Weight increases and decreases show distinct association with Alzheimer’s Disease in different age and APOE‐ε4 status

Abstract

AbstractBackgroundHigh and low body mass index (BMI) may increase the risk of Alzheimer’s disease (AD) in mid‐life (age<65) and late‐life (age≥65) respectively. However, it is still not fully understood about the associations of BMI changes with AD progression as well as how APOE‐ε4 allele modulates their relationships in mid‐life and late‐life. In this study, we aimed to determine how BMI changes and APOE‐ε4 allele relate to longitudinal β‐amyloid (Aβ) accumulation, tau aggregation, neurodegeneration and cognitive decline in mid‐life and late‐life.MethodWe examined 325 cognitively unimpaired and 391 mild cognitive impairment Alzheimer’s Disease Neuroimaging Initiative participants with longitudinal 18F‐florbetapir (FBP) Aβ PET and BMI measurements. Among of them, 486, 707 and 710 had longitudinal 18F‐fluorodeoxyglucos (FDG) PET, adjusted hippocampal volume (aHCV) and memory scores, and 246 participants had follow‐up 18F‐flortaucipir (FTP) tau PET data measured at a median of 5.5 years post baseline FBP scan. We investigated the associations of BMI slopes with longitudinal changes of AD typical summary cortical region FBP PET and FDG PET, aHCV and memory scores, and follow‐up Temporal‐metaROI FTP PET in different Aβ status (Aβ‐ and Aβ+), APOE‐ε4 status (carriers and non‐carriers), age (mid‐life and late‐life).ResultWe found faster BMI decreases accelerated the rates of Aβ accumulation (Fig.1D, standardized β (βstd) = ‐0.29, p = 0.002), hypometabolism (Fig.3D, βstd = 0.24, p = 0.03), hippocampal atrophy (Fig.3H, βstd = 0.29, p = 0.002), and memory decline (Fig.4D, βstd = 0.28, p = 0.005), and induced marginally higher follow‐up tau deposition (Fig.2D, βstd = ‐0.26, p = 0.09) in Aβ+ late‐life APOE‐ε4 non‐carriers but not in APOE‐ε4 carriers. In contrast, BMI increases were related to faster (Fig.1C, βstd = 0.80, p < 0.001) rates of Aβ accumulation in Aβ+ mid‐life APOE‐ε4 carriers but not in APOE‐ε4 non‐carriers.ConclusionThese findings suggest that weight increase in mid‐life APOE‐ε4 carriers and weight loss in late‐life APOE‐ε4 non‐carriers are environmental risk factors of AD, highlighting the importance of tracking BMI data in Aβ+ individuals.