Gender and non motor fluctuations in Parkinson's disease: A prospective study

Introduction: In Parkinson's disease (PD), non motor symptoms can fluctuate either along or irrespective to motor on/off phenomena. Prospective studies suggest that higher motor scores and levodopa dosage, younger age at onset and female gender represent risk factors for motor fluctuations' development. Yet, the predictors of development of non motor fluctuations (NMF) are less clear.In this prospective study, we aimed to assess the relationship between NMF and gender along with other potential risk factors. Methods: Forty-seven (16 women/31 men) de novo, drug-naïve PD patients have been followed for 4 years since diagnosis. Motor and non motor fluctuations were evaluated with the 19-item Wearing off Questionnaire (WOQ-19). The association between gender and NMF was explored with multivariable regression models adjusted for age at onset, motor and non motor symptoms at diagnosis and levodopa intake at follow up. Results: Female gender was more likely associated with a diagnosis of NMF (adjusted odds ratio, AOR = 5.33,95%CI = 1.21-23.4, p = 0.027), but not with a diagnosis of generic wearing off at follow up (OR = 3.66, 95%CI = 0.8-16.8, p = 0.097). Women had greater likelihood of developing higher WOQ-19 Non motor scores (AOR = 4.58, 95%CI = 1.23-17.03, p = 0.023), but not higher WOQ-19 Total scores (AOR = 2.88, 95%CI = 0.86-9.71, p = 0.087) compared to men. Notwithstanding, no gender differences were detected in medication intake. Conclusions: We showed that female gender represents a major risk factor for the development of NMF. There were no gender differences in medication intake, thus NMF in women remain mostly underestimated and not properly treated. From a practical standpoint, clinicians should take into account the role of gender in the management of NMF in PD.