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White matter integrity and vulnerability to Alzheimer’s disease: preliminary findings and future directions
Open accessAbstract
Neuroimaging biomarkers that precede cognitive decline have the potential to aid early diagnosis of Alzheimer's disease (AD). A body of diffusion tensor imaging (DTI) work has demonstrated declines in white matter (WM) microstructure in AD and its typical prodromal state, amnestic mild cognitive impairment. The present review summarizes recent evidence suggesting that WM integrity declines are present in individuals at high AD-risk, prior to cognitive decline. The available data suggest that AD-risk is associated with WM integrity declines in a subset of tracts showing decline in symptomatic AD. Specifically, AD-risk has been associated with WM integrity declines in tracts that connect gray matter structures associated with memory function. These tracts include parahippocampal WM, the cingulum, the inferior fronto-occipital fasciculus, and the splenium of the corpus callosum. Preliminary evidence suggests that some AD-risk declines are characterized by increases of radial diffusivity, raising the possibility that a myelin-related pathology may contribute to AD onset. These findings justify future research aimed at a more complete understanding of the neurobiological bases of DTI-based declines in AD. With continued refinement of imaging methods, DTI holds promise as a method to aid identification of presymptomatic AD. This article is part of a Special Issue entitled: Imaging Brain Aging and Neurodegenerative disease.
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“AD pathology in the white matter includes the loss of myelin and a decrease in oligodendrocyte proteins [62–68].”
From Predominant expression of Alzheimer’s disease-associated BIN1 in mature oligodendrocytes and localization to white matter tracts (2016) · cites this paper as [68]
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“Despite these previous findings in symptomatic Alzheimer’s disease participants, white matter changes in the preclinical phase before the occurrence of cognitive impairment have been examined only in a few studies (Gold et al., 2012).”
From White matter diffusion alterations precede symptom onset in autosomal dominant Alzheimer’s disease (2018) · cites this paper as Gold et al., 2012
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Mayo, C. D., Mazerolle, E. L., Ritchie, L. J., Fisk, J. D., & Gawryluk, J. R. (2016) · NeuroImage Clinical · doi:10.1016/j.nicl.2016.12.012 · Cited by 159
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Demyelination as a rational therapeutic target for ischemic or traumatic brain injury
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“…caudal portions of the cingulum, the inferior fronto-occipital fasciculus, and posterior portions of the corpus callosum, all of which are related to episodic memory impairments in early AD (Bendlin et al., 2010; Douaud et al., 2011; Gold et al., 2012; Gold et al., 2010; Smith et al., 2010).”
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CXCL10 Triggers Early Microglial Activation in the Cuprizone Model
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“sclerosis (MS) (1), schizophrenia (2), Alzheimer’s disease (3), amyotrophic lateral sclerosis (4), or leukodystrophies (5, 6) such as Canavan’s disease (7).”
BackgroundConserved brain myelination networks are altered in Alzheimer’s and other neurodegenerative diseases
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“In addition, the integrity of white matter tracts that connect MTL structures with midline parietal and basal frontal regions such as the cingulum and the fornix are also damaged in early stages of AD [31-33].”
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“…do present some signs of AD-related features, i.e. damage in white matter tracts connected to the medial temporal lobe usually impaired in AD (see Gold et al. 2012 for review), and higher or lower functional connectivity between AD-sensitive brain areas (see Dennis and Thompson 2014 for review).”
BackgroundMemory binding and white matter integrity in familial Alzheimer’s disease
Parra, M. A., Saarimäki, H., Bastin, M. E., Londoño, A. C., Pettit, L., Lopera, F., Della Sala, S., & Abrahams, S. (2015) · Brain · doi:10.1093/brain/awv048 · Cited by 79
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“These findings are in line with those from the present study, in which the concentration of NfL in CSF was negatively associated with FA and positively associated with MD in widespread white matter regions, suggesting that increased concentration of NfL in CSF reflect increased white matter damage (Gold et al., 2012).”
