Progression to Parkinson's dementia is not modulated by genetic risk variants for Alzheimer's or Parkinson's disease
- PMID: 40739885
- DOI: 10.1177/1877718X251356512
Progression to Parkinson's dementia is not modulated by genetic risk variants for Alzheimer's or Parkinson's disease
Abstract
Parkinson's disease (PD) is marked by motor symptoms and often accompanied by mild cognitive impairment (PD-MCI), affecting up to 50% of patients and preceding PD dementia (PDD). Genetic factors may influence this progression, yet the underlying mechanisms remain unclear. This study investigated genetic factors influencing the progression from PD-MCI to PDD using polygenic risk scores (PRS). A genome-wide association study (GWAS) was conducted using data from the LANDSCAPE study. Multivariable Cox regression, Kaplan-Meier survival analysis, and concordance statistics assessed the relationship between PRS and PDD progression. No significant association was found between PD PRS and the risk of developing PDD.
Keywords: Alzheimer's disease; Parkinson's disease; genome-wide association study; mild cognitive impairment; single nucleotide polymorphism.
Plain language summary
This study aimed to understand whether specific genetic factors can help predict if people with mild cognitive impairment (MCI) in Parkinson's disease (PD) will go on to develop dementia, a condition known as Parkinson's disease dementia (PDD). Parkinson's disease is a progressive disorder that affects movement and can also lead to memory and thinking problems in many people. While some research has shown that certain genes are linked to Parkinson's disease itself, it's unclear if these same genetic factors affect the likelihood of developing dementia. To explore this, we used polygenic risk scores (PRS), which combine information from various genes to estimate a person's genetic risk for a disease. We analyzed data from people with Parkinson's disease and mild cognitive impairment, examining whether their genetic profiles could predict dementia progression over time. Statistical models were used to compare the genetic risk scores with actual dementia outcomes. Our findings showed no strong link between the genetic scores and the progression to dementia, suggesting that current genetic markers may not effectively predict this outcome in Parkinson's disease. These results highlight the need for more complex approaches that consider additional factors beyond genetics, including lifestyle or environmental influences. This research underscores that the development of dementia in Parkinson's disease may involve many factors and that genetic risk scores, as they are currently understood, may not be enough to predict who will develop dementia.
