Objective: To discriminate healthy Parkin mutation carriers from healthy non-mutation carriers using sensor-based motion analysis.

Background: Identifying endophenotypes for PD is crucial for testing potential neuroprotective therapies before progressive neurodegeneration occurs. Here, we used the presence of heterozygous Parkin mutations as a genetic risk factor for PD to investigate whether subtle motor alterations are present and whether they can be used to identify an increased susceptibility for PD.

Method: Twenty-five healthy heterozygous Parkin mutation carriers (14 female, age:  49 +/- 13 years) and 25 healthy non-mutation carriers (10 female, age: 48 +/- 15 years) from the CHRIS study (Cooperative Health Research in South Tyrol) were clinically investigated and examined using the Mobility Lab (APDM Wearable Technologies). We performed posturography assessments with (i) feet open or apart or tandem feet, (ii) eyes open or closed and (iii) on firm or foam surface. Participants were also asked to walk for two minutes at (i) comfortable and (ii) fast walking speed and while (iii) performing a dual mental task and (iv) balancing a full glass. Gradient-boosted trees (GBT) were used to discriminate between carriers and non-carriers. The classification accuracy (Acc) and the area under the curve of the receiver-operator characteristics curve (ROC-AUC) were calculated.

Results: Using the MDS-UPDRS III protocol, the clinical examination revealed no differences between groups. The best GBT-based model on posturography measurements (tandem feet, eyes closed, firm surface), however, showed a classification Acc of up to 86 %. The best performing GBT-based model for gait analyses showed classification Acc of up to 87% (dual-tasking (mental maths)).

Conclusion: We demonstrated that subtle motor alterations, not detectable with the MDS-UPDRS III, are present in healthy individuals carrying a genetic risk factor for PD. Postural alterations and dual tasks are potentially useful to discriminate mutation carriers from non-mutation carriers. Our data-driven approach was thus able to identify a genetically defined susceptibility state that is associated with subtle motor signs.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/identifying-healthy-parkin-mutation-carriers-based-on-sensor-based-posturography-and-gait-analysis/