White matter integrity and vulnerability to Alzheimer’s disease: preliminary findings and future directions

Gold, Brian T.; Johnson, Nathan F.; Powell, David K.; Smith, Charles D.

doi:10.1016/j.bbadis.2011.07.009

Cited by 170Dementia and Cognitive Impairment ResearchAdvanced Neuroimaging Techniques and ApplicationsAlzheimer's disease research and treatments

White matter integrity and vulnerability to Alzheimer’s disease: preliminary findings and future directions

Open access

Gold, Brian T., Johnson, Nathan F., Powell, David K., Smith, Charles D.·2012·Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease

DOI 10.1016/j.bbadis.2011.07.009PMC PMC3213315

Open this paper in CoChat — free account Open PDF

Abstract

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.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Integrity signals

Registry

Crossref · 10.1016/j.bbadis.2011.07.009

Cites

69 of 69 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

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?

AD pathology in the white matter includes loss of myelin and a decrease in oligodendrocyte proteins.
“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]
The Introduction reports partial loss of myelin sheaths and oligodendroglial cells in AD. The Neurobiological Mechanisms section says myelin proteins are reduced early in the AD process, but does not identify them specifically as oligodendrocyte proteins. (LLM, conf=0.82)
Experimental — accuracy not yet measured
White matter changes in the preclinical phase before the occurrence of cognitive impairment have been examined only in a few studies.
“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

