Task matters - challenging the motor system allows distinguishing unaffected Parkin mutation carriers from mutation-free controls.

BACKGROUND: Heterozygous carriers of Parkin mutations are suggested to be at risk of developing Parkinson's disease, while biallelic variants are associated with typical autosomal recessive early-onset PD. Investigating unaffected heterozygous mutation carriers holds the potential of a deeper understanding of monogenic PD and has implications for PD in general, in particular regarding the prodromal phase. OBJECTIVES: To discriminate healthy Parkin mutation carriers from healthy non-mutation carriers using a multimodal approach. METHODS: Twenty-seven healthy heterozygous Parkin mutation carriers (13 female. age: 48 ± 13 years) and 24 healthy non-mutation carriers (14 female. age: 48 ± 15 years) from the CHRIS study (Cooperative Health Research in South Tyrol) were recalled based on their genetic profile and underwent a blinded assessment of motor and non-motor PD symptoms, transcranial sonography and sensor-based posturography and gait analyses under different conditions with increasing difficulty. For the latter, gradient-boosted trees were used to discriminate between carriers and non-carriers. The classification accuracy and the area under the curve of the receiver-operator characteristics curve were calculated. RESULTS: We observed no differences concerning motor or non-motor symptoms and substantia nigra hyperechogenicity. The best gradient-boosted trees-based model on posturography measurements (tandem feet, eyes closed, firm surface), however, showed a classification accuracy of up to 86%. The best-performing gradient-boosted trees-based model for gait analyses showed a balanced accuracy of up to 87% (dual-tasking). CONCLUSIONS: Sensor-based quantification of movements allows to discriminate unaffected heterozygous mutation carriers from mutation-free controls. Thereby, it is crucial to challenge the motor system with more difficult tasks to unmask subtle motor alterations.

Qualitative Characteristics of Depression in Parkinson's Patients and Controls.

BACKGROUND: Depression is common in Parkinson's disease (PD); in light of typical PD pathology it may differ phenomenologically from depression in the general population. OBJECTIVE: To assess depressive symptoms in PD patients and control groups and compare symptom profiles. METHODS: After postal screening of 10,000 citizens of Lübeck, 642 participants were examined and the Beck Depression Inventory (BDI) was sufficiently answered by 477 subjects. Based on motor examinations, we distinguished PD patients, Healthy Controls (HC, no motor impairment), and Disease Controls (DC, motor impairment other than PD). RESULTS: The sample comprised 331 men and 311 women, aged 65 ± 8 years. Out of the overall sample, 198 (41.5%) had a BDI score ≥9. BDI results above 9 points occurred in 34.5% of HC, 50.3% of DC, and 42.4% of PD patients. Compared to the control groups (HC, DC) the PD patients endorsed more "dissatisfaction" and "loss of appetite" but less "feelings of guilt," "self-hate," and "loss of libido." CONCLUSION: Depressive symptoms are more frequent in PD patients compared to HC but not DC. Interestingly, the distribution of individual symptoms of the BDI differs between groups with an emphasis on loss of pleasure/enjoyment in the PD group, a symptom typically considered to be dopaminergically transmitted.