Moderating effects of uric acid and sex on non-motor symptoms in asymmetric Parkinson's disease

Abstract Background. Non-motor symptoms (NMS) are an important early feature of Parkinson’s disease (PD), encompassing a variety of cognitive and neuropsychiatric symptoms, that seem to manifest differently depending on the asymmetry of motor symptoms. Different factors, such as uric acid (UA) and sex, also seem to influence NMS expression in PD. However, the interactions between UA, sex, and motor symptom asymmetry remains to be better understood in PD. Methods. Participants taking part in the Parkinson’s Progression Marker Initiative were studied based on the side of motor-symptom asymmetry and sex. Three-way interaction modeling was used to examine the moderating effects of sex and UA in time on NMS. Results. Significant three-way interactions were highlighted at one year follow-up between motor symptom asymmetry, UA and sex, for immediate memory, delayed memory, processing speed and sleepiness for female patients only. Also, female patients exhibiting predominantly right-sided motor symptoms demonstrated the most preserved NMS in the presence of lower serum UA levels. Conclusion. These findings suggest that in the earliest stages of the disease, serum UA and sex moderate NMS expression differently depending on motor asymmetry. This holds important clinical implications for symptom management in early-stage PD patients.