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Neuropathological stageing of Alzheimer-related changes.
Braak, H., & Braak, E. (1991) · Acta Neuropathologica · doi:10.1007/bf00308809 · Cited by 16,123 · cited 3× · see citing works
“This is because the neuropathology of AD in GM brain regions is well established: Amyloid plaques and intracellular neurofibrillary tangles initially target medial temporal lobe (MTL) GM, resulting in prominent neurodegeneration of the hippocampus and entorhinal cortex (ERC) [6, 7].”
Background
Tract-based spatial statistics: Voxelwise analysis of multi-subject diffusion data
Smith, S. M., Jenkinson, M., Johansen-Berg, H., Rueckert, D., Nichols, T. E., Mackay, C., Watkins, K., Ciccarelli, O., Cader, M., Matthews, P., et al. (2006) · NeuroImage · doi:10.1016/j.neuroimage.2006.02.024 · Cited by 6,035 · cited 1× · see citing works
“The TBSS method has several advantages compared to other whole-brain analysis techniques including improved registration of WM tracts across subjects [41] and the lack of a need to apply an arbitrary smoothing kernel, which can produce different results based on kernel size [42].”
Method
MR diffusion tensor spectroscopy and imaging
Basser, P. J., Mattiello, J., & LeBihan, D. (1994) · Biophysical Journal · doi:10.1016/s0006-3495(94)80775-1 · Cited by 5,970 · cited 1× · see citing works
“DTI is an extended form of diffusion-weighted tensor trace imaging that is sensitized to the motion of water molecules as they interact within tissues, thus reflecting characteristics of their immediate structural surroundings [24, 25].”
Background
The basis of anisotropic water diffusion in the nervous system—A technical review.
Beaulieu, C. (2002) · NMR in Biomedicine · doi:10.1002/nbm.782 · Cited by 4,653 · see citing works
Apolipoprotein E: Cholesterol Transport Protein with Expanding Role in Cell Biology
Mahley, R. W. (1988) · Science · doi:10.1126/science.3283935 · Cited by 4,028 · cited 1× · see citing works
“In the brain, APOE is mainly produced by glial cells and is thought to be involved in neuronal growth and regeneration [15].”
Background
Association of apolipoprotein E allele ϵ4 with late‐onset familial and sporadic Alzheimer's disease
Saunders, A. M., Strittmatter, W. J., Schmechel, D., St. George-Hyslop, P. H., Pericak-Vance, M. A., Joo, S. H., Rosi, B. L., Gusella, J. F., Crapper-MacLachlan, D. R., Alberts, M. J., et al. (1993) · Neurology · doi:10.1212/wnl.43.8.1467 · Cited by 3,786 · see citing works
Diffusion tensor MR imaging of the human brain
Pierpaoli, C., Jezzard, P., Basser, P. J., Barnett, A., & Di Chiro, G. (1996) · Radiology · doi:10.1148/radiology.201.3.8939209 · Cited by 2,664 · cited 1× · see citing works
“of axonal orientation compared to the direction orthogonal to the main fiber direction [26, 27].”
Background
Dysmyelination revealed through MRI as increased radial (but unchanged axial) diffusion of water
Song, S.-K., Sun, S.-W., Ramsbottom, M. J., Chang, C., Russell, J., & Cross, A. H. (2002) · NeuroImage · doi:10.1006/nimg.2002.1267 · Cited by 2,582 · cited 1× · see citing works
“Axial diffusivity (DA) reflects the diffusion coefficient along the direction of maximal 'apparent' diffusion (λ1), whereas radial diffusivity (DR) reflects the average diffusion coefficients along the two perpendicular directions ((λ2 + λ3)/2) [30].”
Background
Toward a quantitative assessment of diffusion anisotropy
Pierpaoli, C. M., & Basser, P. J. (1996) · Magnetic Resonance in Medicine · doi:10.1002/mrm.1910360612 · Cited by 2,392 · cited 5× · see citing works
“DTI is an extended form of diffusion-weighted tensor trace imaging that is sensitized to the motion of water molecules as they interact within tissues, thus reflecting characteristics of their immediate structural surroundings [24, 25].”
BackgroundMethodInfluential
Alzheimer's disease: cell-specific pathology isolates the hippocampal formation.
Hyman, B. T., Van Hoesen, G. W., Damasio, A. R., & Barnes, C. L. (1984) · Science · doi:10.1126/science.6474172 · Cited by 2,268 · see citing works
Alzheimer Disease in the US Population: Prevalence Estimates Using the 2000 Census
Hebert, L. E., Scherr, P. A., Bienias, J. L., Bennett, D. A., & Evans, D. A. (2003) · Archives of Neurology · doi:10.1001/archneur.60.8.1119 · Cited by 2,168 · cited 1× · see citing works
“2 million by 2050 [1].”
Common variants at MS4A4/MS4A6E, CD2AP, CD33 and EPHA1 are associated with late-onset Alzheimer's disease
Naj, A. C., Jun, G., Beecham, G. W., Wang, L.-S., Vardarajan, B. N., Buros, J., Gallins, P. J., Buxbaum, J. D., Jarvik, G. P., Crane, P. K., et al. (2011) · Nature Genetics · doi:10.1038/ng.801 · Cited by 1,901 · cited 2× · see citing works
“Apolipoprotein E—Apolipoprotein E (APOE) confers the greatest genetic risk for lateonset AD among at least six other genes recently discovered or confirmed [14].”
BackgroundSelf-citation
Demyelination increases radial diffusivity in corpus callosum of mouse brain
Song, S.-K., Yoshino, J., Le, T. Q., Lin, S.-J., Sun, S.-W., Cross, A. H., & Armstrong, R. C. (2005) · NeuroImage · doi:10.1016/j.neuroimage.2005.01.028 · Cited by 1,658 · see citing works
Frequency of Stages of Alzheimer-Related Lesions in Different Age Categories
Braak, H., & Braak, E. (1997) · Neurobiology of Aging · doi:10.1016/s0197-4580(97)00056-0 · Cited by 1,656 · see citing works
Building Memories: Remembering and Forgetting of Verbal Experiences as Predicted by Brain Activity
Wagner, A. D., Schacter, D. L., Rotte, M., Koutstaal, W., Maril, A., Dale, A. M., Rosen, B. R., & Buckner, R. L. (1998) · Science · doi:10.1126/science.281.5380.1188 · Cited by 1,620 · cited 1× · see citing works
“The IFOF contains connections between occipital visual regions and ventrolateral prefrontal cortex, a region with an established role in memory encoding [53].”
Background
Looking into the functional architecture of the brain with diffusion MRI.
Le Bihan, D. (2003) · Nature Reviews Neuroscience · doi:10.1038/nrn1119 · Cited by 1,571 · cited 1× · see citing works
“of axonal orientation compared to the direction orthogonal to the main fiber direction [26, 27].”
Background
What does the retrosplenial cortex do?
Vann, S. D., Aggleton, J. P., & Maguire, E. A. (2009) · Nature Reviews Neuroscience · doi:10.1038/nrn2733 · Cited by 1,409 · see citing works
Neuropathology of older persons without cognitive impairment from two community-based studies
Bennett, D. A., Schneider, J. A., Arvanitakis, Z., Kelly, J. F., Aggarwal, N. T., Shah, R. C., & Wilson, R. S. (2006) · Neurology · doi:10.1212/01.wnl.0000219668.47116.e6 · Cited by 1,336 · cited 1× · see citing works
“There is now strong evidence that significant Alzheimer's neuropathology is present years before the appearance of clinical symptoms associated with amnestic mild cognitive impairment (aMCI) or AD [2, 3].”
Background
Medial temporal atrophy on MRI in normal aging and very mild Alzheimer's disease
Jack, C. R., Petersen, R. C., Xu, Y. C., Waring, S. C., O'Brien, P. C., Tangalos, E. G., Smith, G. E., Ivnik, R. J., & Kokmen, E. (1997) · Neurology · doi:10.1212/wnl.49.3.786 · Cited by 1,128 · see citing works
A white matter disorder in dementia of the Alzheimer type: A pathoanatomical study
Brun, A., & Englund, E. (1986) · Annals of Neurology · doi:10.1002/ana.410190306 · Cited by 1,014 · cited 2× · see citing works
“However, ever since the work of Brun and Englund [8], it has been known that microscopic WM changes are also present in AD.”
Background
Axon-Glial Signaling and the Glial Support of Axon Function
