Body Mass Index Decrease Has a Distinct Association with Alzheimer's Disease Pathophysiology in APOE 4 Carriers and Non-Carriers

Background: Body mass index (BMI) changes may be related to Alzheimer's disease (AD) alterations, but it is unclear how the apolipoprotein E epsilon 4 (APOE epsilon 4) allele affects their association. Objective: To explore the association of BMI changes with AD pathologies in APOE epsilon 4 carriers and non-carriers. Methods: In 862 non-demented ADNI participants with >= 2 BMI measurements, we investigated the relationships between BMI slopes and longitudinal changes in amyloid-beta (A beta) accumulation, neurodegeneration and cognition, and follow-up tau deposition in different A beta and APOE epsilon 4 statuses. Results: In A beta+ APOE epsilon 4 non-carriers, faster BMI declines were associated with faster rates of A beta accumulation (standardized beta (beta std) = -0.29, p = 0.001), AD meta regions of interest (metaROI) hypometabolism (beta(std) = 0.23, p = 0.026), memory declines (beta(std) = 0.17, p = 0.029), executive function declines (beta(std) = 0.19, p = 0.011), and marginally faster Temporal-metaROI cortical thinning (beta(std) = 0.15, p = 0.067) and higher follow-up Temporal-metaROI tau deposition (beta(std) = -0.17, p = 0.059). Among A beta-individuals, faster BMI decreases were related to faster A beta accumulation (beta(std) = -0.25, p = 0.023) in APOE epsilon 4 carriers, whereas predicted faster declines in memory and executive function in both APOE epsilon 4 carriers (beta(std) = 0.25, p = 0.008; beta(std) = 0.32, p = 0.001) and APOE epsilon 4 non-carriers (beta(std) = 0.11, p = 0.030; beta(std) = 0.12, p = 0.026). Conclusions: This study highlights the significance of tracking BMI data in older adults by providing novel insights into how body weight fluctuations and APOE epsilon 4 interact with AD pathology and cognitive decline.