Potential Sex-Specific Effects of Apolipoprotein E ɛ4 on Cognitive Decline in Early Parkinson's Disease

To compare the longitudinal trajectories of cognition according to the presence of the apolipoprotein E (APOE) ɛ4 allele in male and female Parkinson's disease (PD) patients.

This study included a total of 361 patients with recently diagnosed de novo PD (mean age [standard deviation], 61.4 [9.8] years). The patients were classified into the following groups: APOEɛ4 + /M (n = 65), APOEɛ4-/M (n = 173), APOEɛ4 + /F (n = 25), and APOEɛ4-/F (n = 98). Cognitive decline was assessed annually over 5 years of follow-up using the Montreal Cognitive Assessment (MoCA). To assess the sex-specific impacts of the APOEɛ4 status on cognitive decline, we used generalized linear mixed effects (GLME) models separately for men, women, and the two sexes combined.

In the sex-stratified GLME models adjusted for covariates, the interaction results showed that the males with APOEɛ4 had a steeper rate of cognitive decline than those without APOEɛ4. In contrast, there was no significant interaction between APOEɛ4 and time on longitudinal MoCA performance in the females. The main effect of APOEɛ4 on the change in the MoCA score was not significant for either men or women. When the data from both men and women were used, the APOEɛ4 + /M group exhibited a steeper rate of cognitive decline than did the APOEɛ4 + /F and APOEɛ4-/F groups. These results were consistent with those of sensitivity analyses.

Sex may be considered when APOEɛ4-related vulnerability to early cognitive decline is evaluated in PD patients.