Abstract
Background: Genetics influence cognitive progression in Parkinson's disease, possibly through mechanisms related to Lewy and Alzheimer's disease pathology. Lysosomal polygenic burden has recently been linked to more severe Lewy pathology post mortem. Objectives: To assess the influence of lysosomal polygenic burden on cognitive progression in Parkinson's disease patients with low Alzheimer's disease risk. Methods: Using Cox regression we assessed association between lysosomal polygenic scores and time to Montreal Cognitive Assessment score ≤ 21 in the Parkinson's Progression Markers Initiative cohort (n = 374), with replication in data from the Parkinson's Disease Biomarker Program (n = 777). Patients were stratified by Alzheimer's disease polygenic risk. Results: The lysosomal polygenic score was associated with faster progression of cognitive decline in patients with low Alzheimer's disease risk in both datasets (P = 0.0032 and P = 0.0054, respectively). Conclusion: Our study supports complex interplay between genetics and neuropathology in Parkinson's disease-related cognitive impairment, emphasizing the role of lysosomal polygenic burden.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 596-601 |
| Number of pages | 6 |
| Journal | Movement Disorders |
| Volume | 39 |
| Issue number | 3 |
| DOIs | |
| State | Published - Mar 2024 |
Keywords
- cognition
- lysosomal pathway
- neuropathology
- Parkinson's disease
- polygenic risk score
ASJC Scopus subject areas
- Neurology
- Clinical Neurology