AUTHOR=Osiecka Zuzanna , Fausto Bernadette A. , Gills Joshua L. , Sinha Neha , Malin Steven K. , Gluck Mark A. 

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

JOURNAL=Frontiers in Aging Neuroscience

VOLUME=Volume 15 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2023.1239727

DOI=10.3389/fnagi.2023.1239727

ISSN=1663-4365

ABSTRACT=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. 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 areas for medial temporal lobe subregions and hippocampal subfields). Covariates included age, sex, education, literacy, depressive symptomology, and estimated aerobic fitness. 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=.016, ηp2=.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=.003, ηp2=.23. Thus, being overweight by BMI standards may preserve hippocampal function, but obesity reduces hippocampal structure and function in older African Americans with the APOE-4 Alzheimer’s disease risk allele.