitation
Most dementia cases show mixed pathology, combining Alzheimer's features and ischemic lesions.
“community based clinical-pathological studies revealed that the largest proportion of dementia cases have mixed pathology, comprising features of AD (amyloid plaques and neurofibrillary tangles) as well as ischemic lesions (Launer et al., 2008; Schneider et al., 2009).”
Quote in the paperNot a substantial claim0 of 2 sources checked - Premisecitation
The brain needs a continuous, well-regulated blood supply because it has high energy demands and no fuel reserves.
“Owing to its high energy needs and lack of fuel reserves, the brain requires a continuous and well-regulated supply of blood (Iadecola, 2004).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Iadecola, 2004 source
Not checked in the free run.
- Premisecitation
Neurons, glia, and vascular cells exhibit a functional and pathogenic synergy.
“new experimental findings have revealed a previously unrecognized functional and pathogenic synergy between neurons, glia and vascular cells (Iadecola, 2010; Quaegebeur et al., 2011; Zlokovic, 2011)”
Quote in the paperSubstantial claim0 of 3 sources checked - Interpretationreasoning
Neural activity is the main factor determining dynamic regulation of cerebral blood flow.
“Consequently, neural activity, which uses most of the brain’s energy budget, is the major determinant of the dynamic regulation of CBF.”
Quote in the paperNot a substantial claim - Interpretationnone given
Cerebral blood vessels play a crucial role in brain health, including trophic signaling linking neurons and glia to cerebrovascular cells.
“Central to the disease mechanism is the crucial role that cerebral blood vessels play in brain health, not only for the delivery of oxygen and nutrients, but also for the trophic signaling that links inextricably the well being of neurons and glia to that of cerebrovascular cells.”
Quote in the paperSubstantial claim
- Premisecitation
Reduced global cerebral perfusion can cause brain dysfunction and impair cognition transiently or permanently.
“Reduction in global cerebral perfusion caused by cardiac arrest, arrhythmias, cardiac failure, or hypotension can produce brain dysfunction and impair cognition transiently or permanently (table 1) (Alosco et al., 2013; Justin et al., 2013; Marshall, 2012; Stefansdottir et al., 2013).”
Quote in the paperSubstantial claim0 of 3 sources checked- cites Alosco et al., 2013 source
Not checked in the free run.
- cites Justin et al., 2013
Not checked in the free run.
- cites Marshall, 2012
Not checked in the free run.
- Interpretationnone given
Mixed vascular and neurodegenerative dementia is the leading cause of age-related cognitive impairment.
“Often coexisting with Alzheimer’s disease, mixed vascular and neurodegenerative dementia has emerged as the leading cause of age-related cognitive impairment.”
Quote in the paperNot a substantial claim - Premisenone given
Vascular alterations that cause cognitive impairment are diverse, including systemic conditions affecting global cerebral perfusion and changes in small arterioles or venules.
“The vascular alterations that cause cognitive impairment are diverse, and include systemic conditions affecting global cerebral perfusion or alterations involving cerebral blood vessels, most commonly small size arterioles or venules (fig. 5).”
Quote in the paperNot a substantial claim - Premisecitation
The most prevalent vascular lesions linked to VCI involve small vessels in the hemispheric white matter.
“By far, the most prevalent vascular lesions associated with VCI are related to alterations in small vessels in the hemispheric white matter (Jellinger, 2013).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Jellinger, 2013 source
Not checked in the free run.
- Interpretationcitation
The delayed effect of vascular risk factors may explain why some studies found no cognitive improvement when risk factors were controlled later in life.
“Remarkably, in VCI as in AD, the increase in risk afforded by vascular risk factors is observed decades later, a finding that may explain why some studies did not find a cognitive improvement with risk factor control later in life (Sahathevan et al., 2012).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Sahathevan et al., 2012 source
Not checked in the free run.
- Premisecitation
There is a general correlation between total vascular pathology burden and cognitive deficits.
“As for the other pathologies underlying VCI, there is a general correlation between the total burden of vascular pathology and cognitive deficits (Gelber et al., 2012; Gorelick et al., 2011; Inzitari et al., 2009).”
Quote in the paperSubstantial claim0 of 3 sources checked - Premisecitation
Hypertension, diabetes, hyperlipidemia, smoking, atrial fibrillation, and hyperhomocystinemia increase dementia risk independently of their effect on stroke risk.
“Vascular risk factors, including hypertension, diabetes, hyperlipidemia, smoking, atrial fibrillation, and hyperhomocystinemia, increase the risk of dementia independently of the associated increase in stroke risk (Sahathevan et al., 2012).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Sahathevan et al., 2012 source
Not checked in the free run.
- Premisecitation
Metabolic syndrome, including insulin resistance, hypertension, and dyslipidemia, is associated with lower cognitive performance.
“Furthermore, the metabolic syndrome, including insulin resistance, hypertension and dyslipidemia, has been associated with lower cognitive performance (Yates et al., 2012).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Yates et al., 2012 source
Not checked in the free run.
- Premisecitation
Microinfarcts and microbleeds independently predict cognitive dysfunction.
“Microscopic infarcts (microinfarcts) and hemorrhages (microbleeds) (fig. 5) are independent predictors of cognitive dysfunction, but are commonly associated with other vascular pathologies, such as leukoaraiosis, lacunar infarcts, large infarcts, and hemorrhage (Smith et al., 2012; van Norden et al., 2013), as well as CADASIL and AD (table 1).”
Quote in the paperSubstantial claim0 of 2 sources checked - Premisecitation
White matter lesions grow over time by expanding existing lesions rather than forming new foci.
“The white matter lesions evolve over time by expansion of existing lesions, rather than formation of new foci (Maillard et al., 2012), resembling the patters of progression of amyloid angiopathy (Alonzo et al., 1998; Robbins et al., 2006).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Maillard et al., 2012 source
Not checked in the free run.
- Premisecitation
Many rare genetic mutations are associated with vascular cognitive impairment.
“A host of rare genetic mutations are associated with VCI (Federico et al., 2012; Schmidt et al., 2012).”
Quote in the paperNot a substantial claim0 of 2 sources checked - Interpretationcitation
White matter disruption can strongly affect the precision and fidelity of information transfer that underlies brain function and cognitive health.
“In addition to gray matter damage, disruption of the white matter can have profound effects on the precision and fidelity of the information transfer underlying brain function and cognitive health (Nave, 2010a).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Nave, 2010a
Not checked in the free run.
- Premisecitation
Higher education, used as a proxy for cognitive reserve, is associated with fewer cognitive deficits at a given level of neuropathology.
“The level of education, a surrogate marker of cognitive reserves (Stern, 2012), is an important determinant of the expression of VCI, such that for a given level of neuropathology higher education is associated with less cognitive deficits (Zieren et al., 2013).”
Quote in the paperSubstantial claim0 of 2 sources checked - Premisecitation
In vascular cognitive impairment and Alzheimer disease, the increased risk from vascular risk factors is observed decades later.
“Remarkably, in VCI as in AD, the increase in risk afforded by vascular risk factors is observed decades later, a finding that may explain why some studies did not find a cognitive improvement with risk factor control later in life (Sahathevan et al., 2012).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Sahathevan et al., 2012 source
Not checked in the free run.
- Premisecitation
Cerebral amyloid angiopathy occurs most often in Alzheimer's disease, where it is found in more than 90% of cases.
“Although inherited forms of CAA have been described, CAA is most prevalent in AD, being present in over 90% of cases (Attems et al., 2011; Charidimou et al., 2012).”
Quote in the paperNot a substantial claim0 of 2 sources checked - Premisecitation
Recurrent stroke is one of the strongest predictors of dementia onset.
“However, recurrent stroke is one of the strongest predictors of dementia onset (Pendlebury and Rothwell, 2009).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Pendlebury and Rothwell, 2009 source
Not checked in the free run.
- Premisecitation
Overlap of AD neuropathology with cerebrovascular lesions is seen in up to 50% of dementia cases.
“Overlap of AD neuropathology (amyloid plaques and neurofibrillary tangles) with cerebrovascular lesions is observed in up to 50% of cases of dementia (Jellinger, 2013).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Jellinger, 2013 source
Not checked in the free run.
- Premisecitation
A strong link between ApoE and sporadic vascular cognitive impairment has not been established.
“Nevertheless, a strong link between ApoE and sporadic VCI has not been established (Lee and Kim, 2013; Yu et al., 2013).”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites Lee and Kim, 2013 source
Not checked in the free run.
- cites Yu et al., 2013
Not checked in the free run.
- Premisecitation
Post-mortem studies show that areas of leukoaraiosis are chronically hypoxic, as indicated by hypoxia-inducible factors and related genes.
“Consistent with this hypothesis, post-mortem studies have shown that areas of leukoaraiosis are chronically hypoxic, as indicated by the expression of hypoxia inducible factors and related hypoxia-inducible genes (Fernando et al., 2006; Rosenberg et al., 2001).”
Quote in the paperSubstantial claim0 of 2 sources checked - Interpretationcitation
The reduction in periventricular white matter cerebral blood flow during hypercapnia suggests that upstream vasodilatation diverts blood flow to other regions, an intracerebral steal.
“Even in healthy individuals, hypercapnia, a potent vasodilator, does not increase, but reduces, CBF in the periventricular white matter, suggesting that vasodilatation of upstream vessels diverts blood flow to other regions (intracerebral steal) (Mandell et al., 2008).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Mandell et al., 2008 source
Not checked in the free run.
- Interpretationcitation
Increasing evidence indicates that the cerebral blood supply to white matter is compromised in vascular cognitive impairment.
“Increasing evidence suggests that the white matter cerebral blood supply is compromised in VCI (fig. 6).”
Quote in the paperSubstantial claim - Premisecitation
In the general population, lower global cerebral blood flow and lower cerebrovascular reactivity to hypercapnia are associated with greater white matter lesion volume.
“Indeed, in the general population, lower global CBF and lower cerebrovascular reactivity to hypercapnia is associated with a greater volume of white matter lesions (Bakker et al., 1999; Vernooij et al., 2008).”
Quote in the paperSubstantial claim0 of 2 sources checked - Interpretationcitation
These findings implicate loss of large artery elasticity and increased pulsatile stress on microvessels in the microvascular damage underlying white matter lesions.
“These findings implicate loss of large artery elasticity and increased pulsatile stress on microvessels, especially those branching directly from the circle of Willis, in the microvascular damage underlying white matter lesions (Scuteri et al., 2011).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Scuteri et al., 2011 source
Not checked in the free run.
- Premisecitation
In patients with vascular cognitive impairment risk factors such as hypertension and diabetes, neural activity fails to increase blood flow in the brain or retina.
“In patients with VCI risk factors, like hypertension and diabetes, the ability of neural activity to increase blood flow in brain or retina is compromised (Delles et al., 2004; Jennings et al., 2005; Sorond et al., 2011).”
Quote in the paperSubstantial claim0 of 3 sources checked - Premisecitation
In healthy individuals, hypercapnia reduces rather than increases cerebral blood flow in the periventricular white matter.
“Even in healthy individuals, hypercapnia, a potent vasodilator, does not increase, but reduces, CBF in the periventricular white matter, suggesting that vasodilatation of upstream vessels diverts blood flow to other regions (intracerebral steal) (Mandell et al., 2008).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Mandell et al., 2008 source
Not checked in the free run.
- Interpretationcitation
Similar microvascular changes in other organs suggest that brain small vessel disease may be a manifestation of a systemic vasculopathy.
“Similar microvascular changes occur also in other organs, suggesting that small vessel disease in brain may be the manifestation of a systemic vasculopathy (Thompson and Hakim, 2009).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Thompson and Hakim, 2009 source
Not checked in the free run.
- Interpretationnone given
Cognitive dysfunction in vascular cognitive impairment is most often associated with subtle vascular alterations predominantly affecting the deep hemispheric white matter.
“Although as described in the previous section severe ischemia resulting from arterial occlusion can lead to brain damage and VCI, e.g., multi-infarct dementia, cognitive dysfunction is most often associated with more subtle vascular alterations targeting predominantly the deep hemispheric white matter (fig. 5).”
Quote in the paperSubstantial claim - Premisecitation
Asymmetric dimethylarginine may impair nitric oxide-dependent vasodilatation in peripheral and cerebral arteries.
“ADMA may contribute to the impairment of NO-dependent vasodilatation in peripheral and cerebral arteries (Chen et al., 2006; Knottnerus et al., 2009; Pretnar-Oblak et al., 2006; Stevenson et al., 2010).”
Quote in the paperSubstantial claim0 of 3 sources checked - Premisecitation
Cerebral blood flow reduction is observed before the onset of dementia.
“The CBF reduction is observed prior to the onset of dementia (Ruitenberg et al., 2005).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Ruitenberg et al., 2005 source
Not checked in the free run.
- Premisecitation
Plasma proteins including complement, fibrinogen, albumin, and immunoglobulins are detected in astrocytes in white matter lesions.
“Second, plasma proteins, including complement, fibrinogen, albumin and immunoglobulins are detected in astrocytes in white matter lesions (Akiguchi et al., 1998; Alafuzoff et al., 1985; Simpson et al., 2007; Tomimoto et al., 1996).”
Quote in the paperSubstantial claim0 of 3 sources checked - Premisecitation
White matter lesions and lacunar strokes are associated with increased circulating asymmetric dimethylarginine.
“White matter lesions and lacunar strokes are associated with increases in circulating levels of the NO synthase inhibitor asymmetric dimethylarginine (ADMA) (Notsu et al., 2009; Pikula et al., 2009; Rufa et al., 2008).”
Quote in the paperSubstantial claim0 of 3 sources checked - Premisecitation
Plasma albumin is increased in the cerebrospinal fluid of patients with vascular cognitive impairment, reflecting blood-brain barrier breakdown.
“First, the plasma protein albumin is increased in the CSF of patient with VCI, reflecting BBB breakdown (Candelario-Jalil et al., 2011).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Candelario-Jalil et al., 2011 source
Not checked in the free run.
- Premisecitation
Alterations in blood-brain barrier permeability are associated with leukoaraiosis and lacunar stroke.
“Reflecting another aspect of endothelial dysfunction, alterations in BBB permeability are also associated with leukoaraiosis and lacunar stroke (Wardlaw et al., 2013a; Yang and Rosenberg, 2011).”
Quote in the paperSubstantial claim0 of 2 sources checked- cites Wardlaw et al., 2013a
Not checked in the free run.
- cites Yang and Rosenberg, 2011
Not checked in the free run.
- Premisecitation
The blood-brain barrier is disrupted during the course of vascular cognitive impairment.
“Several lines of evidence indicate that the BBB is disrupted in the course of the disease.”
Quote in the paperSubstantial claim - Premisecitation
The ability of vessels to adjust cerebral perfusion in response to blood pressure changes is blunted in patients with diabetes or hypertension.
“Thus, functional hyperemia and endothelium dependent responses are attenuated in models of aging, hypertension, and diabetes (Ergul, 2011; Kazama et al., 2004; Park et al., 2007), whereas the ability of the vessels to adjust cerebral perfusion in response to changes in blood pressure (autoregulation) is blunted in patients with diabetes or hypertension (Kim et al., 2008b; Novak et al., 2003).”
Quote in the paperSubstantial claim0 of 2 sources checked- cites Kim et al., 2008b
Not checked in the free run.
- cites Novak et al., 2003 source
Not checked in the free run.
- Premisecitation
In stroke-prone spontaneously hypertensive rats, a high salt diet induces fast-developing vasculopathy with blood-brain barrier leakage that leads to ischemic injury without arterial occlusions.
“In stroke prone spontaneously hypertensive rats, which have a strong vascular risk factor profile, a high salt diet induces fast-developing vasculopathy with BBB leakage that leads to ischemic injury in the absence of arterial occlusions (Schreiber et al., 2013).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Schreiber et al., 2013 source
Not checked in the free run.
- Premisecitation
Inhibition or genetic inactivation of NADPH oxidase ameliorates vascular dysfunction.
“NADPH oxidase, a multiunit enzyme particularly enriched in cerebral blood vessels (Miller et al., 2005), has emerges as an important source in vascular oxidative stress in aging, hypertension, hyperlipidemia and diabetes (Faraci, 2011), and inhibition or genetic inactivation of this enzyme has been shown to ameliorate the vascular dysfunction (Drummond et al., 2011).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Drummond et al., 2011 source
Not checked in the free run.
- Premisecitation
Colony-forming units, a subset of endothelial progenitor cells, have impaired ability to form vascular tubes in matrigel in patients with large artery atherosclerosis or lacunar stroke.
“For example, the ability of colony forming units, a subset of EPC, to form vascular tubes in a matrigel assay is impaired patients with large artery atherosclerosis or lacunar stroke (Chu et al., 2008).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Chu et al., 2008 source
Not checked in the free run.
- Premisecitation
Markers of endothelial activation, hemostasis, inflammation, and oxidative stress are upregulated in blood, consistent with systemic effects.
“Markers of endothelial activation, hemostasis, inflammation and oxidative stress are also upregulated in blood, consistent with more widespread effects in the systemic circulation (Gallacher et al., 2010; Knottnerus et al., 2010; Markus et al., 2005; Rouhl et al., 2012a; Shibata et al., 2004; Xu et al., 2010) (fig. 6).”
Quote in the paperNot a substantial claim0 of 3 sources checked - Interpretationcitation
Chronic blood-brain barrier disruption has the potential to induce ischemic damage.
“This finding indicates that chronic BBB disruption has the potential of induce ischemic damage.”
Quote in the paperSubstantial claim - Premisecitation
Reactive oxygen species and inflammation suppress endothelial prosurvival signaling to neurons by reducing BDNF through impaired integrin-linked kinase signaling.
“ROS and inflammation suppress the prosurvival action of endothelial cells on neurons by reducing BDNF levels, an effect mediated by impairing integrin linked kinase signaling (Guo et al., 2008).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Guo et al., 2008 source
Not checked in the free run.
- Premisecitation
In vivo, hypoperfusion produced by bilateral carotid stenosis in rats increases blood-brain barrier permeability.
“In vivo, hypoperfusion produced by bilateral carotid stenosis in rat increases BBB permeability (Ueno et al., 2002).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Ueno et al., 2002 source
Not checked in the free run.
- Premisecitation
Pathological studies show markers of oxidative stress and inflammation in damaged white matter associated with vascular cognitive impairment.
“Pathological studies have shown markers of oxidative stress (isoprostanes) and inflammation (cytokines and adhesion molecules) in the damaged white matter associated with VCI (Back et al., 2011; Candelario-Jalil et al., 2011; Fernando et al., 2006).”
Quote in the paperSubstantial claim0 of 3 sources checked - Premisecitation
Functional hyperemia and endothelium-dependent responses are attenuated in models of aging, hypertension, and diabetes.
“Thus, functional hyperemia and endothelium dependent responses are attenuated in models of aging, hypertension, and diabetes (Ergul, 2011; Kazama et al., 2004; Park et al., 2007), whereas the ability of the vessels to adjust cerebral perfusion in response to changes in blood pressure (autoregulation) is blunted in patients with diabetes or hypertension (Kim et al., 2008b; Novak et al., 2003).”
Quote in the paperSubstantial claim0 of 3 sources checked - Premisecitation
Fibrinogen extravasation activates inflammatory pathways through integrin and Toll-like receptors, leading to microglial and astrocyte activation.
“In particular, fibrinogen extravasation activates inflammatory pathway through its interaction with integrin (CD11b/CD18) and non-integrin receptors (TLRs), leading to activation of microglia and astrocytes (Davalos and Akassoglou, 2012; Davalos et al., 2012) (fig. 6).”
Quote in the paperSubstantial claim0 of 2 sources checked- cites Davalos and Akassoglou, 2012
Not checked in the free run.
- cites Davalos et al., 2012
Not checked in the free run.
- Premisecitation
Microglial activation and reactive astrocytes are present in vascular cognitive impairment lesions.
“Furthermore, microglial activation and reactive astrocytes are also present in the lesions (Akiguchi et al., 1998; Simpson et al., 2007; Tomimoto et al., 1996) (fig. 6).”
Quote in the paperNot a substantial claim0 of 3 sources checked - Interpretationcitation
Extravasation of plasma proteins due to blood-brain barrier alterations likely contributes to inflammation and free radical production because fibrinogen, immunoglobulins, and complement are potent activators.
“Extravasation of plasma proteins, due to the BBB alterations, is also likely to play a role, since fibrinogen, immunoglobulins, and complement are potent activators of inflammation and free radical production (Crehan et al., 2013; Davalos and Akassoglou, 2012; Yoshida et al., 2002).”
Quote in the paperNot a substantial claim0 of 3 sources checked - Premisecitation
Scavenging free radicals or suppressing inflammation counteracts white matter damage and behavioral deficits in rodent models of cerebral hypoperfusion.
“Accordingly, scavenging of free radicals or approaches to suppress inflammation counteract white matter damage and behavioral deficits in rodent models of cerebral hypoperfusion (Dong et al., 2011; Kim et al., 2008a; Maki et al., 2011; Ueno et al., 2009; Wakita et al., 2008; Wang et al., 2010; Washida et al., 2010; Zhang et al., 2011).”
Quote in the paperNot a substantial claim0 of 3 sources checked - Premisecitation
Endothelial progenitor cells may be less functionally competent in patients with vascular risk factors and stroke.
“In addition, EPC may be less functionally competent in patients with vascular risk factors and stroke.”
Quote in the paperNot a substantial claim - Premisecitation
Damage to neurons and glia is associated with endothelial cell atrophy and microvascular rarefaction due to loss of trophic support.
“Owing to their trophic support of vascular cells, dysfunction and damage to neurons and glia is associated with endothelial cell atrophy and microvascular rarefaction (Brown and Thore, 2011).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Brown and Thore, 2011 source
Not checked in the free run.
- Premisecitation
In diabetes models, advanced glycation end-products cause endothelial MMP9 secretion and cleavage of the BDNF receptor TRKB ectodomain on neurons, reducing neurotrophic signaling.
“In models of diabetes, advanced glycation end-products lead to MMP9 secretion by endothelial cells and cleavage of the ectodomain of the BDNF receptor TRKB on neurons, reducing neurotrophic signaling (Navaratna et al., 2013).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Navaratna et al., 2013 source
Not checked in the free run.
- Premisecitation
Attempts to remyelinate are present in damaged white matter in leukoaraiosis.
“Attempts to remyelinate are present in the damaged white matter in leukoaraiosis (Jonsson et al., 2012).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Jonsson et al., 2012 source
Not checked in the free run.
- Premisecitation
Dysregulation of Wnt signaling could contribute to oligodendrocyte progenitor cell developmental arrest.
“Dysregulation of the Wnt signaling pathway could also play a role in the OPC developmental arrest (Fancy et al., 2011b).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Fancy et al., 2011b
Not checked in the free run.
- Interpretationcitation
Focal cortical thinning observed in a prospective CADASIL study after subcortical infarct indicates a causal link between white matter lesions and cortical atrophy.
“Focal cortical thinning was also observed in a prospective study of patients with CADASIL subsequent to a subcortical infarct (Duering et al., 2012), indicating a causal link between white matter lesions and cortical atrophy.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Duering et al., 2012 source
Not checked in the free run.
- Premisecitation
Oligodendrocytes are susceptible to damage by extracellular ATP, which increases in hypoxia-ischemia, through P2X7 purinergic receptors.
“Oligodendrocytes are also susceptible to damage caused by extracellular ATP, which increases in hypoxia-ischemia, through activation of the P2X7 purinergic receptors (Domercq et al., 2010).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Domercq et al., 2010 source
Not checked in the free run.
- Interpretationreasoning
Hypoperfusion and blood-brain barrier disruption cause additional oxidative stress by inducing tissue hypoxia and extravasation of plasma proteins such as fibrinogen.
“In turn, hypoperfusion and BBB disruption lead to additional oxidative stress by inducing tissue hypoxia and by extravasation of plasma proteins, such as fibrinogen.”
Quote in the paperSubstantial claim - Premisecitation
Reductions in white matter cerebral blood flow are found in X-linked adrenoleukodystrophy.
“Reductions in white matter CBF has also been found X-linked adrenoleukodystrophy (ALD), a disease caused by mutations in ABCD1, which encodes a peroxisomal membrane transporter protein, leading to accumulation of very long chain fatty acids in brain, spinal cord and adrenal glands (Moser et al., 2000).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Moser et al., 2000 source
Not checked in the free run.
- Premisecitation
Oligodendrocyte progenitor cells in late development are particularly susceptible to injury under chronic hypoxia and oxidative stress in ischemic white matter.
