Neurobiology of disease · 2025
Influence of WWOX/MAF genes on cognitive performance in patients with Parkinson's disease.
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Yuan Yun-Ting, Hong Wei-Pin, Tan Chun-Hsiang, Yu Rwei-Ling
Аннотация
BACKGROUND: 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.
OBJECTIVES: 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.
PARTICIPANTS: A total of 402 participants were included in this study, comprising 150 individuals with PD and 252 healthy controls (HC).
MEASUREMENTS: 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.
RESULTS: 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).
CONCLUSIONS: 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.
OBJECTIVES: 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.
PARTICIPANTS: A total of 402 participants were included in this study, comprising 150 individuals with PD and 252 healthy controls (HC).
MEASUREMENTS: 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.
RESULTS: 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).
CONCLUSIONS: 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.