Obesity reduces hippocampal structure and function in older African Americans with the APOE-ε4 Alzheimer's disease risk allele.

Introduction: Excess body weight and Alzheimer's disease (AD) disproportionately affect older African Americans. While mid-life obesity increases risk for AD, few data exist on the relationship between late-life obesity and AD, or how obesity-based and genetic risk for AD interact. Although the APOE-ε4 allele confers a strong genetic risk for AD, it is unclear if late-life obesity poses a greater risk for APOE-ε4 carriers compared to non-carriers. Here we assessed: (1) the influence of body mass index (BMI) (normal; overweight; class 1 obese; ≥ class 2 obese) on cognitive and structural MRI measures of AD risk; and (2) the interaction between BMI and APOE-ε4 in older African Americans. Methods: Seventy cognitively normal older African American participants (Mage = 69.50 years; MBMI = 31.01 kg/m2; 39% APOE-ε4 allele carriers; 86% female) completed anthropometric measurements, physical assessments, saliva collection for APOE-ε4 genotyping, cognitive testing, health and lifestyle questionnaires, and structural neuroimaging [volume/surface area (SA) for medial temporal lobe subregions and hippocampal subfields]. Covariates included age, sex, education, literacy, depressive symptomology, and estimated aerobic fitness. Results: Using ANCOVAs, we observed that individuals who were overweight demonstrated better hippocampal cognitive function (generalization of learning: a sensitive marker of preclinical AD) than individuals with normal BMI, p = 0.016, ηp2 = 0.18. However, individuals in the obese categories who were APOE-ε4 non-carriers had larger hippocampal subfield cornu Ammonis region 1 (CA1) volumes, while those who were APOE-ε4 carriers had smaller CA1 volumes, p = 0.003, ηp2 = 0.23. Discussion: Thus, being overweight by BMI standards may preserve hippocampal function, but obesity reduces hippocampal structure and function in older African Americans with the APOE-ε4 Alzheimer's disease risk allele.