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The effect of APOE ɛ2/ɛ4 genotype on the incidence of Alzheimer's disease (AD) and mild cognitive impairment (MCI) in African Americans
Author(s) -
Ren Dianxu,
Lopez Oscar L.,
Lingler Jennifer,
Conley Yvette
Publication year - 2020
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.041188
Subject(s) - hazard ratio , apolipoprotein e , dementia , cohort , medicine , confidence interval , proportional hazards model , gerontology , incidence (geometry) , population , alzheimer's disease , cohort study , cognitive decline , genotype , demography , oncology , disease , genetics , biology , physics , optics , gene , environmental health , sociology
Background The APOE Ɛ2Ɛ4 genotype has been recently reported to associate with increased risk of AD and MCI among non‐Latino whites besides the effects of increased risk of Ɛ4 allele (Ɛ3Ɛ4, Ɛ4Ɛ4). However, there was no study to date on the effects of the Ɛ2Ɛ4 genotype among African American population. The purpose of this study was to examine the associations of APOE Ɛ2Ɛ4 with incident AD dementia and incident of Mild Cognitive Impairment (MCI) among African Americans using the large national dataset from National Alzheimer’s Coordinating Center (NACC). Methods We used NACC dataset from 2005 to September 2019 and restricted our analysis to subjects who were African Americans, had an APOE genotype available, first visit with dementia free for AD cohort and both dementia and MCI free for MCI cohort, had a minimum of one follow‐up visit. The subjects were classified into 4 groups based on APOE genotyping: Ɛ2Ɛ4, Ɛ2 (Ɛ2Ɛ2, Ɛ2Ɛ3), Ɛ4 (Ɛ4Ɛ4, Ɛ3Ɛ4), with Ɛ3Ɛ3 carriers serving as the reference group. Cox proportional hazard models were performed to examine the associations of APOE Ɛ2Ɛ4 with incident AD and MCI respectively after controlling age, gender, education, baseline cognitive status and year of initial visit. Adjusted hazard ratio (aHR) and 95% confidence interval (CI) were reported. Results Among AD cohort (N = 2,007), Ɛ2Ɛ4 accounted for 4.9%, Ɛ2/2 and Ɛ2/3 15%, Ɛ3/4 and Ɛ4/4 34.3%, and Ɛ3Ɛ3 45.8%. Over an average of 4.6 years follow‐up, 216 (10.8%) developed AD dementia with the range from 6.3% to 15.7% across 4 groups. Comparing to Ɛ3Ɛ3 carriers, Ɛ2Ɛ4 carriers had a similar risk of incident AD (7.1% vs 8.9%; aHR = 0.85, 95% CI (0.39, 1.84), P = 0.679). Among MCI cohort (N = 1,480), the average follow‐up was 4.5 years and 336 (22.7%) developed MCI with the range from 20.8% to 26.5% across 4 groups. Comparing to Ɛ3Ɛ3 carriers, Ɛ2Ɛ4 carriers had a similar risk of incident MCI (21.1% vs 20.8%; aHR = 0.88, 95% CI (0.51, 1.50), P = 0.637). Conclusions Unlike the effects on non‐Latino whites, APOE Ɛ2Ɛ4 genotype is not associated with the increased risk of AD and MCI among African Americans.