Adiposity impacts cognitive function in Asian populations: an epidemiological and Mendelian Randomization studyResearch in context

Summary: Background: Obesity and related metabolic disturbances including diabetes, hypertension and hyperlipidemia predict future cognitive decline. Asia has a high prevalence of both obesity and metabolic disease, potentially amplifying the future burden of dementia in the region. We aimed to investigate the impact of adiposity and metabolic risk on cognitive function in Asian populations, using an epidemiological analysis and a two-sample Mendelian Randomization (MR) study. Methods: The Health for Life in Singapore (HELIOS) Study is a population-based cohort of South-East-Asian men and women in Singapore, aged 30–84 years. We analyzed 8769 participants with metabolic and cognitive data collected between 2018 and 2021. Whole-body fat mass was quantified with Dual X-Ray Absorptiometry (DEXA). Cognition was assessed using a computerized cognitive battery. An index of general cognition ‘g’ was derived through factor analysis. We tested the relationship of fat mass indices and metabolic measures with ‘g’ using regression approaches. We then performed inverse-variance-weighted MR of adiposity and metabolic risk factors on ‘g’, using summary statistics for genome-wide association studies of BMI, visceral adipose tissue (VAT), waist-hip-ratio (WHR), blood pressure, HDL cholesterol, triglycerides, fasting glucose, HbA1c, and general cognition. Findings: Participants were 58.9% female, and aged 51.4 (11.3) years. In univariate analysis, all 29 adiposity and metabolic measures assessed were associated with ‘g’ at P