O3‐08‐06: USING GENETIC INFORMATION TO IDENTIFY THE EARLIEST MANIFESTATIONS OF ALZHEIMER'S DISEASE: GENETIC RISK SCORE FOR ALZHEIMER'S DISEASE PREDICTS LOWER BMI BY AGE 58

• DOI: 10.1016/j.jalz.2019.06.4671
• Publication Date: 2019-10-18T11:53:36Z
• Authors: Willa D. Brenowitz; Teresa J. Filshtein; Kristine Yaffe; Stefan Walter; Thomas Hoffmann; Eric Jorgenson; Rachel A. Whitmer; Maria Glymour
• Keywords: 03 medical and health sciences; 0302 clinical medicine

Higher midlife Body Mass Index (BMI) may be a risk factor for Alzheimer's disease (AD). However, weight loss is common in the years before AD diagnosis likely due to appetite changes and worse nutrition. The age at which this change BMI emerges unclear but point earliest manifestations of target prevention. We examined association between genetic across mid late-life as an innovative approach determine indicate preclinical AD. studied 407,386 UK Biobank non-demented participants aged 39–73 with Caucasian ancestry enrolled 2007-2010. (kg/m2) was constructed from height measured during initial visit. A score (AD-GRS) calculated weighted sum 23 variants previously confirmed genome-wide significant predictors (Z-scored). evaluated whether AD-GRS differed by using linear regression adjustment sex stratified grouping (40-60, 61+). Linear quadratic terms interactions determined trends diverged normal age-related BMI. In 39–60 year olds, borderline not significantly associated lower (−0.02 kg/m2 per SD AD-GRS; 95%CI: −0.04,0.00). 60+ olds more strongly (−0.10 1 95%CI:−0.11,-0.07). Model-based age-curves people high versus low scores began diverge after 47. detectable 61 higher 58 2 AD-GRS. Weight manifest early pathophysiologic Genetic factors that increase sporadic begin predict 58, over decade prior average (mid-70s). Additional longitudinal studies are needed can used identify