“First, OPC in the late stage of development are particularly susceptible to injury in conditions of chronic hypoxia and oxidative stress existing in the ischemic white matter (Back et al., 2011; 2002; Fernando et al., 2006; French et al., 2009).”
Quote in the paperSubstantial claim0 of 3 sources checked - Premisecitation
In demyelinating diseases including leukoaraiosis, axons fail to fully remyelinate.
“However, in demyelinating diseases, including leukoaraiosis, axons fail to fully remyelinate (Franklin and Ffrench-Constant, 2008).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Franklin and Ffrench-Constant, 2008 source
Not checked in the free run.
- Premisecitation
Studies coupling cerebral blood flow measurements in normal-appearing white matter to diffusion tensor imaging found that flow reductions are associated with restricted diffusion, not increased fractional anisotropy as expected if secondary to Wallerian degeneration.
“Studies in which CBF measurements in the normal appearing white matter were coupled to diffusion tensor imaging, revealed that the reductions in CBF are associated with restricted diffusion and not with increased fractional anisotropy, as anticipated if the CBF changes were secondary to Wallerian degeneration (Saindane et al., 2007).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Saindane et al., 2007
Not checked in the free run.
- Premisecitation
Patients with leukoaraiosis lose brain volume at about 1% per year, twice the rate of age-matched controls.
“These processes are likely to play a role in the progressive cerebral atrophy observed in patients with leukoaraiosis, who experience a brain volume loss of 1% per year, twice that of age matches controls (Nitkunan et al., 2011).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Nitkunan et al., 2011 source
Not checked in the free run.
- Premisecitation
The energy saved by myelination is partly offset by the high estimated cost of maintaining oligodendrocyte resting potential.
“Some of the energy saving afforded by myelination is offset by the cost of maintaining the resting potential of oligodendrocytes, which is estimated to be high (Harris and Attwell, 2012).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Harris and Attwell, 2012
Not checked in the free run.
- Premisecitation
Capillary density is reduced at lesioned sites and in normal-appearing white matter in patients with vascular cognitive impairment.
“Accordingly, capillary density is reduced not only at lesioned sites, but also in normal appearing white matter in patients with VCI (Brown et al., 2007).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Brown et al., 2007 source
Not checked in the free run.
- Premisecitation
HIF-1α and dependent genes are upregulated in normal-appearing white matter in multiple sclerosis, consistent with the hypoperfusion hypothesis.
“Consistent with the hypoperfusion hypothesis, HIF-1α and dependent genes are upregulated in normal appearing white matter (Graumann et al., 2003).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Graumann et al., 2003
Not checked in the free run.
- Interpretationreasoning
After demyelination, increased energy demand of denuded axons aggravates hypoxic stress, creating a vicious circle that perpetuates pathogenic processes and worsens tissue damage.
“Once demyelination occurs, the increased energy requirement of the denuded axons aggravates the hypoxic stress of the tissue, leading to a vicious circle that perpetuates these pathogenic processes and exacerbates the tissue damage.”
Quote in the paperSubstantial claim - Interpretationcitation
Withdrawal of trophic support from damaged endothelial cells and astrocytes could reduce oligodendrocyte progenitor cell pool vitality and contribute to their demise in hypoxic vulnerable white matter.
“Second, withdrawal of trophic support from damaged endothelial cells and astrocytes could reduce the vitality of the OPC pool and contribute to their demise in the hypoxic environment of the vulnerable white matter (Arai and Lo, 2010).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Arai and Lo, 2010 source
Not checked in the free run.
- Interpretationreasoning
The reviewed evidence suggests a convergence of pathogenic factors on cerebral blood vessels that leads to white matter damage.
“The evidence reviewed above suggests a convergence of pathogenic factors on cerebral blood vessels, which in turn leads to white matter damage (figs. 6, 7).”
Quote in the paperSubstantial claim - Interpretationnone given
Failure to remyelinate could be related to an arrest in oligodendrocyte progenitor cell maturation.
“Third, failure to remyelinate could be related to an arrest in OPC maturation.”
Quote in the paperNot a substantial claim - Premisecitation
Oligodendrocytes release growth factors such as IGF-1 and glial cell-derived neurotrophic factor that support axon survival.
“Oligodendrocytes release growth factors, such as IGF-1 and glial cell-derived neurotrophic factor that support the survival of axons (Wilkins et al., 2003).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Wilkins et al., 2003 source
Not checked in the free run.
- Premisecitation
Intracellular Na+ accumulation reverses the Na+/Ca2+ exchanger, causing intracellular Ca2+ accumulation.
“The resulting accumulation of intracellular Na+ reverses the operation of the Na+/Ca2+ exchanger, resulting in intracellular Ca2+ accumulation (Matute and Ransom, 2012; Stys et al., 1992).”
Quote in the paperSubstantial claim0 of 2 sources checked - Interpretationreasoning
Tissue edema from increased blood-brain barrier permeability may worsen these alterations by compressing blood vessels and further reducing cerebral blood flow.
“Tissue edema resulting from increased BBB permeability may exacerbate these alterations by compressing blood vessels and reducing CBF further.”
Quote in the paperSubstantial claim - Interpretationreasoning
Oxidative stress-induced endothelial dysfunction caused by risk factors is most likely an early event leading to white matter damage.
“Oxidative stress-induced endothelial dysfunction caused by risk factors is most likely an early event leading to white matter damage.”
Quote in the paperSubstantial claim - Interpretationcitation
These processes likely contribute to progressive cerebral atrophy in patients with leukoaraiosis.
“These processes are likely to play a role in the progressive cerebral atrophy observed in patients with leukoaraiosis, who experience a brain volume loss of 1% per year, twice that of age matches controls (Nitkunan et al., 2011).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Nitkunan et al., 2011 source
Not checked in the free run.
- Premisecitation
Blood-brain barrier alterations predict disease progression in adrenoleukodystrophy.
“BBB alterations predict disease progression (Melhem et al., 2000).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Melhem et al., 2000
Not checked in the free run.
- Premisecitation
It has not been established whether white matter lesions cause atrophy independently of age and other risk factors.
“However, it has not been established whether white matter lesions cause the atrophy independently of age and other risk factors (Appelman et al., 2009; 2010).”
Quote in the paperNot a substantial claim0 of 2 sources checked - Interpretationcitation
Emerging evidence suggests that reduced cerebral perfusion may contribute to other diseases characterized by white matter damage.
“There is emerging evidence that reduced cerebral perfusion may contribute to other diseases characterized by white matter damage.”
Quote in the paperSubstantial claim - Interpretationreasoning
Tissue hypoxia and oxidative stress activate inflammatory pathways through NFκb-dependent transcription, producing cytokines and adhesion molecules in vascular cells, reactive astrocytes, and activated microglia.
“Tissue hypoxia and oxidative stress activate inflammatory pathways through NFκb-dependent transcription, leading to production of cytokines and adhesion molecules in vascular cells, reactive astrocytes and activated microglia.”
Quote in the paperSubstantial claim - Interpretationreasoning
Oligodendrocyte damage, oxidative stress, and inflammation lead to demyelination and attempted remyelination through oligodendrocyte progenitor cell proliferation.
“Oligodendrocyte damage, oxidative stress and inflammation lead to demyelination and attempted remyelination through OPC proliferation.”
Quote in the paperSubstantial claim - Interpretationnone given
Damage to myelin and demyelination is a consequence of the oxidative and proinflammatory environment induced by hypoperfusion and blood-brain barrier breakdown.
“One of the consequences of the oxidative and proinflammatory environment induced by hypoperfusion and BBB breakdown is damage to the myelin sheet and demyelination.”
Quote in the paperSubstantial claim - Premisecitation
In active multiple sclerosis lesions with blood-brain barrier disruption, cerebral blood flow is increased, consistent with inflammation-induced vasodilatation.
“In contrast, in active lesions displaying BBB disruption CBF is increased, consistent with vasodilatation caused by inflammation (D’haeseleer et al., 2011).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites D’haeseleer et al., 2011 source
Not checked in the free run.
- Premisecitation
Angiogenic T-cell migration in vitro positively correlates with preserved endothelium-dependent vasodilatation in patients with cardiovascular risk factors.
“Furthermore, angiogenic T-cells migration in vitro is positively correlated with preservation of endothelium-dependent vasodilatation in patients with cardiovascular risk factors (Weil et al., 2011), highlighting their protective role in vascular function.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Weil et al., 2011 source
Not checked in the free run.
- Premisecitation
APP-overexpressing mice sustain greater brain damage after middle cerebral artery occlusion.
“APP-overexpressing mice have increased brain damage following occlusion of the middle cerebral artery (Koistinaho et al., 2002; Zhang et al., 1997)”
Quote in the paperSubstantial claim0 of 2 sources checked - Premisecitation
Hypoperfusion and hypoxia from vascular insufficiency may promote amyloid-beta production by activating the APP cleavage enzyme beta-secretase.
“Hypoperfusion and hypoxia caused by vascular insufficiency may also facilitate Aβ production by activating the APP cleavage enzyme β-secretase (Kitaguchi et al., 2009; Sun et al., 2006; Tesco et al., 2007; Wen et al., 2004a).”
Quote in the paperNot a substantial claim0 of 3 sources checked - Premisecitation
In older individuals with moderate Alzheimer disease pathology, subcortical vascular lesions are a major determinant of dementia expression.
“On the other hand, in older individuals with moderate AD pathology subcortical vascular lesions are a major determinant of the expression of the dementia (Esiri et al., 1999; Schneider et al., 2007b; Snowdon et al., 1997).”
Quote in the paperSubstantial claim0 of 3 sources checked - Premisecitation
Activation of NADPH oxidase involves the amyloid-beta-binding scavenger receptor CD36.
“The mechanisms of NADPH oxidase activation involve the Aβ-binding scavenger receptor CD36 (Park et al., 2011).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Park et al., 2011 source
Not checked in the free run.
- Interpretationreasoning
These observations highlight the importance of neurovascular factors in maintaining white matter health.
“Collectively, these observations highlight the importance of neurovascular factors in maintaining white matter health.”
Quote in the paperSubstantial claim - Interpretationreasoning
Hypoperfusion and blood-brain barrier disruption appear to be necessary correlates of the process leading to white matter damage regardless of the primary disease cause.
“Thus, hypoperfusion and BBB disruption seem necessary correlates of the process leading to white matter damage independently of the primary disease cause.”
Quote in the paperSubstantial claim - Premisecitation
Cerebral ischemia promotes the formation of amyloid plaques.
“Cerebral ischemia promotes amyloid plaque formation (Garcia-Alloza et al., 2011; Kitaguchi et al., 2009; Okamoto et al., 2012)”
Quote in the paperSubstantial claim0 of 3 sources checked - Interpretationnone given
Inherited and autoimmune white matter diseases show cerebrovascular alterations before pathology develops, similar to white matter disease caused by vascular factors.
“It is noteworthy that, despite fundamental differences in their pathogenesis, inherited and autoimmune diseases of the white matter exhibit cerebrovascular alterations before pathology develops, just like in white matter disease caused by vascular factors.”
Quote in the paperSubstantial claim - Premisecitation
Brain amyloid-beta is transported along a perivascular pathway that drains into the cervical lymph nodes.
“Brain Aβ is transported along the perivascular pathway draining into the cervical lymphnodes (Carare et al., 2013; Iliff et al., 2013).”
Quote in the paperNot a substantial claim0 of 2 sources checked - Premisecitation
The cognitive impact of vascular and Alzheimer disease neuropathology depends on the severity of Alzheimer pathology and the location of vascular lesions.
“The cognitive impact of vascular and AD neuropathology depends on the severity of the AD pathology and location of the vascular lesions (Gold et al., 2007).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Gold et al., 2007 source
Not checked in the free run.
- Premisecitation
Reductions in cerebral blood flow before white matter damage were observed in a patient with Alexander disease caused by a dominant GFAP mutation.
“Reductions in CBF prior to white matter damage were also observed in a patient with Alexander disease, a rare childhood disease caused by a dominant mutation of the GFAP gene (Ito et al., 2009).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Ito et al., 2009 source
Not checked in the free run.
- Interpretationcitation
CD36, present in vascular and perivascular cells, may contribute to amyloid-beta accumulation in cerebral blood vessels.
“Thus, CD36, which is located in vascular and perivascular cells, may contribute to the accumulation of Aβ in cerebral blood vessels.”
Quote in the paperSubstantial claim - Premisecitation
The vascular pathway is estimated to be a major route for removing amyloid-beta from the brain.
“The vascular pathway is estimated to be a major route of removal of Aβ from the brain (Castellano et al., 2012; Shibata et al., 2000).”
Quote in the paperNot a substantial claim0 of 2 sources checked - Premisecitation
Cerebral blood volume or cerebral blood flow is reduced in normal-appearing and abnormal white matter in adrenoleukodystrophy.
“Cerebral blood volume, assessed by susceptibility contrast MRI (Musolino et al., 2012), or CBF, assessed by single photon emission tomography (Suhaili et al., 1994), is reduced in the normal appearing and abnormal white matter.”
Quote in the paperSubstantial claim0 of 2 sources checked - Premisecitation
Alzheimer disease and cerebrovascular diseases may share common risk factors such as hypertension, insulin resistance, diabetes, obesity, hyperhomocystinemia, and hyperlipidemia.
“Furthermore, AD and cerebrovascular diseases may have common risk factors, such as hypertension, insulin resistance, diabetes, obesity, hyperhomocystinemia, hyperlipidemia, etc. (Craft, 2009; Fillit et al., 2008; Honjo et al., 2012; Purnell et al., 2009).”
Quote in the paperNot a substantial claim0 of 3 sources checked - Interpretationcitation
The vascular effects of amyloid-beta may impair clearance of the peptide, which is a key factor in brain amyloid-beta accumulation in sporadic Alzheimer's disease.
“The vascular effects of Aβ may also impair the clearance of the peptide, a key factor in brain Aβ accumulation in sporadic AD (Mawuenyega et al., 2010).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Mawuenyega et al., 2010 source
Not checked in the free run.
- Premisecitation
The correlation between vascular risk factors and dementia was most evident when risk factors were considered together rather than individually.
“However, the correlation was most evident when the risk factors were considered together and not individually (Chui et al., 2012).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Chui et al., 2012
Not checked in the free run.
- Premisecitation
Amyloid-beta constricts isolated blood vessels from the brain and systemic circulation.
“Aβ4 constrict isolated cerebral and systemic blood vessels (Niwa et al., 2001; Paris et al., 2003; Thomas et al., 1996)”
Quote in the paperSubstantial claim0 of 3 sources checked - Premisecitation
Prospective cohorts with autopsy-confirmed clinical diagnosis failed to establish a link between Alzheimer disease pathology burden and vascular risk factors.
“In contrast, studies that have prospectively evaluated representative patients cohorts with confirmation of the clinical diagnosis at autopsy failed to establish a link between the burden of AD pathology and vascular risk factors (Chui et al., 2012).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Chui et al., 2012
Not checked in the free run.
- Premisecitation
Cerebral ischemia promotes tau phosphorylation.
“and tau phosphorylation (Koike et al., 2010; Wen et al., 2007; 2004b).”
Quote in the paperNot a substantial claim0 of 3 sources checked - Interpretationreasoning
ROS generated by the enzyme NADPH oxidase are involved in the vascular dysfunction.
“implicating ROS produced by the enzyme NADPH oxidase in the vascular dysfunction.”
Quote in the paperSubstantial claim - Premisecitation
The greater brain damage in APP-overexpressing mice after middle cerebral artery occlusion is partly due to poor collateral circulation from vascular dysregulation.
“an effect in part related to poor collateral circulation due to vascular dysregulation (Zhang et al., 1997)”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Zhang et al., 1997 source
Not checked in the free run.
- Premisecitation
Suppression of LRP1 in vascular smooth muscle cells due to upregulation of serum response factor and myocardin is a key factor in the clearance impairment.
“In particular, suppression of LRP1 in vascular smooth muscle cells due to upregulation of serum response factor and myocardin, is a key factor in the clearance impairment (Bell et al., 2009).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Bell et al., 2009 source
Not checked in the free run.
- Interpretationcitation
Improving vascular health may also help in Alzheimer's disease.
“these observations provide initial evidence that improving vascular health may also help in AD.”
Quote in the paperSubstantial claim - Premisecitation
The most widely used animal model for vascular cognitive impairment has been white matter damage produced by chronic forebrain ischemia.
“the most widely used has been white matter damage produced by chronic forebrain ischemia (Ihara and Tomimoto, 2011).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Ihara and Tomimoto, 2011
Not checked in the free run.
- Interpretationreasoning
Vascular pathology is an integral part of Alzheimer's disease and other late-life neurodegenerative conditions associated with dementia, and plays a defining role in the expression of cognitive dysfunction.
“Vascular pathology is also an integral part of AD and other late-life neurodegenerative conditions associated with dementia, and play a defining role in the expression of the cognitive dysfunction.”
Quote in the paperSubstantial claim - Interpretationreasoning
The resulting demyelination and axonal loss contribute to the broad functional brain changes underlying cognitive impairment and to the associated cerebral atrophy.
“The resulting demyelination and axonal loss plays a role in the broad functional brain changes underlying cognitive impairment and in the associated cerebral atrophy.”
Quote in the paperSubstantial claim - Premisecitation
Control of vascular risk factors may delay disease progression, at least early in the disease course.
“and may delay disease progression (Deschaintre et al., 2009), at least early in the disease course (Richard et al., 2010).”
Quote in the paperSubstantial claim0 of 2 sources checked - Interpretationcitation
Increasing evidence indicates that preventive measures can reduce the risk of vascular cognitive impairment and vascular dementia.
“On the other hand, increasing evidence indicates that the risk of VCI and vascular dementia can be reduced by preventive measures.”
Quote in the paperSubstantial claim - Premisecitation
Experimental studies indicate that the clearance mechanism is altered when vascular dysfunction and damage are present, contributing to parenchymal and vascular amyloid-beta accumulation.
“Experimental studies indicate that this clearance mechanism is altered in the presence of vascular dysfunction and damage, contributing to parenchymal and vascular Aβ accumulation (Deane et al., 2004; Park et al., 2013b).”
Quote in the paperSubstantial claim0 of 2 sources checked- cites Deane et al., 2004 source
Not checked in the free run.
- cites Park et al., 2013b
Not checked in the free run.
- Premisecitation
Treatment with antioxidants, anti-inflammatory agents, or agents that increase cerebral perfusion has not produced consistent results.
“Treatment with antioxidants, anti-inflammatory agents or agents increasing cerebral perfusion have not led to consistent results (Butler and Radhakrishnan, 2012).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Butler and Radhakrishnan, 2012
Not checked in the free run.
- Premisecitation
Other approaches have attempted to promote remyelination by stimulating the survival and differentiation of oligodendrocyte precursor cells.
“Other approaches have attempted to promote remyelination by stimulating the survival and differentiation of OPC (Miyamoto et al., 2010).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Miyamoto et al., 2010 source
Not checked in the free run.
- Interpretationreasoning
Alzheimer's disease is frequently associated with cerebral macro- and microvascular pathology, which can contribute to the expression of dementia.
“These lines of evidence suggest that AD is frequently associated with cerebral macro- and micro-vascular pathology, which can contribute to the expression of the dementia.”
Quote in the paperSubstantial claim - Premisecitation
Amyloid-beta is cleared from the brain through a transvascular transport system involving LRP-1.
“Aβ is cleared from the brain through a transvascular transport system involving LRP-1 (Shibata et al., 2000)”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Shibata et al., 2000 source
Not checked in the free run.
- Premisecitation
ApoE4-positive individuals may develop age-dependent blood-brain barrier breakdown before cognitive decline.
“ApoE4 positive individuals may develop a similar age-dependent BBB breakdown prior to cognitive decline (Halliday et al., 2013).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Halliday et al., 2013 source
Not checked in the free run.
- Premisecitation
Developing treatments for vascular cognitive impairment has been hampered by the lack of a suitable animal model that recapitulates the multifaceted features of the disease.
“The development of treatments for VCI has been hampered by the lack of a suitable animal model recapitulating the multifaceted features of the disease (Gorelick et al., 2011).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Gorelick et al., 2011 source
Not checked in the free run.
- Premisecitation
ApoE4, a major genetic risk factor for Alzheimer's disease, causes blood-brain barrier disruption through a proinflammatory pathway involving cyclophilin A in pericytes.
“ApoE4, a major genetic risk factor for AD, leads to BBB disruption through a proinflammatory pathway involving cyclophilin A in pericytes (Bell et al., 2012).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Bell et al., 2012 source
Not checked in the free run.
- Premisecitation
Preliminary evidence suggests that controlling vascular risk factors reduces vascular lesions in Alzheimer's disease.
“Preliminary evidence suggests that control of vascular risk factors reduces vascular lesions in AD (Richard et al., 2010)”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Richard et al., 2010 source
Not checked in the free run.
- Premisecitation
Activation of this pathway causes MMP-9-mediated degradation of endothelial tight junctions and basement membrane proteins, as shown in human ApoE4 targeted replacement mice.
“Activation of this pathway causes MMP-9-mediated degradation of endothelial tight junctions and basement membrane proteins, as shown in human ApoE4 targeted replacement mice (Bell et al., 2012).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Bell et al., 2012 source
Not checked in the free run.
- Premisecitation
LRP-1 works together with P-glycoprotein, ApoE, ApoJ, and alpha2-macroglobulin to regulate brain amyloid-beta homeostasis.
“a protein that acts in concert with P-glycoprotein, ApoE, ApoJ, and α2-macroglobulin to regulate brain Aβ homeostasis (Zlokovic, 2008).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Zlokovic, 2008 source
Not checked in the free run.
- Interpretationreasoning
Vascular cells play a critical role in maintaining the health of neurons, glia, and myelin.
“This chain of events highlights the critical role that vascular cells play in the maintenance of the health of neurons, glia and myelin.”
Quote in the paperSubstantial claim - Premisecitation
Patients with vascular risk factors such as hypertension, sedentary lifestyle, or ApoE4 genotype show a greater tendency for amyloid accumulation.
“In patients with vascular risk factors, such as hypertension, sedentary life style, or ApoE4 genotype, there is a greater tendency for amyloid accumulation (Head et al., 2012; Rodrigue et al., 2013)”
Quote in the paperSubstantial claim0 of 2 sources checked - Interpretationreasoning
The collected observations suggest a link between cerebrovascular health and brain amyloid-beta clearance.
“Collectively, these observations suggest a link between cerebrovascular health and brain Aβ clearance.”
Quote in the paperSubstantial claim - Interpretationreasoning
The vasoactivity of amyloid-beta and the influence of cerebral perfusion on APP processing and amyloid-beta clearance suggest that cerebral blood vessels can have a role in amyloid-beta accumulation in the brain parenchyma and cerebral blood vessels.
“The vasoactivity of Aβ and the influence of cerebral perfusion on APP processing and Aβ clearance suggest that cerebral blood vessels can have a role the accumulation of Aβ in the brain parenchyma and cerebral blood vessels.”
Quote in the paperSubstantial claim - Premisecitation
Amyloid accumulation is reduced in patients who exercise regularly.
“whereas amyloid accumulation is reduced in patients who exercise regularly (Liang et al., 2010).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Liang et al., 2010 source
Not checked in the free run.
- Premisecitation
Weight control, a healthy diet, nonsmoking, physical activity, and keeping total cholesterol, blood pressure, and fasting glucose at goal levels are associated with better cognitive performance later in life.
“This hypothesis is supported by a study indicating that weight control, a healthy diet, nonsmoking, physical activity, and keeping total cholesterol, blood pressure, and fasting glucose at goal levels are associated with better cognitive performance later in life (Reis et al., 2013).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Reis et al., 2013 source
Not checked in the free run.
- Premisecitation
These models have shown that counteracting some pathogenic factors, including chronic ischemia, inflammation, and oxidative stress, reduces white matter damage and/or behavioral deficits.
“These models have demonstrated that counteracting some of the pathogenic factors, including chronic ischemia, inflammation and oxidative stress, reduce white matter damage and/or behavioral deficits (Dong et al., 2011; Ihara and Tomimoto, 2011; Maki et al., 2011).”
Quote in the paperSubstantial claim0 of 3 sources checked
- May combine two claims. 77
- Classified as probably not a substantial claim. 6
May combine two claims.
InterpretationreasoningThe neurovascular unit acts as an important checkpoint that regulates the afferent and efferent arms of the immune system and shapes brain immune responses.
