Sex-Specific Cognitive Divergence in Parkinson's Disease.

Background

Sex differences in cognitive impairment in Parkinson's disease (PD) have been reported, with several studies suggesting greater cognitive decline in males. However, evidence on long-term trajectories across specific cognitive domains is limited, as most prior work is cross-sectional. Aim: To investigate sex-specific longitudinal changes across multiple cognitive domains over 9 years in idiopathic PD, compared to age- and sex-matched controls.

Methods

We analyzed data from the prospective ParkWest study, including n = 190 persons with PD (PwPs) and n = 202 controls. Regularly assessed cognitive domains included semantic fluency, processing speed, cognitive control, memory, and visuospatial ability. Linear mixed-effect models including a three-way interaction between time, disease status, and sex, to test whether sex-specific cognitive change in PD differed from that observed in controls, were estimated. Models were adjusted for age, years of education, baseline depression, and UPDRS part II.

Results

Male PwPs showed faster decline than female PwPs in most cognitive measures, resulting in gradually increasing sex differences over 9 years. However, compared with controls, the differential sex-specific decline was statistically significant only for semantic fluency (p = 0.013) and processing speed (p = 0.027 and p = 0.035). These findings remained significant after covariate adjustment.

Conclusions

PD was associated with increasing sex differences in semantic fluency and processing speed, likely driven by faster decline in males. Other domains did not show sex-specific divergence over time, suggesting that sex-specific vulnerabilities in cognitive trajectories are domain-specific rather than generalized among PwPs.