Introduction: Longitudinal subtypes in Alzheimer's disease (AD) have been identified based on their distinct brain atrophy trajectories, encompassing mediotemporal and cortical pathways. These subtypes include minimal atrophy, limbic predominant, limbic predominant plus, diffuse atrophy and hippocampal sparing. The impact of sex on the progression of these subtypes remains a crucial area of investigation.
Methods: We analysed MRI data from 320 amyloid-β positive individuals with AD from three international cohorts (ADNI, J-ADNI and AIBL). Longitudinal clustering was conducted to identify atrophy trajectories over eight years from the clinical disease onset, with separate trajectories delineated for women and men.
Results: Women consistently exhibited earlier hippocampal atrophy and a higher burden of white matter abnormalities compared to men, yet women displayed less cognitive decline over time. Additionally, specific risk factors and distinct neuropsychiatric symptoms were associated with sex within specific trajectories.
Conclusions: AD subtypes show sex-specific differences in disease progression, highlighting the need to account for these differences from the early disease stages. Integrating imaging biomarkers with sex differences can enable the identification of more precise treatments for each patient, ensuring that both women and men have equal access to tailored care.
Keywords: Alzheimer’s disease; Cognition; Disease progression; MRI; Sex differences; Subtypes.
© 2025. The Author(s).