ResultFerreira, D., Machado, A., Molina, Y., Nieto, A., Correia, R., Westman, E., & Barroso, J. (2017) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2017.00188 · Cited by 76
“White matter integrity in cingulum and the inferior fronto-occipital fasciculus becomes abnormal prior to cognitive decline in individuals at high risk of AD (Gold et al., 2012).”
BackgroundZhang, R., Beyer, F., Lampe, L., Luck, T., Riedel-Heller, S. G., Loeffler, M., Schroeter, M. L., Stümvoll, M., Villringer, A., & Witte, A. V. (2018) · NeuroImage · doi:10.1016/j.neuroimage.2018.01.028 · Cited by 74
“…major white matter tracts based on previous results linking white matter microstructure with cognitive performance (Borghesani et al., 2013; Gold et al., 2012; Madden et al., 2009a, 2009b; Ryan and Walther, 2014; Salami et al., 2012): uncinate fasciculus, corpus callosum, anterior thalamic…”
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“The current report is the largest examination of the APOE locus and white matter integrity in a single study (Gold et al., 2012; Westlye et al., 2012) and therefore adds a signi fi cant amount of new data to the literature.”
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“In fact, extensive white-matter loss has been reported in postmortem brains from AD patients([93]).”
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“Conversely, the overlap high MD low-FA may reflect water accumulation and gross tissue loss [12].”
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“Gold et al. / Neurobiology of Aging 35 (2014) 2263e2271 2264”
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“…where white matter alterations are less well-known, we aimed to define tracts that might contribute to the pathogenesis of the disease, in the ventral frontal cortex near the inferior fronto-occipital fasciculs and uncinate (Bendlin et al. 2010; Gold et al. 2012), and the parahippocampal cingulum.”
Anckaerts, C., Blockx, I., Summer, P., Michael, J., Hamaide, J., Kreutzer, C., Boutin, H., Couillard‐Després, S., Verhoye, M., & der Linden, A. V. (2018) · Neurobiology of Disease · doi:10.1016/j.nbd.2018.11.010 · Cited by 61
Diffusion Kurtosis Imaging: A Possible MRI Biomarker for AD Diagnosis?
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“A recent DTI review [46] suggested that high-risk for AD among cognitively healthy individuals was associated with WM integrity decline in tracts connecting GM structures associated with memory function, including the splenium of the corpus callosum.”
Ventricular and Periventricular Anomalies in the Aging and Cognitively Impaired Brain
Todd, K. L., Brighton, T., Norton, E. S., Schick, S., Elkins, W., Pletniková, O., Fortinsky, R. H., Troncoso, J. C., Molfese, P. J., Resnick, S. M., et al. (2018) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2017.00445 · Cited by 62
“The functional consequences of these measures include decreased white matter tract integrity, with direct links to cognitive decline (Charlton et al., 2006; Gold et al., 2012; Teipel et al., 2014).”
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“First, there is evidence of alteredWMmicrostructure in the fornix in cognitively normal older adults at high AD-risk compared to their low risk peers (Gold et al., 2010, 2012; Nierenberg et al., 2005; Persson et al., 2006; Ringman et al., 2007).”
Neuroanatomical correlates of verbal fluency in early Alzheimer’s disease and normal aging
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“The major fiber bundles involved are posterior white matter bundles, which matches extant literature showing that white matter abnormalities are concentrated in the posterior regions in AD [Chua et al., 2008; Gold et al., 2012; Medina and Gaviria, 2008].”
BackgroundBuono, V. L., Palmeri, R., Corallo, F., Allone, C., Pria, D., Bramanti, P., & Marino, S. (2019) · International Journal of Neuroscience · doi:10.1080/00207454.2019.1667798 · Cited by 48
“which is known to be disrupted in the early phase of the disease to assess the progression of the disease [46].”
BackgroundAge-related white matter integrity differences in oldest-old without dementia
Bennett, I. J., Greenia, D. E., Maillard, P., Sajjadi, S. A., DeCarli, C., Corrada, M. M., & Kawas, C. H. (2017) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2017.04.013 · Cited by 41
“Importantly, similar dementia-related differences in white matter integrity have also been observed in cognitively normal younger-old adults at increased risk for Alzheimer’s disease (Gold et al., 2012; Rieckmann et al., 2016).”
