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Does dopamine deficiency affect sex-dependent prognosis in Parkinson's disease?

 Seong Ho Jeong  ;  Hye Sun Lee  ;  Phil Hyu Lee  ;  Young H Sohn  ;  Seok Jong Chung 
 PARKINSONISM & RELATED DISORDERS, Vol.102 : 57-63, 2022-09 
Journal Title
Issue Date
Dopamine / metabolism ; Dopamine Plasma Membrane Transport Proteins / metabolism ; Dyskinesias* ; Female ; Gait Disorders, Neurologic* ; Humans ; Levodopa / adverse effects ; Male ; Parkinson Disease* / drug therapy ; Prognosis
Dopamine transporter ; Mediation analysis ; Parkinson's disease ; Prognosis ; Sex
Introduction: A bundle of evidence indicates that biological sex is an important factor for clinical phenotypes as well as prognosis in Parkinson's disease (PD). We investigated the effect of nigrostriatal dopaminergic degeneration on longitudinal outcomes according to sex in patients with PD.

Methods: We recruited 571 consecutive drug-naïve PD patients (279 men and 292 women) who were followed up for ≥2 years after their first visit to the clinic with baseline dopamine transporter (DAT) imaging. A Cox proportional hazard model was used to compare the risk of developing levodopa-induced dyskinesia (LID), wearing-off, freezing of gait (FOG), or PD dementia (PDD) between male and female PD patients. A mediation analysis was used to determine the relationship between biological sex, striatal dopamine deficiency, and longitudinal outcomes.

Results: Female PD patients exhibited less severely decreased DAT availability in all striatal subregions than male PD patients. The future development of wearing-off and FOG did not differ according to sex. LID developed more frequently in female PD patients than in male PD patients, while the risk of PDD conversion was higher in male PD patients than in female PD patients. In the mediation analyses, the direct effect of biological sex on the development of LID or PDD was major, while the mediating effect through the striatal DAT availability was minimal.

Conclusion: Differences in longitudinal outcomes according to biological sex may be ascribed to a non-dopaminergic basis. This study suggests that therapeutic strategies targeting the extra-nigrostriatal pathway should be considered in future trials.
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1. College of Medicine (의과대학) > Dept. of Neurology (신경과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
Yonsei Authors
Sohn, Young Ho(손영호) ORCID logo https://orcid.org/0000-0001-6533-2610
Lee, Phil Hyu(이필휴) ORCID logo https://orcid.org/0000-0001-9931-8462
Lee, Hye Sun(이혜선) ORCID logo https://orcid.org/0000-0001-6328-6948
Chung, Seok Jong(정석종) ORCID logo https://orcid.org/0000-0001-6086-3199
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