Cerebral amyloid angiopathy and cognitive outcomes in community-based older persons
Open accessAbstract
OBJECTIVE: We tested the hypothesis that cerebral amyloid angiopathy (CAA) is related to Alzheimer disease (AD) dementia and decline in multiple cognitive systems in old age, independent of AD plaque and tangle pathology and other common age-related neuropathologies. METHODS: Participants (n = 1,113) came from 2 longitudinal clinical-pathologic studies of aging, the Rush Memory and Aging Project and the Religious Orders Study. All underwent annual clinical evaluations including detailed cognitive testing for a mean of 7.1 years before death. Clinical diagnoses of AD were established after reviewing all clinical data, blinded to neuropathologic information. Neuropathologic examinations provided measures of CAA, AD pathology, macroscopic infarcts, microinfarcts, and neocortical Lewy bodies. The association of CAA with AD dementia was examined using logistic regression models, and its association with cognitive decline was examined using linear mixed models. RESULTS: CAA was common, present in 78.9% of participants, and moderately related to AD pathology (ρ = 0.401, p < 0.0001). In analyses adjusted for plaques, tangles, and other common age-related neuropathologies, CAA was associated with an increased odds of AD dementia (odds ratio = 1.237, 95% confidence interval 1.082-1.414) and an increased rate of decline in global cognition, perceptual speed, episodic memory, and semantic memory. The associations of CAA with cognitive outcomes were not driven by the presence of capillary involvement. CONCLUSIONS: CAA is an important determinant of AD dementia and decline in multiple cognitive systems in old age.
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Human AD studies found that both E4 and E2 carriage were associated with higher CAA compared to E3/E3 individuals.
“These findings may reflect human AD studies in which both E4 and E2 carriage were associated with higher CAA compared to E3/E3 individuals47,48”
From APOE4 to APOE2 allelic switching in mice improves Alzheimer’s disease-related metabolic signatures, neuropathology and cognition (2025) · cites this paper as [47]
The Burden of CAA section reports an association between CAA and AD pathology, but does not compare CAA burden by APOE genotype. Searches for APOE, apolipoprotein E, and the E2/E4 alleles found no passage addressing whether either allele is associated with higher CAA than E3/E3. (LLM, conf=0.76)
Experimental — accuracy not yet measuredAdvanced stage CAA in AD patients aggravates cognitive decline and enhances odds of triggering dementia onset.
“Advanced stage CAA in AD patients aggravates cognitive decline and enhances odds of triggering dementia onset [603].”
From Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease (2020) · cites this paper as [603]
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- Authors
- Boyle, P. A., Yu, L., Nag, S., Leurgans, S., Wilson, R. S., Bennett, D. A., & Schneider, J. A.
- Affiliations
- Rush University Medical Center (US)
- Venue
- Neurology
- Published
- 2015-12
- Volume
- 85
- Issue
- 22
- Pages
- 1930-1936
- ISSN
- 0028-3878 (ISSN-L)
- 1526-632X
- PMC
- PMC4664125
- OpenAlex
- W2166148093
- Cited by
- 423
- References
- 28
- Citations by year
- 2026: 45 · 2025: 55 · 2024: 60 · 2023: 38 · 2022: 46 · 2021: 43 · 2020: 31 · 2019: 31 · 2018: 24 · 2017: 28 · 2016: 20 · 2014: 1
- FWCI
- 19.37
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Neurology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (R01AG017917, R01AG042210, R01AG015819, P30AG010161, RF1AG015819, R01AG034374)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Neurology › Intracerebral and Subarachnoid Hemorrhage Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- cerebral amyloid angiopathy, cognitive decline, older adults, Alzheimer disease pathology, amyloid plaques, neurofibrillary tangles, microinfarcts, Lewy bodies, perceptual speed, episodic memory, semantic memory, global cognition, neuropathology
- MeSH terms
- Aged, Aged, 80 and over, Aging, Alzheimer Disease, Brain, Cognition, Cognition Disorders, Female, Humans, Longitudinal Studies, Male, Neuropsychological Tests, Cerebral Amyloid Angiopathy, Plaque, Amyloid
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