Relation of neuropathology to cognition in persons without cognitive impairment
Open accessAbstract
Objective: A study was undertaken to examine the relation of Alzheimer disease (AD) pathology, cerebral infarcts, and Lewy body (LB) pathology to cognition in persons without cognitive impairment. Methods: Persons without dementia from 2 cohort studies of aging, the Religious Orders Study and the Memory and Aging Project, agreed to annual clinical evaluation and brain donation. The studies had 19 neuropsychological performance tests in common that assessed 5 cognitive domains. For 296 persons without cognitive impairment who died and underwent postmortem assessment, we quantified AD pathology as a global pathology score, and as amyloid load, paired helical filament tau‐positive (PHFtau) tangle density, cerebral infarcts, and LB pathology. Linear regression was used to examine the relation of neuropathology to cognitive abilities, controlling for demographics. Results: Nearly all persons had AD pathology with >¾ exhibiting amyloid; 22% had macroscopic and 24% had microscopic infarctions, and 13% had LB pathology. The global measure of AD pathology was related to global cognition (p = 0.008), whereas infarcts and Lewy bodies were not. Amyloid load was related to global cognition (p < 0.05), with only a trend for tangles (p = 0.08). In analyses of cognitive domains, AD pathology (p = 0.006), PHFtau tangles (p = 0.03), and macroscopic infarctions (p = 0.02) were related to episodic memory, with a trend for amyloid load (p = 0.06); AD pathology (p = 0.02) and amyloid load (p = 0.03) were related to working memory. Findings for global cognition and episodic memory were stronger in additional analyses with neocortical amyloid and mesial temporal tangles. Interpretation: AD pathology and macroscopic infarctions are common in older persons without cognitive impairment and are related to episodic and working memory. ANN NEUROL 2012;72:599–609
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Low levels of pathologic changes are associated with subtle cognitive deficits among CU persons.
“Clinicopathologic studies suggest that low levels of pathologic changes are associated with subtle cognitive deficits among CU persons [8,161].”
From NIA‐AA Research Framework: Toward a biological definition of Alzheimer's disease (2018) · cites this paper as [161]
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Self-citation
- Authors
- Bennett, D. A., Wilson, R. S., Boyle, P. A., Buchman, A. S., & Schneider, J. A.
- Affiliations
- Rush University Medical Center (US)
- Corresponding author
- Bennett, David A.
- Venue
- Annals of Neurology
- Publisher
- Wiley
- Published
- 2012-10
- Volume
- 72
- Issue
- 4
- Pages
- 599-609
- ISSN
- 0364-5134 (ISSN-L)
- 1531-8249
- PMC
- PMC3490232
- OpenAlex
- W2034030646
- Cited by
- 220
- References
- 13
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 10 · 2023: 16 · 2022: 12 · 2021: 22 · 2020: 24 · 2019: 20 · 2018: 20 · 2017: 14 · 2016: 16 · 2015: 14 · 2014: 16 · 2013: 24 · 2012: 2
- FWCI
- 12.79
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Annals of Neurology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (R01AG017917, P30-AG 10161, R01-AG34374, R01‐AG17917, R01 AG15819, R01AG015819, P30AG010161, R01AG034374)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Keywords
- Alzheimer disease pathology, cerebral infarction, Lewy body pathology, amyloid load, episodic memory, working memory, neuropathology, Religious Orders Study, brain donation
- MeSH terms
- Aged, 80 and over, Aging, Alzheimer Disease, Autopsy, Brain, Cognition, Cognition Disorders, Educational Status, Female, Humans, Male, Memory, Memory, Short-Term, Nervous System Diseases, Neuropsychological Tests, Psychomotor Performance, Temporal Lobe, Cohort Studies, Linear Models, Amyloid beta-Peptides, tau Proteins, Neocortex, Brain Infarction, Lewy Body Disease, Memory, Episodic
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