Brain atrophy trajectories predict differential functional performance in Alzheimer's disease: Moderations with apolipoprotein E and sex

Abstract

Introduction: We examine whether distinct brain atrophy patterns (using brain parenchymal fraction [BPF]) differentially predict functional performance and decline in Alzheimer's disease (AD), and are independently moderated by (1) a key AD genetic risk marker (apolipoprotein E [APOE]), (2) sex, and (3) high-risk group (women APOE ɛ4 carriers). Methods: We used a 2-year longitudinal sample of AD patients (baseline N = 170; mean age = 71.3 [9.1] years) from the Sunnybrook Dementia Study. We applied latent class analysis, latent growth modeling, and path analysis. We aimed to replicate our findings (N = 184) in the Alzheimer's Disease Neuroimaging Initiative. Results: We observed that high brain atrophy class predicted lower functional performance and steeper decline. This association was moderated by APOE, sex, and high-risk group. Baseline findings as moderated by APOE and high-risk group were replicated. Discussion: Women APOE ɛ4 carriers may selectively be at a greater risk of functional impairment with higher brain atrophy.