ApoE Genotype, Age, and Cognitive Decline in Old Chinese Individuals Without Dementia: A Population-Based Study With Five-Year Follow-Up.

Background: Apolipoprotein E (ApoE) ε4 genotype is a well-known risk factor for Alzheimer's disease (AD). However, its effect on predicting cognitive decline in individuals without dementia and its association with age are unclear.

Objective: To investigate the relationship between ApoE polymorphism and risk of cognitive decline and dementia incidence in the elderly without dementia.

Methods: This population-based prospective study was conducted between 2011 and 2016. The study involved 767 dementia-free individuals who had undergone ApoE genotype analysis, were aged ≥ 60 years, and lived in rural China. Participants were divided into three ApoE groups: E3 (genotype 3/3), E4 (genotypes 3/4 and 4/4), and E2 (genotype 2/3) groups.

Results: After 5 years, 666 (86.8%) individuals were followed up. The rate of change in MMSE score was faster in the E4 group than in the E3 and E2 groups (5.0 ± 4.4 vs. 3.5 ± 3.8 vs. 3.9 ± 3.9, p = 0.001), after adjusting for age, sex, educational level and baseline MMSE scores, especially in the 70-79 years age group. In the same age group, the incidence rate of dementia was higher in the E4 group than in the E3 group (OR = 2.850; 95% CI: 1.146-7.090). After adjusting for age, sex, hypertensive status, educational level, marital status, engagement in social activities, and past history of stroke, the ApoE ε4 allele remained an independent risk factor for dementia incidence (OR = 3.070; 95% CI: 1.162-8.110) in individuals aged 70-79 years after follow-up.

Conclusions: ApoE ε4 carriers with age ≥ 60 years had faster cognitive decline. The ApoE ε4 allele was an independent risk factor for dementia incidence in extremely old individuals.