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. 2010;34(1):43-9.
doi: 10.1159/000256662. Epub 2009 Nov 11.

The APOE epsilon4 allele is associated with incident mild cognitive impairment among community-dwelling older persons

Patricia A Boyle  1 , Aron S Buchman, Robert S Wilson, Jeremiah F Kelly, David A Bennett
Affiliations

The APOE epsilon4 allele is associated with incident mild cognitive impairment among community-dwelling older persons

Patricia A Boyle et al. Neuroepidemiology. 2010.

Abstract

Background: The apolipoprotein E (APOE) epsilon4 allele is a well-known risk factor for the development of Alzheimer's disease, but little is known about the association of the epsilon4 allele with incident mild cognitive impairment (MCI).

Objective: Test the hypothesis that the epsilon4 allele is associated with an increased risk of developing MCI.

Methods: More than 600 older Catholic clergy members from the Religious Orders Study without any cognitive impairment at baseline underwent APOE genotyping and detailed annual clinical evaluations for up to 16 years of follow-up (mean: 10.17 years; range: 2-16 years) to document incident MCI and rates of decline in global cognition and 5 cognitive domains (i.e. episodic memory, semantic memory, working memory, perceptual speed and visuospatial abilities).

Results: During up to 16 years of annual follow-up, 339 of 607 persons (56%) developed MCI. In a proportional hazards model adjusted for age, sex and education, the presence of the APOE epsilon4 allele was associated with a 1.4-fold increased risk of incident MCI (hazard ratio: 1.36; 95% CI: 1.04, 1.78). Further, this association persisted in analyses that required MCI to persist for at least one year (hazard ratio: 1.50; 95% CI: 1.05, 2.14). Finally, the epsilon4 allele was associated with an increased rate of decline in global cognition and 4 out of 5 cognitive systems (i.e. episodic memory, semantic memory, working memory and perceptual speed).

Conclusion: The presence of the APOE epsilon4 allele is associated with an increased risk of MCI and a more rapid rate of cognitive decline in old age.

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Figures

Fig. 1
Fig. 1
Association of the APOE ∊4 allele with the risk of MCI for a typical participant with versus without the ∊4 allele, derived from a proportional hazards model adjusted for age, sex and education.
Fig. 2
Fig. 2
Association of the APOE ∊4 allele with the rate of change in global cognition for a typical participant with versus without the ∊4 allele, derived from a proportional hazards model adjusted for age, sex and education.
See this image and copyright information in PMC

References

    1. Larrieu S, Letenneur L, Orgogozo JM, et al. Incidence and outcome of mild cognitive impairment in a population-based prospective cohort. Neurology. 2002;59:1594–1599. - PubMed
    1. Fisk JD, Merry HR, Rockwood K. Variations in case definition affect prevalence but not outcomes of mild cognitive impairment. Neurology. 2003;61:1179–1184. - PubMed
    1. Morris JC. Mild cognitive impairment is early-stage Alzheimer disease. Arch Neurol. 2006;63:15–16. - PubMed
    1. Bennett DA, Wilson RS, Schneider JA, et al. Natural history of mild cognitive impairment in older persons. Neurology. 2002;59:198–205. - PubMed
    1. Boyle PA, Wilson RS, Aggarwal NT, Tang Y, Bennett DA. Mild cognitive impairment: risk of Alzheimer disease and rate of cognitive decline. Neurology. 2006;67:441–445. - PubMed

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