Apoe Ε2ϵ4 Genotype, Incident Ad and Mci, Cognitive Decline, and Ad Pathology in Older Adults Publisher Pubmed



Oveisgharan S^{1, 4} ; Buchman AS^{1, 2} ; Yu L^{1, 2} ; Farfel J^{3, 5} ; Hachinski V⁶ ; Gaiteri C¹ ; De Jager PL^{7, 8} ; Schneider JA^{1, 2, 3} ; Bennett DA^{1, 2}
Source: Neurology Published:2018

Abstract

Objective To examine the association of the APOE ϵ2ϵ4 genotype with incident Alzheimer disease (AD), mild cognitive impairment (MCI), cognitive decline, and AD pathology in older adults. Methods We used data from 2,151 older adults of European ancestry who were free of dementia at baseline and underwent structured annual clinical evaluation in a longitudinal study for incident AD and MCI, and cognitive decline. Postmortem examination in decedents documented pathologic AD and quantified β-amyloid and neurofibrillary tangles. Participants were stratified into 4 groups based on APOE genotyping: ϵ2ϵ4, ϵ4 (ϵ4ϵ4, ϵ4ϵ3), ϵ2 (ϵ2ϵ2, ϵ2ϵ3), with ϵ3ϵ3 carriers serving as the reference group. We used Cox proportional hazards models to examine the association of APOE genotype with incident AD and MCI. Linear mixed-effect models were used to examine the association with cognitive decline. Logistic and linear regression models were used to examine AD pathology. All the models controlled for age, sex, and education. Results Of the 2,151 participants included in this study, ϵ2ϵ4 accounted for 2.1%, ϵ3/4 and 4/4 21.8%, ϵ2/3 and 2/2 14.0%, and ϵ3ϵ3 62.1%. We did not observe a difference in the risk of AD for ϵ2ϵ4 compared to ϵ3ϵ3. In cases without cognitive impairment at baseline, ϵ2ϵ4 carriers had an increased risk of incident MCI (hazard ratio 2.13, 95% confidence interval 1.34-3.39, p = 0.002) and a faster rate of cognitive decline (estimate-0.047, SE 0.018, p = 0.008) compared to ϵ3ϵ3 carriers. In decedents (n = 1,100), ϵ2ϵ4 showed a 3-fold increased odds of pathologic AD and a higher β-amyloid load than ϵ3ϵ3. Conclusion APOE ϵ2ϵ4 genotype in older adults is associated with risk of MCI, cognitive decline, and a greater burden of AD pathology, especially β-amyloid. © 2018 American Academy of Neurology.