Sex differences of longitudinal brain changes in cognitively unimpaired adults

Background: There is increasing evidence that AD progression differs by sex.

Objective: The aim of this work was to determine sex differences in the association of baseline levels of cerebrospinal fluid (CSF) biomarkers (Aβ42, p-tau, YKL-40, sTREM2) with longitudinal brain changes in cognitively unimpaired (CU) older adults.

Methods: This pilot study included 36 CU subjects (age 66.5±5.5, 12 male) scanned twice, two years apart. Using a voxel-wise analysis, we determined the sex differences in the association maps between CSF biomarkers and atrophy rates.

Results: We did not find differences related to Aβ42. We found a greater impact of the rest of CSF biomarkers in areas of the Papez circuit in women versus men. Men showed greater involvement in lateral parietal and paracentral areas.

Discussion: Results suggest an early differential progression of brain atrophy between sexes. Further research will elucidate whether the mechanisms responsible for sex-specific atrophy patterns are biological and/or environmental.