Non-motor Symptoms in Parkinson's Disease Patients with Parkin Mutations: More Depression and Less Executive Dysfunction

The purpose of this study was to identify differences between genetically undefined (GU) early-onset Parkinson's disease (EOPD) patients and carriers of Parkin mutations on non-motor symptoms (NMSs). EOPD patients (N = 261) underwent targeted sequencing of Parkinson's disease (PD) related genes. Among them, 53 cases carried homozygous or compound heterozygous Parkin mutations (Parkin group) while 208 did not carry known causative PD mutations or risk factors of GBA or Parkin heterozygous mutations (GU group). NMSs were evaluated by face-to-face interviews, self-completed questionnaires and results on a neuropsychological battery. Linear regression and logistic regression models were applied to assess the predictors of NMSs. Parkin patients had younger ages of onset (AOO) (p < 0.001), longer disease durations (p < 0.001) and lower grades of Hoehn and Yarh (H&Y) (p = 0.007). Results on the neuropsychological battery showed a shorter time in Trail Making Test (TMT) (part B) in Parkin patients (p = 0.034) compared to GU patients. After adjusting for AOO, disease duration, H&Y, and levodopa equivalent daily dose (LEDD), there was a higher depression index on the Beck Depression Inventory (BDI) (p = 0.013) and better performance (p = 0.038) on executive function in the Parkin group compared to the GU group. No significant differences were found for autonomic functions, sleep-wake problems or other domains of cognitive function. Our study showed that the Parkin mutation status might be a good predictor of symptoms of depression without an impact on executive function. While these findings need to be confirmed in larger cohorts, they identify a need to screen for depression. Flow chart of genetic tests