Apolipoprotein E e4 Allele Is Associated with Subjective Cognitive Decline: A Meta-Analysis

Abstract

Background and Purpose: Subjective cognitive decline (SCD) is a condition associated with increased risk of Alzheimer’s disease. This study performs a meta-analysis to estimate the prevalence of the Apolipoprotein E e4 (APOE e4) allele in SCD and the association of APOE e4 with SCD. Methods: The MEDLINE, EMBASE, and Cochrane Library databases were searched. Meta-analyses were conducted using STATA 12.0 software. When significant heterogeneity was present (I² >50% and p < 0.05), we conducted stratified and meta-regression analyses to explore possible reasons for heterogeneity. Results: We selected a total of 28 studies that were conducted in Australia, the United States, northern Europe, middle Europe, southern Europe, and Asia. The sample size of the SCD group was 6,044. Thirteen studies included a healthy control group (total control cohort of 3,822), whereas the remaining 15 studies were single-arm studies of SCD groups. The APOE e4 allele was associated with SCD (OR 1.12 [1.00–1.25]; p = 0.04). The pooled estimate for APOE e4 carrier prevalence was 32% (95% CI 28–35). Due to the significant heterogeneity in prevalence estimates, we performed stratified and meta-regression analyses and found that age and northern European residency were significantly associated with heterogeneity. Conclusion: The results of this meta-analysis indicate a weak association between APOE e4 and SCD. Age and northern European residency are the critical factors that determine heterogeneity in the APOE e4-associated prevalence of SCD.