BackgroundHabes, M., Toledo, J. B., Resnick, S. M., Doshi, J., Van der Auwera, S., Erus, G., Janowitz, D., Hegenscheid, K., Homuth, G., Völzke, H., et al. (2016) · American Journal of Neuroradiology · doi:10.3174/ajnr.a4805 · Cited by 44
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“Also in this framework fits the remarkable correlation of CSF biomarkers with white matter defects in AD, promoting interest in white matter disruption as a diagnostic criterion in AD, as measured by MRI diffusion tensor imaging [9,82,83,96].”
BackgroundComputational methods for corpus callosum segmentation on MRI: A systematic literature review
Cover, G. S., Herrera, W. G., Bento, M., Appenzeller, S., & Rittner, L. (2017) · Computer Methods and Programs in Biomedicine · doi:10.1016/j.cmpb.2017.10.025 · Cited by 42
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“White matter abnormalities are demonstrable by DTI even before detectable cognitive decline (42, 43), but the precise pathological substrate of these imaging abnormalities is unclear.”
BackgroundCerebellar White Matter Disruption in Alzheimer’s Disease Patients: A Diffusion Tensor Imaging Study
Toniolo, S., Serra, L., Olivito, G., Caltagirone, C., Mercuri, N. B., Marra, C., Cercignani, M., & Bozzali, M. (2020) · Journal of Alzheimer s Disease · doi:10.3233/jad-191125 · Cited by 40
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“Although brain WM integrity, in older adults carrying APOE ε4, have been previously investigated in several monocentric studies (Gold et al., 2012, Felsky and Voineskos, 2013, Lyall et al., 2014), the reproducibility of these results in multicenter studies has not been sufficiently examined.”
BackgroundZhang, T., Guan, P., Liu, W., Zhao, G., Fang, Y., Fu, H. Q., Gui, J., Li, G., & Liu, J. (2020) · Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms · doi:10.1016/j.bbagrm.2020.194612 · Cited by 39
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“9 hand not the least because neurodegeneration negatively affects them directly (e.g., Auning et al., 2014; Gold et al., 2012; Zarei et al., 2009).”
BackgroundPrediction of dementia using diffusion tensor MRI measures: the OPTIMAL collaboration
Egle, M. S., Hilal, S., Tuladhar, A. M., Pirpamer, L., Hofer, E., Duering, M., Wason, J. M. S., Morris, R. G., Dichgans, M., Schmidt, R., et al. (2021) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp-2021-326571 · Cited by 40
Blood glucose levels and cortical thinning in cognitively normal, middle-aged adults
Wennberg, A. M. V., Spira, A. P., Pettigrew, C. A., Soldan, A., Zipunnikov, V. M., Rebok, G. W., Roses, A. D., Lutz, M. W., Miller, M. M., Thambisetty, M., et al. (2016) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2016.04.017 · Cited by 41
“We did so because the S allele is associated with poorer cognitive outcomes in APOE ε3 heterozygotes [27–29,44].”
BackgroundAlm, K. H., & Bakker, A. (2019) · Journal of Alzheimer s Disease · doi:10.3233/jad-181210 · Cited by 38
“Therefore, a reduced focus on FA and inclusion of “absolute diffusivities” (MD, DA, and RD) is warranted, since they tend to be more sensitive, specific measures of the underlying microstructure [19,28].”
Microstructural brain abnormalities in Huntington's disease: A two‐year follow‐up
Odish, O. F. F., Leemans, A., Reijntjes, R. H. A. M., van den Bogaard, S. J. A., Dumas, E. M., Wolterbeek, R., Tax, C. M. W., Kuijf, H. J., Vincken, K. L., van der Grond, J., et al. (2015) · Human Brain Mapping · doi:10.1002/hbm.22756 · Cited by 37
“Increased AD may indicate WM axonal atrophy and was suggested to be useful in identifying early changes in persons with a high risk at developing Alzheimer’s disease, prior to cognitive decline [Gold et al., 2012].”