“Therefore, the neurovascular unit is an important checkpoint regulating the afferent and efferent arms of the immune system and shaping the immune responses of the brain.”
Quote in the paperNot a substantial claimMay combine two claims.
PremisecitationCerebrovascular disease is a primary cause of cognitive impairment and also amplifies dementia caused by other factors, including Alzheimer's disease.
“Recent clinical-pathological studies have highlighted the role of cerebrovascular disease, not only as a primary cause of cognitive impairment, but also as an adjuvant to the expression of dementia caused by other factors, including AD and other neurodegenerative pathologies (Gorelick et al., 2011; Schneider et al., 2007a; Toledo et al., 2013).”
Quote in the paperSubstantial claim0 of 3 sources checkedMay combine two claims.
PremisecitationOcclusion of penetrating arterioles or venules cannot be compensated by anastomotic branches and produces small ischemic lesions resembling microinfarcts.
“occlusion of penetrating arterioles or venules, unlike pial vessels, cannot be effectively compensated by anastomotic branches (Blinder et al., 2013), and results in reductions in flow sufficient to produce small ischemic lesions akin to microinfarcts (Nguyen et al., 2011; Nishimura et al., 2010; Shih et al., 2013).”
Quote in the paperSubstantial claim0 of 3 sources checkedMay combine two claims.
PremisecitationDeep white matter is supplied by long penetrating arterioles at border zones between vascular territories and is more vulnerable to reduced blood flow.
“regions of the deep white matter are supplied by long penetrating arterioles arising from the pial cortical network at the border between non-overlapping vascular territories of the anterior and middle cerebral arteries, and as such are more vulnerable to reductions in blood flow (Brown and Thore, 2011; De Reuck, 1971)”
Quote in the paperSubstantial claim0 of 2 sources checkedMay combine two claims.
PremisecitationWhite matter uses one-third less energy and receives one-third less blood flow than gray matter.
“Due to fewer synapses, white matter energy usage, and consequently blood flow, is 1/3 lower of that of the gray matter (Harris and Attwell, 2012).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Harris and Attwell, 2012
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationVascular dementia accounts for at least 20% of dementia cases and is second only to Alzheimer's disease.
“Vascular dementia, a heterogeneous group of brain disorders in which cognitive impairment is attributable to cerebrovascular pathologies, is responsible for at least 20% of cases of dementia, being second only to Alzheimer’s disease (AD) (Gorelick et al., 2011).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Gorelick et al., 2011 source
Not checked in the free run.
May combine two claims.
InterpretationreasoningNeurovascular cells are trophically and metabolically interdependent, so damage to one cell type removes vital support and harms other cell types.
“Therefore, neurovascular cells are trophically and metabolically interdependent, such that damage to one cell type removes a vital source of support to the whole unit and has deleterious consequences also for the other cell types.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationThe neurovascular unit is a functional domain formed by the close developmental, structural, and functional ties between brain vessels and brain tissue.
“The brain vasculature has an intimate developmental, structural and functional relationship with the brain tissue, their cellular elements forming a functional domain termed the neurovascular unit (Iadecola, 2004).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Iadecola, 2004 source
Not checked in the free run.
May combine two claims.
PremisecitationStroke doubles the risk of dementia, and about 30% of stroke patients develop cognitive dysfunction within 3 years.
“Stroke doubles the risk for dementia (post-stroke dementia), and approximately 30% of stroke patients go on to develop cognitive dysfunction within 3 years (Allan et al., 2011; Leys et al., 2005; Pendlebury and Rothwell, 2009).”
Quote in the paperNot a substantial claim0 of 3 sources checkedProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationApoE4 is a well-established susceptibility gene for increased cardiovascular risk and Alzheimer disease.
“The ApoE 4 allele is a well-established susceptibility gene for increased cardiovascular risk and Alzheimer disease (Verghese et al., 2011).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Verghese et al., 2011 source
Not checked in the free run.
May combine two claims.
PremisecitationApoE4 is associated with increased cerebral amyloid angiopathy risk, while ApoE2 and ApoE4 increase the risk of lobar hemorrhages.
“The ApoE4 allele is associated with increased risk of CAA, whereas both ApoE2 and 4 increase the risk of lobar hemorrhages (Charidimou et al., 2012).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Charidimou et al., 2012 source
Not checked in the free run.
May combine two claims.
PremisecitationCADASIL is the most common hereditary vascular cognitive impairment syndrome and is caused by a Notch-3 frameshift mutation that creates or removes a cysteine residue.
“The most common of these is the CADASIL syndrome caused by a frame shift mutation of Notch-3 that either creates or eliminates a cystein residue (Chabriat et al., 2009).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Chabriat et al., 2009 source
Not checked in the free run.
May combine two claims.
PremisecitationAdvanced age is a strong risk factor for vascular cognitive impairment, and the prevalence and incidence of cognitive impairment rise steeply after age 65.
“Advanced age is a powerful risk factor for VCI, and the prevalence and incidence of cognitive impairment increases exponentially after age 65 (Gorelick et al., 2011).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Gorelick et al., 2011 source
Not checked in the free run.
May combine two claims.
PremisecitationReductions in CBF of 40-50% are linked to suppressed brain activity and cognitive dysfunction, which reverse when normal CBF is restored.
“Reductions in CBF by 40–50% are associated with suppression of brain activity and cognitive dysfunction, which are reversible upon re-establishing normal CBF levels (Marshall et al., 1999; Marshall, 2012; Tatemichi et al., 1995).”
Quote in the paperNot a substantial claim0 of 3 sources checkedMay combine two claims.
PremisecitationWhite matter lesions are associated with reduced frontal lobe glucose use, lower global cortical blood flow, disrupted connectivity, and cerebral atrophy.
“Indeed, white matter lesions affect brain structure and function broadly, and are associated with reductions in frontal lobe glucose utilization (Decarli et al., 1995; Haight et al., 2013; Tullberg et al., 2004), global reduction in cortical blood flow (Appelman et al., 2008; Chen et al., 2013a; Dam et al., 2007; Kobari et al., 1990), disruption of brain connectivity (Lawrence et al., 2013; Sun et”
Quote in the paperSubstantial claim0 of 3 sources checkedMay combine two claims.
PremisecitationLinkage studies in patients with MRI white matter lesions discovered several loci, but no specific gene has been identified and the findings await replication and validation.
“Linkage studies in patients with white matter lesions on MRI have discovered several loci (Schmidt et al., 2012), but no specific gene has been identified and the findings await replication and validation (Lee and Kim, 2013; Markus, 2008).”
Quote in the paperNot a substantial claim0 of 3 sources checkedMay combine two claims.
PremisecitationGWAS of vascular dementia show a small effect of SNPs at the androgen receptor gene locus, a finding not observed in all ethnic groups.
“GWAS of vascular dementia have shown small effect of SNPs in the androgen receptor gene locus (Schrijvers et al., 2012), a finding not observed in all ethnic groups (Lee and Kim, 2013).”
Quote in the paperNot a substantial claim0 of 2 sources checkedMay combine two claims.
PremisecitationExpansion of white matter lesions correlates with cognitive decline, and new lacunes cause a steeper decline, especially in motor speed and executive functions.
“The expansion of the white matter lesions correlates with the evolution of the cognitive impairment (Maillard et al., 2012), new lacunes causing a steeper decline, especially in motor speed and executive functions (Jokinen et al., 2011).”
Quote in the paperSubstantial claim0 of 2 sources checkedMay combine two claims.
InterpretationcitationMyelin damage could impair neuroplasticity and skilled motor learning and thereby contribute to cognitive impairment.
“In addition, since myelination of previously naked fibers participates in neuroplasticity and skilled motor learning (Fields, 2010; Richardson et al., 2011), myelin damage could also compromise these important functions and contribute to cognitive impairment.”
Quote in the paperNot a substantial claim0 of 2 sources checkedMay combine two claims.
PremisecitationEducation level does not affect the rate at which vascular cognitive impairment progresses and loses its impact in advanced disease.
“However, the education level does not influence the rate of progression of VCI and no longer has an impact in advanced disease (Elbaz et al., 2013; Zieren et al., 2013).”
Quote in the paperNot a substantial claim0 of 2 sources checkedMay combine two claims.
PremisecitationConfluent white matter lesions and lacunes occur commonly in VCI and show strong links to cardiovascular risk factors such as hypertension, diabetes, hyperlipidemia, and smoking.
“Confluent white matter lesions, the imaging correlate of which is termed leukoaraiosis (fig. 3), and lacunes, small (<1.5 cm) white matter infarcts typically in the basal ganglia, are common occurrence in VCI and are strongly associated with cardiovascular risk factors, especially hypertension, diabetes, hyperlipidemia and smoking (Gorelick et al., 2011; Wardlaw et al., 2013b).”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites Gorelick et al., 2011 source
Not checked in the free run.
- cites Wardlaw et al., 2013b
Not checked in the free run.
May combine two claims.
PremisecitationResting cerebral blood flow is reduced and vascular reactivity is attenuated in areas of leukoaraiosis.
“Resting flow is reduced in areas of leukoaraiosis and vascular reactivity attenuated (Kobari et al., 1990; Makedonov et al., 2013; Markus et al., 2000; 1994; Marstrand et al., 2002; O’Sullivan et al., 2002; Yao et al., 1992).”
Quote in the paperSubstantial claim0 of 3 sources checkedMay combine two claims.
PremisecitationCerebrovascular autoregulation is impaired in vascular cognitive impairment, increasing white matter susceptibility to damage during blood pressure fluctuations.
“Cerebrovascular autoregulation is impaired, increasing the susceptibility of the white matter to damage during fluctuation in blood pressure (Matsushita et al., 1994).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Matsushita et al., 1994 source
Not checked in the free run.
May combine two claims.
PremisecitationLarge vessel stiffness and increased pulsatility are associated with reduced white matter cerebral blood flow and strongly predict leukoaraiosis and lacunes, independently of vascular risk factors.
“Furthermore, stiffness of large vessels and increased pulsatility are associated with reduced white matter CBF and are strong predictors of leukoaraiosis and lacunes (Brisset et al., 2013; Tarumi et al., 2011; Webb et al., 2012), independently of vascular risk factors (Kearney-Schwartz et al., 2009).”
Quote in the paperSubstantial claim0 of 3 sources checkedMay combine two claims.
PremisecitationDeep white matter tracts are especially vulnerable to vascular insufficiency because they lie at distal borders between vascular territories and their vasculature is susceptible to risk factors.
“Owing to their location at the distal border between different vascular territories (De Reuck, 1971) (fig 4) and to the susceptibility of their vasculature to risk factors (Brown and Thore, 2011), deep white matter tracts are particularly vulnerable to vascular insufficiency.”
Quote in the paperSubstantial claim0 of 2 sources checkedMay combine two claims.
InterpretationcitationCerebral blood flow alterations occur in normal-appearing white matter, suggesting that flow reduction precedes and may contribute to white matter damage.
“Interestingly, CBF alterations have also been described in normal appearing white matter (O’Sullivan et al., 2002), suggesting that the flow reduction precedes and, as such, may contribute to the white matter damage.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites O’Sullivan et al., 2002 source
Not checked in the free run.
May combine two claims.
PremisecitationEndothelial progenitor cells are reduced by stroke risk factors and predict cardiovascular morbidity and mortality.
“EPC are reduced by stroke risk factors (Hill et al., 2003) and predict cardiovascular morbidity and mortality (Werner et al., 2005).”
Quote in the paperNot a substantial claim0 of 2 sources checkedMay combine two claims.
InterpretationreasoningBlood-brain barrier disruption may precede white matter injury and contribute to its development.
“The latter finding suggests that the BBB disruption could precede white matter injury and contribute to its development.”
Quote in the paperSubstantial claimMay combine two claims.
PremisecitationHypoxia-ischemia damages endothelial cells and increases blood-brain barrier leakage in vitro.
“Hypoxia-ischemia, which has been demonstrated in white matter lesions, is well known to damage endothelial cells leading to increased BBB leakage in vitro (Ahmad et al., 2012).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Ahmad et al., 2012 source
Not checked in the free run.
May combine two claims.
PremisecitationEndothelial progenitor cells are reduced in age-associated white matter lesions, and the reduction correlates with lesion burden.
“EPC are reduced in age associated white matter lesions, the reduction correlating with lesion burden (Jickling et al., 2009).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Jickling et al., 2009 source
Not checked in the free run.
May combine two claims.
InterpretationcitationBlood-brain barrier leakiness in white matter occurs in lacunar strokes but not cortical strokes, suggesting a specific association with small vessel disease of the deep white matter.
“BBB leakiness in white matter was found in lacunar strokes, but not cortical strokes (Wardlaw et al., 2008), raising the possibility of a specific association with small vessel disease of the deep white matter.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Wardlaw et al., 2008 source
Not checked in the free run.
May combine two claims.
PremisecitationNADPH oxidase is enriched in cerebral blood vessels and is an important source of vascular oxidative stress in aging, hypertension, hyperlipidemia, and diabetes.
“NADPH oxidase, a multiunit enzyme particularly enriched in cerebral blood vessels (Miller et al., 2005), has emerges as an important source in vascular oxidative stress in aging, hypertension, hyperlipidemia and diabetes (Faraci, 2011), and inhibition or genetic inactivation of this enzyme has been shown to ameliorate the vascular dysfunction (Drummond et al., 2011).”
Quote in the paperSubstantial claim0 of 2 sources checkedMay combine two claims.
PremisecitationAngiogenic T-cells are reduced in patients with vascular risk factors and in hypertensive patients with small vessel disease.
“Angiogenic T-cells are reduced in patients with vascular risk factors (Hur et al., 2007; Weil et al., 2011), and in hypertensive patients with small vessels disease (Rouhl et al., 2012b).”
Quote in the paperSubstantial claim0 of 3 sources checkedMay combine two claims.
PremisecitationEndothelial progenitor cell colony-forming units are reduced in Alzheimer disease patients, and the reduction correlates with cognitive impairment severity.
“Interestingly, EPC colony forming units are also reduced in AD patients, in whom the magnitude of the reduction correlates with the degree of cognitive impairment (Lee et al., 2009).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Lee et al., 2009 source
Not checked in the free run.
May combine two claims.
PremisecitationCerebral hypoperfusion is associated with white matter inflammation and oxidative stress in rodent models, indicating that hypoxia-ischemia is sufficient to trigger these responses.
“Cerebral hypoperfusion is associated with white matter inflammation and oxidative stress in rodent models (Dong et al., 2011; Huang et al., 2010; Ihara et al., 2001; Juma et al., 2011; Masumura et al., 2001; Reimer et al., 2011; Yoshizaki et al., 2008), indicating that hypoxia-ischemia is sufficient to trigger these responses.”
Quote in the paperNot a substantial claim0 of 3 sources checkedMay combine two claims.
InterpretationreasoningNeurovascular dysfunction would worsen cerebral blood flow reduction in critically perfused deep white matter and contribute to white matter damage.
“Such neurovascular dysfunction would aggravate the CBF reduction in critically perfused deep white matter regions and contribute to the white matter damage.”
Quote in the paperSubstantial claimMay combine two claims.
PremisecitationPermeability to MRI tracers is increased in white matter lesions and in normal-appearing white matter.
“Third, the permeability to MRI tracers is increased in white matter lesions (Hanyu et al., 2002; Taheri et al., 2011; Wardlaw et al., 2009) and in normal appearing white matter (Topakian et al., 2010).”
Quote in the paperSubstantial claim0 of 3 sources checkedMay combine two claims.
PremisecitationIn a similar model, blood-brain barrier alteration was due to MMP9 production by oligodendrocyte precursors, which are increased in ischemic white matter injury in rodents and in patients with vascular cognitive impairment.
“In a similar model, the BBB alteration was found to be due to MMP9 production by oligodendrocyte precursors, which are increased in ischemic white matter injury in rodent models (Seo et al., 2013) and in patients with VCI (Candelario-Jalil et al., 2011).”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites Seo et al., 2013
Not checked in the free run.
- cites Candelario-Jalil et al., 2011 source
Not checked in the free run.
May combine two claims.
InterpretationreasoningEndothelial dysfunction has two major pathogenic consequences: reduced resting cerebral blood flow in marginally perfused white matter and altered blood-brain barrier permeability.
“Endothelial dysfunction has two major pathogenic consequences: reductions in resting CBF in the marginally perfused white matter, and alterations in the permeability of the BBB.”
Quote in the paperSubstantial claimMay combine two claims.
PremisecitationOligodendrocyte progenitor cells produce MMP9, which promotes blood-brain barrier breakdown and perpetuates the cytotoxic milieu underlying demyelination.
“In addition, OPC produce MMP9, which, as seen in the previous sections, promotes BBB breakdown perpetuating the cytotoxic milieu underlying demyelination (Seo et al., 2013).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Seo et al., 2013
Not checked in the free run.
May combine two claims.
PremisecitationIn multiple sclerosis patients, cerebral blood flow is reduced in normal-appearing white matter and in gray matter.
“However, in MS patients CBF is reduced in the normal appearing white matter (Law et al., 2004), as well as in the gray matter (D’haeseleer et al., 2011).”
Quote in the paperSubstantial claim0 of 2 sources checkedMay combine two claims.
InterpretationreasoningVascular risk factors may suppress angiogenic T-cell production, reduce endothelial progenitor cell repair potential, and contribute to microvascular degeneration underlying leukoaraiosis and lacunar stroke.
“These findings, raise the possibility that vascular risk factors suppress the production of angiogenic T-cells, reduce the repair potential of EPC, and contribute to the microvascular degeneration underlying leukoaraiosis and lacunar stroke.”
Quote in the paperSubstantial claimMay combine two claims.
PremisecitationIn white matter lesions, hyaluronan is degraded by hyaluronidase PH20, and its cleavage products inhibit oligodendrocyte progenitor cell maturation into myelinating oligodendrocytes.
“In white matter lesions, HA is degraded by the hyaluronidase PH20 and its cleavage products inhibit the maturation of OPC into oligodendrocytes capable of myelination (Preston et al., 2013) (fig. 7).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Preston et al., 2013 source
Not checked in the free run.
May combine two claims.
InterpretationreasoningDemyelination exposes axons to cytokines and free radicals in hypoxic white matter, impairing axonal energy production and causing Na+/K+ ATPase failure.
“In addition, demyelination exposes the axons to the deleterious effects of cytokine and free radicals in the hypoxic white matter, which may impair axonal energy production leading to failure of the Na+/K+ ATPase.”
Quote in the paperSubstantial claimMay combine two claims.
PremisecitationMyelination allows axons to conduct about 100 times faster and reduces energy expenditure by restricting depolarization to Na+ channel-rich Ranvier nodes.
“Myelination allows axons to conduct 100 times faster, and reduce energy expenditures by restricting the depolarization of the axonal membrane to the Na+ channel rich Ranvier nodes (Nave, 2010b).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Nave, 2010b
Not checked in the free run.
May combine two claims.
PremisecitationInfantile adrenoleukodystrophy starts between 4 and 8 years of age and is characterized by progressive cognitive decline with inflammatory demyelination of white matter.
“In its infantile form, the disease starts between 4 and 8 years of age and is characterized by a progressive cognitive decline associated with rampant inflammatory demyelination of the white matter (Moser et al., 2000).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Moser et al., 2000 source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationMultiple sclerosis is the prototypical neuroinflammatory disease in which demyelination is thought to result from a T-cell mediated autoimmune attack on myelin.
“Multiple sclerosis (MS) is the prototypical neuroinflammatory disease in which demyelination is thought to be related to a T-cell mediated autoimmune attack on myelin (McFarland and Martin, 2007).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites McFarland and Martin, 2007 source
Not checked in the free run.
May combine two claims.
InterpretationreasoningVessels devoid of endothelium, called string vessels, are often observed, reflecting failed endothelial repair possibly due to endothelial progenitor cell dysfunction or loss of growth factors.
“Vessels devoid of endothelium (string vessels) are often observed, reflecting a failure of endothelial repair, possibly due to EPC dysfunction or loss of neuron and/or glial-derived growth factors.”
Quote in the paperSubstantial claimMay combine two claims.
PremisecitationUpregulation of VNa+1.2 channels increases Na+/K+ ATPase activity, further stressing the energy budget of marginally perfused white matter.
“Upregulation of VNa+1.2 channels increases the activity of the Na+/K+ ATPase, stressing further the energy budget of the marginally perfused white matter (Trapp and Stys, 2009).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Trapp and Stys, 2009 source
Not checked in the free run.
May combine two claims.
PremisecitationLoss of myelin slows axon potential transmission and threatens axon integrity, leading to axonal loss.
“In addition to the brain dysfunction caused by slowing down the transmission of axon potentials, demyelination threatens the integrity of the axons and leads to axonal loss (Franklin and Ffrench-Constant, 2008; Matute and Ransom, 2012).”
Quote in the paperSubstantial claim0 of 2 sources checkedMay combine two claims.
InterpretationreasoningLoss of myelin deprives axons of trophic support and increases their vulnerability.
“Thus, loss of myelin deprives the axons of trophic support and increases their vulnerability.”
Quote in the paperSubstantial claimMay combine two claims.
PremisecitationUpregulation of voltage-dependent Na+ channels in denuded internodal axoplasm attempts to preserve impulse propagation but increases Na+ entry and worsens energy deficit and Ca2+ overload.
“Furthermore, the adaptive upregulation of voltage-dependent Na+ channels (VNa+) in the denuded internodal axoplasm, attempting to preserve impulse propagation in demyelinated axons, leads to Na+ entry and aggravates the energy deficit and Ca2+ overload.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Trapp and Stys, 2009 source
Not checked in the free run.
May combine two claims.
PremisecitationExcess intracellular Ca2+ activates protease-dependent processes that fragment microtubules and perturb axonal flow.
“In turn, excess intracellular Ca2+ activates protease dependent processes that lead to microtubule fragmentation and perturbation of axonal flow (Franklin and Ffrench-Constant, 2008; Matute and Ransom, 2012).”
Quote in the paperSubstantial claim0 of 2 sources checkedProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationX-linked adrenoleukodystrophy is caused by mutations in ABCD1, which encodes a peroxisomal membrane transporter, leading to accumulation of very long chain fatty acids in brain, spinal cord, and adrenal glands.
“Reductions in white matter CBF has also been found X-linked adrenoleukodystrophy (ALD), a disease caused by mutations in ABCD1, which encodes a peroxisomal membrane transporter protein, leading to accumulation of very long chain fatty acids in brain, spinal cord and adrenal glands (Moser et al., 2000).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Moser et al., 2000 source
Not checked in the free run.
May combine two claims.
PremisecitationLeukoaraiosis is associated with focal cortical thinning, especially in frontal cortex, and this finding correlates with executive dysfunction.
“Leukoaraiosis is associated with focal cortical thinning especially in frontal cortex, a finding correlated with executive dysfunction (Seo et al., 2012).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Seo et al., 2012 source
Not checked in the free run.
May combine two claims.
InterpretationreasoningHypoxia, inflammation, and oxidative stress damage oligodendrocytes and cause trophic uncoupling in the neurovascular unit, contributing to damage to vascular cells and oligodendrocytes.
“Hypoxia, inflammation and oxidative stress damage oligodendrocytes and leads to trophic uncoupling in the neurovascular unit, which, in turn, contribute to the damage to vascular cells and oligodendrocytes.”
Quote in the paperSubstantial claimMay combine two claims.
PremisecitationAged APP mice lacking CD36 are protected from cerebrovascular alterations and behavioral deficits, with reduced cerebral amyloid angiopathy compared with controls but no reduction in amyloid plaques.
“Aged APP mice deficient in CD36 are protected from cerebrovascular alterations and behavioral deficits, effects associated with reduced CAA compared to controls, but no reduction of amyloid plaques (Park et al., 2013b).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Park et al., 2013b
Not checked in the free run.
May combine two claims.
InterpretationreasoningAlzheimer disease brains have a wide variety of vascular lesions, suggesting a potential pathogenic interaction between vascular factors and Alzheimer disease.
“As discussed in the section on “Mixed lesions”, AD brains have a wide variety of vascular lesions, suggesting a potential pathogenic interaction between vascular factors and AD.”
Quote in the paperNot a substantial claimMay combine two claims.
PremisecitationThe vascular changes caused by amyloid-beta are prevented by overexpressing the ROS-scavenging enzyme superoxide dismutase or by lacking the NADPH oxidase subunit NOX2.
