Publication date: Jun 25, 2025
Resilience factors are crucial in the progression of neurodegenerative diseases. However, it remains unclear whether a genetic predisposition to cognitive reserve influences clinical heterogeneity in the prognosis of Parkinson’s disease (PD). The aim is to evaluate the utility of polygenic scores (PGSs) for cognitive reserve proxies, including intelligence (INT), educational attainment (EA), and occupational attainment (OA), in predicting the clinical progression of PD. Genetic and clinical data for progression of PD (progression to Hoehn and Yahr stage ≥3, progression to a Montreal Cognitive Assessment score ≤24, and occurrence of psychosis) were obtained from the Accelerating Medicine Partnership Parkinson’s Disease database. We conducted multivariate Cox regression analysis, adjusting for relevant covariates, including years of education, variants in APOE, GBA1, LRRK2, and other cognitive reserve-related PGSs. All cognitive reserve-related PGSs significantly reduced the risk of cognitive decline, and EA-PGS (hazard ratio [HR], 0. 550; 95% confidence interval [CI], 0. 447-0. 676; P
| Concepts | Keywords |
|---|---|
| Genetic | cognitive reserve |
| Neurodegenerative | motor progression |
| Parkinson | Parkinson’s disease |
| Stage | polygenic score |
| psychosis |
Semantics
| Type | Source | Name |
|---|---|---|
| disease | MESH | Parkinson’s Disease |
| disease | MESH | neurodegenerative diseases |
| pathway | REACTOME | Neurodegenerative Diseases |
| disease | MESH | educational attainment |
| disease | MESH | clinical progression |
| disease | MESH | psychosis |
| disease | MESH | cognitive decline |