Sex Differences in Progression of Neurodegeneration: The Age, Gene/Environment Susceptibility-Reykjavik Study

INTRODUCTION: Advancing age is associated with global brain atrophy. Cross-sectional studies have found sex differences in neuroanatomy; however, longitudinal studies assessing sex differences in neurodegeneration are currently scarce. The effects of age and sex on brain atrophy may not be uniform across the whole brain and may partially explain the sex differences observed in dementia. The current study aimed to examine sex differences in longitudinal atrophy patterns in gray and white matter regions in older adults.

METHODS: The study sample included 1,480 individuals from the Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study, a population-based cohort study, that underwent two magnetic resonance imaging scans within an average of 5 years between assessments. Individuals were also followed-up for incident dementia diagnosis. Linear regression models were used to assess sex differences between mean differences in gray and white matter regions, correcting for age, education, baseline intracranial volume, baseline regional volumes, hypertension, body mass index, and apolipoprotein (APOE) e4 allele status.

RESULTS: Men showed increased longitudinal atrophy in the total gray matter, as well as in the parietal cortex, cingulate cortex, caudate nucleus, brainstem, left cerebellum, precentral gyrus, putamen, globus pallidus, and orbitofrontal cortex. Whereas women exhibited greater atrophy over time in total white matter, but not in specific regions. No moderation was found between sex differences in incident dementia regarding atrophy patterns.

CONCLUSIONS: While men show larger gray matter volumes cross-sectionally, their rates of atrophy over time are steeper compared to women. Sex differences in brain atrophy seem to be specifically detrimental in men in regions related to executive functioning, motor control, and emotion processing.