4.6 Article

Differences in the Presentation and Progression of Parkinson's Disease by Sex

Journal

MOVEMENT DISORDERS
Volume 36, Issue 1, Pages 106-117

Publisher

WILEY
DOI: 10.1002/mds.28312

Keywords

Parkinson's disease; gender; sex; dyskinesias; cognitive impairment; activities of daily livings

Funding

  1. Michael J. Fox Foundation for Parkinson's Research
  2. AbbVie
  3. Allergan
  4. Avid Radiopharmaceuticals
  5. Biogen
  6. BioLegend
  7. BristolMyers Squibb
  8. Celgene
  9. Denali Incorporated
  10. GE Healthcare
  11. Genentech
  12. GlaxoSmithKline
  13. Eli Lilly and Company
  14. Lundbeck
  15. Merck Co.
  16. Meso Scale Discovery
  17. Pfizer
  18. Piramal
  19. Prevail Therapeutics
  20. Roche
  21. Sanofi Genzyme
  22. Servier Laboratories
  23. Takeda
  24. Teva
  25. UCB
  26. Verily
  27. Voyager Therapeutics
  28. Golub Capital
  29. National Institute of Neurological Disorders and Stroke (NINDS) [NS24778]
  30. General Clinical Research Centers Program of the National Institutes of Health at Columbia University [RR00645]
  31. General Clinical Research Centers Program of the National Institutes of Health at University of Virginia [RR00847]
  32. General Clinical Research Centers Program of the National Institutes of Health at University of Pennsylvania [RR00040]
  33. General Clinical Research Centers Program of the National Institutes of Health at University of Iowa [RR00059]
  34. General Clinical Research Centers Program of the National Institutes of Health at Ohio State University [RR00034]
  35. General Clinical Research Centers Program of the National Institutes of Health at Massachusetts General Hospital [RR01066]
  36. General Clinical Research Centers Program of the National Institutes of Health at University of Rochester [RR00044]
  37. General Clinical Research Centers Program of the National Institutes of Health at Brown University [RR02038]
  38. General Clinical Research Centers Program of the National Institutes of Health at Oregon Health Sciences University [RR00334]
  39. General Clinical Research Centers Program of the National Institutes of Health at Baylor College of Medicine [RR00350]
  40. General Clinical Research Centers Program of the National Institutes of Health at University of California [RR00827]
  41. General Clinical Research Centers Program of the National Institutes of Health at Johns Hopkins University [RR00035]
  42. General Clinical Research Centers Program of the National Institutes of Health at University of Michigan [RR00042]
  43. General Clinical Research Centers Program of the National Institutes of Health at Washington University [RR00036]
  44. Parkinson's Disease Foundation at Columbia-Presbyterian Medical Center
  45. National Parkinson Foundation
  46. Parkinson Foundation of Canada
  47. United Parkinson Foundation, Chicago
  48. American Parkinson's Disease Association, New York
  49. University of Rochester
  50. Assistance Publique Hopitaux de Paris - French Ministry of Health (PHRC 2008) [AOM08010]
  51. Agence Nationale pour la Securite des Medicaments (ANSM)
  52. Harvard NeuroDiscovery Center
  53. Michael J Fox Foundation
  54. NINDS [U01NS082157, U01NS100603, U01NS043128, 5U01NS050095-05]
  55. Massachusetts Alzheimer's Disease Research Center [NIA P50AG005134]
  56. ZonMw (Netherlands Organization for Health Research and Development) [75020012]
  57. Michael J Fox Foundation for Parkinson's research
  58. VGZ (health insurance company)
  59. Research Council of Norway
  60. Western Norway Regional Health Authority
  61. Stavanger University Hospital Research Funds
  62. Norwegian Parkinson's Disease Association
  63. Cure Parkinson's Trust
  64. Van Geest Foundation
  65. National Institute of Health Research Cambridge Biomedical Research Centre
  66. Department of Defense Neurotoxin Exposure Treatment Parkinson's Research Program [W23RRYX7022N606]
  67. Parkinson's Disease Foundation
  68. Lundbeck Pharmaceuticals
  69. Cephalon Inc
  70. Lundbeck Inc
  71. John Blume Foundation
  72. Smart Family Foundation
  73. RJG Foundation
  74. Kinetics Foundation
  75. Amarin Neuroscience LTD
  76. CHDI Foundation Inc
  77. National Institutes of Health (NHGRI, NINDS)
  78. Columbia Parkinson's Disease Research Center
  79. Alkemade-Keuls Foundation
  80. Stichting Parkinson Fonds
  81. Parkinson Vereniging
  82. Netherlands Organisation for Health Research and Development
  83. NINDS

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This study examined sex associations to PD phenotypes cross-sectionally and longitudinally in large-scale data. Female PD patients were found to have a higher risk of developing dyskinesia early during the follow-up period, with slower progression in daily living difficulties, and a lower risk of developing cognitive impairments compared with male patients. The findings were consistent in both longitudinal, clinic-based cohorts and an online-only cohort.
Background Previous studies reported various symptoms of Parkinson's disease (PD) associated with sex. Some were conflicting or confirmed in only one study. 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. (c) 2020 International Parkinson and Movement Disorder Society

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