The overlap between neurodegenerative and vascular factors in the pathogenesis of dementia
Open accessAbstract
There is increasing evidence that cerebrovascular dysfunction plays a role not only in vascular causes of cognitive impairment but also in Alzheimer's disease (AD). Vascular risk factors and AD impair the structure and function of cerebral blood vessels and associated cells (neurovascular unit), effects mediated by vascular oxidative stress and inflammation. Injury to the neurovascular unit alters cerebral blood flow regulation, depletes vascular reserves, disrupts the blood-brain barrier, and reduces the brain's repair potential, effects that amplify the brain dysfunction and damage exerted by incident ischemia and coexisting neurodegeneration. Clinical-pathological studies support the notion that vascular lesions aggravate the deleterious effects of AD pathology by reducing the threshold for cognitive impairment and accelerating the pace of the dementia. In the absence of mechanism-based approaches to counteract cognitive dysfunction, targeting vascular risk factors and improving cerebrovascular health offers the opportunity to mitigate the impact of one of the most disabling human afflictions.
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Co-occurrence of beta amyloid (Aβ) and white matter hyperintensities (WMHs) increases the risk of dementia.
“Co-occurrence of beta amyloid (Aβ) (a hallmark pathologic feature of AD) and white matter hyperintensities (WMHs) (reflecting CSVD burden) increase the risk of dementia [5].”
From Amyloid-PET and White Matter Hyperintensities Have Independent Effects on Baseline Cognitive Function and Synergistic Effects on Longitudinal Executive Function (2023) · cites this paper as [5]
In “Does the vascular pathology worsen the cognitive dysfunction in AD?” (page unavailable), the review says ischemic white matter lesions alongside AD pathology are associated with greater cognitive impact and more severe dementia. It does not specifically identify those lesions as MRI-defined WMHs or establish that co-occurring Aβ and WMHs increase the risk of developing dementia. (LLM, conf=0.85)
Experimental — accuracy not yet measuredQuestionnaire data rely on the recall of subjects who may be cognitively impaired.
“Questionnaire data rely on the recall of subjects who by definition of the research may be cognitively impaired.263”
From Vascular Contributions to Cognitive Impairment and Dementia: A Statement for Healthcare Professionals From the American Heart Association/American Stroke Association (2011) · cites this paper as [263]
The Introduction describes cognitive impairment in dementia, but does not discuss questionnaires or subjects’ ability to recall information. Searches for questionnaire recall and recall bias found no passage addressing that methodological concern; page numbers were not available in our copy. (LLM, conf=0.72)
Experimental — accuracy not yet measuredThe neurovascular unit clears unwanted products of brain activity and metabolism, such as beta-amyloid and tau, to prevent their accumulation in brain tissue.
“Another important function of the NVU is to dispose of unwanted products of brain activity and metabolism, such as β-amyloid and tau to prevent their accumulation in the brain tissue.31”
From Defining Optimal Brain Health in Adults: A Presidential Advisory From the American Heart Association/American Stroke Association (2017) · cites this paper as [31]
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)”
From The Pathobiology of Vascular Dementia (2013) · cites this paper as Iadecola, 2010
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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-citationThe Pathobiology of Vascular Dementia
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“…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…”
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The overlap between vascular disease and Alzheimer’s disease - lessons from pathology
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“On the other hand, CVD has been associated with worse cognitive performance in AD and neuropathological studies report that CVD lowers the threshold for dementia in subjects with a pathological diagnosis of AD [5,6,8,9,13,17,23,51,53,81-83].”
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Self-citationHypertension: A Harbinger of Stroke and Dementia
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Early Adult to Midlife Cardiovascular Risk Factors and Cognitive Function
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“Co-occurrence of beta amyloid (Aβ) (a hallmark pathologic feature of AD) and white matter hyperintensities (WMHs) (reflecting CSVD burden) increase the risk of dementia [5].”
Background
- Authors
- Iadecola, C.
- Affiliations
- Cornell University (US)
- Corresponding author
- Iadecola, Costantino
- ORCID
- Iadecola, Costantino
- Venue
- Acta Neuropathologica
- Published
- 2010-07-11
- Volume
- 120
- Issue
- 3
- Pages
- 287-296
- ISSN
- 0001-6322 (ISSN-L)
- 1432-0533
- PMC
- PMC3001188
- OpenAlex
- W2084484659
- Cited by
- 557
- References
- 141
- Citations by year
- 2026: 12 · 2025: 28 · 2024: 32 · 2023: 24 · 2022: 32 · 2021: 24 · 2020: 41 · 2019: 31 · 2018: 28 · 2017: 35 · 2016: 42 · 2015: 52 · 2014: 55 · 2013: 33 · 2012: 41
- FWCI
- 3.26
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Acta Neuropathologica (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Heart, Lung, and Blood Institute (HL-96571, P01HL096571)
- National Institute of Neurological Disorders and Stroke (NS37806, R01NS037853)
- Topics
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Keywords
- dementia, Alzheimer's disease, cerebrovascular dysfunction, vascular risk factors, neurovascular unit, oxidative stress, neuroinflammation, cerebral autoregulation, vascular reserve, blood-brain barrier, ischemia, neurodegeneration, vascular lesions, cognitive impairment
- MeSH terms
- Alzheimer Disease, Animals, Brain, Cerebrovascular Circulation, Cerebrovascular Disorders, Dementia, Humans, Nerve Degeneration
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.
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 ›
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