Differences in the Presentation and Progression of Parkinson's Disease by Sex.
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Iwaki Hirotaka, Blauwendraat Cornelis, Leonard Hampton L, Makarious Mary B, Kim Jonggeol J, Liu Ganqiang, Maple-Grødem Jodi, Corvol Jean-Christophe, Pihlstrøm Lasse, van Nimwegen Marlies, Smolensky Luba, Amondikar Ninad, Hutten Samantha J, Frasier Mark, Nguyen Khanh-Dung H, Rick Jacqueline, Eberly Shirley, Faghri Faraz, Auinger Peggy, Scott Kirsten M, Wijeyekoon Ruwani, Van Deerlin Vivianna M, Hernandez Dena G, Gibbs Raphael J, Day-Williams Aaron G, Brice Alexis, Alves Guido, Noyce Alastair J, Tysnes Ole-Bjørn, Evans Jonathan R, Breen David P, Estrada Karol, Wegel Claire E, Danjou Fabrice, Simon David K, Andreassen Ole A, Ravina Bernard, Toft Mathias, Heutink Peter, Bloem Bastiaan R, Weintraub Daniel, Barker Roger A, Williams-Gray Caroline H, van de Warrenburg Bart P, Van Hilten Jacobus J, Scherzer Clemens R, Singleton Andrew B, Nalls Mike A
Аннотация
OBJECTIVES: We examined sex associations to PD phenotypes cross-sectionally and longitudinally in large-scale data.
METHODS: We tested 40 clinical phenotypes, using longitudinal, clinic-based patient cohorts, consisting of 5946 patients, with a median follow-up of 3.1 years. For continuous outcomes, we used linear regressions at baseline to test sex-associated differences in presentation, and linear mixed-effects models to test sex-associated differences in progression. For binomial outcomes, we used logistic regression models at baseline and Cox regression models for survival analyses. We adjusted for age, disease duration, and medication use. In the secondary analyses, data from 17 719 PD patients and 7588 non-PD participants from an online-only, self-assessment PD cohort were cross-sectionally evaluated to determine whether the sex-associated differences identified in the primary analyses were consistent and unique to PD.
RESULTS: Female PD patients had a higher risk of developing dyskinesia early during the follow-up period, with a slower progression in activities of daily living difficulties, and a lower risk of developing cognitive impairments compared with male patients. The findings in the longitudinal, clinic-based cohorts were mostly consistent with the results of the online-only cohort.
CONCLUSIONS: We observed sex-associated contributions to PD heterogeneity. These results highlight the necessity of future research to determine the underlying mechanisms and importance of personalized clinical management. © 2020 International Parkinson and Movement Disorder Society.