BackgroundDefrancesco, M., Egger, K. E., Marksteiner, J., Esterhammer, R., Hinterhuber, H., Deisenhammer, E., & Schocke, M. (2014) · PLoS ONE · doi:10.1371/journal.pone.0106062 · Cited by 38
“2012 reported that WM integrity in a subset of tracts declines already in pre-clinical stages of AD [12].”
BackgroundMethodGraewe, B., Lemos, R., Ferreira, C., Santana, I. J., Farivar, R., Weerd, P. D., & Castelo-Branco, M. S. (2012) · Cerebral Cortex · doi:10.1093/cercor/bhs246 · Cited by 36
Schoemaker, D., Zotin, M. C. Z., Chen, K., Igwe, K. C., Vila‐Castelar, C., Martinez, J. E., Baena, A. Y., Fox‐Fuller, J. T., Lopera, F. J., Reiman, E. M., et al. (2022) · Alzheimer s Research & Therapy · doi:10.1186/s13195-022-01030-7 · Cited by 32
Socioeconomic status is positively correlated with frontal white matter integrity in aging
Johnson, N. F., Kim, C., & Gold, B. T. (2012) · AGE · doi:10.1007/s11357-012-9493-8 · Cited by 35
“An increased understanding of the neurobiological bases for potential SES–WM integrity relationships can be gained from the joint consideration of FA, radial diffusivity (DR), and axial diffusivity (DA) (Assaf and Pasternak 2008; Burzynska et al. 2010; Gold et al. 2012).”
BackgroundSprooten, E., Knowles, E. E. M., McKay, D., Göring, H. H. H., Curran, J. E., Kent, J. W., Carless, M. A., Dyer, T. D., Drigalenko, E. I., Olvera, R. L., et al. (2014) · NeuroImage · doi:10.1016/j.neuroimage.2014.04.021 · Cited by 33
“…increasing evidence that compromised white matter microstructure is part of the inherited risk for these disorders , as indicated by reduced FA in unaffected relatives (Gold et al., 2012; Hoptman et al., 2008; Sprooten et al., 2011a, 2013a), and polygenic risk score analysis (Whalley et al., 2013).”
BackgroundGorelick, P. B., & Nyenhuis, D. L. (2015) · JAMA · doi:10.1001/jama.2015.7149 · Cited by 33
Solodkin, A., Chen, E. E., Hoesen, G. W. V., Heimer, L., Shereen, A. D., Kruggel, F., & Mastrianni, J. A. (2013) · The Journal of Comparative Neurology · doi:10.1002/cne.23418 · Cited by 28
“…method for resolving changes in the structure of neuronal fiber bundles within the brain, and it has been applied to the study of several neurological diseases (Kunimatsu et al., 2003; Mori et al., 2002), including AD (for review see Ewers et al., 2011; Gold et al., 2012; Matthews et al., 2013).”
MethodResultSharp, F. R., DeCarli, C. S., Jin, L., & Zhan, X. (2023) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2023.1096206 · Cited by 31
“Interest in white matter (WM) injury was stirred by the development of brain MRI techniques (Diffusion Tensor Imaging– DTI, and Diffusion Imaging) that made it possible to detect early injury to WM (Gold et al., 2012; Radanovic et al., 2013; Nasrabady et al., 2018; Xiao et al., 2022).”
BackgroundStone, D. B., Ryman, S. G., Hartman, A. P., Wertz, C. J., Vakhtin, A. A., & Initiative, A. D. N. (2021) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2021.711579 · Cited by 28
Simone, J. J., Green, M. R., Hodges, T. E., & McCormick, C. M. (2014) · Behavioural Brain Research · doi:10.1016/j.bbr.2014.11.012 · Cited by 30
Perea, R. D. (2013) · Journal of Alzheimer’s Disease & Parkinsonism · doi:10.4172/2161-0460.1000123 · Cited by 30
“The ILF provides a direct connection from occipital cortex to temporal lobe [45,46].”
