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, 257 Males) in the Alzheimer's Disease Neuroimaging Initiative-1 (ADNI-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 ADAS-Cog (p=0.001) and CDR-SB (p=0.003). Quadratic fit for change over time was significant for both ADAS-Cog (p=0.001) and CDR-SB (p=0.004), 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 ApoE4 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.

Keywords: disease modification; gender differences; prevalence; secondary prevention.

Fig. 1

ADAS-Cog changes over time by gender. Average trajectories of ADAS-Cog scores by gender. Pointwise 95% confidence bands for the mean are based on the number of subjects at any given time point. The figure depicts time in years from baseline on the x-axis and ADAS-Cog 11 total scores on the y-axis. Increasing ADAS-Cog scores indicate worsening. Solid lines indicate mean ADAS-Cog scores, and dashed lines indicate 95% confidence intervals for these scores. The actual visit date of each subject was used (rather than pooling visits as “annual”) to give a more precise depiction of variability and progression. Abbreviation: ADAS-Cog, Alzheimer's disease assessment scale-cognitive subscale.

Fig. 2

Median rates of ADAS-Cog change by gender and APOE ε4 status. Median rates of ADAS-Cog change per year by gender and number of APOE ε4 alleles. APOE ε4− indicates no APOE ε4 alleles, APOE ε4+ is one allele, and APOE ε4++ is two alleles. Women had higher median annual rate of change than men regardless of APOE ε4 genotype group. Abbreviation: ADAS-Cog, Alzheimer's disease assessment scale-cognitive subscale.

Fig. 3

CDR-SB changes over time by gender. Average trajectories of CDR-SB scores by gender. Pointwise 95% confidence bands for the mean are based on the number of subjects at risk at any given time point. The figure depicts time in years from baseline on the x-axis and CDR-SB scores on the y-axis. Higher CDR-SB scores indicate worsening. Solid lines indicate mean ADAS-Cog scores, and dashed lines indicate 95% confidence intervals for these scores. The actual visit date of each subject was used (rather than pooling visits as “annual”) to give a more precise depiction of variability and progression. Abbreviations: CDR-SB, clinical dementia rating-sum of boxes; ADAS-Cog, Alzheimer's disease assessment scale-cognitive subscale.