“The vascular alterations induced by Aβ are abrogated by overexpression of the ROS scavenging enzyme superoxide dismutase or deficiency of the NADPH oxidase subunit NOX2 (Iadecola et al., 1999; Park et al., 2005; 2008)”
Quote in the paperSubstantial claim0 of 3 sources checkedMay combine two claims.
InterpretationreasoningThe cerebrovascular effects of amyloid-beta are not explained by cerebral amyloid angiopathy or amyloid plaques, nor by neuronal energy hypometabolism.
“These data suggest that the cerebrovascular effects of Aβ are not attributable to CAA or amyloid plaques, and are not a consequence of neuronal energy hypometabolism.”
Quote in the paperSubstantial claimMay combine two claims.
PremisecitationSome studies, but not others, have reported increased amyloid deposition in stroke patients, implicating that ischemia promotes Alzheimer disease pathology.
“Conversely, some studies (Jendroska et al., 1995; Ly et al., 2012), but not others (Aho et al., 2006; Mastaglia et al., 2003), have reported increased amyloid deposition in stroke patients, implicating that ischemia promotes AD pathology.”
Quote in the paperNot a substantial claim0 of 3 sources checkedMay combine two claims.
InterpretationreasoningMost dementia cases have mixed pathological features, raising the possibility that vascular factors contribute to Alzheimer disease and other neurodegenerative diseases.
“The realization that most cases of dementia have mixed pathological features has raised the intriguing possibility that vascular factors play role in AD and other neurodegenerative diseases.”
Quote in the paperSubstantial claimMay combine two claims.
PremisecitationApplying amyloid-beta to the exposed cerebral cortex of mice lowers cerebral blood flow and blunts the increase in cerebral blood flow caused by endothelium-dependent vasodilators and functional hyperemia.
“application of Aβ4 to the exposed cerebral cortex of mice reduces CBF and impairs the increase in CBF induced by endothelium-dependent vasodilators and functional hyperemia (Niwa et al., 2000a; 2000b)”
Quote in the paperSubstantial claim0 of 2 sources checked- cites Niwa et al., 2000a
Not checked in the free run.
- cites Niwa et al., 2000b
Not checked in the free run.
May combine two claims.
InterpretationcitationIn advanced Alzheimer disease, vascular lesions do not appear to have a major influence on progression of cognitive deficits, suggesting Alzheimer pathology is the major driver.
“In advanced cases of AD, vascular lesions do not seem to have a major influence on the progression of the cognitive deficits, suggesting the AD pathology is the major driver of the cognitive dysfunction (Chui et al., 2006; Jellinger, 2001).”
Quote in the paperNot a substantial claim0 of 2 sources checkedMay combine two claims.
PremisecitationYoung mice overexpressing mutated APP with elevated brain amyloid-beta but without plaques, behavioral changes, or reduced resting glucose use show profound impairment of functional hyperemia, endothelium-dependent responses, and autoregulation.
“functional hyperemia, endothelium-dependent responses and autoregulation are profoundly impaired in young mice overexpressing mutated forms of APP, in which brain Aβ is elevated, but there are no plaques, behavioral alterations, or reductions in resting glucose utilization (Niwa et al., 2000b; 2002; Tong et al., 2012)”
Quote in the paperSubstantial claim0 of 3 sources checkedMay combine two claims.
InterpretationcitationCerebrovascular function is reduced in patients with early Alzheimer disease or at risk for Alzheimer disease, implicating reduced cerebral perfusion in the pathobiology of the disease.
“Cerebrovascular function is reduced in patients with early AD or at risk for AD (Claassen et al., 2009; Gao et al., 2013; Luckhaus et al., 2008; Mentis et al., 1996; Niedermeyer, 2006; Ruitenberg et al., 2005; Sabayan et al., 2012; Tanaka et al., 2002), implicating reduced cerebral perfusion in the pathobiology of the disease (Iadecola, 2004).”
Quote in the paperNot a substantial claim0 of 3 sources checkedMay combine two claims.
InterpretationcitationThe correlation was strongest for vascular dementia and weakest for Alzheimer disease, suggesting vascular risk factors may independently increase dementia likelihood without exacerbating Alzheimer pathology.
“Furthermore, the correlation was strongest for vascular dementia and weakest for AD, suggesting that vascular risk factors may independently increase the likelihood of dementia without exacerbating AD pathology (Chui et al., 2012).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Chui et al., 2012
Not checked in the free run.
May combine two claims.
PremisecitationRigorous blood pressure control reduces white matter damage and delays cognitive decline.
“Indeed, rigorous blood pressure control reduces white matter damage and staves off cognitive decline (Sharp et al., 2011; Sörös et al., 2013).”
Quote in the paperSubstantial claim0 of 2 sources checked- cites Sharp et al., 2011 source
Not checked in the free run.
- cites Sörös et al., 2013
Not checked in the free run.
May combine two claims.
PremisecitationSome agents, such as the neurotrophic factor cerebrolysin, produced modest cognitive improvement, but the evidence is not strong enough to justify clinical use.
“Some agents, like the neurotrophic factor cerebrolysin, showed a modest cognitive improvement, but the evidence is not sufficiently strong to justify clinical use (Chen et al., 2013b).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Chen et al., 2013b
Not checked in the free run.
Probably not a substantial claim: may not pass S4 (based). May combine two claims.
Interpretationnone givenVascular cognitive impairment and vascular dementia are major contributors to age-related dementing illnesses and comprise a heterogeneous group of cognitive disorders attributable to vascular causes.
“VCI and vascular dementia are major contributors to age-relate dementing illnesses and comprise a heterogeneous group of cognitive disorders attributable to vascular causes.”
Quote in the paperNot a substantial claimMay combine two claims.
PremisecitationBecause vascular cognitive impairment frequently overlaps with Alzheimer's disease, its diagnosis can be challenging, complicating the choice of the best therapeutic approach.
“Furthermore, due to frequent overlap with AD, the diagnosis of VCI can be challenging, complicating the choice of the best therapeutic approach (Wang et al., 2012).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Wang et al., 2012 source
Not checked in the free run.
May combine two claims.
PremisecitationPhysical and mental activity, social engagement, and a diet rich in antioxidants or polyunsaturated fatty acids reduce dementia risk.
“Physical and mental activity, social engagement, and a diet rich in antioxidants or polyunsaturated fatty acids reduce dementia risk (Aarsland et al., 2010; Akinyemi et al., 2013; Middleton and Yaffe, 2009; Verdelho et al., 2012).”
Quote in the paperSubstantial claim0 of 3 sources checkedMay combine two claims.
PremisecitationA UK population study suggests that dementia prevalence may be decreasing, a finding interpreted as reflecting the beneficial effects of controlling blood pressure and other risk factors.
“A study in the UK population suggests that the prevalence of dementia may be decreasing, a finding interpreted to reflect the beneficial effects of controlling blood pressure and other risk factors (Matthews et al., 2013).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Matthews et al., 2013 source
Not checked in the free run.
May combine two claims.
PremisecitationDespite positive results in models of hypoperfusion-induced white matter damage, there are no FDA-approved treatments for vascular cognitive impairment and vascular dementia.
“Despite these positive results in models of hypoperfusion-induced white matter damage, there are no FDA approved treatments for VCI and vascular dementia (Butler and Radhakrishnan, 2012).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Butler and Radhakrishnan, 2012
Not checked in the free run.
May combine two claims.
Interpretationnone givenDespite diversity in underlying brain pathology, vascular alterations share similar pathogenic bases, arising from hypoperfusion, oxidative stress, and inflammation, which lead to endothelial damage, blood-brain barrier breakdown, innate immune activation, and disruption of trophic coupling between vascular and brain cells.
“Despite the diversity of the underlying brain pathology, the vascular alterations have a similar pathogenic bases, resulting from hypoperfusion, oxidative stress and inflammation, which in turn lead to endothelial damage, BBB breakdown, activation of innate immunity and disruption of trophic coupling between vascular and brain cells.”
Quote in the paperNot a substantial claimMay combine two claims.
Interpretationnone givenThe hemispheric white matter is particularly susceptible to the harmful effects of vascular risk factors and is a major target of these vascular alterations.
“The hemispheric white matter, which is particularly susceptible to the deleterious effects of vascular risk factors, is a major target of these vascular alterations.”
Quote in the paperSubstantial claimMay combine two claims.
InterpretationreasoningThe role of hypoperfusion, blood-brain barrier disruption, oxidative stress, and inflammation is well established in animal models of white matter damage, but therapies based on these pathogenic mechanisms have not been successful.
“The role of hypoperfusion, BBB disruption, oxidative stress and inflammation is well established in animal models of white matter damage, but therapies based on these pathogenic mechanisms have not been successful.”
Quote in the paperSubstantial claimMay combine two claims.
Study design and conductcitationMost evidence for risk factor modification comes from observational studies and has not been confirmed by randomized clinical trials.
“However, most of the evidence is based on observational studies, which have not been confirmed by randomized clinical trials of risk factor modification, stressing the need for further large scale studies (Dichgans and Zietemann, 2012; Middleton and Yaffe, 2009).”
Quote in the paperSubstantial claim0 of 2 sources checkedMay combine two claims.
InterpretationreasoningVascular risk factors can increase amyloid accumulation and the risk of clinically defined Alzheimer's disease.
“Vascular risk factors can increase amyloid accumulation and the risk of clinically defined AD.”
Quote in the paperSubstantial claim
The paper relies on this without support.
Mechanisms observed in animal models of cerebral hypoperfusion and white matter injury are representative of the pathogenic processes in human vascular cognitive impairment.
“Cerebral hypoperfusion is associated with white matter inflammation and oxidative stress in rodent models (Dong et al., 2011; Huang et al., 2010; Ihara et al., 2001; Juma et al., 2011; Masumura et al., 2001; Reimer et al., 2011; Yoshizaki et al., 2008), indicating that hypoxia-ischemia is sufficient to trigger these responses.”
“In vivo, hypoperfusion produced by bilateral carotid stenosis in rat increases BBB permeability (Ueno et al., 2002).”
The paper relies on this without support.
The vascular risk factors and pathological processes identified in the reviewed studies are representative of the general population with vascular cognitive impairment.
“Ascertaining the genetic and modifiable risk factors of VCI is problematic due to the multiplicity of underlying pathologies, coexistence with cardiovascular diseases, and the frequent overlap with AD and other neurodegenerative diseases (Gorelick et al., 2011).”
The paper relies on this without support.
Mixed dementia is the most common cause of dementia in the elderly.
“Considering that mixed dementia is the most common cause of dementia in the elderly”
The paper relies on this without support.
Dementia has a long preclinical phase.
“the long preclinical phase of dementia is problematic, since, in VCI as in AD, initiating therapy when patients become symptomatic may be too late.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Different cell types of the neurovascular unit (NVU) including vascular cells, glia, and neurons contribute to regulation of BBB permeability, neurovascular coupling, cell-matrix interactions, neurotransmitter turnover, and angiogenesis and neurogenesis.
“Different cell types of the neurovascular unit (NVU) including vascular cells [e.g., endothelium and mural cells including pericytes and smooth muscle cells (SMCs)], glia (e.g., astrocytes, microglia), and neurons contribute to regulation of BBB permeability, neurovascular coupling, cell-matrix interactions, neurotransmitter turnover, and angiogenesis and neurogenesis (270, 271, 692, 693)”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [270]
The sections on neurovascular control mechanisms and trophic coupling describe neurons, astrocytes, and vascular cells acting together in neurovascular coupling, BBB maintenance, angiogenesis, and neurogenesis. The passages do not establish the claimed roles in cell-matrix interactions or neurotransmitter turnover. Page numbers were not available in our copy. (LLM, conf=0.86)
Experimental — accuracy not yet measuredIn patients and mouse models of AD, fibrinogen extravasates in the brain at sites of impaired blood-brain barrier integrity and cerebrovascular dysfunction, which are early features of AD pathogenesis.
“In patients and mouse models of AD, fibrinogen extravasates in the brain at sites of impaired blood-brain barrier integrity and cerebrovascular dysfunction, which are early features of AD pathogenesis.21,39-42”
From Machine learning reveals prominent spontaneous behavioral changes and treatment efficacy in humanized and transgenic Alzheimer's disease models (2024) · cites this paper as [41]
The sections on white matter injury describe fibrinogen extravasation following BBB disruption, while the section on overlap with neurodegenerative dementia describes early cerebrovascular dysfunction in AD and BBB disruption associated with ApoE4. The paper does not establish that fibrinogen extravasates specifically in patients and mouse models of AD at those sites; its fibrinogen discussion concerns vascular white matter injury. (LLM, conf=0.87)
Experimental — accuracy not yet measuredBBB breakdown and dysfunction is associated with cerebral blood flow (CBF) reductions and dysregulation, contributing to neurological deficits.
“which is associated with cerebral blood flow (CBF) reductions and dysregulation (269-271, 318), contributing to neurological deficits.”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [270]
Any of the multiple causes of clinical stroke can cause vascular cognitive impairment.
“In principle, any of the multiple causes of clinical stroke can cause vascular cognitive impairment.”
From Vascular Cognitive Impairment (2017) · cites this paper as [44]
Deterioration of the vascular bed may occur alone or with other pathologies, leading to progressive demyelination and white matter loss.
“Deterioration of the vascular bed may occur alone or in combination with other pathologies (97), leading to progressive demyelination and loss of white matter (98).”
From Glymphatic failure as a final common pathway to dementia (2020) · cites this paper as [97]
Cites
Wardlaw, J. M., Smith, E. E., Biessels, G. J., Cordonnier, C., Fazekas, F., Frayne, R., Lindley, R. I., O'Brien, J. T., Barkhof, F., Benavente, O. R., et al. (2013) · The Lancet Neurology · doi:10.1016/s1474-4422(13)70124-8 · Cited by 5,560 · see citing works
Molecular mechanisms and clinical applications of angiogenesis
Carmeliet, P., & Jain, R. K. (2011) · Nature · doi:10.1038/nature10144 · Cited by 5,467 · cited 1× · see citing works
“In the developing nervous system, prototypical neural guidance signals, ephrins, netrins, slit glycoproteins, and semaphorins also contribute to endothelial tip cell guidance (Carmeliet and Jain, 2011).”
Glenner, G. G., & Wong, C. W. (1984) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(84)80190-4 · Cited by 5,404 · cited 1× · see citing works
“…considered a major player in dementia well into the 20th century, until, in the 1980s, the Ab peptide was identified as the main component of parenchymal (amyloid plaque) and vascular (amyloid angiopathy) amyloid deposits, pathological hallmarks of AD (Glenner and Wong, 1984; Kang et al., 1987).”
Román, G. C., Tatemichi, T. K., Erkinjuntti, T., Cummings, J. L., Masdeu, J. C., Garcia, J. H., Amaducci, L., Orgogozo, J.-M., Brun, A., Hofman, A., et al. (1993) · Neurology · doi:10.1212/wnl.43.2.250 · Cited by 4,921 · see citing works
The precursor of Alzheimer's disease amyloid A4 protein resembles a cell-surface receptor
Kang, J., Lemaire, H.-G., Unterbeck, A., Salbaum, J. M., Masters, C. L., Grzeschik, K.-H., Multhaup, G., Beyreuther, K., & Müller-Hill, B. (1987) · Nature · doi:10.1038/325733a0 · Cited by 4,619 · cited 2× · see citing works
“Vascular factors were considered a major player in dementia well into the 20 century, until, in the 1980s, the Ab peptide was identified as the main component of parenchymal (amyloid plaque) and vascular (amyloid angiopathy) amyloid deposits, pathological hallmarks of AD (Glenner and Wong, 1984; Kang et al., 1987).”
Gorelick, P. B., Scuteri, A., Black, S. E., DeCarli, C., Greenberg, S. M., Iadecola, C., Launer, L. J., Laurent, S., Lopez, O. L., Nyenhuis, D., et al. (2011) · Stroke · doi:10.1161/str.0b013e3182299496 · Cited by 3,811 · see citing works
Self-citationCognitive reserve in ageing and Alzheimer's disease
Stern, Y. (2012) · The Lancet Neurology · doi:10.1016/s1474-4422(12)70191-6 · Cited by 3,557 · cited 1× · see citing works
“The level of education, a surrogate marker of cognitive reserves (Stern, 2012), is an important determinant of the expression of VCI, such that for a given level of neuropathology higher education is associated with less cognitive deficits (Zieren et al., 2013).”
Circulating endothelial progenitor cells, vascular function, and cardiovascular risk
Hill, J. M., Zalos, G., Halcox, J. P. J., Schenke, W. H., Waclawiw, M. A., Quyyumi, A. A., & Finkel, T. (2003) · New England Journal of Medicine · doi:10.1056/nejmoa022287 · Cited by 3,423 · see citing works
The Blood-Brain Barrier in Health and Chronic Neurodegenerative Disorders
Zlokovic, B. V. (2008) · Neuron · doi:10.1016/j.neuron.2008.01.003 · Cited by 3,280 · see citing works
Neurovascular pathways to neurodegeneration in Alzheimer’s disease and other disorders
Zlokovic, B. V. (2011) · Nature Reviews Neuroscience · doi:10.1038/nrn3114 · Cited by 2,969 · cited 2× · see citing works
“…a previously unrecognized functional and pathogenic synergy between neurons, glia, and vascular cells (Iadecola, 2010; Quaegebeur et al., 2011; Zlokovic, 2011), providing a new framework to reevaluate how alterations in cerebral blood vessels could contribute to the neuronal dysfunction…”
Pericytes regulate the blood–brain barrier
Armulik, A., Genové, G., Mäe, M., Nisancioglu, M. H., Wallgard, E., Niaudet, C., He, L., Norlin, J., Lindblom, P., Strittmatter, K., et al. (2010) · Nature · doi:10.1038/nature09522 · Cited by 2,843 · cited 1× · see citing works
“In capillaries, smooth muscle cells are replaced by pericytes, contractile cells that are particularly abundant in brain vessels and are involved in the development and maintenance of the BBB (Armulik et al., 2010; Bell et al., 2010; Quaegebeur et al., 2011).”
The immunology of stroke: from mechanisms to translation
Iadecola, C., & Anrather, J. (2011) · Nature Medicine · doi:10.1038/nm.2399 · Cited by 2,596 · see citing works
Self-citationNeurovascular regulation in the normal brain and in Alzheimer's disease
Iadecola, C. (2004) · Nature Reviews Neuroscience · doi:10.1038/nrn1387 · Cited by 2,213 · cited 5× · see citing works
“…with early AD or at risk for AD (Claassen et al., 2009; Gao et al., 2013; Luckhaus et al., 2008; Mentis et al., 1996; Niedermeyer, 2006; Ruitenberg et al., 2005; Sabayan et al., 2012; Tanaka et al., 2002), implicating reduced cerebral perfusion in the pathobiology of the disease (Iadecola, 2004).”
InfluentialSelf-citationObservations on the brains of demented old people
Tomlinson, B. E., Blessed, G., & Roth, M. (1970) · Journal of the Neurological Sciences · doi:10.1016/0022-510x(70)90063-8 · Cited by 2,084 · see citing works
Decreased Clearance of CNS β-Amyloid in Alzheimer’s Disease
Mawuenyega, K. G., Sigurdson, W., Ovod, V., Munsell, L., Kasten, T., Morris, J. C., Yarasheski, K. E., & Bateman, R. J. (2010) · Science · doi:10.1126/science.1197623 · Cited by 2,078 · see citing works
Circulating endothelial progenitor cells and cardiovascular outcomes
Werner, N., Kosiol, S., Schiegl, T., Ahlers, P., Walenta, K., Link, A., Böhm, M., & Nickenig, G. (2005) · New England Journal of Medicine · doi:10.1056/nejmoa043814 · Cited by 2,048 · see citing works
Mixed brain pathologies account for most dementia cases in community-dwelling older persons
Schneider, J. A., Arvanitakis, Z., Bang, W., & Bennett, D. A. (2007) · Neurology · doi:10.1212/01.wnl.0000271090.28148.24 · Cited by 1,992 · see citing works
The Science of Stroke: Mechanisms in Search of Treatments
Moskowitz, M. A., Lo, E. H., & Iadecola, C. (2010) · Neuron · doi:10.1016/j.neuron.2010.07.002 · Cited by 1,930 · cited 1× · see citing works
“On the other hand, if the reduction in CBF is sustained and severe, ischemic stroke ensues (Moskowitz et al., 2010).”
Self-citationPendlebury, S. T., & Rothwell, P. M. (2009) · The Lancet Neurology · doi:10.1016/s1474-4422(09)70236-4 · Cited by 1,853 · cited 2× · see citing works
“Stroke doubles the risk for dementia (poststroke dementia), and approximately 30% of stroke patients go on to develop cognitive dysfunction within 3 years (Allan et al., 2011; Leys et al., 2005; Pendlebury and Rothwell, 2009).”
Synaptic Energy Use and Supply
Harris, J. J., Jolivet, R., & Attwell, D. (2012) · Neuron · doi:10.1016/j.neuron.2012.08.019 · Cited by 1,747 · cited 1× · see citing works
“Most energy is used by neurons to fuel ionic pumps to maintain and restore the ionic gradients dissipated by synaptic activity (Harris et al., 2012).”
Mechanisms of sporadic cerebral small vessel disease: insights from neuroimaging
Wardlaw, J. M., Smith, C., & Dichgans, M. (2013) · The Lancet Neurology · doi:10.1016/s1474-4422(13)70060-7 · Cited by 1,657 · see citing works
Snowdon, D. A. (1997) · JAMA: The Journal of the American Medical Association · doi:10.1001/jama.1997.03540340047031 · Cited by 1,590 · see citing works
Remyelination in the CNS: from biology to therapy
Franklin, R. J. M., & ffrench-Constant, C. (2008) · Nature Reviews Neuroscience · doi:10.1038/nrn2480 · Cited by 1,544 · cited 5× · see citing works
“In turn, excess intracellular Ca2+ activates protease dependent processes that lead to microtubule fragmentation and perturbation of axonal flow (Franklin and Ffrench-Constant, 2008; Matute and Ransom, 2012).”
InfluentialEndothelial Cells Stimulate Self-Renewal and Expand Neurogenesis of Neural Stem Cells
Shen, Q., Goderie, S. K., Jin, L., Karanth, N., Sun, Y., Abramova, N. E., Vincent, P. A., Pumiglia, K. M., & Temple, S. (2004) · Science · doi:10.1126/science.1095505 · Cited by 1,538 · cited 1× · see citing works
“Endothelial cells have the potential to stimulate the proliferation of neuronal precursors and to stir their differentiation toward the neuronal lineage (Shen et al., 2004).”
Alzheimer’s Disease Neuroimaging Initiative
Mueller, S. G., Weiner, M. W., Thal, L. J., Petersen, R. C., Jack, C. R., Jagust, W. J., Trojanowski, J. Q., Toga, A. W., & Beckett, L. A. (2007) · Springer eBooks · doi:10.1007/978-0-387-72076-0_18 · Cited by 1,493 · see citing works
Monetary Costs of Dementia in the United States
Hurd, M. D., Martorell, P., Delavande, A., Mullen, K. J., & Langa, K. M. (2013) · New England Journal of Medicine · doi:10.1056/nejmsa1204629 · Cited by 1,484 · see citing works
Bell, R. D., Winkler, E. A., Sagare, A. P., Singh, I., LaRue, B., Deane, R., & Zlokovic, B. V. (2010) · Neuron · doi:10.1016/j.neuron.2010.09.043 · Cited by 1,448 · see citing works
Shibata, M., Yamada, S., Kumar, S. R., Calero, M., Bading, J., Frangione, B., Holtzman, D. M., Miller, C. A., Strickland, D. K., Ghiso, J., et al. (2000) · Journal of Clinical Investigation · doi:10.1172/jci10498 · Cited by 1,413 · cited 3× · see citing works
“The vascular pathway is estimated to be a major route of removal of Ab from the brain (Castellano et al., 2012; Shibata et al., 2000).”
Apolipoprotein E controls cerebrovascular integrity via cyclophilin A
Bell, R. D., Winkler, E. A., Singh, I., Sagare, A. P., Deane, R., Wu, Z., Holtzman, D. M., Betsholtz, C., Armulik, A., Sallstrom, J., et al. (2012) · Nature · doi:10.1038/nature11087 · Cited by 1,293 · see citing works
Matthews, F. E., Arthur, A., Barnes, L. E., Bond, J., Jagger, C., Robinson, L., & Brayne, C. (2013) · The Lancet · doi:10.1016/s0140-6736(13)61570-6 · Cited by 1,155 · see citing works
Brain-wide pathway for waste clearance captured by contrast-enhanced MRI
Iliff, J. J., Lee, H., Yu, M., Feng, T., Logan, J., Nedergaard, M., & Benveniste, H. (2013) · Journal of Clinical Investigation · doi:10.1172/jci67677 · Cited by 1,148 · cited 1× · see citing works
“Images are courtesy of Dr. Hooman Kamel. has emerged as critically important for the disposal of unwanted proteins and peptides, e.g., Ab (Carare et al., 2013; Iliff et al., 2013; Laman and Weller, 2013).”