Nave, K., & Trapp, B. D. (2008) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.30.051606.094309 · Cited by 659 · cited 1× · see citing works
“The signaling scheme between axons and investing glia, particularly oligodendroglia in the CNS, is not yet well defined [67].”
Background
Substantial sulfatide deficiency and ceramide elevation in very early Alzheimer's disease: potential role in disease pathogenesis
Han, X., M. Holtzman, D., W. McKeel, D., Kelley, J., & Morris, J. C. (2002) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2002.00997.x · Cited by 626 · cited 1× · see citing works
“This pattern of DTI-based findings is consistent with data demonstrating that myelin and its components such as cholesterol and myelin proteins are reduced early in the AD process [64, 65] and with a recently proposed theory suggesting that disruption of myelin integrity is an early event in the course of AD [66].”
Result
The effect of filter size on VBM analyses of DT-MRI data
Jones, D. K., Symms, M. R., Cercignani, M., & Howard, R. J. (2005) · NeuroImage · doi:10.1016/j.neuroimage.2005.02.013 · Cited by 562 · cited 1× · see citing works
“The TBSS method has several advantages compared to other whole-brain analysis techniques including improved registration of WM tracts across subjects [41] and the lack of a need to apply an arbitrary smoothing kernel, which can produce different results based on kernel size [42].”
Method
Alzheimer's disease as homeostatic responses to age-related myelin breakdown
Bartzokis, G. (2011) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2009.08.007 · Cited by 546 · cited 1× · see citing works
“This pattern of DTI-based findings is consistent with data demonstrating that myelin and its components such as cholesterol and myelin proteins are reduced early in the AD process [64, 65] and with a recently proposed theory suggesting that disruption of myelin integrity is an early event in the course of AD [66].”
Result
DTI measures in crossing-fibre areas: increased diffusion anisotropy reveals early white matter alteration in MCI and mild Alzheimer’s disease
Douaud, G., Jbabdi, S., Behrens, T. E. J., Menke, R. A., Gass, A., Monsch, A. U., Rao, A., Whitcher, B., Kindlmann, G., Matthews, P. M., et al. (2011) · NeuroImage · doi:10.1016/j.neuroimage.2010.12.008 · Cited by 514 · cited 1× · see citing works
“association bundles [51].”
White matter changes in mild cognitive impairment and AD: a diffusion tensor imaging study
Medina, D., deToledo-Morrell, L., Urresta, F., Gabrieli, J. D. E., Moseley, M., Fleischman, D., Bennett, D. A., Leurgans, S., Turner, D. A., & Stebbins, G. T. (2006) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2005.03.026 · Cited by 492 · cited 1× · see citing works
“However, the most prominent decreases have been reported in tracts with direct or secondary connections to MTL structures, including tracts showing decreases in AD-risk studies (parahippocampal WM, the cingulum, the IFOF / UNC, and the corpus callosum) [44–50].”
Background
Noninvasive detection of cuprizone induced axonal damage and demyelination in the mouse corpus callosum
Sun, S., Liang, H., Trinkaus, K., Cross, A. H., Armstrong, R. C., & Song, S. (2006) · Magnetic Resonance in Medicine · doi:10.1002/mrm.20774 · Cited by 461 · cited 2× · see citing works
“In contrast, a decrease in DA has been reported in both rodents and humans with axonal damage associated with axonal swelling, fragmentation and organelle accumulations [32, 33].”
BackgroundResult
Specific Hippocampal Volume Reductions in Individuals at Risk for Alzheimer’s Disease
Convit, A., De Leon, M. J., Tarshish, C., De Santi, S., Tsui, W., Rusinek, H., & George, A. (1997) · Neurobiology of Aging · doi:10.1016/s0197-4580(97)00001-8 · Cited by 427 · cited 1× · see citing works
“Neuropathology affects the hippocampus and entorhinal cortex (ERC) early in the course of AD [6, 7], and atrophy of these MTL structures is evident with MR imaging early in the AD disease process [59–61].”
Background
Meta-analysis Confirms CR1, CLU, and PICALM as Alzheimer Disease Risk Loci and Reveals Interactions With APOE Genotypes
Jun, G. (2010) · Archives of Neurology · doi:10.1001/archneurol.2010.201 · Cited by 422 · see citing works
Axonal prion protein is required for peripheral myelin maintenance
Bremer, J., Baumann, F., Tiberi, C., Wessig, C., Fischer, H., Schwarz, P., Steele, A. D., Toyka, K. V., Nave, K., Weis, J., et al. (2010) · Nature Neuroscience · doi:10.1038/nn.2483 · Cited by 395 · see citing works
Absolute diffusivities define the landscape of white matter degeneration in Alzheimer’s disease
Acosta-Cabronero, J., Williams, G. B., Pengas, G., & Nestor, P. J. (2010) · Brain · doi:10.1093/brain/awp257 · Cited by 393 · cited 1× · see citing works
“The DA increases reported were widespread, prominently affecting not simply medial temporal lobe tracts such as the fornix and cingulum, but also tracts of temporo-parietal regions such as the superior longitudinal fasciculus [55, 57, 58].”
Background
Risk of Dementia Among White and African American Relatives of Patients With Alzheimer Disease
Green, R. C. (2002) · JAMA · doi:10.1001/jama.287.3.329 · Cited by 391 · cited 1× · see citing works
“Individuals with a first-degree relative affected with AD have been found to have between a 4 to 10 fold increase in AD-risk [19, 20, 21].”
Background
Genetic aspects of Alzheimer disease.
Bird, T. D. (2008) · Genetics in Medicine · doi:10.1097/gim.0b013e31816b64dc · Cited by 356 · see citing works
Quantitative Diffusion-Tensor Anisotropy Brain MR Imaging: Normative Human Data and Anatomic Analysis
Shimony, J. S., McKinstry, R. C., Akbudak, E., Aronovitz, J. A., Snyder, A. Z., Lori, N. F., Cull, T. S., & Conturo, T. E. (1999) · Radiology · doi:10.1148/radiology.212.3.r99au51770 · Cited by 310 · cited 1× · see citing works
“Within WM, water diffusion is highest in tracts that contain the largest numbers of fibers running in parallel, such as the corpus callosum [29].”
Background
Decreased white matter integrity in late-myelinating fiber pathways in Alzheimer's disease supports retrogenesis
Stricker, N. H., Schweinsburg, B. C., Delano‐Wood, L., Wierenga, C. E., Bangen, K. J., Haaland, K. Y., Frank, L. R., Salmon, D. P., & Bondi, M. W. (2008) · NeuroImage · doi:10.1016/j.neuroimage.2008.11.027 · Cited by 308 · cited 1× · see citing works
“In each of these studies except one [56] symptomatic AD was associated with increases in DA (in addition to DR).”
Background
Diffusion tensor imaging in preclinical and presymptomatic carriers of familial Alzheimer’s disease mutations
Ringman, J. M., O'Neill, J., Geschwind, D., Medina, L., Apostolova, L. G., Rodriguez, Y., Schaffer, B., Varpetian, A., Tseng, B., Ortiz, F., et al. (2007) · Brain · doi:10.1093/brain/awm102 · Cited by 290 · see citing works
Diffusion tensor imaging of time-dependent axonal and myelin degradation after corpus callosotomy in epilepsy patients
Concha, L., Gross, D. W., Wheatley, B. M., & Beaulieu, C. (2006) · NeuroImage · doi:10.1016/j.neuroimage.2006.04.187 · Cited by 286 · cited 2× · see citing works
“In contrast, a decrease in DA has been reported in both rodents and humans with axonal damage associated with axonal swelling, fragmentation and organelle accumulations [32, 33].”
BackgroundResult
Increased Aβ Peptides and Reduced Cholesterol and Myelin Proteins Characterize White Matter Degeneration in Alzheimer's Disease
Roher, A. E., Weiss, N., Kokjohn, T. A., Kuo, Y.-M., Kalback, W., Anthony, J., Watson, D., Luehrs, D. C., Sue, L., Walker, D., et al. (2002) · Biochemistry · doi:10.1021/bi026173d · Cited by 279 · cited 1× · see citing works
