背景:患有脆性X相关震颤/共济失调综合征(FXTAS)的男性通常会出现执行功能障碍,以抑制为特征,额叶运动控制失调,工作记忆和注意力的变化。尽管横断面研究表明,早期的执行功能变化可能先于FXTAS,缺乏纵向研究使得很难解决这一假设。
目的:确定预突变携带者(PC)在日常生活中经历的执行功能恶化是否先于并预测FXTAS。
方法:这项研究包括66个FMR1PC,范围为40至78年(平均值,59.5)和31名年龄在40至75岁之间的匹配良好的健康对照(HC)(平均值,57.7)在基线。84名参与者在1至9年的时间内返回2至5次随访(平均,4.6);28个PC开发了FXTAS。参与者及其配偶/伴侣在每次访问中完成了执行功能-成人版(BRIEF-A)的行为评级清单。
结果:纵向混合模型回归分析显示,与元认知指数上的HC相比,PC随年龄的下降更大(MI;自我启动,工作记忆,组织,任务监控)。转换为FXTAS与MI和行为调节指数(BRI;抑制,灵活性,情绪调制)。对于配偶/伴侣报告,FXTAS转化与MI恶化相关。最后,基线时自我报告执行功能问题的增加显着预测了FXTAS的后期发展。
结论:男性PC经历的执行功能变化代表了后期运动障碍的前驱症状。©2023作者。由WileyPeriodicalsLLC代表国际帕金森症和运动障碍协会出版的运动障碍。
BACKGROUND: Men with fragile X-associated tremor/ataxia syndrome (FXTAS) often develop executive dysfunction, characterized by disinhibition, frontal dyscontrol of movement, and working memory and attention changes. Although cross-sectional studies have suggested that earlier executive function changes may precede FXTAS, the lack of longitudinal studies has made it difficult to address this hypothesis.
OBJECTIVE: To determine whether executive function deterioration experienced by premutation carriers (PC) in daily life precedes and predicts FXTAS.
METHODS: This study included 66 FMR1 PC ranging from 40 to 78 years (mean, 59.5) and 31 well-matched healthy controls (HC) ages 40 to 75 (mean, 57.7) at baseline. Eighty-four participants returned for 2 to 5 follow up visits over a duration of 1 to 9 years (mean, 4.6); 28 of the PC developed FXTAS. The Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) was completed by participants and their spouses/partners at each visit.
RESULTS: Longitudinal mixed model regression analyses showed a greater decline with age in PC compared to HC on the Metacognition Index (MI; self-initiation, working memory, organization, task monitoring). Conversion to FXTAS was associated with worsening MI and Behavioral Regulation Index (BRI; inhibition, flexibility, emotion modulation). For spouse/partner report, FXTAS conversion was associated with worsening MI. Finally, increased self-report executive function problems at baseline significantly predicted later development of FXTAS.
CONCLUSIONS: Executive function changes experienced by male PC represent a prodrome of the later movement disorder. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.