APOE genotype and cognitive decline in a middle-aged cohort
Abstract
Background Most longitudinal studies of nondemented persons have reported greater cognitive decline among APOE epsilon4 carriers vs noncarriers. However, most studies involved elderly samples (aged 65+) and were not large enough to examine the three APOE alleles separately. Methods Change in cognitive function was examined over a 6-year period using three neuropsychological tests among four APOE genotype groups (epsilon2/2 + epsilon2/3, epsilon3/3 (referent), epsilon4/2 + epsilon4/3, epsilon4/4). The population-based sample included 1,693 African Americans and 6,202 Caucasians initially ages 47 to 68. Results There was increasingly greater cognitive decline from the epsilon2 group to the epsilon4/4 group in Caucasians for two of the three tests. The combination of APOE epsilon4 with hypercholesterolemia or diabetes showed the greatest cognitive decline. Among African Americans, only the test measuring psychomotor speed showed associations with APOE genotype. Conclusions APOE epsilon4 is associated with greater cognitive decline in middle-aged Caucasian individuals, with a reduced decline among epsilon2 carriers. This suggests that the processes by which APOE genotype mediates dementia risk are operative well in advance of overt dementia.
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Neither APOE2 nor APOE4 carriers were enriched in the TCGA-SKCM study compared to a control group with similar age and ethnic composition, indicating that neither genotype associated with increased melanoma incidence.
“Neither APOE2 nor APOE4 carriers were enriched in the TCGA-SKCM study in comparison to a control group with similar age and ethnic composition23, indicating that neither genotype associated with increased melanoma incidence (Extended Data Fig. 6a–b).”
From Common germline variants of the human APOE gene modulate melanoma progression and survival (2020) · cites this paper as [23]
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- Authors
- Blair, C. K., Folsom, A. R., Knopman, D. S., Bray, M. S., Mosley, T. H., & Boerwinkle, E.
- Affiliations
- University of Minnesota (US)
- Venue
- Neurology
- Published
- 2005-01-25
- Volume
- 64
- Issue
- 2
- Pages
- 268-276
- ISSN
- 0028-3878 (ISSN-L)
- 1526-632X
- OpenAlex
- W2014342740
- Cited by
- 143
- References
- 3
- Citations by year
- 2026: 5 · 2025: 4 · 2024: 3 · 2023: 4 · 2022: 7 · 2021: 8 · 2020: 5 · 2019: 6 · 2018: 6 · 2017: 9 · 2016: 4 · 2015: 8 · 2014: 13 · 2013: 11 · 2012: 6
- FWCI
- 4.01
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neurology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (n01hc55021-47-0-1, n01hc55020-39-0-0, n01hc55016-37-0-0, 5r01hl073366-04, n01hc055022-024, n01hc55019-35-0-1, n01hc55018-38-0-1, n01hc55015-48-0-1)
- Centers for Disease Control and Prevention (UR6/CCU617218)
- National Heart, Lung, and Blood Institute (N01-HC55022, N01-HC-55018, N01 HC 55020, N01 HC 55019, HL 073366, N01-HC55016, N01‐HC‐55015, N01-HC55021)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Cognitive Abilities and Testing
- Keywords
- APOE genotype, APOE ε4, cognitive decline, middle-aged adults, APOE ε2, hypercholesterolemia, diabetes mellitus, psychomotor speed, African Americans, Caucasians, dementia risk, genetic risk factors
- MeSH terms
- Aged, Alleles, Apolipoproteins E, Black or African American, Carotid Artery Diseases, Cognition Disorders, Diabetes Mellitus, Female, Genotype, Humans, Hypercholesterolemia, Male, Middle Aged, Neuropsychological Tests, Prospective Studies, Ultrasonography, Cohort Studies, Disease Progression, Genetic Predisposition to Disease, White People, Apolipoprotein E4, Apolipoprotein E2
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