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The Effect of the APOE ε2ε4 Genotype on the Development of Alzheimer's Disease (AD) and Mild Cognitive Impairment (MCI) in Non‐Latino Whites
Author(s) -
Ren Dianxu,
Lopez Oscar L.,
Lingler Jennifer H.,
Conley Yvette
Publication year - 2020
Publication title -
journal of the american geriatrics society
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.992
H-Index - 232
eISSN - 1532-5415
pISSN - 0002-8614
DOI - 10.1111/jgs.16337
Subject(s) - medicine , dementia , cohort , hazard ratio , apolipoprotein e , alzheimer's disease , prospective cohort study , gerontology , confidence interval , cohort study , disease
OBJECTIVES To examine the associations of APOE ε2ε4 with the development of Alzheimerʼs disease (AD) and mild cognitive impairment (MCI) in non‐Latino whites. DESIGN Prospective longitudinal cohort study. SETTING Uniform Data Set from the National Alzheimerʼs 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 Alzheimerʼs 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