BackgroundDissociable Effects of Aging and Mild Cognitive Impairment on Bottom-Up Audiovisual Integration
Festa, E. K., Katz, A. P., Ott, B. R., Tremont, G. N., & Heindel, W. C. (2017) · Journal of Alzheimer s Disease · doi:10.3233/jad-161062 · Cited by 29
Correlation of microglial activation with white matter changes in dementia with Lewy bodies
Nicastro, N., Mak, E., Williams, G. B., Surendranathan, A., Bevan-Jones, W. R., Passamonti, L., Rodríguez, P. V., Su, L., Arnold, R. J., Fryer, T. D., et al. (2020) · NeuroImage Clinical · doi:10.1016/j.nicl.2020.102200 · Cited by 29
“Several pathological mechanisms for such white matter changes have been described in dementia, including ischaemia, demyelination and amyoid angiopathy (Gold et al., 2012; Chao et al., 2013; Kantarci et al., 2017).”
BackgroundGreater Diffusion Restriction in White Matter in Preclinical Alzheimer Disease
Benitez, A. M., Jensen, J. H., Thorn, K. E., Dhiman, S., Fountain‐Zaragoza, S., Rieter, W. J., Spampinato, M. V., Hamlett, E. D., Nietert, P. J., Falangola, M. F., et al. (2022) · Annals of Neurology · doi:10.1002/ana.26353 · Cited by 29
“The genu contains proportionally more smaller caliber axons compared to the splenium, which contains more large-caliber, directionally coherent axons that are less vulnerable to aging, albeit both (as well as the body and isthmus) have been observed to be altered in symptomatic AD.(34,35) Thus, we selected these ROIs…”
MethodInfluentialSun, X., Salat, D. H., Upchurch, K., Deason, R. G., Kowall, N. W., & Budson, A. E. (2014) · Journal of Investigative Medicine · doi:10.1097/jim.0000000000000102 · Cited by 25
Burhan, A. M., Bartha, R., Bocti, C., BORRIE, M. J., Laforce, R. J., Rosa‐Neto, P., & Soucy, J. (2013) · Alzheimer s Research & Therapy · doi:10.1186/alzrt200 · Cited by 24
White matter tauopathy: Transient functional loss and novel myelin remodeling
Jackson, J., Bianco, G., Rosa, A. O., Cowan, K., Bond, P., Anichtchik, O. V., & Fern, R. F. (2018) · Glia · doi:10.1002/glia.23286 · Cited by 24
“Microstructural WM changes are also apparent years before the onset of symptoms in sporadic AD of genetic origin (Bendlin et al., 2010; Gold et al., 2012).”
BackgroundBilingual experience affects white matter integrity across the lifespan
DeLuca, V., & Voits, T. (2022) · Neuropsychologia · doi:10.1016/j.neuropsychologia.2022.108191 · Cited by 25
“, 2012), but also in neurodegenerative diseases such as Alzheimer’s disease (Gold et al., 2012), Parkinson’s disease (Auning et al.”
BackgroundSteketee, R. M. E., Meijboom, R., de Groot, M., Bron, E. E., Niessen, W. J., van der Lugt, A., Swieten, J. C. V., & Smits, M. (2016) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2016.03.031 · Cited by 22
Liu, M., Wu, Y., Wu, X., Ma, X., Yin, Y., Fang, H., Huang, S., Su, H., & Jiang, G. (2020) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.559117 · Cited by 23
Roher, A. E., Maarouf, C. L., & Kokjohn, T. A. (2016) · Journal of Alzheimer s Disease · doi:10.3233/jad-150757 · Cited by 22
Initiative, A. D. N., Farrar, D. C., Mian, A. Z., Budson, A. E., Moss, M. B., Koo, B., & Killiany, R. (2017) · European Radiology · doi:10.1007/s00330-017-4951-4 · Cited by 21
“Gold et al. [5] described widespread increases in RD in a pre-AD state, which may be related to breakdown of myelin.”
Diffusion Tensor Imaging in the Study of Aging and Age-Associated Neural Disease
Salat, D. H. (2014) · Elsevier eBooks · doi:10.1016/b978-0-12-396460-1.00012-3 · Cited by 21
Myelination may be impaired in neonates following birth asphyxia
Olivieri, B., Rampakakis, E., Gilbert, G., Fezoua, A., & Wintermark, P. (2021) · NeuroImage: Clinical · doi:10.1016/j.nicl.2021.102678 · Cited by 19
“Impairment of the myelination process is known to disturb motor and sensory functions, and to cause cognitive impairments (Gold et al. 2012; Nave and Trapp 2008; Saab et al. 2013).”