MULTI-INFARCT DEMENTIA A CAUSE OF MENTAL DETERIORATION IN THE ELDERLY
HACHINSKI, V (1974) · The Lancet · doi:10.1016/s0140-6736(74)91496-2 · Cited by 1,093 · cited 2× · see citing works
“The construct of multi-infarct dementia, by attributing cognitive impairment to multiple strokes, raised the possibility that preventing cerebrovascular diseases could also prevent dementia (Hachinski et al., 1974).”
Chabriat, H., Joutel, A., Dichgans, M., Tournier-Lasserve, E., & Bousser, M.-G. (2009) · The Lancet Neurology · doi:10.1016/s1474-4422(09)70127-9 · Cited by 1,088 · see citing works
Myelination and support of axonal integrity by glia
Nave, K.-A. (2010) · Nature · doi:10.1038/nature09614 · Cited by 1,062 · see citing works
Spike Timing-Dependent Plasticity of Neural Circuits
Dan, Y., & Poo, M. (2004) · Neuron · doi:10.1016/j.neuron.2004.09.007 · Cited by 1,029 · see citing works
Multiple sclerosis: a complicated picture of autoimmunity
McFarland, H. F., & Martin, R. (2007) · Nature Immunology · doi:10.1038/ni1507 · Cited by 985 · cited 1× · see citing works
“Multiple sclerosis (MS) is the prototypical neuroinflammatory disease in which demyelination is thought to be related to a T cell mediated autoimmune attack on myelin (McFarland and Martin, 2007).”
The neural basis of functional brain imaging signals
Attwell, D., & Iadecola, C. (2002) · Trends in Neurosciences · doi:10.1016/s0166-2236(02)02264-6 · Cited by 957 · see citing works
Self-citationThe neuropathology of probable Alzheimer disease and mild cognitive impairment
Schneider, J. A., Arvanitakis, Z., Leurgans, S. E., & Bennett, D. A. (2009) · Annals of Neurology · doi:10.1002/ana.21706 · Cited by 935 · see citing works
Fibrinogen as a key regulator of inflammation in disease
Davalos, D., & Akassoglou, K. (2011) · Seminars in Immunopathology · doi:10.1007/s00281-011-0290-8 · Cited by 926 · cited 2× · see citing works
“Extravasation of plasma proteins, due to the BBB alterations, is also likely to play a role, since fibrinogen, immunoglobulins, and complement are potent activators of inflammation and free radical production (Crehan et al., 2013; Davalos and Akassoglou, 2012; Yoshida et al., 2002).”
Combating oxidative stress in vascular disease: NADPH oxidases as therapeutic targets
Drummond, G. R., Selemidis, S., Griendling, K. K., & Sobey, C. G. (2011) · Nature Reviews Drug Discovery · doi:10.1038/nrd3403 · Cited by 899 · cited 1× · see citing works
“…(Miller et al., 2005), has emerges as an important source in vascular oxidative stress in aging, hypertension, hyperlipidemia and diabetes (Faraci et al., 2011), and inhibition or genetic inactivation of this enzyme has been shown to ameliorate the vascular dysfunction (Drummond et al., 2011).”
Apolipoprotein E in Alzheimer’s disease and other neurological disorders
Verghese, P. B., Castellano, J. M., & Holtzman, D. M. (2011) · The Lancet Neurology · doi:10.1016/s1474-4422(10)70325-2 · Cited by 857 · cited 1× · see citing works
“The ApoE 4 allele is a well-established susceptibility gene for increased cardiovascular risk and Alzheimer disease (Verghese et al., 2011).”
Toledo, J. B., Arnold, S. E., Raible, K., Brettschneider, J., Xie, S. X., Grossman, M., Monsell, S. E., Kukull, W. A., & Trojanowski, J. Q. (2013) · Brain · doi:10.1093/brain/awt188 · Cited by 849 · see citing works
LRP/Amyloid β-Peptide Interaction Mediates Differential Brain Efflux of Aβ Isoforms
Deane, R., Wu, Z., Sagare, A., Davis, J., Du Yan, S., Hamm, K., Xu, F., Parisi, M., LaRue, B., Hu, H. W., et al. (2004) · Neuron · doi:10.1016/j.neuron.2004.07.017 · Cited by 828 · see citing works
Blood–Brain Barrier Breakdown in Acute and Chronic Cerebrovascular Disease
Yang, Y. R., & Rosenberg, G. A. (2011) · Stroke · doi:10.1161/strokeaha.110.608257 · Cited by 795 · see citing works
Selective Vulnerability of Late Oligodendrocyte Progenitors to Hypoxia–Ischemia
Back, S. A., Han, B. H., Luo, N. L., Chricton, C. A., Xanthoudakis, S., Tam, J., Arvin, K. L., & Holtzman, D. M. (2002) · The Journal of Neuroscience · doi:10.1523/jneurosci.22-02-00455.2002 · Cited by 795 · see citing works
What is immune privilege (not)?
Galea, I., Bechmann, I., & Perry, V. H. (2007) · Trends in Immunology · doi:10.1016/j.it.2006.11.004 · Cited by 768 · cited 1× · see citing works
“The perivascular space, which drains into the subarachnoid space and then into cervical lymphnodes (Laman and Weller, 2013), is the ‘‘afferent arm’’ through which brain antigens reach the systemic immune system (Galea et al., 2007).”
Heterogeneity of small vessel disease: a systematic review of MRI and histopathology correlations
Gouw, A. A., Seewann, A., van der Flier, W. M., Barkhof, F., Rozemuller, A. M., Scheltens, P., & Geurts, J. J. G. (2011) · Journal of Neurology, Neurosurgery & Psychiatry · doi:10.1136/jnnp.2009.204685 · Cited by 766 · see citing works
Hachinski, V. C., Potter, P., & Merskey, H. (1987) · Archives of Neurology · doi:10.1001/archneur.1987.00520130013009 · Cited by 755 · see citing works
Review: Cerebral microvascular pathology in ageing and neurodegeneration
Brown, W. R., & Thore, C. R. (2011) · Neuropathology and Applied Neurobiology · doi:10.1111/j.1365-2990.2010.01139.x · Cited by 749 · cited 7× · see citing works
“…at the distal border between different vascular territories (De Reuck, 1971) (Figure 4) and to the ovember 20, 2013 ª2013 Elsevier Inc. 851 susceptibility of their vasculature to risk factors (Brown and Thore, 2011), deep white matter tracts are particularly vulnerable to vascular insufficiency.”
InfluentialThirty years of Alzheimer's disease genetics: the implications of systematic meta-analyses
Bertram, L., & Tanzi, R. E. (2008) · Nature Reviews Neuroscience · doi:10.1038/nrn2494 · Cited by 747 · cited 1× · see citing works
“Shortly after, mutations in the amyloid precursor protein (APP) gene were identified in familial forms of AD (Bertram and Tanzi, 2008).”
Cerebral hypoperfusion and clinical onset of dementia: the Rotterdam Study
Ruitenberg, A., den Heijer, T., Bakker, S. L. M., van Swieten, J. C., Koudstaal, P. J., Hofman, A., & Breteler, M. M. B. (2005) · Annals of Neurology · doi:10.1002/ana.20493 · Cited by 733 · see citing works
β-Amyloid-mediated vasoactivity and vascular endothelial damage
Thomas, T., Thomas, G., McLendon, C., Sutton, T., & Mullan, M. (1996) · Nature · doi:10.1038/380168a0 · Cited by 703 · cited 1× · see citing works
“Ab1 40 constrict isolated cerebral and systemic blood vessels (Niwa et al., 2001; Paris et al., 2003; Thomas et al., 1996), whereas application of Ab1 40 to the exposed cerebral cortex of mice reduces CBF and impairs the increase in CBF induced by endothelium-dependent vasodilators and functional…”
Brain Infarction and the Clinical Expression of Alzheimer Disease-Reply
Snowdon, D. A. (1997) · JAMA · doi:10.1001/jama.1997.03550020046024 · Cited by 683 · cited 2× · see citing works
“On the other hand, in older individuals with moderate AD pathology subcortical vascular lesions are a major determinant of the expression of the dementia (Esiri et al., 1999; Schneider et al., 2007b; Snowdon et al., 1997).”
Stys, P., Waxman, S., & Ransom, B. (1992) · The Journal of Neuroscience · doi:10.1523/jneurosci.12-02-00430.1992 · Cited by 662 · see citing works
Myelination and the trophic support of long axons
Nave, K.-A. (2010) · Nature Reviews Neuroscience · doi:10.1038/nrn2797 · Cited by 648 · see citing works
Virtual hypoxia and chronic necrosis of demyelinated axons in multiple sclerosis
Trapp, B. D., & Stys, P. K. (2009) · The Lancet Neurology · doi:10.1016/s1474-4422(09)70043-2 · Cited by 621 · see citing works
Charidimou, A., Gang, Q., & Werring, D. J. (2012) · Journal of Neurology, Neurosurgery & Psychiatry · doi:10.1136/jnnp-2011-301308 · Cited by 611 · see citing works
Leys, D., Hénon, H., Mackowiak-Cordoliani, M.-A., & Pasquier, F. (2005) · The Lancet Neurology · doi:10.1016/s1474-4422(05)70221-0 · Cited by 609 · see citing works
Hypoxia facilitates Alzheimer's disease pathogenesis by up-regulating <i>BACE1</i> gene expression
Sun, X., He, G., Qing, H., Zhou, W., Dobie, F., Cai, F., Staufenbiel, M., Huang, L. E., & Song, W. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0606298103 · Cited by 605 · cited 1× · see citing works
“Ab Production and Clearance Hypoperfusion and hypoxia caused by vascular insufficiency may also facilitate Ab production by activating the APP cleavage enzyme b-secretase (Kitaguchi et al., 2009; Sun et al., 2006; Tesco et al., 2007; Wen et al., 2004a).”
Fernando, M. S., Simpson, J. E., Matthews, F., Brayne, C., Lewis, C. E., Barber, R., Kalaria, R. N., Forster, G., Esteves, F., Wharton, S. B., et al. (2006) · Stroke · doi:10.1161/01.str.0000221308.94473.14 · Cited by 587 · cited 3× · see citing works
“Consistent with this hypothesis, postmortem studies have shown that areas of leukoaraiosis are chronically hypoxic, as indicated by the expression of hypoxia inducible factors and related hypoxia-inducible genes (Fernando et al., 2006; Rosenberg et al., 2001).”
Butler, J. M., Kobayashi, H., & Rafii, S. (2010) · Nature Reviews Cancer · doi:10.1038/nrc2791 · Cited by 578 · cited 1× · see citing works
“In turn, classical angiogenic molecules, such as VEGF, participate in neurogenesis (neurovascular niche), neuronal cellmigration, axonguidance, dendritogenesis, and oligodendrocyte precursor migration (Butler et al., 2010; Carmeliet and Ruiz de Almodovar, 2013; Quaegebeur et al., 2011).”
Engaging neuroscience to advance translational research in brain barrier biology
Neuwelt, E. A., Bauer, B., Fahlke, C. M., Fricker, G., Iadecola, C., Janigro, D., Leybaert, L., Molnár, Z., O’Donnell, M. E., Povlishock, J. T., et al. (2011) · Nature reviews. Neuroscience · doi:10.1038/nrn2995 · Cited by 577 · cited 1× · see citing works
“For example, GLUT1 and aminoacid transporters regulate the transfer of glucose and aminoacids into the brain, whereas ‘‘efflux transporters,’’ such as LRP-1, ABC transporters, and others, remove drugs and metabolic by-products from the brain, including Ab and lactate (Neuwelt et al., 2011).”
Self-citationThe cortical angiome: an interconnected vascular network with noncolumnar patterns of blood flow
Blinder, P., Tsai, P. S., Kaufhold, J. P., Knutsen, P. M., Suhl, H., & Kleinfeld, D. (2013) · Nature Neuroscience · doi:10.1038/nn.3426 · Cited by 573 · cited 1× · see citing works
“…arrangement is that occlusion of penetrating arterioles or venules, unlike pial vessels, cannot be effectively compensated by anastomotic branches (Blinder et al., 2013), and results in reductions in flow sufficient to produce small ischemic lesions akin to microinfarcts (Nguyen et al., 2011;…”
Davalos, D., Kyu Ryu, J., Merlini, M., Baeten, K. M., Le Moan, N., Petersen, M. A., Deerinck, T. J., Smirnoff, D. S., Bedard, C., Hakozaki, H., et al. (2012) · Nature Communications · doi:10.1038/ncomms2230 · Cited by 568 · see citing works
The overlap between neurodegenerative and vascular factors in the pathogenesis of dementia
Iadecola, C. (2010) · Acta Neuropathologica · doi:10.1007/s00401-010-0718-6 · Cited by 557 · cited 1× · see citing works
“…time, new experimental findings have revealed a previously unrecognized functional and pathogenic synergy between neurons, glia, and vascular cells (Iadecola, 2010; Quaegebeur et al., 2011; Zlokovic, 2011), providing a new framework to reevaluate how alterations in cerebral blood vessels could…”
Self-citationHypertension and Cerebrovascular Dysfunction
Iadecola, C., & Davisson, R. L. (2008) · Cell Metabolism · doi:10.1016/j.cmet.2008.03.010 · Cited by 557 · cited 1× · see citing works
“…insulin resistance, and diabetes, lead to vascular oxidative stress and inflammation, both in animal models and in humans (Cohen and Tong, 2010; Iadecola and Davisson, 2008; Yates et al., 2012), which, in turn, impair the factors regulating the cerebral circulation (Faraci et al., 2011).”
Self-citationThe Role of Metabolic Disorders in Alzheimer Disease and Vascular Dementia: Two Roads Converged
Craft, S. (2009) · Archives of Neurology · doi:10.1001/archneurol.2009.27 · Cited by 547 · cited 1× · see citing works
“Furthermore, AD and cerebrovascular diseases may have common risk factors, such as hypertension, insulin resistance, diabetes, obesity, hyperhomocystinemia, hyperlipidemia, etc. (Craft, 2009; Fillit et al., 2008; Honjo et al., 2012; Purnell et al., 2009).”
DeCarli, C., Murphy, D. G. M., Tranh, M., Grady, C. L., Haxby, J. V., Gillette, J. A., Salerno, J. A., Gonzales-Aviles, A., Honvitz, B., Rapoport, S. I., et al. (1995) · Neurology · doi:10.1212/wnl.45.11.2077 · Cited by 531 · see citing works
White matter lesions impair frontal lobe function regardless of their location
Tullberg, M., Fletcher, E., DeCarli, C., Mungas, D., Reed, B. R., Harvey, D. J., Weiner, M. W., Chui, H. C., & Jagust, W. J. (2004) · Neurology · doi:10.1212/01.wnl.0000130530.55104.b5 · Cited by 530 · cited 1× · see citing works
“…structure and function broadly and are associated with reductions in frontal lobe glucose utilization (DeCarli et al., 1995; Haight et al., 2013; Tullberg et al., 2004), global reduction in cortical blood flow (Appelman et al., 2008; Chen et al., 2013a; ten Dam et al., 2007; Kobari et al.,…”
The energetics of CNS white matter
Harris, J. J., & Attwell, D. (2012) · The Journal of Neuroscience · doi:10.1523/jneurosci.3430-11.2012 · Cited by 505 · cited 2× · see citing works
“Due to fewer synapses, white matter energy usage, and consequently blood flow, is 1/3 lower of that of the gray matter (Harris and Attwell, 2012).”
Cerebrovascular disease and threshold for dementia in the early stages of Alzheimer's disease
Esiri, M. M., Nagy, Z., Smith, M. Z., Barnetson, L., & Smith, A. D. (1999) · The Lancet · doi:10.1016/s0140-6736(99)02355-7 · Cited by 493 · see citing works
Cerebral microinfarcts: the invisible lesions
Smith, E. E., Schneider, J. A., Wardlaw, J. M., & Greenberg, S. M. (2012) · The Lancet Neurology · doi:10.1016/s1474-4422(11)70307-6 · Cited by 456 · cited 2× · see citing works
“…d CADASIL d CAA, AD d Vascular risk factors d Arterioles (<300 mm Ø) d Small vessel ATS d Arteriolosclerosis d Infarcts not visible by naked eye Smith et al., 2012 Microbleeds and hemorrhages d CAA, AD d CADASIL d Vascular risk factors d Arterioles (<300 mm Ø) d Vascular rupture d…”
Impact of Metabolic Syndrome on Cognition and Brain: A Selected Review of the Literature
Yates, K. F., Sweat, V., Yau, P. L., Turchiano, M. M., & Convit, A. (2012) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/atvbaha.112.252759 · Cited by 444 · cited 2× · see citing works
“Furthermore, the metabolic syndrome, including insulin resistance, hypertension, and dyslipidemia, has been associated with lower cognitive performance (Yates et al., 2012).”
Neurological Diseases in Relation to the Blood–Brain Barrier
Rosenberg, G. A. (2012) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.2011.197 · Cited by 442 · cited 1× · see citing works
“Consistent with this hypothesis, postmortem studies have shown that areas of leukoaraiosis are chronically hypoxic, as indicated by the expression of hypoxia inducible factors and related hypoxia-inducible genes (Fernando et al., 2006; Rosenberg et al., 2001).”
Brain endothelial cells and the glio-vascular complex
Wolburg, H., Noell, S., Mack, A., Wolburg-Buchholz, K., & Fallier-Becker, P. (2009) · Cell and Tissue Research · doi:10.1007/s00441-008-0658-9 · Cited by 438 · cited 1× · see citing works
“In addition to theirwell-established interactionswith neurons, astrocytes are also needed for the development andmaintenance of BBB characteristics in endothelial cells (Wolburg et al., 2009) and for the reorganization of vascular networks after brain injury (Hayakawa et al., 2012).”
Inzitari, D., Pracucci, G., Poggesi, A., Carlucci, G., Barkhof, F., Chabriat, H., Erkinjuntti, T., Fazekas, F., Ferro, J. M., Hennerici, M., et al. (2009) · BMJ · doi:10.1136/bmj.b2477 · Cited by 415 · cited 1× · see citing works
“As for the other pathologies underlying VCI, there is a general correlation between the total burden of vascular pathology and cognitive deficits (Gelber et al., 2012; Gorelick et al., 2011; Inzitari et al., 2009).”
SOD1 rescues cerebral endothelial dysfunction in mice overexpressing amyloid precursor protein
Iadecola, C., Zhang, F., Niwa, K., Eckman, C., Turner, S. K., Fischer, E., Younkin, S., Borchelt, D. R., Hsiao, K. K., & Carlson, G. A. (1999) · Nature Neuroscience · doi:10.1038/5715 · Cited by 399 · cited 1× · see citing works
“The vascular alterations induced by Ab are abrogated by overexpression of the ROS scavenging enzyme superoxide dismutase or deficiency of the NADPH oxidase subunit NOX2 (Iadecola et al., 1999; Park et al., 2005; 2008), implicating ROS produced by the enzyme NADPH oxidase in the vascular dysfunction.”
Self-citationPromising Strategies for the Prevention of Dementia
Middleton, L. E., & Yaffe, K. (2009) · Archives of Neurology · doi:10.1001/archneurol.2009.201 · Cited by 396 · see citing works
Black, S., Gao, F., & Bilbao, J. (2009) · Stroke · doi:10.1161/strokeaha.108.537704 · Cited by 379 · cited 8× · see citing works
“Collagen deposits are observed in venules (venous collagenosis) (Black et al., 2009; Brown and Thore, 2011).”
InfluentialTran, E., Hoekstra, K., van Rooijen, N., Dijkstra, C., & Owens, T. (1998) · Journal of Immunology · doi:10.4049/jimmunol.161.7.3767 · Cited by 373 · see citing works
Review: sporadic cerebral amyloid angiopathy
Attems, J., Jellinger, K., Thal, D. R., & Van Nostrand, W. (2011) · Neuropathology and Applied Neurobiology · doi:10.1111/j.1365-2990.2010.01137.x · Cited by 371 · cited 4× · see citing works
“%) elderly people (Attems et al., 2011; Charidimou et al., 2012).”
InfluentialLacunar stroke is associated with diffuse blood-brain barrier dysfunction
Wardlaw, J. M., Doubal, F., Armitage, P., Chappell, F., Carpenter, T., Muñoz Maniega, S., Farrall, A., Sudlow, C., Dennis, M., & Dhillon, B. (2009) · Annals of Neurology · doi:10.1002/ana.21549 · Cited by 364 · see citing works
Patterns of cerebral blood flow reduction in patients with ischemic leukoaraiosis
O’Sullivan, M., Lythgoe, D. J., Pereira, A. C., Summers, P. E., Jarosz, J. M., Williams, S. C. R., & Markus, H. S. (2002) · Neurology · doi:10.1212/wnl.59.3.321 · Cited by 360 · see citing works
Pathology and pathogenesis of vascular cognitive impairment—a critical update
Jellinger, K. A. (2013) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2013.00017 · Cited by 353 · cited 6× · see citing works
“…of the circle of Willis and its branches, leukoaraiosis, and lacunar infarcts, microbleeds, microinfarcts, and CAA (Benedictus et al., 2013; Charidimou et al., 2012; Honig et al., 2005; Jellinger, 2013; Richardson et al., 2012; Roher et al., 2004; Toledo et al., 2013; Yarchoan et al., 2012).”
InfluentialThe smallest stroke: occlusion of one penetrating vessel leads to infarction and a cognitive deficit
Shih, A. Y., Blinder, P., Tsai, P. S., Friedman, B., Stanley, G., Lyden, P. D., & Kleinfeld, D. (2013) · Nature Neuroscience · doi:10.1038/nn.3278 · Cited by 351 · cited 1× · see citing works
“…arterioles or venules, unlike pial vessels, cannot be effectively compensated by anastomotic branches (Blinder et al., 2013), and results in reductions in flow sufficient to produce small ischemic lesions akin to microinfarcts (Nguyen et al., 2011; Nishimura et al., 2010; Shih et al., 2013).”
Axin2 as regulatory and therapeutic target in newborn brain injury and remyelination
Fancy, S. P. J., Harrington, E. P., Yuen, T. J., Silbereis, J. C., Zhao, C., Baranzini, S. E., Bruce, C. C., Otero, J. J., Huang, E. J., Nusse, R., et al. (2011) · Nature Neuroscience · doi:10.1038/nn.2855 · Cited by 349 · see citing works
Snapyan, M., Lemasson, M., Brill, M. S., Blais, M., Massouh, M., Ninkovic, J., Gravel, C., Berthod, F., Götz, M., Barker, P. A., et al. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.4956-08.2009 · Cited by 346 · cited 1× · see citing works
“In the adult nervous system, neuroblasts migrate along blood vessels, a process dependent on BDNF secretion by endothelial cells (Snapyan et al., 2009).”
Exercise and Alzheimer’s disease biomarkers in cognitively normal older adults
Liang, K. Y., Mintun, M. A., Fagan, A. M., Goate, A. M., Bugg, J. M., Holtzman, D. M., Morris, J. C., & Head, D. (2010) · Annals of Neurology · doi:10.1002/ana.22096 · Cited by 340 · see citing works
Wilkins, A., Majed, H., Layfield, R., Compston, A., & Chandran, S. (2003) · The Journal of Neuroscience · doi:10.1523/jneurosci.23-12-04967.2003 · Cited by 337 · cited 1× · see citing works
“The resulting OPC maturation arrest prevents efficient remyelination. of axons (Wilkins et al., 2003).”
Depletion of GGA3 Stabilizes BACE and Enhances β-Secretase Activity
Tesco, G., Koh, Y. H., Kang, E. L., Cameron, A. N., Das, S., Sena-Esteves, M., Hiltunen, M., Yang, S.-H., Zhong, Z., Shen, Y., et al. (2007) · Neuron · doi:10.1016/j.neuron.2007.05.012 · Cited by 337 · see citing works
Park, L., Zhou, P., Pitstick, R., Capone, C., Anrather, J., Norris, E. H., Younkin, L., Younkin, S., Carlson, G., McEwen, B. S., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0711568105 · Cited by 332 · see citing works
Self-citationMyelin Regeneration: A Recapitulation of Development?
