Cerebral amyloid angiopathy pathology and cognitive domains in older persons
Open accessAbstract
Objective: To examine the relation of cerebral amyloid angiopathy (CAA) to cognitive domains in older community‐dwelling persons with and without dementia. Methods: Subjects were 404 persons in the Religious Orders Study, a cohort study of aging, who underwent annual clinical evaluations, including 19 neuropsychological tests from which 5 cognitive domain and global summary scores were derived, and brain autopsy at time‐of‐death (mean age‐at‐death 86). Using amyloid‐β immunostaining, CAA severity was graded in 5 regions (midfrontal, inferior temporal, angular, calcarine, and hippocampal cortices), as 0 = none, 1 = mild, 2 = moderate, 3 = severe, and 4 = very severe. Because severity was related across regions (all r s > 0.63), and almost all persons had some CAA, we averaged regional CAA scores and created class variable predictors for no‐to‐minimal (<0.5), mild‐to‐moderate (0.5‐2.5) and moderate‐to‐very severe CAA (>2.5). Results: CAA was very common (84.9%; 94 had no‐to‐minimal, 233 mild‐to‐moderate, and 76 moderate‐to‐very severe disease) and was related to AD pathology (r s = 0.68). In linear regression analyses controlling for age, sex, education, AD pathology, infarcts, and Lewy bodies, moderate‐to‐very severe CAA was associated with lower perceptual speed ( p = 0.012) and episodic memory ( p = 0.047), but not semantic memory, working memory, visuospatial skills, or a composite of all cognitive measures. No associations of mild‐to‐moderate CAA with cognition were found. Dementia did not modify these findings. Interpretation: CAA pathology is very common in older community‐dwelling persons and is associated with AD pathology. Moderate‐to‐very severe CAA, but not mild‐to‐moderate CAA, is associated with lower performance in specific cognitive domains, most notably perceptual speed, separately from the effect of AD pathology. ANN NEUROL 2011
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Population-based clinical-pathological studies show that advanced cerebral amyloid angiopathy is associated with worse cognitive performance, independent of Alzheimer disease pathology severity.
“Population-based clinical-pathological studies have identified associations between advanced CAA and worse cognitive performance, and these associations remain independent after controlling for severity of Alzheimer disease pathology.55,140,141”
From Vascular Contributions to Cognitive Impairment and Dementia: A Statement for Healthcare Professionals From the American Heart Association/American Stroke Association (2011) · cites this paper as [140]
The Results and Discussion report that moderate-to-very severe CAA was associated with lower perceptual speed and episodic memory after controlling for AD pathology. The study found no association with the composite cognitive measure, and the Discussion cautions that its Religious Orders cohort may not be representative of the general population. Thus, the source supports an independent association in specific cognitive domains, but not an unqualified population-based finding of worse cognitive performance overall. (LLM, conf=0.86)
Experimental — accuracy not yet measuredSeveral well-defined arteriopathies, such as hereditary and sporadic forms of CAA or hereditary forms of ischemic SVD, typically manifest with cognitive decline or dementia.
“Several well-defined arteriopathies, such as hereditary and sporadic forms of CAA 107-109 or hereditary forms of ischemic SVD, 110 typically manifest with cognitive decline or dementia.”
From Vascular Cognitive Impairment (2017) · cites this paper as [109]
Diffuse AβPs may be associated with cerebral amyloid angiopathy, which could produce impairments separately.
“Furthermore, diffuse AβPs may be associated with cerebral amyloid angiopathy, which could produce impairments separately (103, 104), although see Nelson et al (105).”
From Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature (2012) · cites this paper as [104]
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References 44 · Cited by 383
- Authors
- Arvanitakis, Z., Leurgans, S. E., Wang, Z., Wilson, R. S., Bennett, D. A., & Schneider, J. A.
- Affiliations
- Rush University Medical Center (US)
- Corresponding author
- Arvanitakis, Zoe
- Venue
- Annals of Neurology
- Publisher
- Wiley
- Published
- 2010-11-08
- Volume
- 69
- Issue
- 2
- Pages
- 320-327
- ISSN
- 0364-5134 (ISSN-L)
- 1531-8249
- PMC
- PMC3228518
- OpenAlex
- W1964251512
- Cited by
- 383
- References
- 44
- Citations by year
- 2026: 17 · 2025: 23 · 2024: 27 · 2023: 14 · 2022: 30 · 2021: 50 · 2020: 29 · 2019: 35 · 2018: 14 · 2017: 28 · 2016: 26 · 2015: 27 · 2014: 21 · 2013: 13 · 2012: 15
- FWCI
- 9.18
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Annals of Neurology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Chinese Academy of Agricultural Sciences
- National Institute on Aging (P30-AG 10161, K23 AG 23675, R01 AG15819, R01AG015819, P30AG010161, K23AG023675)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Neurology › Intracerebral and Subarachnoid Hemorrhage Research
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Keywords
- cerebral amyloid angiopathy, cognitive domain, Alzheimer's disease pathology, perceptual speed, episodic memory, semantic memory, working memory, visuospatial ability, dementia, Religious Orders Study, brain autopsy
- MeSH terms
- Aging, Amyloid, Brain, Cognition, Cognition Disorders, Dementia, Humans, Longitudinal Studies, Neuropsychological Tests, Severity of Illness Index, Linear Models, Cerebral Amyloid Angiopathy
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