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Histopathologic correlates of white matter changes on MRI in Alzheimer's disease and normal aging
Abstract
We investigated the histopathologic correlates of white matter changes in Alzheimer's disease (AD) patients (n = 6) and controls (n = 9) using postmortem MRI. White matter changes were rated on a 0 to 3 scale in 51 regions. Histopathologically, we subjectively rated the loss of myelinated axons in the deep and periventricular white matter, denudation of the ventricular ependyma, gliosis, width of the perivascular spaces, and leptomeningeal congophilic angiopathy; we measured structural changes in the walls of the blood vessels in the white matter in micrometers. The AD brains displayed significantly more white matter hyperintensities on MRI than controls. Histopathologically, the denudation of the ventricular ependyma and the gliosis were significantly more severe in AD than in controls, and there was a trend toward more loss of myelinated axons in the deep white matter in the AD brains (p = 0.07). The MRI abnormalities correlated with the loss of myelinated axons in the deep white matter (r' = 0.37; p < 0.01) and with the denudation of the ventricular lining (r' = 0.54; p < 0.01). We could not find any evidence for arteriolosclerosis, but the mean thickness of the adventitia of the arteries of the deep white matter in AD almost doubled the value in control brains (p = 0.0009). We conclude that white matter abnormalities in AD patients and controls consist of loss of myelinated axons, probably caused by arterial changes and breakdown of the ventricular lining. Since imaging/histopathologic correlation was similar in AD patients and controls, these changes probably represent some form of accelerated aging.
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“AD subjects show more pervasive white matter change [42–46].”
From Brain aging, Alzheimer's disease, and mitochondria (2011) · cites this paper as [45]
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Wahlund, L., Barkhof, F., Fazekas, F., Bronge, L., Augustin, M., Sjögren, M., Wallin, A., Adèr, H., Leys, D., Pantoni, L., et al. (2001) · Stroke · doi:10.1161/01.str.32.6.1318 · Cited by 1,838
“Five different regions were rated in the right and left hemispheres separately: (1) the frontal area, which was the frontal lobe anterior to the central sulcus; (2) the parieto-occipital area, which consisted of the parietal and occipital lobes together; (3) the temporal area, which was the temporal lobe (the border b…”
BackgroundSelf-citationLongstreth, W. T., Manolio, T. A., Arnold, A., Burke, G. L., Bryan, N., Jungreis, C. A., Enright, P. L., O'Leary, D., & Fried, L. (1996) · Stroke · doi:10.1161/01.str.27.8.1274 · Cited by 1,464
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Brain atrophy in Alzheimer’s Disease and aging
Pini, L., Pievani, M., Bocchetta, M., Altomare, D., Bosco, P., Cavedo, E., Galluzzi, S., Marizzoni, M., & Frisoni, G. B. (2016) · Ageing Research Reviews · doi:10.1016/j.arr.2016.01.002 · Cited by 836
Metadata
- Authors
- Scheltens, P., Barkhof, F., Leys, D., Wolters, E. C., Ravid, R., & Kamphorst, W.
- Affiliations
- From the Departments of Neurology (Drs. Scheltens and Wolters), Diagnostic Radiology (Dr. BarkhoO, and Neuropathology (Dr. Kamphorst), Academisch Ziekenhuis W, and the Netherlands Brain Bank (Dr. Ravid), Amsterdam, the Netherlands; and the Department of Neurology (Dr. Leys), Hospital B, University of Lille, Lille, France.
- Université de Lille (FR)
- Venue
- Neurology
- Published
- 1995-05
- Volume
- 45
- Issue
- 5
- Pages
- 883-888
- ISSN
- 0028-3878 (ISSN-L)
- 1526-632X
- OpenAlex
- W2043592305
- Cited by
- 344
- References
- 0
- Citations by year
- 2026: 5 · 2025: 3 · 2024: 6 · 2023: 6 · 2022: 6 · 2021: 4 · 2020: 10 · 2019: 7 · 2018: 6 · 2017: 9 · 2016: 10 · 2015: 13 · 2014: 22 · 2013: 11 · 2012: 10
- FWCI
- 8.04
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neurology (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Keywords
- Alzheimer's disease, white matter hyperintensities, normal aging, gliosis, arteriolosclerosis, adventitial thickening, postmortem MRI, accelerated aging
- MeSH terms
- Aged, Aged, 80 and over, Aging, Alzheimer Disease, Brain, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged
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