Association of Long‐Term BMI Change with Alzheimer‐Signature Cerebral Glucose Metabolism in Non‐Demented Older Adults

Abstract Background Growing evidence suggests that low body mass index (BMI) or BMI decline from midlife is related to the risk of Alzheimer’s disease (AD) and related cognitive decline in later life. However, limited information is yet available regarding the underlying brain change that could explain such relationship. This study aims to investigate whether BMI and BMI change after midlife are associated with cerebral metabolism in late life. Method A total of 268 non‐demented (193 cognitive normal and 75 mild cognitive impairment) older adults from 55 to 90 years of age were enrolled from the Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer’s Disease (KBASE). Current or late‐life BMI was calculated using the measured height and body weight. Midlife (40 ∼ 50 years of age) BMI was calculated using self‐recall based midlife body weight and height. Self‐recall past body weight in cognitively healthy older adults was well‐validated 1 . All participant received [ 18 F] fludeoxyglucose (FDG)‐PET at baseline. General linear model analysis was performed to assess the association between BMI and BMI changers with AD‐signature cerebral glucose metabolism (AD‐CM). Result Midlife BMI had significant negative association with AD‐CM (p = 0.007). even after adjusting for age, sex, clinical deterioration rating (CDR) sum of box score, and apolipoprotein E ε4 positivity. Three strata of BMI change from midlife to late‐life (i.e., decreasing pattern: ≤ ‐4%, stable pattern: ‐4% < BMI change < 4%, increasing pattern: ≥ 4%) showed significantly different AD‐CM (p = 0.045). Post hoc comparison revealed that decreasing BMI pattern had significantly lower AD‐CM than increasing BMI pattern, while no difference was found between the decreasing pattern and stable pattern. Sensitivity analyses for cognitively normal participants showed similar results. Conclusion The findings suggest a close association between long‐term BMI decline from midlife and cerebral hypometabolism in late life. Such brain hypometabolism may serve as a potential neural substrate for BMI reduction‐related cognitive decline or increased risk of AD in older adults. References 1. Kyulo NL et al. (2012) Validation of recall of body weight over a 26‐year period in cohort members of the Adventist Health Study 2. Ann Epidemiol 22, 744‐746.