Objective: Identifying the contribution of sex to the heterogeneity in presentation and progression of Parkinson’s disease (PD).

Background: The different prevalence of Parkinson’s disease (PD) in males and females suggests that sex-associated mechanisms interplay with the disease process. Investigating the contribution of sex to the disease heterogeneity will lead to uncovering these disease processes which can be potential drug targets. Also, understanding the sex differences in phenotypes will result in better patient management and the planning of more efficient clinical trials.

Method: We tested 46 phenotypes using longitudinal clinic-based patient cohorts consisting of 5946 patients with the median follow-up of 3.7 years. For continuous outcomes, we used linear regressions at baseline to test the sex-associated differences in presentation and linear mixed effect models to test the sex-associated differences in progression. For binomial outcomes, we used logistic regression at baseline and Cox models for survival analyses. Linear and non-linear age and disease duration plus the uses of levodopa and/or agonist were adjusted. In the secondary analyses, data of 28,809 PD patients and 10,556 non-PD participants from Fox Insight, an online-only cohort for Parkinson’s disease, were analyzed to check whether the sex-associated differences observed in the primary analyses were also consistent in the cohort and whether the differences are unique to PD or not.

Results: We identified that female PD patients had higher risk for developing dyskinesia in the follow-up period but not wearing off; milder presentation and progression in the difficulty of daily activity of livings measured by Unified Parkinson’s Disease Rating Scale (classic/MDS-revised version); and lower risk of developing mild cognitive impairment than male patients. The findings in the longitudinal clinic-based cohorts were mostly consistent with the results from the online-only cohort.

Conclusion: This large scale analysIs showed the sex contribution on heterogeneIty of Parkinson’s disease. Also it showed the usefulness of an online study for research.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/sex-associated-difference-in-the-presentation-and-progression-of-parkinsons-disease/