Fancy, S. P. J., Chan, J. R., Baranzini, S. E., Franklin, R. J. M., & Rowitch, D. H. (2011) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-061010-113629 · Cited by 321 · see citing works
The human periventricular arterial blood supply and the anatomy of cerebral infarctions
de Reuck, J. (2008) · European Neurology · doi:10.1159/000114088 · Cited by 317 · see citing works
Brain microbleeds and Alzheimer’s disease: innocent observation or key player?
Cordonnier, C., & van der Flier, W. M. (2011) · Brain · doi:10.1093/brain/awq321 · Cited by 310 · see citing works
Johnston, S. C., O'Meara, E. S., Manolio, T. A., Lefkowitz, D., O'Leary, D. H., Goldstein, S., Carlson, M. C., Fried, L. P., & Longstreth, W. T. (2004) · Annals of Internal Medicine · doi:10.7326/0003-4819-140-4-200402170-00005 · Cited by 304 · cited 2× · see citing works
“…d Large vessel ATS d Vascular stiffening d ‘‘Watershed’’ infarcts d Cortical laminar necrosis d Incomplete white matter infarcts Jellinger, 2013; Johnston et al., 2004; Marshall et al., 2012 ‘‘Strategic infarct’’ dementia d Arterial occlusion d Large-medium size arteries d Infarct in…”
Webb, A. J. S., Simoni, M., Mazzucco, S., Kuker, W., Schulz, U., & Rothwell, P. M. (2012) · Stroke · doi:10.1161/strokeaha.112.655837 · Cited by 304 · see citing works
NG2-glia as multipotent neural stem cells: fact or fantasy?
Richardson, W. D., Young, K. M., Tripathi, R. B., & McKenzie, I. (2011) · Neuron · doi:10.1016/j.neuron.2011.05.013 · Cited by 300 · cited 1× · see citing works
“In addition, since myelination of previously naked fibers participates in neuroplasticity and skilled motor learning (Fields, 2010; Richardson et al., 2011), myelin damage could also compromise these important functions and contribute to cognitive impairment.”
Atherosclerosis and AD: Analysis of data from the US National Alzheimer’s Coordinating Center
Honig, L. S., Kukull, W., & Mayeux, R. (2005) · Neurology · doi:10.1212/01.wnl.0000150886.50187.30 · Cited by 284 · see citing works
Innate Immunity in the CNS: Redefining the Relationship between the CNS and Its Environment
Lampron, A., ElAli, A., & Rivest, S. (2013) · Neuron · doi:10.1016/j.neuron.2013.04.005 · Cited by 282 · cited 2× · see citing works
“Pericytes and perivascular macrophages have the potential for antigen presentation, the first step in adaptive immunity, whereas endothelial cells and microglia are richly endowed with innate immunity receptors including CD36, toll-like receptors (TLR), and the receptor for advances glycation endproducts (RAGE) (Lampr…”
Topakian, R., Barrick, T. R., Howe, F. A., & Markus, H. S. (2010) · Journal of Neurology, Neurosurgery & Psychiatry · doi:10.1136/jnnp.2009.172072 · Cited by 281 · see citing works
Nox2-Derived Reactive Oxygen Species Mediate Neurovascular Dysregulation in the Aging Mouse Brain
Park, L., Anrather, J., Girouard, H., Zhou, P., & Iadecola, C. (2007) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/sj.jcbfm.9600491 · Cited by 275 · cited 1× · see citing works
“…hyperemia and endothelium dependent responses are attenuated in models of aging, hypertension, and diabetes (Ergul, 2011; Kazama et al., 2004; Park et al., 2007), whereas the ability of the vessels to adjust cerebral perfusion in response to changes in blood pressure (autoregulation) is…”
Self-citationKearney-Schwartz, A., Rossignol, P., Bracard, S., Felblinger, J., Fay, R., Boivin, J.-M., Lecompte, T., Lacolley, P., Benetos, A., & Zannad, F. (2009) · Stroke · doi:10.1161/strokeaha.108.532853 · Cited by 274 · see citing works
Head (2012) · doi:10.1001/archneurol.2011.845 · Cited by 267 · see citing works
Change in the Brain's White Matter
Fields, R. D. (2010) · Science · doi:10.1126/science.1199139 · Cited by 265 · see citing works
White matter hyperintensities and cognition: Testing the reserve hypothesis
Brickman, A. M., Siedlecki, K. L., Muraskin, J., Manly, J. J., Luchsinger, J. A., Yeung, L., Brown, T. R., DeCarli, C. S., & Stern, Y. (2009) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2009.10.013 · Cited by 265 · see citing works
Subcortical infarcts, Alzheimer's disease pathology, and memory function in older persons
Schneider, J. A., Boyle, P. A., Arvanitakis, Z., Bienias, J. L., & Bennett, D. A. (2007) · Annals of Neurology · doi:10.1002/ana.21142 · Cited by 264 · cited 1× · see citing works
“Furthermore, community-based clinical-pathological studies revealed that the largest proportion of dementia cases have mixed pathology, comprising features of AD (amyloid plaques and neurofibrillary tangles) as well as ischemic lesions (Launer et al., 2008; Schneider et al., 2009).”
Cerebrovascular atherosclerosis correlates with Alzheimer pathology in neurodegenerative dementias
Yarchoan, M. M., Xie, S. X., Kling, M. A., Toledo, J. B., Wolk, D. A., Lee, E. B., Deerlin, V. M. V., Lee, V. M. Y., Trojanowski, J. Q., & Arnold, S. E. (2012) · Brain · doi:10.1093/brain/aws271 · Cited by 263 · see citing works
SRF and myocardin regulate LRP-mediated amyloid-β clearance in brain vascular cells
Bell, R. D., Deane, R., Chow, N., Long, X., Sagare, A., Singh, I., Streb, J. W., Guo, H., Rubio, A., Van Nostrand, W., et al. (2009) · Nature Cell Biology · doi:10.1038/ncb1819 · Cited by 261 · see citing works
Hur, J., Yang, H.-M., Yoon, C.-H., Lee, C.-S., Park, K.-W., Kim, J.-H., Kim, T.-Y., Kim, J.-Y., Kang, H.-J., Chae, I.-H., et al. (2007) · Circulation · doi:10.1161/circulationaha.107.694778 · Cited by 255 · see citing works
Neuroprotection via matrix-trophic coupling between cerebral endothelial cells and neurons
Guo, S., Kim, W. J., Lok, J., Lee, S.-R., Besancon, E., Luo, B.-H., Stins, M. F., Wang, X., Dedhar, S., & Lo, E. H. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0801105105 · Cited by 253 · cited 2× · see citing works
“Furthermore, through BDNF, insulin growth factor 2, chemokine (C-X-Cmotif) ligand 12, and pleiotrophin, endothelial cells support neuronal survival andprotect them from injury (Dugas et al., 2008; Guo et al., 2008).”
Angiotensin II Impairs Neurovascular Coupling in Neocortex Through NADPH Oxidase–Derived Radicals
Kazama, K., Anrather, J., Zhou, P., Girouard, H., Frys, K., Milner, T. A., & Iadecola, C. (2004) · Circulation Research · doi:10.1161/01.res.0000148637.85595.c5 · Cited by 253 · cited 6× · see citing works
“Owing to its high energy needs and lack of fuel reserves, the brain requires a continuous and well-regulated supply of blood (Iadecola, 2004).”
InfluentialSelf-citationRegulation of blood flow in the microcirculation: role of conducted vasodilation
Bagher, P., & Segal, S. S. (2010) · Acta Physiologica · doi:10.1111/j.1748-1716.2010.02244.x · Cited by 249 · cited 1× · see citing works
“Consequently, elaborate vascular signaling mechanisms coordinate changes in vascular diameter of pial arterioles on the brain’s surface with those of the intracerebral microvasculature (Bagher and Segal, 2011; Iadecola, 2004).”
Cerebral hypoperfusion accelerates cerebral amyloid angiopathy and promotes cortical microinfarcts
Okamoto, Y., Yamamoto, T., Kalaria, R. N., Senzaki, H., Maki, T., Hase, Y., Kitamura, A., Washida, K., Yamada, M., Ito, H., et al. (2012) · Acta Neuropathologica · doi:10.1007/s00401-011-0925-9 · Cited by 249 · see citing works
Risk Factors for β-Amyloid Deposition in Healthy Aging: Vascular and Genetic Effects
Rodrigue, K. M., Rieck, J. R., Kennedy, K. M., Devous, M. D., Diaz-Arrastia, R., & Park, D. C. (2013) · JAMA Neurology · doi:10.1001/jamaneurol.2013.1342 · Cited by 249 · see citing works
Blood-brain barrier permeability abnormalities in vascular cognitive impairment
Taheri, S., Gasparovic, C., Huisa, B. N., Adair, J. C., Edmonds, E., Prestopnik, J., Grossetete, M., Shah, N. J., Wills, J., Qualls, C., et al. (2011) · Stroke · doi:10.1161/strokeaha.110.611731 · Cited by 248 · cited 1× · see citing works
“Third, the permeability to MRI tracers is increased in white matter lesions (Hanyu et al., 2002; Taheri et al., 2011; Wardlaw et al., 2009) and in normal appearing white matter (Topakian et al., 2010).”
COL4A1 Mutations as a Monogenic Cause of Cerebral Small Vessel Disease
Lanfranconi, S., & Markus, H. S. (2010) · Stroke · doi:10.1161/strokeaha.110.581918 · Cited by 248 · cited 1× · see citing works
“…the autosomal dominant retinal vasculopathy with cerebral leukodystro- Neuron 80, N phy caused by frameshift deletions in the exonuclease TREX1, and mutations of the COL4A1 gene encoding the type IV collagen alpha 1 chain (Federico et al., 2012; Gorelick et al., 2011; Lanfranconi and Markus, 2010).”
Cognitive impact of subcortical vascular and Alzheimer’s disease pathology
Chui, H. C., Zarow, C., Mack, W. J., Ellis, W. G., Zheng, L., Jagust, W. J., Mungas, D., Reed, B. R., Kramer, J. H., DeCarli, C. C., et al. (2006) · Annals of Neurology · doi:10.1002/ana.21009 · Cited by 247 · see citing works
The neurovascular link in health and disease: molecular mechanisms and therapeutic implications
Quaegebeur, A., Lange, C., & Carmeliet, P. (2011) · Neuron · doi:10.1016/j.neuron.2011.07.013 · Cited by 247 · see citing works
Oxidative stress disrupts oligodendrocyte maturation
French, H. M., Reid, M., Mamontov, P., Simmons, R. A., & Grinspan, J. B. (2009) · Journal of Neuroscience Research · doi:10.1002/jnr.22139 · Cited by 246 · cited 1× · see citing works
“First, OPC in the late stage of development are particularly susceptible to injury in conditions of chronic hypoxia and oxidative stress existing in the ischemic white matter (Back et al., 2011; 2002; Fernando et al., 2006; French et al., 2009).”
Arai, K., & Lo, E. H. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.0035-09.2009 · Cited by 246 · see citing works
Park, L., Anrather, J., Zhou, P., Frys, K., Pitstick, R., Younkin, S., Carlson, G. A., & Iadecola, C. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.5207-04.2005 · Cited by 244 · cited 1× · see citing works
“The vascular alterations induced by Ab are abrogated by overexpression of the ROS scavenging enzyme superoxide dismutase or deficiency of the NADPH oxidase subunit NOX2 (Iadecola et al., 1999; Park et al., 2005; 2008), implicating ROS produced by the enzyme NADPH oxidase in the vascular dysfunction.”
Self-citationAβ1–40-related reduction in functional hyperemia in mouse neocortex during somatosensory activation
Niwa, K., Younkin, L. H., Ebeling, C., Turner, S. K., Westaway, D. A., Younkin, S. G., Ashe, K. H., Carlson, G. A., & Iadecola, C. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.17.9735 · Cited by 244 · see citing works
Self-citationLaw, M., Saindane, A. M., Ge, Y., Babb, J. S., Johnson, G., Mannon, L. J., Herbert, J., & Grossman, R. I. (2004) · Radiology · doi:10.1148/radiol.2313030996 · Cited by 242 · see citing works
Hypertension is a potential risk factor for vascular dementia: systematic review
Sharp, S. I., Aarsland, D., Day, S., Sønnesyn, H., Alzheimer's Society Vascular Dementia Systematic Review Group, & Ballard, C. (2011) · International Journal of Geriatric Psychiatry · doi:10.1002/gps.2572 · Cited by 241 · see citing works
Vascular aspects of multiple sclerosis
D'haeseleer, M., Cambron, M., Vanopdenbosch, L., & De Keyser, J. (2011) · The Lancet Neurology · doi:10.1016/s1474-4422(11)70105-3 · Cited by 241 · see citing works
Revisiting the role of neurons in neurovascular coupling
Cauli, B. (2010) · Frontiers in Neuroenergetics · doi:10.3389/fnene.2010.00009 · Cited by 236 · cited 1× · see citing works
“…are mediated by vasoactive agents with opposing vascular actions (vasodilatation or vasoconstriction), generated by synaptic activity, astrocytes, interneurons, and afferent projections from the basal forebrain and brainstem (Cauli and Hamel, 2010; Drake and Iadecola, 2007; Kleinfeld et al., 2011).”
Endothelial influences on cerebrovascular tone
Andresen, J., Shafi, N. I., & Bryan, R. M. (2006) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00937.2005 · Cited by 235 · see citing works
Cerebral Hypoperfusion Generates Cortical Watershed Microinfarcts in Alzheimer Disease
Suter, O.-C., Sunthorn, T., Kraftsik, R., Straubel, J., Pushpa Darekar, B., Khalili, K., & Judith Miklossy, A. (2002) · Stroke · doi:10.1161/01.str.0000024523.82311.77 · Cited by 235 · see citing works
Graumann, U., Reynolds, R., Steck, A. J., & Schaeren‐Wiemers, N. (2003) · Brain Pathology · doi:10.1111/j.1750-3639.2003.tb00485.x · Cited by 233 · see citing works
Treatment of vascular risk factors is associated with slower decline in Alzheimer disease
Deschaintre, Y., Richard, F., Leys, D., & Pasquier, F. (2009) · Neurology · doi:10.1212/wnl.0b013e3181b59bf3 · Cited by 232 · see citing works
Dementia, stroke, and vascular risk factors; a review
Sahathevan, R., Brodtmann, A., & Donnan, G. A. (2012) · International Journal of Stroke · doi:10.1111/j.1747-4949.2011.00731.x · Cited by 230 · cited 2× · see citing works
“Remarkably, in VCI as in AD, the increase in risk afforded by vascular risk factors is observed decades later, a finding that may explain why some studies did not find a cognitive improvement with risk factor control later in life (Sahathevan et al., 2012).”
Heart disease as a risk factor for dementia
Hakim, A., Ng, & Turek (2013) · Clinical Epidemiology · doi:10.2147/clep.s30621 · Cited by 229 · cited 1× · see citing works
“Reduction in global cerebral perfusion caused by cardiac arrest, arrhythmias, cardiac failure, or hypotension can produce brain dysfunction and impair cognition transiently or permanently (Table 1) (Alosco et al., 2013; Justin et al., 2013; Marshall, 2012; Stefansdottir et al., 2013).”
Allan, L. M., Rowan, E. N., Firbank, M. J., Thomas, A. J., Parry, S. W., Polvikoski, T. M., O'Brien, J. T., & Kalaria, R. N. (2011) · Brain · doi:10.1093/brain/awr273 · Cited by 225 · cited 1× · see citing works
“Stroke doubles the risk for dementia (poststroke dementia), and approximately 30% of stroke patients go on to develop cognitive dysfunction within 3 years (Allan et al., 2011; Leys et al., 2005; Pendlebury and Rothwell, 2009).”
Cardiovascular risk factors and dementia
Fillit, H., Nash, D. T., Rundek, T., & Zuckerman, A. (2008) · The American Journal of Geriatric Pharmacotherapy · doi:10.1016/j.amjopharm.2008.06.004 · Cited by 225 · see citing works
Thal, D. R., Grinberg, L. T., & Attems, J. (2012) · Experimental Gerontology · doi:10.1016/j.exger.2012.05.023 · Cited by 223 · cited 14× · see citing works
“…d Venous collagenosis d Axonal damage d Demyelination d Lacunar infarcts d Microinfarcts d Microbleeds Black et al., 2009; Brown and Thore, 2011; Thal et al., 2012 Microinfarcts d CADASIL d CAA, AD d Vascular risk factors d Arterioles (<300 mm Ø) d Small vessel ATS d…”
InfluentialBechmann, I., Mor, G., Nilsen, J., Eliza, M., Nitsch, R., & Naftolin, F. N. (1999) · Glia · doi:10.1002/(sici)1098-1136(199907)27:1 · Cited by 221 · cited 1× · see citing works
“Astrocytes express ‘‘death’’ ligands (CD95L) on their perivascular end feet and control immune trafficking by triggering apoptosis of CD95+ lymphocytes attempting to enter the brain (Bechmann et al., 1999).”
P2X7 receptors mediate ischemic damage to oligodendrocytes
Domercq, M., Perez‐Samartin, A., Aparicio, D., Alberdi, E., Pampliega, O., & Matute, C. (2010) · Glia · doi:10.1002/glia.20958 · Cited by 221 · see citing works
Genome‐wide association studies of cerebral white matter lesion burden
Fornage, M., Debette, S., Bis, J. C., Schmidt, H., Ikram, M. A., Dufouil, C., Sigurdsson, S. O., Lumley, T., DeStefano, A. L., Fazekas, F., et al. (2011) · Annals of Neurology · doi:10.1002/ana.22403 · Cited by 220 · cited 1× · see citing works
“Studies of candidate genes have revealed weak associations with genes involved in the reninangiotensin system, endothelial nitric oxide synthase, oxidative stress, lipid metabolism and inflammation, but have not been replicated (Fornage et al., 2011; Lee and Kim, 2013; Markus, 2008).”
Vascular inflammation in cerebral small vessel disease
Rouhl, R. P. W., Damoiseaux, J. G. M. C., Lodder, J., Theunissen, R. O. M. F. I. H., Knottnerus, I. L. H., Staals, J., Henskens, L. H. G., Kroon, A. A., de Leeuw, P. W., Tervaert, J. W. C., et al. (2012) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2011.04.008 · Cited by 219 · cited 2× · see citing works
“Angiogenic T cells are reduced in patients with vascular risk factors (Hur et al., 2007; Weil et al., 2011), and in hypertensive patients with small vessels disease (Rouhl et al., 2012b).”
Niwa, K., Kazama, K., Younkin, S. G., Carlson, G. A., & Iadecola, C. (2002) · Neurobiology of Disease · doi:10.1006/nbdi.2001.0460 · Cited by 218 · cited 1× · see citing works
“…endothelium-dependent responses and autoregulation are profoundly impaired in young mice overexpressing mutated forms of APP, in which brain Ab is elevated, but there are no plaques, behavioral alterations, or reductions in resting glucose utilization (Niwa et al., 2000b; 2002; Tong et al., 2012).”
Self-citationIncident subcortical infarcts induce focal thinning in connected cortical regions
Duering, M., Righart, R., Csanadi, E., Jouvent, E., Hervé, D., Chabriat, H., & Dichgans, M. (2012) · Neurology · doi:10.1212/wnl.0b013e3182749f39 · Cited by 218 · cited 1× · see citing works
“Focal cortical thinning was also observed in a prospective study of patients with CADASIL subsequent to a subcortical infarct (Duering et al., 2012), indicating a causal link between white matter lesions and cortical atrophy.”
Cerebral Perfusion and Cerebrovascular Reactivity Are Reduced in White Matter Hyperintensities
Marstrand, J. R., Garde, E., Rostrup, E., Ring, P., Rosenbaum, S., Mortensen, E. L., & Larsson, H. B. W. (2002) · Stroke · doi:10.1161/01.str.0000012808.81667.4b · Cited by 215 · cited 1× · see citing works
“Resting flow is reduced in areas of leukoaraiosis and vascular reactivity attenuated (Kobari et al., 1990; Makedonov et al., 2013; Markus et al., 2000; 1994; Marstrand et al., 2002; O’Sullivan et al., 2002; Yao et al., 1992).”
Simpson, J. E., Fernando, M. S., Clark, L., Ince, P. G., Matthews, F., Forster, G., O'Brien, J. T., Barber, R., Kalaria, R. N., Brayne, C., et al. (2007) · Neuropathology and Applied Neurobiology · doi:10.1111/j.1365-2990.2007.00828.x · Cited by 215 · see citing works
NADPH oxidase activity and function are profoundly greater in cerebral versus systemic arteries
Miller, A. A., Drummond, G. R., Schmidt, H. H. H. W., & Sobey, C. G. (2005) · Circulation Research · doi:10.1161/01.res.0000189301.10217.87 · Cited by 211 · cited 2× · see citing works
“NADPH oxidase, a multiunit enzyme particularly enriched in cerebral blood vessels (Miller et al., 2005), has emerges as an important source in vascular oxidative stress in aging, hypertension, hyperlipidemia and diabetes (Faraci et al., 2011), and inhibition or genetic inactivation of this enzyme…”
Moser, H. W., Loes, D. J., Melhem, E. R., Raymond, G. V., Bezman, L., Cox, C. S., & Lu, S.-E. (2000) · Neuropediatrics · doi:10.1055/s-2000-9236 · Cited by 210 · cited 1× · see citing works
“On the other hand, if the reduction in CBF is sustained and severe, ischemic stroke ensues (Moskowitz et al., 2010).”
Thompson, C. S., & Hakim, A. M. (2009) · Stroke · doi:10.1161/strokeaha.108.542266 · Cited by 208 · cited 1× · see citing works
“Similar microvascular changes occur also in other organs, suggesting that small vessel disease in brain may be themanifestation of a systemic vasculopathy (Thompson and Hakim, 2009).”
Carare, R. O., Hawkes, C. A., Jeffrey, M., Kalaria, R. N., & Weller, R. O. (2013) · Neuropathology and Applied Neurobiology · doi:10.1111/nan.12042 · Cited by 207 · cited 1× · see citing works
“Images are courtesy of Dr. Hooman Kamel. has emerged as critically important for the disposal of unwanted proteins and peptides, e.g., Ab (Carare et al., 2013; Iliff et al., 2013; Laman and Weller, 2013).”
Cerebral vasomotor reactivity and cerebral white matter lesions in the elderly
Bakker, S. L. M., de Leeuw, F.-E., de Groot, J. C., Hofman, A., Koudstaal, P. J., & Breteler, M. M. B. (1999) · Neurology · doi:10.1212/wnl.52.3.578 · Cited by 207 · cited 1× · see citing works
“Indeed, in the general population, lower global CBF and lower cerebrovascular reactivity to hypercapnia is associated with a greater volume of white matter lesions (Bakker et al., 1999; Vernooij et al., 2008).”
White matter damage is associated with matrix metalloproteinases in vascular dementia
Rosenberg, G. A., Sullivan, N., & Esiri, M. M. (2001) · Stroke · doi:10.1161/01.str.32.5.1162 · Cited by 207 · cited 1× · see citing works
“Consistent with this hypothesis, postmortem studies have shown that areas of leukoaraiosis are chronically hypoxic, as indicated by the expression of hypoxia inducible factors and related hypoxia-inducible genes (Fernando et al., 2006; Rosenberg et al., 2001).”
Zhang, F., Eckman, C., Younkin, S., Hsiao, K. K., & Iadecola, C. (1997) · The Journal of Neuroscience · doi:10.1523/jneurosci.17-20-07655.1997 · Cited by 205 · cited 3× · see citing works
“APP-overexpressing mice have increased brain damage following occlusion of the middle cerebral artery (Koistinaho et al., 2002; Zhang et al., 1997), an effect in part related to poor collateral circulation due to vascular dysregulation (Zhang et al., 1997).”
Self-citationTomimoto, H., Akiguchi, I., Suenaga, T., Nishimura, M., Wakita, H., Nakamura, S., & Kimura, J. (1996) · Stroke · doi:10.1161/01.str.27.11.2069 · Cited by 204 · cited 2× · see citing works
“Second, plasma proteins, including complement, fibrinogen, albumin, and immunoglobulins are detected in astrocytes in white matter lesions (Akiguchi et al., 1998; Alafuzoff et al., 1985; Simpson et al., 2007; Tomimoto et al., 1996).”
