Body Mass Index Decrease Has a Distinct Association with Alzheimer's Disease Pathophysiology in APOE ɛ4 Carriers and Non-Carriers.

Abstract

Body mass index (BMI) changes may be related to Alzheimer's disease (AD) alterations, but it is unclear how the apolipoprotein E ɛ4 (APOE ɛ4) allele affects their association. To explore the association of BMI changes with AD pathologies in APOE ɛ4 carriers and non-carriers. In 862 non-demented ADNI participants with≥2 BMI measurements, we investigated the relationships between BMI slopes and longitudinal changes in amyloid-β (Aβ) accumulation, neurodegeneration and cognition, and follow-up tau deposition in different Aβ and APOE ɛ4 statuses. In Aβ+ APOE ɛ4 non-carriers, faster BMI declines were associated with faster rates of Aβ accumulation (standardized β (βstd) = -0.29, p = 0.001), AD meta regions of interest (metaROI) hypometabolism (βstd = 0.23, p = 0.026), memory declines (βstd = 0.17, p = 0.029), executive function declines (βstd = 0.19, p = 0.011), and marginally faster Temporal-metaROI cortical thinning (βstd = 0.15, p = 0.067) and higher follow-up Temporal-metaROI tau deposition (βstd = -0.17, p = 0.059). Among Aβ- individuals, faster BMI decreases were related to faster Aβ accumulation (βstd = -0.25, p = 0.023) in APOE ɛ4 carriers, whereas predicted faster declines in memory and executive function in both APOE ɛ4 carriers (βstd = 0.25, p = 0.008; βstd = 0.32, p = 0.001) and APOE ɛ4 non-carriers (βstd = 0.11, p = 0.030; βstd = 0.12, p = 0.026). This study highlights the significance of tracking BMI data in older adults by providing novel insights into how body weight fluctuations and APOE ɛ4 interact with AD pathology and cognitive decline.