“This pattern of DTI-based findings is consistent with data demonstrating that myelin and its components such as cholesterol and myelin proteins are reduced early in the AD process [64, 65] and with a recently proposed theory suggesting that disruption of myelin integrity is an early event in the course of AD [66].”
Result
White matter pathology isolates the hippocampal formation in Alzheimer's disease
Salat, D. H., Tuch, D. S., van der Kouwe, A. J. W., Greve, D. N., Pappu, V., Lee, S. Y., Hevelone, N. D., Zaleta, A. K., Growdon, J. H., Corkin, S., et al. (2010) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2008.03.013 · Cited by 279 · cited 1× · see citing works
“The DA increases reported were widespread, prominently affecting not simply medial temporal lobe tracts such as the fornix and cingulum, but also tracts of temporo-parietal regions such as the superior longitudinal fasciculus [55, 57, 58].”
Background
Some observations on the course and composition of the cingulum bundle in the rhesus monkey
Mufson, E. J., & Pandya, D. Ν. (1984) · The Journal of Comparative Neurology · doi:10.1002/cne.902250105 · Cited by 277 · cited 1× · see citing works
“Specifically, the caudal portion of the cingulum contains fibers that connect the posterior cingulate cortex with the entorhinal cortex and hippocampus [52].”
Background
Diffusion tensor imaging in mild cognitive impairment and Alzheimerʼs disease: a review
Chua, T. C., Wen, W., Slavin, M. J., & Sachdev, P. S. (2008) · Current Opinion in Neurology · doi:10.1097/wco.0b013e3282f4594b · Cited by 273 · cited 3× · see citing works
“Recent reviews have summarized evidence that WM microstructural integrity is decreased in AD and aMCI [12, 13].”
Background
Multiple DTI index analysis in normal aging, amnestic MCI and AD. Relationship with neuropsychological performance
Bosch, B., Arenaza-Urquijo, E. M., Rami, L., Sala-Llonch, R., Junqué, C., Solé-Padullés, C., Peña-Gómez, C., Bargalló, N., Molinuevo, J. L., & Bartrés-Faz, D. (2012) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2010.02.004 · Cited by 272 · see citing works
Cerebral White Matter Integrity Mediates Adult Age Differences in Cognitive Performance
Madden, D. J., Spaniol, J., Costello, M. C., Bucur, B., White, L. E., Cabeza, R., Davis, S. W., Dennis, N. A., Provenzale, J. M., & Huettel, S. A. (2008) · Journal of Cognitive Neuroscience · doi:10.1162/jocn.2009.21047 · Cited by 265 · cited 1× · see citing works
“DTI-based declines have been shown to contribute to age-related cognitive declines [9–11], suggesting they are functionally significant to the study of healthy and pathological forms of aging.”
Background
Diffusion tensor imaging in Alzheimer’s disease and mild cognitive impairment.
Stebbins, G. T., & Murphy, C. M. (2009) · Behavioural Neurology · doi:10.1155/2009/915041 · Cited by 245 · see citing works
Expanding the association between the APOE gene and the risk of Alzheimer's disease: possible roles for APOE promoter polymorphisms and alterations in APOE transcription
Laws, S. M., Hone, E., Gandy, S., & Martins, R. N. (2003) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2003.01615.x · Cited by 223 · cited 1× · see citing works
“One theory is that APOE-4 may result in decreased plasticity of neuronal synapses, and decreased ability to repair damaged neurons compared to other allelic variants [18].”
Background
Impact of APOE on the Healthy Aging Brain: A Voxel-Based MRI and DTI Study
Honea, R. A., Vidoni, E. D., Harsha, A., & Burns, J. M. (2009) · Journal of Alzheimer s Disease · doi:10.3233/jad-2009-1163 · Cited by 222 · cited 1× · see citing works
“Study Technique N WM Tract Nierenberg et al., 2005 ROI 29 PHW Persson et al., 2006 ROI, SPM-VBM 60 CC, CING/IFOF, HC Honea et al., 2009 FSL-TBSS 53 PHW Gold et al., 2010 FSL-TBSS 57 CING, FORNIX, CC, ILF, IFOF/UNC Smith et al., 2010 FSL-TBSS 65 PHW, CING, CC, ILF/IFOF Bendlin et al., 2010 SPM-VBM…”
MRI and CSF studies in the early diagnosis of Alzheimer's disease
de Leon, M. J., DeSanti, S., Zinkowski, R. P., Mehta, P. D., Praticò, D., Segal, S., Clark, C. M., Kerkman, D. J., DeBernardis, J. F., Li, J., et al. (2004) · Journal of Internal Medicine · doi:10.1111/j.1365-2796.2004.01381.x · Cited by 221 · cited 1× · see citing works
“Neuropathology affects the hippocampus and entorhinal cortex (ERC) early in the course of AD [6, 7], and atrophy of these MTL structures is evident with MR imaging early in the AD disease process [59–61].”
Background
Diffusion Tensor Imaging of Normal-Appearing White Matter in Mild Cognitive Impairment and Early Alzheimer Disease: Preliminary Evidence of Axonal Degeneration in the Temporal Lobe
Huang, J., Friedland, R. P., & Auchus, A. P. (2007) · American Journal of Neuroradiology · doi:10.3174/ajnr.a0700 · Cited by 220 · cited 1× · see citing works
“However, the most prominent decreases have been reported in tracts with direct or secondary connections to MTL structures, including tracts showing decreases in AD-risk studies (parahippocampal WM, the cingulum, the IFOF / UNC, and the corpus callosum) [44–50].”
Background
Diffusion tensor imaging in Alzheimer's disease and mild cognitive impairment.
Stebbins, G. T., & Murphy, C. M. (2009) · PubMed · doi:10.3233/ben-2009-0234 · Cited by 210 · cited 3× · see citing works
“Recent reviews have summarized evidence that WM microstructural integrity is decreased in AD and aMCI [12, 13].”
Background
Voxel-based detection of white matter abnormalities in mild Alzheimer disease
Xie, S., Xiao, J., Gong, G., Zang, Y., Wang, Y., Wu, H., & Jiang, X. X. (2006) · Neurology · doi:10.1212/01.wnl.0000219625.77625.aa · Cited by 208 · cited 1× · see citing works
“However, the most prominent decreases have been reported in tracts with direct or secondary connections to MTL structures, including tracts showing decreases in AD-risk studies (parahippocampal WM, the cingulum, the IFOF / UNC, and the corpus callosum) [44–50].”
Background
Age-related slowing of memory retrieval: Contributions of perceptual speed and cerebral white matter integrity
Bucur, B., Madden, D. J., Spaniol, J., Provenzale, J. M., Cabeza, R., White, L. E., & Huettel, S. A. (2008) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2007.02.008 · Cited by 198 · cited 1× · see citing works
“DTI-based declines have been shown to contribute to age-related cognitive declines [9–11], suggesting they are functionally significant to the study of healthy and pathological forms of aging.”
Background
Diffusion indices on magnetic resonance imaging and neuropsychological performance in amnestic mild cognitive impairment
Rose, S. (2006) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.2005.074336 · Cited by 189 · cited 1× · see citing works
“However, the most prominent decreases have been reported in tracts with direct or secondary connections to MTL structures, including tracts showing decreases in AD-risk studies (parahippocampal WM, the cingulum, the IFOF / UNC, and the corpus callosum) [44–50].”
Background
Preclinical Alzheimer's disease: diagnosis and prediction of progression
Chong, M. S., & Sahadevan, S. (2005) · The Lancet Neurology · doi:10.1016/s1474-4422(05)70168-x · Cited by 173 · cited 1× · see citing works
“There is an emerging consensus that the focus of AD research should move toward identification of presymptomatic biomarkers [4, 5].”
Background
Multivariate network analysis of fiber tract integrity in Alzheimer’s disease