Aβ-peptides enhance vasoconstriction in cerebral circulation
Niwa, K., Porter, V. A., Kazama, K., Cornfield, D., Carlson, G. A., & Iadecola, C. (2001) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.2001.281.6.h2417 · Cited by 202 · cited 1× · see citing works
“Ab1 40 constrict isolated cerebral and systemic blood vessels (Niwa et al., 2001; Paris et al., 2003; Thomas et al., 1996), whereas application of Ab1 40 to the exposed cerebral cortex of mice reduces CBF and impairs the increase in CBF induced by endothelium-dependent vasodilators and functional…”
Self-citationMarkus, H. S. (2000) · Journal of Neurology, Neurosurgery & Psychiatry · doi:10.1136/jnnp.69.1.48 · Cited by 202 · see citing works
Cipolla, M. J. (2009) · Colloquium Series on Integrated Systems Physiology From Molecule to Function · doi:10.4199/c00005ed1v01y200912isp002 · Cited by 202 · see citing works
Incident lacunes influence cognitive decline: The LADIS study
Jokinen, H., Gouw, A. A., Madureira, S., Ylikoski, R., van Straaten, E. C. W., van der Flier, W. M., Barkhof, F., Scheltens, P., Fazekas, F., Schmidt, R., et al. (2011) · Neurology · doi:10.1212/wnl.0b013e31821d752f · Cited by 200 · cited 1× · see citing works
“The expansion of the white matter lesions correlates with the evolution of the cognitive impairment (Maillard et al., 2012), new lacunes causing a steeper decline, especially in motor speed and executive functions (Jokinen et al., 2011).”
Reduced cerebral blood flow response and compensation among patients with untreated hypertension
Jennings, J. R., Muldoon, M. F., Ryan, C., Price, J. C., Greer, P., Sutton-Tyrrell, K., van der Veen, F. M., & Meltzer, C. C. (2005) · Neurology · doi:10.1212/01.wnl.0000158283.28251.3c · Cited by 198 · cited 1× · see citing works
“In patients with VCI risk factors, like hypertension and diabetes, the ability of neural activity to increase blood flow in brain or retina is compromised (Delles et al., 2004; Jennings et al., 2005; Sorond et al., 2011).”
Flow detection and calcium signalling in vascular endothelial cells
Ando, J., & Yamamoto, K. (2013) · Cardiovascular Research · doi:10.1093/cvr/cvt084 · Cited by 198 · see citing works
Protecting against vascular disease in brain
Faraci, F. M. (2011) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.01310.2010 · Cited by 196 · see citing works
Is physical activity a potential preventive factor for vascular dementia? A systematic review
Aarsland, D., Sardahaee, F. S., Anderssen, S., Ballard, C., & the Alzheimer's Society Systematic Review group (2010) · Aging & Mental Health · doi:10.1080/13607860903586136 · Cited by 195 · see citing works
Oligodendrocyte precursors induce early blood-brain barrier opening after white matter injury
Seo, J. H., Miyamoto, N., Hayakawa, K., Pham, L. D., Maki, T., Ayata, C., Kim, K., Lo, E. H., & Arai, K. (2013) · Journal of Clinical Investigation · doi:10.1172/jci65863 · Cited by 195 · see citing works
Markus, H. S., Hunt, B., Palmer, K., Enzinger, C., Schmidt, H., & Schmidt, R. (2005) · Stroke · doi:10.1161/01.str.0000169924.60783.d4 · Cited by 193 · see citing works
Niwa, K., Carlson, G. A., & Iadecola, C. (2000) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1097/00004647-200012000-00005 · Cited by 191 · cited 2× · see citing works
“…systemic blood vessels (Niwa et al., 2001; Paris et al., 2003; Thomas et al., 1996), whereas application of Ab1 40 to the exposed cerebral cortex of mice reduces CBF and impairs the increase in CBF induced by endothelium-dependent vasodilators and functional hyperemia (Niwa et al., 2000a; 2000b).”
Self-citationYoshizaki, K., Adachi, K., Kataoka, S., Watanabe, A., Tabira, T., Takahashi, K., & Wakita, H. (2007) · Experimental Neurology · doi:10.1016/j.expneurol.2007.12.005 · Cited by 190 · see citing works
Cardiovascular Risk Factors and Incident Alzheimer Disease: A Systematic Review of the Literature
Purnell, C., Gao, S., Callahan, C. M., & Hendrie, H. C. (2009) · Alzheimer Disease & Associated Disorders · doi:10.1097/wad.0b013e318187541c · Cited by 189 · cited 3× · see citing works
“Furthermore, AD and cerebrovascular diseases may have common risk factors, such as hypertension, insulin resistance, diabetes, obesity, hyperhomocystinemia, hyperlipidemia, etc. (Craft, 2009; Fillit et al., 2008; Honjo et al., 2012; Purnell et al., 2009).”
Long-Term Cognitive Impairment After First-Ever Ischemic Stroke in Young Adults
Schaapsmeerders, P., Maaijwee, N. A. M., van Dijk, E. J., Rutten‐Jacobs, L. C. A., Arntz, R. M., Schoonderwaldt, H. C., Dorresteijn, L. D. A., Kessels, R. P. C., & de Leeuw, F. (2013) · Stroke · doi:10.1161/strokeaha.111.000792 · Cited by 189 · see citing works
Cerebrovascular lesions induce transient -amyloid deposition
Garcia-Alloza, M., Gregory, J., Kuchibhotla, K. V., Fine, S., Wei, Y., Ayata, C., Frosch, M. P., Greenberg, S. M., & Bacskai, B. J. (2011) · Brain · doi:10.1093/brain/awr300 · Cited by 187 · see citing works
Increased β-secretase activity and expression in rats following transient cerebral ischemia
Wen, Y., Onyewuchi, O., Yang, S., Liu, R., & Simpkins, J. W. (2004) · Brain Research · doi:10.1016/j.brainres.2003.09.086 · Cited by 187 · see citing works
Hayakawa, K., Pham, L.-D. D., Katušić, Z. S., Arai, K., & Lo, E. H. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1121146109 · Cited by 185 · cited 1× · see citing works
“In addition to theirwell-established interactionswith neurons, astrocytes are also needed for the development andmaintenance of BBB characteristics in endothelial cells (Wolburg et al., 2009) and for the reorganization of vascular networks after brain injury (Hayakawa et al., 2012).”
Progression of Cerebral Amyloid Angiopathy: Accumulation of Amyloid-ß40 in Affected Vessels
Alonzo, N. C., Hyman, B. T., Rebeck, G. W., & Greenberg, S. M. (1998) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/00005072-199804000-00008 · Cited by 185 · cited 1× · see citing works
“The white matter lesions evolve over time by expansion of existing lesions, rather than formation of new foci (Maillard et al., 2012), resembling the patterns of progression of amyloid angiopathy (Alonzo et al., 1998; Robbins et al., 2006).”
Glial Progenitor Cell–Based Treatment and Modeling of Neurological Disease
Goldman, S. A., Nedergaard, M., & Windrem, M. S. (2012) · Science · doi:10.1126/science.1218071 · Cited by 182 · cited 1× · see citing works
“, (Goldman et al., 2012).”
Sabayan, B., Jansen, S. W. M., Oleksik, A. M., van Osch, M. J. P., van Buchem, M. A., van Vliet, P., de Craen, A. J. M., & Westendorp, R. G. J. (2011) · Ageing Research Reviews · doi:10.1016/j.arr.2011.12.009 · Cited by 180 · cited 1× · see citing works
“…with early AD or at risk for AD (Claassen et al., 2009; Gao et al., 2013; Luckhaus et al., 2008; Mentis et al., 1996; Niedermeyer, 2006; Ruitenberg et al., 2005; Sabayan et al., 2012; Tanaka et al., 2002), implicating reduced cerebral perfusion in the pathobiology of the disease (Iadecola, 2004).”
The role of neuronal signaling in controlling cerebral blood flow
DRAKE, C., & IADECOLA, C. (2007) · Brain and Language · doi:10.1016/j.bandl.2006.08.002 · Cited by 177 · see citing works
Self-citationCandelario-Jalil, E., Thompson, J., Taheri, S., Grossetete, M., Adair, J. C., Edmonds, E., Prestopnik, J., Wills, J., & Rosenberg, G. A. (2011) · Stroke · doi:10.1161/strokeaha.110.600825 · Cited by 173 · cited 3× · see citing works
“First, the plasma protein albumin is increased in the CSF of patient with VCI, reflecting BBB breakdown (Candelario-Jalil et al., 2011).”
VEGF ligands and receptors: implications in neurodevelopment and neurodegeneration
Carmeliet, P., & de Almodovar, C. R. (2013) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-013-1283-7 · Cited by 173 · see citing works
Coevolution of white matter hyperintensities and cognition in the elderly
Maillard, P., Carmichael, O., Fletcher, E., Reed, B., Mungas, D., & DeCarli, C. (2012) · Neurology · doi:10.1212/wnl.0b013e3182617136 · Cited by 172 · cited 4× · see citing works
“The expansion of the white matter lesions correlates with the evolution of the cognitive impairment (Maillard et al., 2012), new lacunes causing a steeper decline, especially in motor speed and executive functions (Jokinen et al.”
InfluentialHachinski, V. C., Bowler, J. V., & Loeb, C. (1993) · Neurology · doi:10.1212/wnl.43.10.2159-a · Cited by 171 · see citing works
Cardiovascular health through young adulthood and cognitive functioning in midlife
Reis, J. P., Loria, C. M., Launer, L. J., Sidney, S., Liu, K., Jacobs, D. R., Zhu, N., Lloyd‐Jones, D. M., He, K., & Yaffe, K. (2013) · Annals of Neurology · doi:10.1002/ana.23836 · Cited by 168 · see citing works
Stefansdottir, H., Arnar, D. O., Aspelund, T., Sigurdsson, S., Jonsdottir, M. K., Hjaltason, H., Launer, L. J., & Gudnason, V. (2013) · Stroke · doi:10.1161/strokeaha.12.679381 · Cited by 166 · see citing works
Drainage of Cells and Soluble Antigen from the CNS to Regional Lymph Nodes
Laman, J. D., & Weller, R. O. (2013) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-013-9470-8 · Cited by 165 · see citing works
Ischemic stress induces deposition of amyloid ? immunoreactivity in human brain
Jendroska, K., Poewe, W., Pluess, J., Iwerssen-Schmidt, H., Paulsen, J., Barthel, S., Schelosky, L., Cerv�s-Navarro, J., Daniel, S. E., & DeArmond, S. J. (1995) · Acta Neuropathologica · doi:10.1007/bf00294806 · Cited by 163 · see citing works
. Identification of Alzheimer and vascular lesion thresholds for mixed dementia.
Gold, G., Giannakopoulos, P., Herrmann, F. R., Bouras, C., & Kovari, E. (2007) · Brain · doi:10.1093/brain/awm228 · Cited by 163 · see citing works
Brown, W. R., Moody, D. M., Thore, C. R., Challa, V. R., & Anstrom, J. A. (2007) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2007.01.015 · Cited by 162 · see citing works
Cdk5 is involved in NFT-like tauopathy induced by transient cerebral ischemia in female rats
Wen, Y., Yang, S.-H., Liu, R., Perez, E. J., Brun-Zinkernagel, A. M., Koulen, P., & Simpkins, J. W. (2007) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2006.10.011 · Cited by 162 · see citing works
Age-dependent rescue by simvastatin of Alzheimer’s disease cerebrovascular and memory deficits
Tong, X.-K., Lecrux, C., & Hamel, E. (2012) · The Journal of Neuroscience · doi:10.1523/jneurosci.0169-12.2012 · Cited by 160 · cited 1× · see citing works
“…endothelium-dependent responses and autoregulation are profoundly impaired in young mice overexpressing mutated forms of APP, in which brain Ab is elevated, but there are no plaques, behavioral alterations, or reductions in resting glucose utilization (Niwa et al., 2000b; 2002; Tong et al., 2012).”
Park, J., Seo, S. W., Kim, C., Kim, G. H., Noh, H. J., Kim, S. T., Kwak, K., Yoon, U., Lee, J. M., Lee, J. W., et al. (2013) · Annals of Neurology · doi:10.1002/ana.23845 · Cited by 160 · see citing works
Koistinaho, M., Kettunen, M. I., Goldsteins, G., Keinänen, R., Salminen, A., Ort, M., Bures, J., Liu, D., Kauppinen, R. A., Higgins, L. S., et al. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.032670899 · Cited by 159 · cited 1× · see citing works
“APP-overexpressing mice have increased brain damage following occlusion of the middle cerebral artery (Koistinaho et al., 2002; Zhang et al., 1997), an effect in part related to poor collateral circulation due to vascular dysregulation (Zhang et al., 1997).”
Periventricular white matter lucency and cerebral blood flow autoregulation in hypertensive patients
Matsushita, K., Kuriyama, Y., Nagatsuka, K., Nakamura, M., Sawada, T., & Omae, T. (1994) · Hypertension · doi:10.1161/01.hyp.23.5.565 · Cited by 157 · see citing works
Vernooij, M. W., van der Lugt, A., Ikram, M. A., Wielopolski, P. A., Vrooman, H. A., Hofman, A., Krestin, G. P., & Breteler, M. M. (2008) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/sj.jcbfm.9600526 · Cited by 156 · cited 1× · see citing works
“Indeed, in the general population, lower global CBF and lower cerebrovascular reactivity to hypercapnia is associated with a greater volume of white matter lesions (Bakker et al., 1999; Vernooij et al., 2008).”
Park, L., Wang, G., Zhou, P., Zhou, J., Pitstick, R., Previti, M. L., Younkin, L., Younkin, S. G., Van Nostrand, W. E., Cho, S., et al. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1015413108 · Cited by 156 · see citing works
Self-citationLarge-vessel correlates of cerebral small-vessel disease
Brisset, M., Boutouyrie, P., Pico, F., Zhu, Y., Zureik, M., Schilling, S., Dufouil, C., Mazoyer, B., Laurent, S., Tzourio, C., et al. (2013) · Neurology · doi:10.1212/wnl.0b013e318281ccc2 · Cited by 155 · cited 2× · see citing works
“and lacunes (Brisset et al., 2013; Tarumi et al., 2011; Webb et al., 2012), independently of vascular risk factors (KearneySchwartz et al.”
Castellano, J. M., Deane, R., Gottesdiener, A. J., Verghese, P. B., Stewart, F. R., West, T., Paoletti, A. C., Kasper, T. R., DeMattos, R. B., Zlokovic, B. V., et al. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1206446109 · Cited by 154 · see citing works
Alzheimer’s disease, cerebrovascular disease, and the β-amyloid cascade
Honjo, K., Black, S. E., & Verhoeff, N. P. L. G. (2012) · Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques · doi:10.1017/s0317167100015547 · Cited by 152 · cited 1× · see citing works
“Furthermore, AD and cerebrovascular diseases may have common risk factors, such as hypertension, insulin resistance, diabetes, obesity, hyperhomocystinemia, hyperlipidemia, etc. (Craft, 2009; Fillit et al., 2008; Honjo et al., 2012; Purnell et al., 2009).”
Akinyemi, R., Mukaetova-Ladinska, E., Attems, J., Ihara, M., & Kalaria, R. (2013) · Current Alzheimer Research · doi:10.2174/15672050113109990037 · Cited by 152 · see citing works
Scuteri, A., Nilsson, P. M., Tzourio, C., Redon, J., & Laurent, S. (2011) · Journal of Hypertension · doi:10.1097/hjh.0b013e328347cc17 · Cited by 151 · cited 3× · see citing works
“These findings implicate loss of large artery elasticity and increased pulsatile stress on microvessels, especially those branching directly from the circle of Willis, in the microvascular damage underlying white matter lesions (Scuteri et al., 2011).”
Transient cerebral ischemia induces site-specific hyperphosphorylation of tau protein
Wen, Y., Yang, S., Liu, R., & Simpkins, J. W. (2004) · Brain Research · doi:10.1016/j.brainres.2004.05.106 · Cited by 149 · see citing works
The Honolulu-Asia Aging Study: epidemiologic and neuropathologic research on cognitive impairment
P. Gelber, R., J. Launer, L., & R. White, L. (2012) · Current Alzheimer Research · doi:10.2174/156720512801322618 · Cited by 149 · see citing works
Ueno, M., Tomimoto, H., Akiguchi, I., Wakita, H., & Sakamoto, H. (2002) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1097/00004647-200201000-00012 · Cited by 147 · cited 1× · see citing works
“In vivo, hypoperfusion produced by bilateral carotid stenosis in rat increases BBB permeability (Ueno et al., 2002).”
Leukoaraiosis: correlation of MR and CT findings with blood flow, atrophy, and cognition.
Kobari, M., Meyer, J. S., Ichijo, M., & Oravez, W. T. (1990) · PubMed Central · Cited by 147 · see citing works
Atherosclerosis of Cerebral Arteries in Alzheimer Disease
Roher, A. E., Esh, C. L., Rahman, A., Kokjohn, T. A., & Beach, T. G. (2004) · Stroke · doi:10.1161/01.str.0000143317.70478.b3 · Cited by 146 · see citing works
Endothelin-1 and diabetic complications: focus on the vasculature
Ergul, A. (2011) · Pharmacological Research · doi:10.1016/j.phrs.2011.01.012 · Cited by 144 · see citing works
Flagged first, then by citations
23 of the 364 references couldn’t be matched to a known paper.
Research works printed but not linked: 1
- Butler, 2012, Dementia, Clin. Evid. (Online)
Cited by
Sorted by citations
Dementia prevention, intervention, and care: 2024 report of the Lancet standing Commission
Livingston, G., Huntley, J., Liu, K. Y., Costafreda, S. G., Selbæk, G., Alladi, S., Ames, D., Banerjee, S., Burns, A., Brayne, C., et al. (2024) · The Lancet · doi:10.1016/s0140-6736(24)01296-0 · Cited by 3,860 · see citing works
Blood–brain barrier breakdown in Alzheimer disease and other neurodegenerative disorders
Sweeney, M. D., Sagare, A. P., & Zlokovic, B. V. (2018) · Nature Reviews Neurology · doi:10.1038/nrneurol.2017.188 · Cited by 3,076 · see citing works
The Neurovascular Unit Coming of Age: A Journey through Neurovascular Coupling in Health and Disease
Iadecola, C. (2017) · Neuron · doi:10.1016/j.neuron.2017.07.030 · Cited by 2,480 · see citing works
Self-citationBlood-Brain Barrier: From Physiology to Disease and Back
Sweeney, M. D., Zhao, Z., Montagne, A., Nelson, A. R., & Zlokovic, B. V. (2019) · Physiological Reviews · doi:10.1152/physrev.00050.2017 · Cited by 2,294 · see citing works
Blood-brain barrier breakdown in the aging human hippocampus
Montagne, A., Barnes, S. R., Sweeney, M. D., Halliday, M. R., Sagare, A. P., Zhao, Z., Toga, A. W., Jacobs, R. E., Liu, C. Y., Amezcua, L., et al. (2015) · Neuron · doi:10.1016/j.neuron.2014.12.032 · Cited by 2,102 · see citing works
A molecular atlas of cell types and zonation in the brain vasculature
Vanlandewijck, M., He, L., Mäe, M. A., Andrae, J., Ando, K., Del Gaudio, F., Nahar, K., Lebouvier, T., Laviña, B., Gouveia, L., et al. (2018) · Nature · doi:10.1038/nature25739 · Cited by 2,074 · see citing works
Establishment and Dysfunction of the Blood-Brain Barrier
Zhao, Z., Nelson, A. R., Betsholtz, C., & Zlokovic, B. V. (2015) · Cell · doi:10.1016/j.cell.2015.10.067 · Cited by 1,670 · see citing works
Cognitive decline and dementia in diabetes mellitus: mechanisms and clinical implications
Biessels, G. J., & Despa, F. (2018) · Nature Reviews Endocrinology · doi:10.1038/s41574-018-0048-7 · Cited by 1,454 · see citing works
Cerebral blood flow regulation and neurovascular dysfunction in Alzheimer disease
Kisler, K., Nelson, A. R., Montagne, A., & Zlokovic, B. V. (2017) · Nature Reviews Neuroscience · doi:10.1038/nrn.2017.48 · Cited by 1,243 · see citing works
Iturria-Medina, Y., Sotero, R. C., Toussaint, P. J., Mateos-Pérez, J. M., Evans, A. C., Initiative, T. A. D. N., Weiner, M. W., Aisen, P., Petersen, R., Jack, C. R., et al. (2016) · Nature Communications · doi:10.1038/ncomms11934 · Cited by 1,202 · see citing works
Glymphatic failure as a final common pathway to dementia
Nedergaard, M., & Goldman, S. A. (2020) · Science · doi:10.1126/science.abb8739 · Cited by 1,145 · see citing works
O'Brien, J. T., & Thomas, A. (2015) · The Lancet · doi:10.1016/s0140-6736(15)00463-8 · Cited by 1,136 · see citing works
Pericytes of the neurovascular unit: key functions and signaling pathways
Sweeney, M. D., Ayyadurai, S., & Zlokovic, B. V. (2016) · Nature Neuroscience · doi:10.1038/nn.4288 · Cited by 1,125 · see citing works
The role of brain vasculature in neurodegenerative disorders
Sweeney, M. D., Kisler, K., Montagne, A., Toga, A. W., & Zlokovic, B. V. (2018) · Nature Neuroscience · doi:10.1038/s41593-018-0234-x · Cited by 998 · see citing works
What are White Matter Hyperintensities Made of?
Wardlaw, J. M., Hernández, M. C. V., & Maniega, S. M. (2015) · Journal of the American Heart Association · doi:10.1161/jaha.114.001140 · Cited by 902 · see citing works
Regulation of cerebral blood flow in humans: physiology and clinical implications of autoregulation
Claassen, J. A. H. R., Thijssen, D. H. J., Panerai, R. B., & Faraci, F. M. (2021) · Physiological Reviews · doi:10.1152/physrev.00022.2020 · Cited by 947 · see citing works
A human brain vascular atlas reveals diverse mediators of Alzheimer’s risk
Yang, A. C., Vest, R. T., Kern, F., Lee, D. P., Agam, M., Maat, C. A., Losada, P. M., Chen, M. B., Schaum, N., Khoury, N., et al. (2022) · Nature · doi:10.1038/s41586-021-04369-3 · Cited by 797 · see citing works
Post-Stroke Cognitive Impairment and Dementia
Rost, N. S., Brodtmann, A. G., Pase, M. P., van Veluw, S. J., Biffi, A., Duering, M., Hinman, J. D., & Dichgans, M. (2022) · Circulation Research · doi:10.1161/circresaha.122.319951 · Cited by 837 · see citing works
Microglia constitute a barrier that prevents neurotoxic protofibrillar Aβ42 hotspots around plaques
Condello, C., Yuan, P., Schain, A., & Grutzendler, J. (2015) · Nature Communications · doi:10.1038/ncomms7176 · Cited by 718 · see citing works
Iadecola, C., Yaffe, K., Biller, J., Bratzke, L. C., Faraci, F. M., Gorelick, P. B., Gulati, M., Kamel, H., Knopman, D. S., Launer, L. J., et al. (2016) · Hypertension · doi:10.1161/hyp.0000000000000053 · Cited by 746 · see citing works
Self-citationVascular dysfunction—The disregarded partner of Alzheimer's disease
Sweeney, M. D., Montagne, A., Sagare, A. P., Nation, D. A., Schneider, L. S., Chui, H. C., Harrington, M. G., Pa, J., Law, M., Wang, D. J. J., et al. (2019) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2018.07.222 · Cited by 711 · see citing works
Self-citationThe overlap between vascular disease and Alzheimer’s disease - lessons from pathology
Attems, J., & Jellinger, K. A. (2014) · BMC Medicine · doi:10.1186/s12916-014-0206-2 · Cited by 739 · see citing works
“The pathophysiology of VaD has been critically reviewed recently [48,144-146].”
BackgroundAlzheimer’s disease: A matter of blood–brain barrier dysfunction?
