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

IF 5.6 2区医学 Q1 NEUROSCIENCES Neurobiology of Disease Pub Date : 2025-03-24 DOI:10.1016/j.nbd.2025.106887

Yun-Ting Yuan , Wei-Pin Hong , Chun-Hsiang Tan , Rwei-Ling Yu

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Abstract

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.

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WWOX/MAF基因对帕金森病患者认知能力的影响

除了其标志性的运动症状外，帕金森病（PD）还包括一系列非运动障碍，特别是认知障碍，这严重影响患者的生活质量。认知障碍是帕金森病和阿尔茨海默病（AD）这两种常见的神经退行性疾病的共同表现。现有文献已经确定WWOX/MAF基因是AD的潜在危险因素，但其在PD认知功能中的作用尚不清楚。目的探讨AD相关风险基因，特别是WWOX/MAF对PD认知功能的影响，旨在弥合AD与PD之间的神经病理差距。参与者本研究共纳入402名参与者，其中包括150名PD患者和252名健康对照（HC）。测量：参与者接受了全面的神经心理学评估和基因分型。采用适度回归模型评估WWOX/MAF单核苷酸多态性对认知功能的影响及PD的潜在调节作用。结果发现WWOX基因影响整个队列的语言流畅性表现。此外，PD显著调节了遗传变异对注意力（p = 0.000040）、非言语记忆（p = 0.000007）和视觉空间功能（p = 0.000303）的影响，表明在这一组中有明显的影响。进一步的分析表明，在整个队列中，认知状态调节了遗传变异对言语记忆的影响(p <；0.001)。在PD患者中，基因变异也会影响言语流畅性（p = 0.000113）和言语记忆（p = 0.000440和p = 0.000032）。结论这些发现强调了WWOX/MAF基因在PD相关认知障碍中的关键作用，增强了我们对其与AD之间联系的理解，并为神经退行性疾病的进展提供了更深入的见解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Neurobiology of Disease 医学-神经科学

CiteScore

11.20

自引率

3.30%

发文量

270

审稿时长

76 days

期刊介绍： Neurobiology of Disease is a major international journal at the interface between basic and clinical neuroscience. The journal provides a forum for the publication of top quality research papers on: molecular and cellular definitions of disease mechanisms, the neural systems and underpinning behavioral disorders, the genetics of inherited neurological and psychiatric diseases, nervous system aging, and findings relevant to the development of new therapies.