Teipel, S. J., Stahl, R., Dietrich, O., Schoenberg, S. O., Perneczky, R., Bokde, A. L. W., Reiser, M. F., Möller, H., & Hampel, H. J. (2006) · NeuroImage · doi:10.1016/j.neuroimage.2006.07.047 · Cited by 169 · cited 1× · see citing works
“However, the most prominent decreases have been reported in tracts with direct or secondary connections to MTL structures, including tracts showing decreases in AD-risk studies (parahippocampal WM, the cingulum, the IFOF / UNC, and the corpus callosum) [44–50].”
Background
Estimating risk curves for first-degree relatives of patients with Alzheimer’s disease: The REVEAL study
Cupples, L. A., Farrer, L. A., Sadovnick, A. S. D., Relkin, N. R., Whitehouse, P. J., & Green, R. C. (2004) · Genetics in Medicine · doi:10.1097/01.gim.0000132679.92238.58 · Cited by 166 · cited 1× · see citing works
“Individuals with a first-degree relative affected with AD have been found to have between a 4 to 10 fold increase in AD-risk [19, 20, 21].”
Background
Age-related slowing of task switching is associated with decreased integrity of frontoparietal white matter
Gold, B. T., Powell, D. K., Xuan, L., Jicha, G. A., & Smith, C. D. (2008) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2008.04.005 · Cited by 163 · cited 3× · see citing works
“Study Technique N WM Tract Nierenberg et al., 2005 ROI 29 PHW Persson et al., 2006 ROI, SPM-VBM 60 CC, CING/IFOF, HC Honea et al., 2009 FSL-TBSS 53 PHW Gold et al., 2010 FSL-TBSS 57 CING, FORNIX, CC, ILF, IFOF/UNC Smith et al., 2010 FSL-TBSS 65 PHW, CING, CC, ILF/IFOF Bendlin et al., 2010 SPM-VBM 136 HC, CING, IFOF/UN…”
Background
Brain structural alterations before mild cognitive impairment
Smith, C. D., Chebrolu, H., Wekstein, D. R., Schmitt, F. A., Jicha, G. A., Cooper, G., & Markesbery, W. R. (2007) · Neurology · doi:10.1212/01.wnl.0000259542.54830.34 · Cited by 161 · cited 1× · see citing works
“In addition, recent results suggest that smaller MTL volumes can be detected several years prior to aMCI diagnosis [62, 63].”
ResultSelf-citation
Altered brain white matter integrity in healthy carriers of the APOE ε4 allele
Persson, J., Lind, J., Larsson, A., Ingvar, M., Cruts, M., Broeckhoven, C. V., Adolfsson, R., Nilsson, L. G., & Nyberg, L. H. (2006) · Neurology · doi:10.1212/01.wnl.0000204180.25361.48 · Cited by 161 · cited 2× · see citing works
“Study Technique N WM Tract Nierenberg et al., 2005 ROI 29 PHW Persson et al., 2006 ROI, SPM-VBM 60 CC, CING/IFOF, HC Honea et al., 2009 FSL-TBSS 53 PHW Gold et al., 2010 FSL-TBSS 57 CING, FORNIX, CC, ILF, IFOF/UNC Smith et al., 2010 FSL-TBSS 65 PHW, CING, CC, ILF/IFOF Bendlin et al., 2010 SPM-VBM 136 HC, CING, IFOF/UN…”
Alzheimer's Prevention Initiative: A Proposal to Evaluate Presymptomatic Treatments as Quickly as Possible
Reiman, E. M., Langbaum, J. B. S., & Tariot, P. N. (2010) · Biomarkers in Medicine · doi:10.2217/bmm.09.91 · Cited by 156 · cited 1× · see citing works
“There is an emerging consensus that the focus of AD research should move toward identification of presymptomatic biomarkers [4, 5].”
Background
The APOE ɛ4 allele modulates brain white matter integrity in healthy adults
Heise, V, Filippini, N., Ebmeier, K. P., & Mackay, C. E. (2011) · Molecular Psychiatry · doi:10.1038/mp.2010.90 · Cited by 152 · see citing works
Effects of Age, Sex, and Ethnicity on the Association Between Apolipoprotein E Genotype and Alzheimer Disease: A Meta-analysis
Farrer, L. A. (1997) · JAMA · doi:10.1001/jama.1997.03550160069041 · Cited by 124 · see citing works
White matter is altered with parental family history of Alzheimer's disease
Bendlin, B. B., Ries, M. L., Canu, E., Sodhi, A., Lazar, M., Alexander, A. L., Carlsson, C. M., Sager, M. A., Asthana, S., & Johnson, S. C. (2010) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2009.11.003 · Cited by 124 · cited 7× · see citing works
“…et al., 2009 FSL-TBSS 53 PHW Gold et al., 2010 FSL-TBSS 57 CING, FORNIX, CC, ILF, IFOF/UNC Smith et al., 2010 FSL-TBSS 65 PHW, CING, CC, ILF/IFOF Bendlin et al., 2010 SPM-VBM 136 HC, CING, IFOF/UNC, CC Heise et al., in press FSL-TBSS 39 CING, CC, SLF Notes: ROI, region of interest; SPM-VBM,…”
BackgroundInfluential
Alterations in multiple measures of white matter integrity in normal women at high risk for Alzheimer's disease
Gold, B. T., Powell, D. K., Andersen, A. H., & Smith, C. D. (2010) · NeuroImage · doi:10.1016/j.neuroimage.2010.05.036 · Cited by 112 · cited 7× · see citing works
“Of the AD-risk studies conducted to date, four have explored component diffusivities in addition to FA and MD [34, 38, 39, 40].”
BackgroundInfluential
White matter diffusion alterations in normal women at risk of Alzheimer's disease
Smith, C. D., Chebrolu, H., Andersen, A. H., Powell, D. K., Lovell, M. A., Xiong, S., & Gold, B. T. (2008) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2008.08.006 · Cited by 99 · cited 8× · see citing works
“Adapted from Smith et al. (2010) with permission.”
BackgroundInfluential
Abnormal white matter integrity in healthy apolipoprotein E epsilon4 carriers
Nierenberg, J. J., Pomara, N., Hoptman, M. J., Sidtis, J. J., Ardekani, B. A., & Lim, K. O. (2005) · Neuroreport · doi:10.1097/01.wnr.0000174058.49521.16 · Cited by 98 · cited 7× · see citing works
“Tracts showing declines in individuals at high AD-risk involve a subset of tracts showing decline in symptomatic AD, including WM of the parahippocampal region, the cingulum, IFOF, and splenium of the corpus callosum.”
BackgroundInfluential
Atrophy is associated with posterior cingulate white matter disruption in dementia with Lewy bodies and Alzheimer's disease
Firbank, M., Blamire, A., Krishnan, M. S., Teodorczuk, A., English, P., Gholkar, A., Harrison, R., & O'Brien, J. (2007) · NeuroImage · doi:10.1016/j.neuroimage.2007.02.027 · Cited by 89 · cited 1× · see citing works
“However, the most prominent decreases have been reported in tracts with direct or secondary connections to MTL structures, including tracts showing decreases in AD-risk studies (parahippocampal WM, the cingulum, the IFOF / UNC, and the corpus callosum) [44–50].”
Background
Fiber Connections between the Cerebral Cortex and the Corpus Callosum in Alzheimer's Disease: A Diffusion Tensor Imaging and Voxel-Based Morphometry Study
Sydykova, D., Stahl, R., Dietrich, O., Ewers, M., Reiser, M. F., Schoenberg, S. O., Möller, H. ‐., Hampel, H. J., & Teipel, S. J. (2006) · Cerebral Cortex · doi:10.1093/cercor/bhl136 · Cited by 84 · cited 1× · see citing works
“However, the most prominent decreases have been reported in tracts with direct or secondary connections to MTL structures, including tracts showing decreases in AD-risk studies (parahippocampal WM, the cingulum, the IFOF / UNC, and the corpus callosum) [44–50].”
Background
Evidence that volume of anterior medial temporal lobe is reduced in seniors destined for mild cognitive impairment
Martin, S. B., Smith, C. D., Collins, H. R., Schmitt, F. A., & Gold, B. T. (2008) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2008.08.010 · Cited by 80 · cited 1× · see citing works
“In addition, recent results suggest that smaller MTL volumes can be detected several years prior to aMCI diagnosis [62, 63].”
Result
Variability of Familial Risk of Alzheimer Disease Across the Late Life Span
Silverman, J. M., Ciresi, G., Smith, C. J., Marin, D. B., & Beeri, M. S. (2005) · Archives of General Psychiatry · doi:10.1001/archpsyc.62.5.565 · Cited by 80 · cited 1× · see citing works
“Individuals with a first-degree relative affected with AD have been found to have between a 4 to 10 fold increase in AD-risk [19, 20, 21].”
Background

