Influence of WWOX/MAF genes on cognitive performance in patients with Parkinson's disease

Beyond its hallmark motor symptoms, Parkinson's disease (PD) encompasses a range of non-motor disturbances, particularly cognitive impairment, which significantly affects patients' quality of life. Cognitive impairment is a shared manifest in both PD and Alzheimer's disease (AD), two prevalent neurodegenerative disorders. Existing literature has identified the WWOX/MAF genes as potential risk factors for AD, but their role in cognitive functions among PD remains unclear.

This study examines the influence of AD-associated risk genes, specifically WWOX/MAF, on cognitive function in PD, aiming to bridge the neuropathological gap between AD and PD.

A total of 402 participants were included in this study, comprising 150 individuals with PD and 252 healthy controls (HC).

Participants underwent comprehensive neuropsychological assessment and genotyping. A moderation regression model was employed to assess the impact of WWOX/MAF single nucleotide polymorphisms on cognitive function and the potential modulatory effect of PD.

The WWOX gene was found to influence verbal fluency performance across the entire cohort. Additionally, PD significantly moderated the effect of genetic variants on attention (p = 0.000040), non-verbal memory (p = 0.000007), and visuospatial function (p = 0.000303), suggesting a distinct impact within this group. Further analysis indicated that cognitive status moderated the effect of genetic variants on verbal memory across the entire cohort (p < 0.001). Among individuals with PD, genetic variants also influenced verbal fluency (p = 0.000113) and verbal memory (p = 0.000440 and p = 0.000032).

These findings underscore the critical role of WWOX/MAF genes in cognitive impairments associated with PD, enhancing our understanding of their connection to AD and providing deeper insights into neurodegenerative disease progression.