Potential Sex-Specific Effects of Apolipoprotein E ε4 on Cognitive Decline in Early Parkinson's Disease

초록

Background/Objective: To compare the longitudinal trajectories of cognition according to the presence of the apolipoprotein E (APOE) epsilon 4 allele in male and female Parkinson's disease (PD) patients. Methods: 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: APOE epsilon 4 + /M (n = 65), APOE epsilon 4-/M (n = 173), APOE epsilon 4 + /F (n = 25), and APOE epsilon 4-/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 APOE epsilon 4 status on cognitive decline, we used generalized linear mixed effects (GLME) models separately for men, women, and the two sexes combined. Results: In the sex-stratified GLME models adjusted for covariates, the interaction results showed that the males with APOE epsilon 4 had a steeper rate of cognitive decline than those without APOE epsilon 4. In contrast, there was no significant interaction between APOE epsilon 4 and time on longitudinal MoCA performance in the females. The main effect of APOE epsilon 4 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 APOE epsilon 4 + /M group exhibited a steeper rate of cognitive decline than did the APOE epsilon 4 + /F and APOE epsilon 4-/F groups. These results were consistent with those of sensitivity analyses. Conclusion: Sex may be considered when APOE epsilon 4-related vulnerability to early cognitive decline is evaluated in PD patients.

키워드