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. 2020 May;68(5):1044-1049.
doi: 10.1111/jgs.16337. Epub 2020 Feb 4.

The Effect of the APOE ε2ε4 Genotype on the Development of Alzheimer's Disease (AD) and Mild Cognitive Impairment (MCI) in Non-Latino Whites

Dianxu Ren  1   2 , Oscar L Lopez  3   4 , Jennifer H Lingler  1   4 , Yvette Conley  1   5
Affiliations

The Effect of the APOE ε2ε4 Genotype on the Development of Alzheimer's Disease (AD) and Mild Cognitive Impairment (MCI) in Non-Latino Whites

Dianxu Ren et al. J Am Geriatr Soc. 2020 May.

Abstract

Objectives: To examine the associations of APOE ε2ε4 with the development of Alzheimer's disease (AD) and mild cognitive impairment (MCI) in non-Latino whites.

Design: Prospective longitudinal cohort study.

Setting: Uniform Data Set from the National Alzheimer's Coordinating Center (NACC) between 2005 and August 2018 (data freeze in September 2018).

Participants: Participants who were non-Latino white, had an APOE genotype available, first visit with dementia free for AD cohort and both dementia and MCI free for MCI cohort, and had a minimum of one follow-up visit (n = 11 871 for AD cohort, and n = 8305 for MCI cohort).

Measurements: The incidences of AD and MCI were determined based on consensus meetings at each Alzheimer's disease center. We used NACC-derived variables to define individuals experiencing incidents of AD and MCI at the initial visit as well as the follow-up visits.

Results: Among participants in the AD cohort (N = 11 871), ε2ε4 accounted for 2.5%, ε2ε2 accounted for 0.4%, ε2ε3 accounted for 11.0%, ε4ε4 accounted for 4.4%, ε3ε4 accounted for 27.3%, and ε3ε3 accounted for 54.4%. Over an average of 4.6 years follow-up, 1857 (15.6%) developed AD dementia, with the range from 6.0% to 35.2% across the six groups. Compared to ε3ε3 carriers, ε2ε4 carriers exhibited an increased risk of incident AD (18.4% vs 11.7%; adjusted hazard ratio [aHR] = 1.74; 95% confidence interval [CI] = 1.32-2.30; P < .0001). Among participants in the MCI cohort (N = 8305), the average follow-up was 4.7 years, and 1912 (23.0%) developed MCI, with the range from 20.4% to 33.9% across the six groups. Compared to ε3ε3 carriers, ε2ε4 carriers exhibited an increased risk of incident MCI (27.5% vs 21.5%; aHR = 1.52; 95% CI = 1.15-1.99; P = .003).

Conclusions: The APOE ε2ε4 genotype is associated with the increased risk of AD and MCI in non-Latino whites. J Am Geriatr Soc 68:1044-1049, 2020.

Keywords: APOE ε2ε4 genotype; Alzheimerʼs disease; mild cognitive impairment.

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Conflict of interest statement

Conflict of Interest: The authors declare no conflicts of interest.

Figures

Figure 1.
Figure 1.
Diagram displaying derivation of study sample for the analyses with source of exclusion. AD indicates Alzheimerʼs disease; MCI, mild cognitive impairment; NACC, National Alzheimerʼs Coordinating Center.
Figure 2.
Figure 2.
Cumulative incidence of Alzheimer’s disease (AD) dementia during 10 years of follow-up among participants with APOE ε2ε4 genotype compared with other APOE genotype groups.
Figure 3.
Figure 3.
Cumulative incidence of mild cognitive impairment (MCI) during 10 years of follow-up among participants with APOE ε2ε4 genotype compared with other APOE genotype groups.
See this image and copyright information in PMC

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