Associations of motor and neuropsychiatric symptoms with comorbidities in prodromal Parkinson's disease.

Objective: To investigate the associations between comorbidities and multimorbidity patterns with motor and neuropsychiatric symptoms in patients with Parkinson's disease (PD) in prodromal PD.

Methods: Multimorbidity is defined as the coexistence of two or more long-term conditions (LTCs) (also known as multiple comorbidities). A total of 921 participants without PD were included in the Parkinson's Progression Markers Initiative (PPMI) database and were categorized according to the LTC count. Participants were evaluated on motor and psychiatric symptoms. Pearson correlation to examine relationship of comorbidities and target symptoms. The baseline population was analyzed using Multiple linear regression model, while mixed effects model was utilized for longitudinal analysis. Fuzzy C-means clustering analysis was conducted to identify comorbidity patterns, followed by multiple linear regression for further analysis.

Results: At baseline, a higher LTC count was significantly correlated with more severe motor (MDS-UPDRS I, II, ADL, all < 0.05) and neuropsychiatric symptoms (QUIP, < 0.001). Three multimorbidity patterns were identified. Among them, the cardiometabolic multimorbidity pattern (CAR) had the most significant correlation with the aforementioned symptoms. Our longitudinal analysis indicated that an increase in the LTC count was associated with the exacerbation of motor and neuropsychiatric symptoms.

Conclusion: Comorbidities were cross-sectionally and longitudinally associated with the motor and neuropsychiatric symptoms of patients with prodromal PD. Among the three multimorbidity patterns, CAR posed the highest threat to the risk of more severe motor and neuropsychiatric symptoms.