BackgroundZhao, H., Cheng, J., Liu, T., Jiang, J., Koch, F. C., Sachdev, P. S., Basser, P. J., Wen, W. X., & Initiative, A. D. N. (2021) · Human Brain Mapping · doi:10.1002/hbm.25628 · Cited by 19
Martin, E., Blais, M., Albaret, J., Pariente, J., & Tallet, J. (2017) · Human Movement Science · doi:10.1016/j.humov.2017.07.007 · Cited by 19
Fornix degeneration in risk factors of Alzheimer's disease, possible trigger of cognitive decline
Lacalle‐Aurioles, M., & Iturria‐Medina, Y. (2023) · Cerebral Circulation - Cognition and Behavior · doi:10.1016/j.cccb.2023.100158 · Cited by 20
“4 increase the risk of late-onset AD [104,105], have also shown microstructural WM changes in the fornix at pre-symptomatic phases of the disease [59,94].”
BackgroundGold, B. T., Jiang, Y., Powell, D. K., & Smith, C. D. (2012) · Journal of Alzheimer s Disease · doi:10.3233/jad-2012-112165 · Cited by 17
“Reduced FA and/or increased MD has been observed in AD and its typical prodromal state of amnestic mild cognitive impairment (aMCI) [7], and even in cognitively normal seniors at high AD-risk [8].”
Roher, A. E., Maarouf, C. L., Malek‐Ahmadi, M. H., Wilson, J., Kokjohn, T. A., Daugs, I. D., Whiteside, C. M., Kalback, W. M., Macias, M. M. P., Jacobson, S. A., et al. (2013) · Europe PMC (PubMed Central) · Cited by 17
Bilingualism, cognitive reserve and Alzheimer’s disease
Gold, B. T. (2017) · Studies in bilingualism · doi:10.1075/sibil.53.09gol · Cited by 16
Leptin bioavailability and markers of brain atrophy and vascular injury in the middle age
Charisis, S., Short, M. I., Bernal, R., Kautz, T. F., Trevino, H., Mathews, J. J., Velarde, A. G., Muhammad, J. A. S., Luckey, A. M., Aslam, A., et al. (2024) · Alzheimer s & Dementia · doi:10.1002/alz.13879 · Cited by 15
Bankston, A. N., Li, W., Zhang, H., Ku, L., Liu, G., Papa, F., Zhao, L., Bibb, J. A., Cambi, F., Tiwari-Woodruff, S. K., et al. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.453688 · Cited by 16
Kang, K., Yoon, U., Choi, W., & Lee, H. (2016) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2016.02.067 · Cited by 16
“The caudal portion of the cingulum is known to contain fibers that connect the posterior cingulate cortex with the hippocampus [45].”
Lam, C. L. M., Yiend, J., & Lee, T. M. C. (2017) · Neurorehabilitation · doi:10.3233/nre-171471 · Cited by 17
Foley, J. M., Salat, D. H., Stricker, N. H., Zink, T. A., Grande, L. J., McGlinchey, R. E., Milberg, W., & Leritz, E. C. (2013) · American Journal of Alzheimer s Disease & Other Dementias® · doi:10.1177/1533317513517045 · Cited by 15
High-resolution fluorescence microscopy of myelin without exogenous probes
Christensen, P. C., Brideau, C., Poon, K. W. C., Döring, A., Yong, V. W., & Stys, P. K. (2013) · NeuroImage · doi:10.1016/j.neuroimage.2013.10.050 · Cited by 15
Müller, T., Payton, N. M., Kalpouzos, G., Jessen, F., Grande, G., Bäckman, L., & Laukka, E. J. (2020) · Journal of Alzheimer s Disease · doi:10.3233/jad-200445 · Cited by 14
“This is in line with other studies, showing that the corpus callosum and inferior fronto-occipital fasciculus show lower microstructural white matter integrity in persons at risk of AD [21, 22].”