Flagged first, then by citations

Sorted by citations

The role of myelin and oligodendrocytes in axonal energy metabolism
Saab, A. S., Tzvetanova, I. D., & Nave, K. (2013) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2013.09.008 · Cited by 339 · see citing works
“It is tempting to speculate that the progression of other neuro-psychiatric disorders, including Alzheimer’s disease [3,61] and schizophrenia [62], could be likewise influenced by glycolytic oligodendrocytes and white matter abnormalities.”
Background
Fibre-specific white matter reductions in Alzheimer’s disease and mild cognitive impairment
Mito, R., Raffelt, D., Dhollander, T., Vaughan, D. N., Tournier, J.-D., Salvado, O., Brodtmann, A., Rowe, C. C., Villemagne, V. L., & Connelly, A. (2018) · Brain · doi:10.1093/brain/awx355 · Cited by 309 · see citing works
“…the past decade, numerous DTI studies have re- ported spatial and temporal changes in white matter that arise over the course of Alzheimer’s disease, the results of which are summarized in a number of extensive reviews (Chua et al., 2008; Sexton et al., 2011; Gold et al., 2012; Mak et al., 2017).”
Background
Aging in Down Syndrome and the Development of Alzheimer's Disease Neuropathology
Head, E., T. Lott, I., M. Wilcock, D., & A. Lemere, C. (2015) · Current Alzheimer Research · doi:10.2174/1567205012666151020114607 · Cited by 289 · see citing works
Cellular senescence and Alzheimer disease: the egg and the chicken scenario
Saez-Atienzar, S., & Masliah, E. (2020) · Nature Reviews Neuroscience · doi:10.1038/s41583-020-0325-z · Cited by 257 · see citing works
Aging of Cerebral White Matter
Liu, H., Yang, Y.-Y., Xia, Y., Zhu, W., Leak, R., Wei, Z., Wang, J.-Y., & Hu, X.-M. (2016) · Ageing Research Reviews · doi:10.1016/j.arr.2016.11.006 · Cited by 249 · see citing works
p75 neurotrophin receptor signaling in nervous system injury and degeneration: paradox and opportunity
Ibáñez, C. F., & Simi, A. (2012) · Trends in Neurosciences · doi:10.1016/j.tins.2012.03.007 · Cited by 238 · see citing works
On the early diagnosis of Alzheimer's Disease from multimodal signals: A survey
Alberdi, A., Aztiria, A., & Basarab, A. (2016) · Artificial Intelligence in Medicine · doi:10.1016/j.artmed.2016.06.003 · Cited by 222 · see citing works
“Some few studies have also shown abnormalities in MD values in healthy subjects at risk of AD [171,172], which could lead to a very early diagnosis when cognitive changes have not yet started.”
Background
Lifelong Bilingualism Contributes to Cognitive Reserve against White Matter Integrity Declines in Aging
Gold, B. T., Johnson, N. F., & Powell, D. (2013) · Neuropsychologia · doi:10.1016/j.neuropsychologia.2013.09.037 · Cited by 185 · see citing works
White matter diffusion alterations precede symptom onset in autosomal dominant Alzheimer’s disease
Araque Caballero, M. Á., Suárez-Calvet, M., Duering, M., Franzmeier, N., Benzinger, T., Fagan, A. M., Bateman, R. J., Jack, C. R., Levin, J., Dichgans, M., et al. (2018) · Brain · doi:10.1093/brain/awy229 · Cited by 179 · see citing works
“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).”
Result
Longitudinal changes in microstructural white matter metrics in Alzheimer's disease
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 · see citing works
“These findings indicate widespread whole brain grey matter atrophy in individuals with AD, including enlarged ventricles and decreased hippocampal volume (Gold, 2012; Hampel et al., 2014; Perl, 2010; Teipel et al., 2010).”
Demyelination as a rational therapeutic target for ischemic or traumatic brain injury
Shi, H., Hu, X., Leak, R. K., Shi, Y., An, C., Suenaga, J., Chen, J., & Gao, Y. (2015) · Experimental Neurology · doi:10.1016/j.expneurol.2015.03.017 · Cited by 148 · see citing works
“…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).”
Background
Predominant expression of Alzheimer’s disease-associated BIN1 in mature oligodendrocytes and localization to white matter tracts
De Rossi, P., Buggia-Prévot, V., Clayton, B. L. L., Vasquez, J. B., van Sanford, C., Andrew, R. J., Lesnick, R., Botté, A., Deyts, C., Salem, S., et al. (2016) · Molecular Neurodegeneration · doi:10.1186/s13024-016-0124-1 · Cited by 151 · see citing works
“AD (n = 29) and non-AD (n = 28) human samples used for qPCR analysis have been previously described (Cited Ref: [19, 32, 68]) PMI post mortem interval De Rossi et al.”
CXCL10 Triggers Early Microglial Activation in the Cuprizone Model
Clarner, T., Janssen, K., Nellessen, L., Stangel, M., Skripuletz, T., Krauspe, B., Hess, F.-M., Denecke, B., Beutner, C., Linnartz-Gerlach, B., et al. (2015) · The Journal of Immunology · doi:10.4049/jimmunol.1401459 · Cited by 150 · see citing works
“sclerosis (MS) (1), schizophrenia (2), Alzheimer’s disease (3), amyotrophic lateral sclerosis (4), or leukodystrophies (5, 6) such as Canavan’s disease (7).”
Background
Conserved brain myelination networks are altered in Alzheimer’s and other neurodegenerative diseases
Allen, M., Wang, X., Burgess, J. D., Watzlawik, J., Serie, D. J., Younkin, C. S., Nguyen, T., Malphrus, K. G., Lincoln, S., Carrasquillo, M. M., et al. (2018) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2017.09.012 · Cited by 143 · see citing works
“Neuroimaging studies in living patients support WM [43,44] and specifically myelin alterations [45] in preclinical AD.”
Alzheimer's Disease in Down Syndrome.
Head, E., Powell, D. K., Gold, B. T., & Schmitt, F. A. (2012) · PubMed · Cited by 139 · see citing works
Brain gene expression patterns differentiate mild cognitive impairment from normal aged and Alzheimer’s disease
Berchtold, N. C., Sabbagh, M. N., Beach, T. G., Kim, R. C., Cribbs, D. H., & Cotman, C. W. (2014) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2014.03.031 · Cited by 124 · see citing works
Change in retinal structural anatomy during the preclinical stage of Alzheimer's disease
Santos, C. Y., Johnson, L. N., Sinoff, S. E., Festa, E. K., Heindel, W. C., & Snyder, P. J. (2018) · Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring · doi:10.1016/j.dadm.2018.01.003 · Cited by 124 · see citing works
A Connectomic Atlas of the Human Cerebrum—Chapter 13: Tractographic Description of the Inferior Fronto-Occipital Fasciculus
Conner, A. K., Briggs, R. G., Sali, G., Rahimi, M., Baker, C. M., Burks, J. D., Glenn, C. A., Battiste, J. D., & Sughrue, M. E. (2018) · Operative Neurosurgery · doi:10.1093/ons/opy267 · Cited by 121 · see citing works
Neuroinflammation is independently associated with brain network dysfunction in Alzheimer’s disease
Leng, F., Hinz, R., Gentleman, S., Hampshire, A., Dani, M., Brooks, D. J., & Edison, P. (2022) · Molecular Psychiatry · doi:10.1038/s41380-022-01878-z · Cited by 120 · see citing works
Lifelong bilingualism and neural reserve against Alzheimer's disease: A review of findings and potential mechanisms
Gold, B. T. (2014) · Behavioural Brain Research · doi:10.1016/j.bbr.2014.12.006 · Cited by 110 · see citing works
“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].”
Background
Associations between modifiable risk factors and white matter of the aging brain: insights from diffusion tensor imaging studies
Wassenaar, T. M., Yaffe, K. S., van der Werf, Y. D., & Sexton, C. E. (2019) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2019.04.006 · Cited by 106 · see citing works
White matter hyperintensities mediate the association between blood-brain barrier leakage and information processing speed
Freeze, W. M., Jacobs, H. I. L., de Jong, J. J. A., Verheggen, I. C. M., Gronenschild, E. H. B. M., Palm, W. M., Hoff, E. I., Wardlaw, J. M., Jansen, J. F. A., Verhey, F. R. J., et al. (2019) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2019.09.017 · Cited by 85 · see citing works
Imaging Brain Effects of APOE4 in Cognitively Normal Individuals Across the Lifespan
Fouquet, M., Besson, F. L., Gonneaud, J., Joie, R. L., & Chételat, G. (2014) · Neuropsychology Review · doi:10.1007/s11065-014-9263-8 · Cited by 83 · see citing works
“…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).”
Background
Memory 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 · see citing works
A Novel Texture Extraction Technique with T1 Weighted MRI for the Classification of Alzheimer’s Disease
Vaithinathan, K., & Parthiban, L. (2019) · Journal of Neuroscience Methods · doi:10.1016/j.jneumeth.2019.01.011 · Cited by 80 · see citing works
Blood and cerebrospinal fluid neurofilament light differentially detect neurodegeneration in early Alzheimer’s disease
Andersson, E., Janelidze, S., Lampinen, B., Nilsson, M., Leuzy, A., Stomrud, E., Blennow, K., Zetterberg, H., & Hansson, O. (2020) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2020.07.018 · Cited by 79 · see citing works
“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).”
Result
Cognitive Variability during Middle-Age: Possible Association with Neurodegeneration and Cognitive Reserve
Ferreira, 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 75 · see citing works
“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).”
Background
White matter microstructural variability mediates the relation between obesity and cognition in healthy adults
Zhang, 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 73 · see citing works
“…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…”
An emerging role of dysfunctional axon-oligodendrocyte coupling in neurodegenerative diseases
Mot, A. I., Depp, C., & Nave, K. (2018) · Dialogues in Clinical Neuroscience · doi:10.31887/dcns.2018.20.4/amot · Cited by 70 · see citing works
Alzheimer's disease susceptibility genes APOE and TOMM40, and brain white matter integrity in the Lothian Birth Cohort 1936
Lyall, D. M., Harris, S. E., Bastin, M. E., Maniega, S. M., Murray, C. L., Lutz, M. W., Saunders, A. M., Roses, A. D., Hernández, M. D. C. V., Royle, N. A., et al. (2014) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2014.01.006 · Cited by 71 · see citing works
“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.”
BackgroundResultInfluential
Oligodendroglia and neurotrophic factors in neurodegeneration
Bankston, A. N., Mandler, M. D., & Feng, Y. (2013) · Neuroscience Bulletin · doi:10.1007/s12264-013-1321-3 · Cited by 70 · see citing works
“In fact, extensive white-matter loss has been reported in postmortem brains from AD patients([93]).”
Background
Different Patterns of White Matter Degeneration Using Multiple Diffusion Indices and Volumetric Data in Mild Cognitive Impairment and Alzheimer Patients
Alves, G. S., O’Dwyer, L., Jurcoane, A., Oertel‐Knöchel, V., Knöchel, C., Prvulovic, D., Sudo, F. K., Alves, C. E. D. O., Valente, L., Moreira, D., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0052859 · Cited by 65 · see citing works
“Conversely, the overlap high MD low-FA may reflect water accumulation and gross tissue loss [12].”
BackgroundInfluential
<scp>LINGO</scp>‐1 antibody ameliorates myelin impairment and spatial memory deficits in the early stage of 5<scp>XFAD</scp> mice
Wu, D., Tang, X., Gu, L., Li, X., Qi, X., Bai, F., Chen, X., Wang, J., Ren, Q., & Zhang, Z. (2018) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.12809 · Cited by 64 · see citing works
White matter integrity is associated with cerebrospinal fluid markers of Alzheimer's disease in normal adults
Gold, B. T., Zhu, Z., Brown, C., Andersen, A. H., LaDu, M. J., Tai, L. M., Jicha, G. A., Kryscio, R. J., Estus, S., Nelson, P. T., et al. (2014) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2014.04.030 · Cited by 64 · see citing works
“Gold et al. / Neurobiology of Aging 35 (2014) 2263e2271 2264”
An advanced white matter tract analysis in frontotemporal dementia and early-onset Alzheimer’s disease
Daianu, M., Mendez, M. F., Baboyan, V. G., Jin, Y., Melrose, R. J., Jimenez, E. E., & Thompson, P. M. (2016) · Brain Imaging and Behavior · doi:10.1007/s11682-015-9458-5 · Cited by 64 · see citing works
“…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.”
Early functional connectivity deficits and progressive microstructural alterations in the TgF344-AD rat model of Alzheimer’s Disease: A longitudinal MRI study
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 62 · see citing works
Diffusion Kurtosis Imaging: A Possible MRI Biomarker for AD Diagnosis?
Struyfs, H., Hecke, W. V., Veraart, J., Sijbers, J., Slaets, S., Belder, M. D., Wuyts, L. L., Peters, B., Sleegers, K., Robberecht, C., et al. (2015) · Journal of Alzheimer s Disease · doi:10.3233/jad-150253 · Cited by 61 · see citing works
“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 60 · see citing works
“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).”
Background
Association of Retinal Changes With Alzheimer Disease Neuroimaging Biomarkers in Cognitively Normal Individuals
Byun, M. S., Park, S. W., Lee, J. H., Yi, D., Jeon, S. Y., Choi, H. J., Joung, H., Ghim, U. H., Park, U. C., Kim, Y., et al. (2021) · JAMA Ophthalmology · doi:10.1001/jamaophthalmol.2021.0320 · Cited by 60 · see citing works
Development, validation and application of a new fornix template for studies of aging and preclinical Alzheimer's disease
Brown, C. A., Johnson, N. F., Anderson-Mooney, A. J., Jicha, G. A., Shaw, L. M. J., Trojanowski, J. Q., Eldik, L. J. V., Schmitt, F. A., Smith, C. D., & Gold, B. T. (2016) · NeuroImage Clinical · doi:10.1016/j.nicl.2016.11.024 · Cited by 60 · see citing works
