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Dynamic Digital Biomarkers of Motor and Cognitive Function in Parkinson's Disease
Published on: July 24, 2019
Self-report data as a tool for subtype identification in genetically-defined Parkinson's Disease.
Ashley R Winslow1,2, Craig L Hyde3, Jemma B Wilk4
1Human Genetics and Computational Biomedicine, Pfizer Worldwide Research and Development, 1 Portland Street, Cambridge, MA, 02139, USA. awinslow@upenn.edu.
Scientific Reports
|August 30, 2018
Summary
Genetic data and patient-reported symptoms reveal distinct Parkinson disease (PD) progression in GBA and LRRK2 carriers. LRRK2 G2019S carriers reported milder daily symptoms, suggesting unique disease pathways.
Area of Science:
- Genetics
- Neurology
- Personalized Medicine
Background:
- Parkinson disease (PD) is a complex neurodegenerative disorder with diverse genetic underpinnings.
- Idiopathic PD (iPD) represents cases without known specific genetic mutations.
- Understanding genetic subtypes is crucial for personalized treatment and research.
Purpose of the Study:
- To evaluate the utility of web-based, patient-reported symptom data in genetically defined PD populations.
- To compare disease natural history and symptomology between GBA mutation carriers, LRRK2 G2019S carriers, and idiopathic PD.
- To explore potential differences in pathophysiology and disease progression based on genetic status.
Main Methods:
- Utilized a large dataset of over 10,000 individuals with physician-verified PD diagnoses from 23andMe.
- Employed targeted recruitment for genetic data and patient-reported symptoms via web-based questionnaires.
- Analyzed symptom data in relation to GBA and LRRK2 G2019S carrier status, comparing them to idiopathic PD.
Main Results:
- GBA mutation carriers showed a significantly lower average age-at-diagnosis compared to iPD, but no significant symptom differences.
- LRRK2 G2019S carriers reported milder daily symptoms, including less lightheadedness upon standing.
- LRRK2 G2019S carriers also showed differences in initial symptoms (walking changes) and daily functioning, observed at a false discovery rate < 0.1.
Conclusions:
- Self-reported symptom data combined with genetic information can effectively analyze large PD populations and specific genetic subgroups.
- Subclinical symptom differences in LRRK2 G2019S carriers suggest distinct underlying pathophysiology or disease progression.
- Web-based questionnaires are a valuable tool for rapid assessment of disease natural history in genetically defined PD cohorts.
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