Montagne, A., Zhao, Z., & Zlokovic, B. V. (2017) · Journal of Experimental Medicine · doi:10.1084/jem.20171406 · Cited by 672 · see citing works
Amyloid β oligomers constrict human capillaries in Alzheimer's disease via signaling to pericytes
Nortley, R., Korte, N., Izquierdo, P., Hirunpattarasilp, C., Mishra, A., Jaunmuktane, Z., Kyrargyri, V., Pfeiffer, T., Khennouf, L., Madry, C., et al. (2019) · Science · doi:10.1126/science.aav9518 · Cited by 682 · see citing works
Blood-Brain Barrier Leakage in Patients with Early Alzheimer Disease
van de Haar, H. J., Burgmans, S., Jansen, J. F. A., van Osch, M. J. P., van Buchem, M. A., Muller, M., Hofman, P. A. M., Verhey, F. R. J., & Backes, W. H. (2016) · Radiology · doi:10.1148/radiol.2016152244 · Cited by 601 · see citing works
Claudin-5: gatekeeper of neurological function
Greene, C., Hanley, N., & Campbell, M. (2019) · Fluids and Barriers of the CNS · doi:10.1186/s12987-019-0123-z · Cited by 583 · see citing works
The role of brain barriers in fluid movement in the CNS: is there a ‘glymphatic’ system?
Abbott, N. J., Pizzo, M. E., Preston, J. E., Janigro, D., & Thorne, R. G. (2018) · Acta Neuropathologica · doi:10.1007/s00401-018-1812-4 · Cited by 593 · see citing works
Neurovascular dysfunction and neurodegeneration in dementia and Alzheimer's disease
Nelson, A. R., Sweeney, M. D., Sagare, A. P., & Zlokovic, B. V. (2016) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2015.12.016 · Cited by 559 · see citing works
Fibrinogen in neurological diseases: mechanisms, imaging and therapeutics
Petersen, M. A., Ryu, J. K., & Akassoglou, K. (2018) · Nature reviews. Neuroscience · doi:10.1038/nrn.2018.13 · Cited by 527 · see citing works
El Husseini, N., Katzan, I. L., Rost, N. S., Blake, M. L., Byun, E., Pendlebury, S. T., Aparicio, H. J., Marquine, M. J., Gottesman, R. F., Smith, E. E., et al. (2023) · Stroke · doi:10.1161/str.0000000000000430 · Cited by 539 · see citing works
Toth, P., Tarantini, S., Csiszar, A., & Ungvari, Z. (2017) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00581.2016 · Cited by 522 · see citing works
Homocysteine, B Vitamins, and Cognitive Impairment
Smith, A. D., & Refsum, H. (2016) · Annual Review of Nutrition · doi:10.1146/annurev-nutr-071715-050947 · Cited by 524 · see citing works
Neurovascular and Cognitive Dysfunction in Hypertension
Iadecola, C., & Gottesman, R. F. (2019) · Circulation Research · doi:10.1161/circresaha.118.313260 · Cited by 518 · see citing works
Self-citationPericyte degeneration leads to neurovascular uncoupling and limits oxygen supply to brain
Kisler, K., Nelson, A. R., Rege, S. V., Ramanathan, A., Wang, Y., Ahuja, A., Lazic, D., Tsai, P. S., Zhao, Z., Zhou, Y., et al. (2017) · Nature Neuroscience · doi:10.1038/nn.4489 · Cited by 497 · see citing works
The Meningeal Lymphatic System: A New Player in Neurophysiology
Da Mesquita, S., Fu, Z., & Kipnis, J. (2018) · Neuron · doi:10.1016/j.neuron.2018.09.022 · Cited by 479 · see citing works
The neuropathology and cerebrovascular mechanisms of dementia
Raz, L., Knoefel, J. E., & Bhaskar, K. (2015) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.2015.164 · Cited by 470 · see citing works
Merlini, M., Rafalski, V. A., Rios Coronado, P. E., Gill, T. M., Ellisman, M., Muthukumar, G., Subramanian, K. S., Ryu, J. K., Syme, C. A., Davalos, D., et al. (2019) · Neuron · doi:10.1016/j.neuron.2019.01.014 · Cited by 431 · see citing works
Cerebral Vascular Disease and Neurovascular Injury in Ischemic Stroke
Hu, X., Silva, T. M. D., Chen, J., & Faraci, F. M. (2017) · Circulation Research · doi:10.1161/circresaha.116.308427 · Cited by 444 · see citing works
Astrocyte Regulation of Blood Flow in the BrainPreprint
MacVicar, B. A., & Newman, E. A. (2015) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a020388 · Cited by 420 · see citing works
Tarantini, S., Tran, C. H. T., Gordon, G. R., Ungvari, Z., & Csiszar, A. (2017) · Experimental Gerontology · doi:10.1016/j.exger.2016.11.004 · Cited by 411 · see citing works
Mapping the Fine-Scale Organization and Plasticity of the Brain Vasculature
Kirst, C., Skriabine, S., Prado, A. V., Topilko, T., Bertin, P., Gerschenfeld, G., Verny, F., Topilko, P., Michalski, N., Tessier‐Lavigne, M., et al. (2020) · Cell · doi:10.1016/j.cell.2020.01.028 · Cited by 370 · see citing works
Smith, E. E., Saposnik, G., Biessels, G. J., Doubal, F. N., Fornage, M., Gorelick, P. B., Greenberg, S. M., Higashida, R. T., Kasner, S. E., & Seshadri, S. (2017) · Stroke · doi:10.1161/str.0000000000000116 · Cited by 404 · see citing works
Alzheimer’s Disease and Vascular Aging
Cortes-Canteli, M., & Iadecola, C. (2020) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2019.10.062 · Cited by 400 · see citing works
“Multiple factors may contribute to vascular rarefaction in AD, including Aβ toxicity to vascular cells (20) and vascular risk factors such as hypertension (21).”
BackgroundSelf-citationTraumatic Brain Injury and Alzheimer's Disease: The Cerebrovascular Link
Ramos‐Cejudo, J., Wısnıewskı, T., Marmar, C. R., Zetterberg, H., Blennow, K., de Leon, M. J., & Fossati, S. (2018) · EBioMedicine · doi:10.1016/j.ebiom.2018.01.021 · Cited by 390 · see citing works
Beyond the neuron–cellular interactions early in Alzheimer disease pathogenesis
Henstridge, C. M., Hyman, B. T., & Spires-Jones, T. L. (2019) · Nature Reviews Neuroscience · doi:10.1038/s41583-018-0113-1 · Cited by 348 · see citing works
A Critical Role for the Vascular Endothelium in Functional Neurovascular Coupling in the Brain
Chen, B. R., Kozberg, M. G., Bouchard, M. B., Shaik, M. A., & Hillman, E. M. C. (2014) · Journal of the American Heart Association · doi:10.1161/jaha.114.000787 · Cited by 346 · see citing works
Han, L., & Jiang, C. (2021) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2020.11.023 · Cited by 358 · see citing works
Understanding the role of the perivascular space in cerebral small vessel disease
Brown, R., Benveniste, H., Black, S. E., Charpak, S., Dichgans, M., Joutel, A., Nedergaard, M., Smith, K. J., Zloković, B. V., & Wardlaw, J. M. (2018) · Cardiovascular Research · doi:10.1093/cvr/cvy113 · Cited by 342 · see citing works
Zhan, X.-H., Stamova, B., & Sharp, F. (2018) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2018.00042 · Cited by 335 · see citing works
Faraco, G., Sugiyama, Y., Lane, D., Garcia-Bonilla, L., Chang, H., Santisteban, M. M., Racchumi, G., Murphy, M., Van Rooijen, N., Anrather, J., et al. (2016) · Journal of Clinical Investigation · doi:10.1172/jci86950 · Cited by 350 · see citing works
Self-citationB-Lymphocyte-Mediated Delayed Cognitive Impairment following Stroke
Doyle, K. P., Quach, L. N., Solé, M., Axtell, R. C., Nguyen, T. V., Soler-Llavina, G. J., Jurado, S., Han, J., Steinman, L., Longo, F. M., et al. (2015) · Journal of Neuroscience · doi:10.1523/jneurosci.4098-14.2015 · Cited by 338 · see citing works
Montagne, A., Nikolakopoulou, A. M., Zhao, Z., Sagare, A. P., Si, G., Lazic, D., Barnes, S. R., Daianu, M., Ramanathan, A., Go, A., et al. (2018) · Nature Medicine · doi:10.1038/nm.4482 · Cited by 344 · see citing works
RetractedDietary salt promotes neurovascular and cognitive dysfunction through a gut-initiated TH17 response
Faraco, G., Brea, D., Garcia-Bonilla, L., Wang, G., Racchumi, G., Chang, H., Buendia, I., Santisteban, M. M., Segarra, S. G., Koizumi, K., et al. (2018) · Nature Neuroscience · doi:10.1038/s41593-017-0059-z · Cited by 343 · see citing works
Self-citationCan physical exercise in old age improve memory and hippocampal function?
Duzel, E., van Praag, H., & Sendtner, M. (2016) · Brain · doi:10.1093/brain/awv407 · Cited by 329 · see citing works
Preventing dementia by preventing stroke: The Berlin Manifesto
Hachinski, V., Einhäupl, K. M., Ganten, D., Alladi, S., Brayne, C., Stephan, B. C. M., Sweeney, M. D., Zloković, B. V., Iturria‐Medina, Y., Iadecola, C., et al. (2019) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2019.06.001 · Cited by 314 · see citing works
Self-citationInoue, Y., Shue, F., Bu, G., & Kanekiyo, T. (2023) · Molecular Neurodegeneration · doi:10.1186/s13024-023-00640-5 · Cited by 356 · see citing works
“Epidemiological studies have demonstrated that VCID is the second most common form of dementia after Alzheimer’s disease (AD), accounting for approximately 20% of dementia cases [2].”
BackgroundAnimal Models of Hypertension: A Scientific Statement From the American Heart Association
Lerman, L. O., Kurtz, T. W., Touyz, R. M., Ellison, D. H., Chade, A., Crowley, S. D., Mattson, D. L., Mullins, J. J., Osborn, J. L., Eirin, A., et al. (2019) · Hypertension · doi:10.1161/hyp.0000000000000090 · Cited by 332 · see citing works
Self-citationCardiovascular risk factors and future risk of Alzheimer’s disease
de Bruijn, R. F. A. G., & Ikram, M. A. (2014) · BMC Medicine · doi:10.1186/s12916-014-0130-5 · Cited by 325 · see citing works
Cerebrospinal fluid dynamics and intracranial pressure elevation in neurological diseases
Bothwell, S. W., Janigro, D., & Patabendige, A. (2019) · Fluids and Barriers of the CNS · doi:10.1186/s12987-019-0129-6 · Cited by 331 · see citing works
Vascular Cognitive Impairment (VCI)
Rundek, T., Tolea, M. I., Ariko, T., Fagerli, E. A., & Camargo, C. J. (2021) · Neurotherapeutics · doi:10.1007/s13311-021-01170-y · Cited by 325 · see citing works
“these etiologies is chronic age-related dysregulation of CBF, but hypoxia, increased permeability of blood–brain barrier (BBB), endothelial dysfunction, systemic inflammation, and inflammatory clock of aging (iAge), which are tracked with multimorbidity, immunosenescence, frailty, and cardiovascular aging, are additio…”
BackgroundBlanchard, J. W., Bula, M., Davila-Velderrain, J., Akay, L. A., Zhu, L., Frank, A., Victor, M. B., Bonner, J. M., Mathys, H., Lin, Y.-T., et al. (2020) · Nature Medicine · doi:10.1038/s41591-020-0886-4 · Cited by 283 · see citing works
Blood‐brain barrier breakdown, neuroinflammation, and cognitive decline in older adults
Bowman, G. L., Dayon, L., Kirkland, R. E., Wojcik, J., Peyratout, G., Severin, I. C., Henry, H., Oikonomidi, A., Migliavacca, E., Bacher, M., et al. (2018) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2018.06.2857 · Cited by 295 · see citing works
Rajeev, V., Fann, D. Y., Dinh, Q. N., Kim, H. A., Silva, T. M. D., Lai, M. K. P., Chen, C., Drummond, G. R., Sobey, C. G., & Arumugam, T. V. (2022) · Theranostics · doi:10.7150/thno.68304 · Cited by 314 · see citing works
“The degree of association between the risk factors and the vascular disease is thought to be dependent on age, lifestyle, genetic susceptibility, comorbidity of other diseases and even differential brain reserves as reviewed in detail previously [2,14,15].”
BackgroundBlood-Brain Barrier Overview: Structural and Functional Correlation
Alahmari, A. (2021) · Neural Plasticity · doi:10.1155/2021/6564585 · Cited by 299 · see citing works
“The brain requires 20% of the body’s glucose and oxygen, while accounting for just 2% of total body mass, and can quickly increase blood supply and oxygen transfer to its active areas, a mechanism that is known as neurovascular coupling [1, 2].”
BackgroundThe Pericyte: A Forgotten Cell Type with Important Implications for A lzheimer's Disease?
Winkler, E. A., Sagare, A. P., & Zloković, B. V. (2014) · Brain Pathology · doi:10.1111/bpa.12152 · Cited by 275 · see citing works
The interneuron energy hypothesis: Implications for brain disease
Kann, O. (2015) · Neurobiology of Disease · doi:10.1016/j.nbd.2015.08.005 · Cited by 266 · see citing works
Wang, Q., Davis, P. B., Gurney, M. E., & Xu, R. (2021) · Alzheimer's & Dementia · doi:10.1002/alz.12296 · Cited by 257 · see citing works
Wardlaw, J. M., Makin, S., Hernández, M. C. V., Armitage, P. A., Heye, A. K., Chappell, F. M., Maniega, S. M., Sakka, E., Shuler, K., Dennis, M. S., et al. (2016) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2016.09.006 · Cited by 262 · see citing works
Hussain, B., Fang, C., & Chang, J. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.688090 · Cited by 251 · see citing works
“These pathological markers are associated with BBB impairment, which causes microglial activation, neuroinflammation, degeneration of neurons, and cognitive impairment (Bhaskar et al., 2010; Iadecola, 2013).”
BackgroundBrain Perivascular Macrophages Initiate the Neurovascular Dysfunction of Alzheimer Aβ Peptides
Park, L., Uekawa, K., Garcia-Bonilla, L., Koizumi, K., Murphy, M., Pistik, R., Younkin, L., Younkin, S., Zhou, P., Carlson, G., et al. (2017) · Circulation Research · doi:10.1161/circresaha.117.311054 · Cited by 259 · see citing works
Self-citationClinical presentations and epidemiology of vascular dementia
Smith, E. E. (2017) · Clinical Science · doi:10.1042/cs20160607 · Cited by 250 · see citing works
Circulating biologic markers of endothelial dysfunction in cerebral small vessel disease: A review
Poggesi, A., Pasi, M., Pescini, F., Pantoni, L., & Inzitari, D. (2015) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.2015.116 · Cited by 257 · see citing works
Modifiable Risk Factors for Alzheimer’s Disease
Edwards III, G. A., Gamez, N., Escobedo Jr., G., Calderon, O., & Moreno-Gonzalez, I. (2019) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2019.00146 · Cited by 253 · see citing works
The Role of Autophagy in Vascular Biology
Nussenzweig, S. C., Verma, S., & Finkel, T. (2015) · Circulation Research · doi:10.1161/circresaha.116.303805 · Cited by 243 · see citing works
Xiao, W., Su, J., Gao, X., Yang, H., Weng, R., Ni, W., & Gu, Y. (2022) · Microbiome · doi:10.1186/s40168-022-01255-6 · Cited by 252 · see citing works
Inflammatory markers and the risk of dementia and Alzheimer's disease: a meta-analysis
Darweesh, S. K. L., Wolters, F. J., Ikram, M. A., de Wolf, F., Bos, D., & Hofman, A. (2018) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2018.02.014 · Cited by 244 · see citing works
VEGF-A in Cardiomyocytes and Heart Diseases
Braile, M., Marcella, S., Cristinziano, L., Galdiero, M. R., Modestino, L., Ferrara, A. L., Varricchi, G., Marone, G., & Loffredo, S. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21155294 · Cited by 240 · see citing works
Brain Endothelial Cells Are Exquisite Sensors of Age-Related Circulatory Cues
Chen, M. B., Yang, A. C., Yousef, H., Lee, D., Chen, W., Schaum, N., Lehallier, B., Quake, S. R., & Wyss-Coray, T. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.03.012 · Cited by 233 · see citing works
“Dysfunction and breakdown of this unit have been implicated in age-related neurodegeneration and manifest in reduced cerebral blood flow, leakage of toxic factors, and a general inability to maintain an optimal environment for neuronal and stem cell function (Bell et al., 2012; Iadecola, 2013; Sweeney et al., 2018; Zh…”
Ishii, M., & Iadecola, C. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.08.016 · Cited by 237 · see citing works
Self-citationCorriveau, R. A., Bosetti, F., Emr, M., Gladman, J. T., Koenig, J. I., Moy, C. S., Pahigiannis, K., Waddy, S. P., & Koroshetz, W. (2016) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-016-0334-7 · Cited by 240 · see citing works
Zloković, B. V., Gottesman, R. F., Bernstein, K. E., Seshadri, S. S., McKee, A. C., Snyder, H. M., Greenberg, S. M., Yaffe, K. S., Schaffer, C. B., Yuan, C., et al. (2020) · Alzheimer s & Dementia · doi:10.1002/alz.12157 · Cited by 241 · see citing works
Microglia exacerbate white matter injury via complement C3/C3aR pathway after hypoperfusion
Zhang, L.-Y., Pan, J., Mamtilahun, M., Zhu, Y., Wang, L., Venkatesh, A., Shi, R., Tu, X.-Q., Jin, K., Wang, Y., et al. (2019) · Theranostics · doi:10.7150/thno.35841 · Cited by 219 · see citing works
“Chronic cerebral hypoperfusion is closely related to cognitive impairment and vascular dementia [1, 2].”
BackgroundDietary salt promotes cognitive impairment through tau phosphorylation
Faraco, G., Hochrainer, K., Segarra, S. G., Schaeffer, S., Santisteban, M. M., Menon, A., Jiang, H., Holtzman, D. M., Anrather, J., & Iadecola, C. (2019) · Nature · doi:10.1038/s41586-019-1688-z · Cited by 236 · see citing works
Self-citationRemote ischaemic conditioning—a new paradigm of self-protection in the brain
Hess, D. C., Blauenfeldt, R. A., Andersen, G., Hougaard, K. D., Hoda, M. N., Ding, Y., & Ji, X. (2015) · Nature Reviews Neurology · doi:10.1038/nrneurol.2015.223 · Cited by 231 · see citing works
Emerging Concepts in Vascular Dementia: A Review
Bir, S. C., Khan, M. W., Javalkar, V., Toledo, E. G., & Kelley, R. E. (2021) · Journal of Stroke and Cerebrovascular Diseases · doi:10.1016/j.jstrokecerebrovasdis.2021.105864 · Cited by 230 · see citing works
Consensus statement for diagnosis of subcortical small vessel disease
Rosenberg, G. A., Wallin, A., Wardlaw, J. M., Markus, H. S., Montaner, J., WOLFSON, L. I., Iadecola, C., Zloković, B. V., Joutel, A., Dichgans, M., et al. (2015) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.2015.172 · Cited by 224 · see citing works
Self-citationNeurovascular unit impairment in early Alzheimer's disease measured with magnetic resonance imaging
van de Haar, H. J., Jansen, J. F. A., van Osch, M. J. P., van Buchem, M. A., Muller, M., Wong, S. M., Hofman, P. A. M., Burgmans, S., Verhey, F. R. J., & Backes, W. H. (2016) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2016.06.006 · Cited by 207 · see citing works
Takeda, S., Sato, N., & Morishita, R. (2014) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2014.00171 · Cited by 226 · see citing works
Rajeev, V., Chai, Y. L., Poh, L., Selvaraji, S., Fann, D. Y., Jo, D., Silva, T. M. D., Drummond, G. R., Sobey, C. G., Arumugam, T. V., et al. (2023) · Acta Neuropathologica Communications · doi:10.1186/s40478-023-01590-1 · Cited by 237 · see citing works
Post-Stroke Cognitive Impairment: Epidemiology, Risk Factors, and Management
Huang, Y.-Y., Chen, S.-D., Leng, X.-Y., Kuo, K., Wang, Z.-T., Cui, M., Tan, L., Wang, K., Dong, Q., & Yu, J.-T. (2022) · Journal of Alzheimer s Disease · doi:10.3233/jad-215644 · Cited by 252 · see citing works
Yan, N., Xu, Z., Qu, C., & Zhang, J. (2021) · International Immunopharmacology · doi:10.1016/j.intimp.2021.107844 · Cited by 219 · see citing works
Cognitive Impairment in Multiple Sclerosis: Clinical, Radiologic and Pathologic Insights
DeLuca, G. C., Yates, R., Beale, H., & Morrow, S. (2015) · Brain Pathology · doi:10.1111/bpa.12220 · Cited by 215 · see citing works
The Relationship between Obstructive Sleep Apnea and Alzheimer’s Disease
Andrade, A. G., Bubu, O. M., Varga, A. W., & Osorio, R. S. (2018) · Journal of Alzheimer's Disease · doi:10.3233/jad-179936 · Cited by 216 · see citing works
Neuroprotective Effects of Angiotensin Receptor Blockers
Villapol, S., & Saavedra, J. M. (2014) · American Journal of Hypertension · doi:10.1093/ajh/hpu197 · Cited by 214 · see citing works
Cognitive impairment and cardiovascular diseases in the elderly. A heart–brain continuum hypothesis
Abete, P., Della‐Morte, D., Gargiulo, G., Basile, C., Langellotto, A., Galizia, G., Testa, G., Canonico, V., Bonaduce, D., & Cacciatore, F. (2014) · Ageing Research Reviews · doi:10.1016/j.arr.2014.07.003 · Cited by 208 · see citing works
Single-Cell Analysis of Blood-Brain Barrier Response to Pericyte Loss
Mäe, M. A., He, L., Nordling, S., Vázquez-Liébanas, E., Nahar, K., Jung, B., Li, X., Tan, B. C., Foo, J. C., Cazenave‐Gassiot, A., et al. (2020) · Circulation Research · doi:10.1161/circresaha.120.317473 · Cited by 203 · see citing works
The impact of cerebrovascular aging on vascular cognitive impairment and dementia
Yang, T., Sun, Y., Lu, Z., Leak, R. K., & Zhang, F. (2016) · Ageing Research Reviews · doi:10.1016/j.arr.2016.09.007 · Cited by 206 · see citing works
Transcriptional profiling and therapeutic targeting of oxidative stress in neuroinflammation
Mendiola, A. S., Ryu, J. K., Bardehle, S., Meyer-Franke, A., Ang, K. K.-H., Wilson, C., Baeten, K. M., Hanspers, K., Merlini, M., Thomas, S., et al. (2020) · Nature Immunology · doi:10.1038/s41590-020-0654-0 · Cited by 199 · see citing works
Aβ Amyloid Pathology Affects the Hearts of Patients With Alzheimer’s Disease
Troncone, L., Luciani, M., Coggins, M., Wilker, E. H., Ho, C.-Y., Codispoti, K. E., Frosch, M. P., Kayed, R., & del Monte, F. (2016) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2016.08.073 · Cited by 204 · see citing works
Sipilä, P. N., Heikkilä, N., Lindbohm, J. V., Hakulinen, C., Vahtera, J., Elovainio, M., Suominen, S., Väänänen, A., Koskinen, A., Nyberg, S. T., et al. (2021) · The Lancet Infectious Diseases · doi:10.1016/s1473-3099(21)00144-4 · Cited by 197 · see citing works
- Authors
- Iadecola, C.
- Affiliations
- Weill Cornell Medicine (US)
- Corresponding author
- Iadecola, Costantino
- ORCID
- Iadecola, Costantino
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2013-11
- Volume
- 80
- Issue
- 4
- Pages
- 844-866
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC3842016
- OpenAlex
- W2037426713
- Cited by
- 1,857
- References
- 364
- Citations by year
- 2026: 162 · 2025: 197 · 2024: 160 · 2023: 145 · 2022: 184 · 2021: 164 · 2020: 176 · 2019: 150 · 2018: 135 · 2017: 119 · 2016: 112 · 2015: 100 · 2014: 51
- FWCI
- 8.51
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Heart, Lung, and Blood Institute (HL-96571, P01HL096571)
- National Institute of Neurological Disorders and Stroke (NS-37853, R01NS073666, R01NS037853)
- Topics
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Neurology › Cerebrovascular and genetic disorders
- Keywords
- vascular dementia, vascular cognitive impairment, Alzheimer's disease, mixed dementia, cerebrovascular disease, cerebral vasculature, white matter, neurovascular interactions, glia, vascular risk factors, dementia prevention, dementia treatment
- MeSH terms
- Alzheimer Disease, Cerebrovascular Circulation, Cognition Disorders, Humans, Dementia, Vascular, Stroke, Atherosclerosis
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-04.
Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-04.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
