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White Matter Lesions Are Prevalent but Differentially Related With Cognition in Aging and Early Alzheimer Disease
Abstract
BACKGROUND: White matter lesions (WMLs) are prevalent in nondemented aging and in Alzheimer disease (AD). Their relationship with cognition in the earliest stages of AD is unknown. OBJECTIVE: To assess the relationship between WMLs and cognition in nondemented aging and in early-stage AD. DESIGN: Cross-sectional study. SETTING: Alzheimer Disease Research Center, St Louis, MO. PARTICIPANTS: Participants were nondemented (n = 88) or had very mild (n = 48) or mild (n = 20) AD. MAIN OUTCOME MEASURES: Regression coefficients for deep WMLs and periventricular WMLs (PVWMLs) as predictors of cognition, after controlling for age, educational achievement, brain atrophy, and infarctlike lesions. RESULTS: White matter lesions were present in nondemented aging and in early-stage AD, with no group differences in deep WML burden and a modest PVWML burden increase in the AD group. The prevalence of infarctlike lesions was equivalent between groups. Age and hypertension were related to deep WML burden and PVWML burden. Deep WML burden and PVWML burden were associated with reduced global cognition in AD but not in nondemented aging. A PVWML x AD status interaction for global cognition suggests that the relationship between PVWMLs and cognition is modified by AD. In AD, global cognitive reductions were related to impairments in visual memory, processing speed, and executive function. CONCLUSIONS: White matter lesions are prevalent in nondemented aging and in early-stage AD, and their presence influences cognitive impairment in the earliest stages of AD. Individuals with early-stage AD may be more vulnerable to the cognitive effect of WMLs than nondemented aging individuals with similar WML burden.
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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 [43]
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Metadata
- Authors
- Burns, J. M., Church, J. A., Johnson, D. K., Xiong, C., Marcus, D., Fotenos, A. F., Snyder, A. Z., Morris, J. C., & Buckner, R. L.
- Affiliations
- University of Kansas (US)
- Washington University in St. Louis (US)
- Neurology, Inc (US)
- ORCID
- Venue
- Archives of Neurology
- Publisher
- American Medical Association (AMA)
- Published
- 2005-12-01
- Volume
- 62
- Issue
- 12
- Pages
- 1870
- ISSN
- 0003-9942 (ISSN-L)
- OpenAlex
- W2124948998
- Cited by
- 155
- References
- 42
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 3 · 2023: 4 · 2022: 3 · 2021: 5 · 2020: 2 · 2019: 12 · 2018: 9 · 2017: 5 · 2016: 6 · 2015: 7 · 2014: 9 · 2013: 7 · 2012: 6
- FWCI
- 7.11
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Archives of Neurology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (P50AG005681, P01AG003991)
- National Institute of Neurological Disorders and Stroke (T32 NS070521)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Clinical Neurology › Cerebrovascular and genetic disorders
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Keywords
- white matter lesions, Alzheimer's disease, early Alzheimer's disease, aging, cognition, periventricular white matter lesions, deep white matter lesions, visual memory, processing speed, executive function, hypertension, brain atrophy
- MeSH terms
- Aged, Aged, 80 and over, Aging, Alzheimer Disease, Brain, Cognition Disorders, Cross-Sectional Studies, Diagnosis, Differential, Female, Humans, Magnetic Resonance Imaging, Male, Nerve Fibers, Myelinated, Neuropsychological Tests, Predictive Value of Tests, Prevalence, Age of Onset, Plaque, Amyloid
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