Marked gender differences in progression of mild cognitive impairment over 8 years

Abstract Introduction This study examined whether, among subjects with mild cognitive impairment (MCI), women progressed at faster rates than men. Methods We examine longitudinal rates of change from baseline in 398 MCI subjects (141 females and 257 males) in the Alzheimer's Disease Neuroimaging Initiative-1, followed for up to 8 years (mean, 4.1 ± 2.5 years) using mixed-effects models incorporating all follow-ups (mean, 8 ± 4 visits). Results Women progressed at faster rates than men on the Alzheimer's disease assessment scale-cognitive subscale (ADAS-Cog; P = .001) and clinical dementia rating-sum of boxes (CDR-SB; P = .003). Quadratic fit for change over time was significant for both ADAS-Cog ( P = .001) and CDR-SB ( P = .004), and the additional acceleration in women was 100% for ADAS-Cog and 143% for CDR-SB. The variability of change was greater in women. The gender effect was greater in apolipoprotein E ( APOE ) ε4 carriers. Discussion Women with MCI have greater longitudinal rates of cognitive and functional progression than men. Studies to confirm and uncover potential mechanisms appear to be warranted. Trial Registration ADNI ClinicalTrials.gov identifier: NCT00106899.