BackgroundResultProgressive mechanical and structural changes in anterior cerebral arteries with Alzheimer’s disease
Liu, X., Halvorsen, S., Blanke, N., Downs, M. J., Stein, T. D., Bigio, I. J., Zaia, J., & Zhang, Y. (2023) · Alzheimer s Research & Therapy · doi:10.1186/s13195-023-01331-5 · Cited by 14
“ACA supplies blood to the frontal lobe, where integrity changes of the white matter mainly occur when AD first develops [28].”
BackgroundAlm, K. H., Faria, A. V., Moghekar, A., Pettigrew, C. A., Soldan, A., Mori, S., Albert, M., & Bakker, A. (2019) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2019.11.011 · Cited by 13
“In fact, microstructural aberrations have been demonstrated in cognitively normal older adults, as well as patients with mild cognitive impairment (MCI; Amlien and Fjell, 2014; Clerx et al., 2012; Gold et al., 2012; Lam et al., 2017; Nobili et al., 2014; Teipel et al., 2016; Zhang et al., 2014), and suggest a spatiote…”
BackgroundDattola, S., Ielo, A., Varone, G., Cacciola, A., Quartarone, A., & Bonanno, L. (2025) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2025.1547727 · Cited by 16
Rogojin, A., Gorbet, D. J., Hawkins, K. M., & Sergio, L. E. (2023) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.1054516 · Cited by 12
“Previous studies in preclinical Alzheimer’s populations found similar patterns of changes in diffusion measure of white matter in the same tracts (Bendlin et al., 2010; Gold et al., 2012; Westlye et al., 2012; Adluru et al., 2014), some of which overlap tracts important for visuomotor integration, namely the SLF, IFOF…”
BackgroundMoon, H. S., Mahzarnia, A., Stout, J. A., Anderson, R. J., Han, Z. Y., Tremblay, J. T., Badea, C. T., & Badea, A. (2024) · Imaging Neuroscience · doi:10.1162/imag_a_00245 · Cited by 14
“The top 30 connections linked either the left or right cingulum to other regions, supporting the important role of the cingulum and its subnet-works in aging, and in relation to AD risk ( Bennett et al., 2015; Gold et al., 2012).”
Quantitative MRI Evidence for Cognitive Reserve in Healthy Elders and Prodromal Alzheimer’s Disease
Fingerhut, H., Gozdas, E., & Hosseini, S. M. H. (2022) · Journal of Alzheimer s Disease · doi:10.3233/jad-220197 · Cited by 14
Metadata
- Authors
- Gold, B. T., Johnson, N. F., Powell, D. K., & Smith, C. D.
- Affiliations
- University of Kentucky (US)
- Corresponding author
- Gold, Brian T.
- Venue
- Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease
- Publisher
- Elsevier BV
- Published
- 2012-03
- Volume
- 1822
- Issue
- 3
- Pages
- 416-422
- ISSN
- 0925-4439 (ISSN-L)
- PMC
- PMC3213315
- OpenAlex
- W1984939243
- Cited by
- 170
- References
- 68
- Citations by year
- 2026: 10 · 2025: 9 · 2024: 13 · 2023: 10 · 2022: 12 · 2021: 6 · 2020: 9 · 2019: 8 · 2018: 12 · 2017: 16 · 2016: 16 · 2015: 12 · 2014: 15 · 2013: 16 · 2012: 6
- FWCI
- 1.55
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NINDS (R01 NS-36660)
- NIA (R01 AG033036)
- NSF (BCS-0814302)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced Neuroimaging Techniques and Applications
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Keywords
- Alzheimer's disease, white matter integrity, diffusion tensor imaging, amnestic mild cognitive impairment, neuroimaging biomarkers, early diagnosis, radial diffusivity, myelin pathology, cingulum, inferior fronto-occipital fasciculus, splenium of corpus callosum, white matter microstructure
- MeSH terms
- Alzheimer Disease, Brain, Cognition Disorders, Humans, Nerve Fibers, Myelinated, Risk Factors, Diffusion Tensor Imaging
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