“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
Rodríguez‐Aranda, C., Waterloo, K. K., Johnsen, S. H., Eldevik, P., Sparr, S., Wikran, G., Herder, M., & Vangberg, T. R. (2016) · Brain and Language · doi:10.1016/j.bandl.2016.03.001 · Cited by 53 · see citing works
Cdk5-p25 as a key element linking amyloid and tau pathologies in Alzheimer's disease: Mechanisms and possible therapeutic interventions
Maitra, S., & Vincent, B. (2022) · Life Sciences · doi:10.1016/j.lfs.2022.120986 · Cited by 54 · see citing works
Abnormalities of cortical thickness, subcortical shapes, and white matter integrity in subcortical vascular cognitive impairment
Thong, J. Y. J., Du, J., Ratnarajah, N., Dong, Y., Soon, H. W., Saini, M., Tan, M., Tuan, T. A., Chen, C., & Qiu, A. (2013) · Human Brain Mapping · doi:10.1002/hbm.22330 · Cited by 49 · see citing works
“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].”
Background
Diffusion tensor imaging of white matter degeneration in early stage of Alzheimer's disease: a review
Buono, 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 45 · see citing works
“which is known to be disrupted in the early phase of the disease to assess the progression of the disease [46].”
Background
Age-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 · see citing works
“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).”
Background
Relationship betweenAPOEGenotype and Structural MRI Measures throughout Adulthood in the Study of Health in Pomerania Population-Based Cohort
Habes, 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 · see citing works
Early Structural and Functional Defects in Synapses and Myelinated Axons in Stratum Lacunosum Moleculare in Two Preclinical Models for Tauopathy
Maurin, H., Chong, S., Kraev, I., Davies, H. A., Kremer, A., Seymour, C. M., Lechat, B., Jaworski, T., Borghgraef, P., Devijver, H., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0087605 · Cited by 42 · see citing works
“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].”
Background
Computational 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 · see citing works
White Matter Hypoperfusion and Damage in Dementia: Post‐Mortem Assessment
Love, S., & Miners, J. S. (2014) · Brain Pathology · doi:10.1111/bpa.12223 · Cited by 41 · see citing works
“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.”
Background
Cerebellar 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 · see citing works
Disrupted white matter structural networks in healthy older adult APOE ε4 carriers – An international multicenter DTI study
Cavedo, E., Lista, S., Rojkova, K., Chiesa, P. A., Houot, M., Brueggen, K., Blautzik, J., Bokde, A. L. W., Dubois, B., Barkhof, F., et al. (2017) · Neuroscience · doi:10.1016/j.neuroscience.2017.05.048 · Cited by 40 · see citing works
“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.”
Background
Copper stress induces zebrafish central neural system myelin defects via WNT/NOTCH-hoxb5b signaling and pou3f1/fam168a/fam168b DNA methylation
Zhang, 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 40 · see citing works
Beyond Alzheimer's disease: Can bilingualism be a more generalized protective factor in neurodegeneration?
Voits, T., Pliatsikas, C., Robson, H., & Rothman, J. (2020) · Neuropsychologia · doi:10.1016/j.neuropsychologia.2020.107593 · Cited by 40 · see citing works
“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).”
Background
Prediction 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 · see citing works
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 39 · see citing works
“We did so because the S allele is associated with poorer cognitive outcomes in APOE ε3 heterozygotes [27–29,44].”
Background
Relationships Between Diffusion Tensor Imaging and Cerebrospinal Fluid Metrics in Early Stages of the Alzheimer’s Disease Continuum
Alm, K. H., & Bakker, A. (2019) · Journal of Alzheimer s Disease · doi:10.3233/jad-181210 · Cited by 36 · see citing works
“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 · see citing works
“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].”
Background
Changes in White Matter Integrity before Conversion from Mild Cognitive Impairment to Alzheimer’s Disease
Defrancesco, 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 37 · see citing works
“2012 reported that WM integrity in a subset of tracts declines already in pre-clinical stages of AD [12].”
BackgroundMethod
Impaired Processing of 3D Motion-Defined Faces in Mild Cognitive Impairment and Healthy Aging: An fMRI Study
Graewe, 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 · see citing works
White matter hyperintensities are a prominent feature of autosomal dominant Alzheimer’s disease that emerge prior to dementia
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 · see citing works
Socioeconomic status is positively correlated with frontal white matter integrity in aging
Johnson, N. F., Kim, C., & Gold, B. T. (2013) · AGE · doi:10.1007/s11357-012-9493-8 · Cited by 40 · see citing works
“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).”
Background
Common genetic variants and gene expression associated with white matter microstructure in the human brain
Sprooten, 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 · see citing works
“…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).”
Background
Stroke and Cognitive Decline
Gorelick, P. B., & Nyenhuis, D. L. (2015) · JAMA · doi:10.1001/jama.2015.7149 · Cited by 33 · see citing works
In vivo parahippocampal white matter pathology as a biomarker of disease progression to Alzheimer's disease
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 · see citing works
“…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).”
MethodResult
White matter injury, cholesterol dysmetabolism, and APP/Abeta dysmetabolism interact to produce Alzheimer’s disease (AD) neuropathology: A hypothesis and review
Sharp, F. R., DeCarli, C. S., Jin, L., & Zhan, X. (2023) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2023.1096206 · Cited by 30 · see citing works
“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).”
Background
Specific white matter tracts and diffusion properties predict conversion from mild cognitive impairment to Alzheimer’s disease.
Stone, 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 · see citing works
Differential effects of CB1 receptor agonism in behavioural tests of unconditioned and conditioned fear in adult male rats
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 28 · see citing works
A Comparative White Matter Study with Parkinson′s disease,Parkinson′s Disease with Dementia and Alzheimer′s Disease
Perea, R. D. (2013) · Journal of Alzheimer’s Disease & Parkinsonism · doi:10.4172/2161-0460.1000123 · Cited by 28 · see citing works
“The ILF provides a direct connection from occipital cortex to temporal lobe [45,46].”
Background
Dissociable 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 28 · see citing works
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 27 · see citing works
“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).”
Background
Greater 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 27 · see citing works
“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…”
MethodInfluential
Destruction of White Matter Integrity in Patients with Mild Cognitive Impairment and Alzheimer Disease
Sun, 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 · see citing works
Role of emerging neuroimaging modalities in patients with cognitive impairment: a review from the Canadian Consensus Conference on the Diagnosis and Treatment of Dementia 2012
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 · see citing works
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 23 · see citing works
“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).”
Background
Bilingual experience affects white matter integrity across the lifespan
DeLuca, V., & Voits, T. (2022) · Neuropsychologia · doi:10.1016/j.neuropsychologia.2022.108191 · Cited by 23 · see citing works
“, 2012), but also in neurodegenerative diseases such as Alzheimer’s disease (Gold et al., 2012), Parkinson’s disease (Auning et al.”
Background
Concurrent white and gray matter degeneration of disease-specific networks in early-stage Alzheimer's disease and behavioral variant frontotemporal dementia
Steketee, 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 · see citing works
White Matter Microstructure Changes and Cognitive Impairment in the Progression of Chronic Kidney Disease
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 22 · see citing works
Familial Presenilin Mutations and Sporadic Alzheimer’s Disease Pathology: Is the Assumption of Biochemical Equivalence Justified?
Roher, A. E., Maarouf, C. L., & Kokjohn, T. A. (2016) · Journal of Alzheimer s Disease · doi:10.3233/jad-150757 · Cited by 21 · see citing works
Retained executive abilities in mild cognitive impairment are associated with increased white matter network connectivity
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 · see citing works
“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 · see citing works
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 · see citing works
“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).”
Background
Orientational changes of white matter fibers in Alzheimer's disease and amnestic mild cognitive impairment
Zhao, 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 20 · see citing works
Alteration of rhythmic unimanual tapping and anti-phase bimanual coordination in Alzheimer’s disease: A sign of inter-hemispheric disconnection?
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 · see citing works
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 18 · see citing works
“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].”
Background
Multimodal Imaging Evidence for Axonal and Myelin Deterioration in Amnestic Mild Cognitive Impairment
Gold, 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 · see citing works
“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].”
Subjects harboring presenilin familial Alzheimer's disease mutations exhibit diverse white matter biochemistry alterations.
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 · see citing works
Chapter 9. Bilingualism, cognitive reserve and Alzheimer’s disease: A review of findings
Gold, B. T. (2017) · Studies in bilingualism · doi:10.1075/sibil.53.09gol · Cited by 1 · see citing works
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 · see citing works
p39, the Primary Activator for Cyclin-dependent Kinase 5 (Cdk5) in Oligodendroglia, Is Essential for Oligodendroglia Differentiation and Myelin Repair
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 · see citing works
Diffusion tensor imaging of idiopathic normal-pressure hydrocephalus and the cerebrospinal fluid tap test
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 · see citing works
“The caudal portion of the cingulum is known to contain fibers that connect the posterior cingulate cortex with the hippocampus [45].”
Imaging and neuropsychological correlates of white matter lesions in different subtypes of Mild Cognitive Impairment: A systematic review
Lam, C. L. M., Yiend, J., & Lee, T. M. C. (2017) · Neurorehabilitation · doi:10.3233/nre-171471 · Cited by 15 · see citing works
Interactive Effects of Apolipoprotein E4 and Diabetes Risk on Later Myelinating White Matter Regions in Neurologically Healthy Older Aged Adults
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 · see citing works
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 · see citing works
Cognitive, Genetic, Brain Volume, and Diffusion Tensor Imaging Markers as Early Indicators of Dementia
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 · see citing works
“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].”
BackgroundResult
Progressive 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 · see citing works
“ACA supplies blood to the frontal lobe, where integrity changes of the white matter mainly occur when AD first develops [28].”
Background
Medial temporal lobe white matter pathway variability is associated with individual differences in episodic memory in cognitively normal older adults
Alm, 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 · see citing works
“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…”
Background
Frontotemporal dementia: a systematic review of artificial intelligence approaches in differential diagnosis
Dattola, S., Ielo, A., Varone, G., Cacciola, A., Quartarone, A., & Bonanno, L. (2025) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2025.1547727 · Cited by 14 · see citing works
Differences in structural MRI and diffusion tensor imaging underlie visuomotor performance declines in older adults with an increased risk for Alzheimer’s disease
Rogojin, A., Gorbet, D., Hawkins, K., & Sergio, L. (2023) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.1054516 · Cited by 8 · see citing works
“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…”
Background
Feature attention graph neural network for estimating brain age and identifying important neural connections in mouse models of genetic risk for Alzheimer’s disease
Moon, 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 12 · see citing works
“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 · see citing works

