Sex differences in LRRK2 G2019S and idiopathic Parkinson's Disease.

Objective: To evaluate sex differences and the relative effect of G2019S mutations in Parkinson's disease (PD).

Methods: 530 PD carriers and 759 noncarrier PD (idiopathic, IPD) evaluated as part of the Fox Foundation (MJFF) Consortium were included. All participants completed a study visit including information on clinical features, treatment, examination, and motor and nonmotor questionnaires. Clinical features were compared between men and women separately for IPD and PD; and features were compared between IPD and PD separately for men and women.

Results: : men had higher levodopa equivalency dose (LED), worse activities of daily living and motoric severity but lower complications of therapy (UPDRS-IV). IPD women had higher olfaction and thermoregulatory scores and were more likely to report family history of PD. Among : Male predominance was not observed among G2019S cases. Women had worse UPDRS-IV but better olfaction. : men and women had better olfaction than IPD counterparts. men demonstrated lower motor and higher cognitive, RBD and thermoregulation scores than IPD men and women had greater UDPRS-IV and rates of dyskinesia.

Interpretation: There were clinical differences between sexes with a more severe phenotype in IPD men and more complications of therapy in women. The more severe male phenotype was moderated by , with men and women showing less diversity of phenotype. Our study supports that both genetics and sex drive phenotype, and thus trials in and IPD should consider gender stratification in design or analysis.