Cerebral white matter rarefaction has both neurodegenerative and vascular causes and may primarily be a distal axonopathy
Document Type
Article
Abstract
Cerebral white matter rarefaction (CWMR) was considered by Binswanger and Alzheimer to be due to cerebral arteriolosclerosis. Renewed attention came with CT and MR brain imaging, and neuropathological studies finding a high rate of CWMR in Alzheimer disease (AD). The relative contributions of cerebrovascular disease and AD to CWMR are still uncertain. In 1181 autopsies by the Arizona Study of Aging and Neurodegenerative Disorders (AZSAND), large-format brain sections were used to grade CWMR and determine its vascular and neurodegenerative correlates. Almost all neurodegenerative diseases had more severe CWMR than the normal control group. Multivariable logistic regression models indicated that Braak neurofibrillary stage was the strongest predictor of CWMR, with additional independently significant predictors including age, cortical and diencephalic lacunar and microinfarcts, body mass index, and female sex. It appears that while AD and cerebrovascular pathology may be additive in causing CWMR, both may be solely capable of this. The typical periventricular pattern suggests that CWMR is primarily a distal axonopathy caused by dysfunction of the cell bodies of long-association corticocortical projection neurons. A consequence of these findings is that CWMR should not be viewed simply as "small vessel disease" or as a pathognomonic indicator of vascular cognitive impairment or vascular dementia.
Medical Subject Headings
Female; Humans; White Matter (pathology); Brain (pathology); Cerebrovascular Disorders (complications, diagnostic imaging, pathology); Alzheimer Disease (diagnostic imaging, pathology); Dementia, Vascular (pathology)
Publication Date
5-25-2023
Publication Title
Journal of neuropathology and experimental neurology
E-ISSN
1554-6578
Volume
82
Issue
6
First Page
457
Last Page
466
PubMed ID
37071794
Digital Object Identifier (DOI)
10.1093/jnen/nlad026
Recommended Citation
Beach, Thomas G.; Sue, Lucia I.; Scott, Sarah; Intorcia, Anthony J.; Walker, Jessica E.; Arce, Richard A.; Glass, Michael J.; Borja, Claryssa I.; Cline, Madison P.; Hemmingsen, Spencer J.; Qiji, Sanaria; Stewart, Analisa; Martinez, Kayleigh N.; Krupp, Addison; McHattie, Rylee; Mariner, Monica; Lorenzini, Ileana; Kuramoto, Angela; Long, Kathy E.; Tremblay, Cécilia; Caselli, Richard J.; Woodruff, Bryan K.; Rapscak, Steven Z.; Belden, Christine M.; Goldfarb, Danielle; Choudhury, Parichita; Driver-Dunckley, Erika D.; Mehta, Shyamal H.; Sabbagh, Marwan N.; Shill, Holly A.; Atri, Alireza; and Adler, Charles H., "Cerebral white matter rarefaction has both neurodegenerative and vascular causes and may primarily be a distal axonopathy" (2023). Neurology. 1468.
https://scholar.barrowneuro.org/neurology/1468