Alterations in multiple measures of white matter integrity in normal women at high risk for Alzheimer's disease
Gold, B. T., Powell, D. K., Andersen, A. H., & Smith, C. D. (2010) · NeuroImage · doi:10.1016/j.neuroimage.2010.05.036 · Cited by 112 · see citing works
White matter integrity and key structures affected in Alzheimer's disease characterized by diffusion tensor imaging
Xiao, D., Wang, K., Theriault, L., Charbel, E., & Initiative, A. D. N. (2022) · European Journal of Neuroscience · doi:10.1111/ejn.15815 · Cited by 40 · see citing works
Diffusion tensor imaging of white matter degeneration in Alzheimer’s disease and mild cognitive impairment
Amlien, I. K., & Fjell, A. M. (2014) · Neuroscience · doi:10.1016/j.neuroscience.2014.02.017 · Cited by 219 · see citing works
Cognition-related white matter integrity dysfunction in Alzheimer's disease with diffusion tensor image
Li, Y., Feng, F., Lin, P., Huang, Z., Liu, T., Zhou, B., Yao, H., Zheng, L., Li, C., Wang, P., et al. (2018) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2018.09.010 · Cited by 23 · see citing works
Diffusion tensor imaging of white matter degeneration in early stage of Alzheimer's disease: a review
Buono, 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 45 · see citing works

Authors: Gold, B. T., Johnson, N. F., Powell, D. K., & Smith, C. D.
Affiliations: University of Kentucky (US)
Corresponding author: Gold, Brian T.
ORCID: Gold, Brian T.
Johnson, Nathan F.
Powell, David K.
Smith, Charles D.
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)
DOI: 10.1016/j.bbadis.2011.07.009
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: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 504 d)
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
Health Sciences › Medicine › Physiology › 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

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 ›

Are you an author, or do you see a problem with this page? Request a review

White matter integrity and vulnerability to Alzheimer’s disease: preliminary findings and future directions

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Self-check

Cites

Cited by

Related

Record

About these checks