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APOE ε4 allele predicts faster cognitive decline in mild Alzheimer disease
Open accessAbstract
OBJECTIVE: To determine whether APOE epsilon 4 predicts rate of cognitive change in incident and prevalent Alzheimer disease (AD). METHODS: Individuals were recruited from two longitudinal cohort studies-the Washington Heights and Inwood Columbia Aging Project (WHICAP; population-based) and the Predictors Study (clinic-based)--and were followed for an average of 4 years. Three samples of participants diagnosed with AD, with diverse demographic characteristics and baseline cognitive functioning, were studied: 1) 199 (48%) of the incident WHICAP cases; 2) 215 (54%) of the prevalent WHICAP cases; and 3) 156 (71%) of the individuals diagnosed with AD in the Predictors Study. Generalized estimating equations were used to test whether rate of cognitive change, measured using a composite cognitive score in WHICAP and the Mini-Mental State Examination in Predictors, varied as a function of epsilon 4 status in each sample. RESULTS: The presence of at least one epsilon 4 allele was associated with faster cognitive decline in the incident population-based AD group (p = 0.01). Parallel results were produced for the two prevalent dementia samples only when adjusting for disease severity or excluding the most impaired participants from the analyses. CONCLUSION: APOE epsilon 4 may influence rate of cognitive decline most significantly in the earliest stages of Alzheimer disease.
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“Our findings are consistent with recent work suggesting that APOE ε4 exerts deleterious effects early in the disease course.(12)”
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“Some studies suggest that the effect of the ε4 allele on cognitive decline is stronger in the earlier clinical stages of disease and is weaker during the later and more severe clinical stages (Cosentino et al., 2008; Juva et al., 2000).”
From The role of apolipoprotein E in Alzheimer's disease (2009) · cites this paper as Cosentino et al., 2008
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Metadata
- Authors
- Cosentino, S., Scarmeas, N., Helzner, E., Glymour, M. M., Brandt, J., Albert, M., Blacker, D., & Stern, Y.
- Affiliations
- Columbia University Irving Medical Center (US)
- Venue
- Neurology
- Published
- 2008-05-06
- Volume
- 70
- Issue
- 19_part_2
- Pages
- 1842-1849
- ISSN
- 0028-3878 (ISSN-L)
- 1526-632X
- PMC
- PMC2676693
- OpenAlex
- W1999864873
- Cited by
- 214
- References
- 53
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 8 · 2023: 6 · 2022: 9 · 2021: 23 · 2020: 11 · 2019: 7 · 2018: 11 · 2017: 9 · 2016: 8 · 2015: 13 · 2014: 18 · 2013: 15 · 2012: 11
- FWCI
- 12.88
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Neurology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (5r01ag007370-30)
- National Institute on Aging (AG00261, Z01AG000732, P01AG007232, R01-AG007370, Z01AG000261, L30 AG026603, T32AG000261)
- National Center for Research Resources (RR 00645, M01RR000645)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Cognitive Abilities and Testing
- Keywords
- APOE ε4, Alzheimer's disease, cognitive decline, genetic risk factors, mild cognitive impairment, disease severity, Mini-Mental State Examination
- MeSH terms
- Aged, Aged, 80 and over, Aging, Alzheimer Disease, Cognition Disorders, DNA Mutational Analysis, Female, Gene Frequency, Genetic Testing, Genotype, Humans, Longitudinal Studies, Male, Memory Disorders, Polymorphism, Genetic, Prospective Studies, Time Factors, Cohort Studies, Disease Progression, Genetic Predisposition to Disease, Apolipoprotein E4
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