Center for Mind and Brain, University of California, Davis, Davis, CA; Department of Neurology, University of California, Davis, Sacramento, CA.
Ann Neurol. 2013 Aug;74(2):275-83. doi: 10.1002/ana.23933.
To investigate the nature of cognitive impairments and underlying brain mechanisms in older female fragile X premutation carriers with and without fragile X-associated tremor/ataxia syndrome (FXTAS).
Extensive neuropsychological testing and cognitive event-related brain potentials (ERPs; particularly, the auditory P300) were examined in 84 female participants: 33 fragile X premutation carriers with FXTAS (mean age = 62.8 years), 25 premutation carriers without FXTAS (mean age = 55.4 years), and 26 normal healthy controls (mean age = 59.3 years).
Both premutation groups exhibited executive dysfunction on the Behavioral Dyscontrol Scale, with subtle impairments in inhibition and performance monitoring in female carriers without FXTAS, and more substantial deficits in FXTAS women. However, the female carrier group without FXTAS showed more pronounced deficiencies in working memory. Abnormal ERPs were recorded over the frontal lobes, where FXTAS patients showed both P300 amplitude reduction and latency prolongation, whereas only decreased frontal P300 amplitudes were found in carriers without FXTAS. These frontal P300 measures correlated with executive function and information processing speed.
The neuropsychological testing and ERP results of the present study provide support for the hypothesis that executive dysfunction is the primary cognitive impairment among older female premutation carriers both with and without FXTAS, although these deficits are relatively mild compared to those in FXTAS males. These findings are consistent with a synergistic effect of the premutation and aging on cognitive impairment among older female fragile X premutation carriers, even in those without FXTAS symptoms.
探究老年女性脆性 X 前突变携带者（伴或不伴脆性 X 相关震颤/共济失调综合征，FXTAS）认知障碍的性质及其潜在的大脑机制。
对 84 名女性参与者（33 名 FXTAS 脆性 X 前突变携带者[平均年龄=62.8 岁]、25 名无 FXTAS 的前突变携带者[平均年龄=55.4 岁]和 26 名正常健康对照者[平均年龄=59.3 岁]）进行了广泛的神经心理学测试和认知事件相关脑电位（ERPs；特别是听觉 P300）检查。
两组前突变携带者在行为控制障碍量表上均表现出执行功能障碍，无 FXTAS 的女性携带者表现出抑制和表现监测方面的细微障碍，而 FXTAS 女性的障碍更为严重。然而，无 FXTAS 的女性携带者在工作记忆方面表现出更为明显的缺陷。在前额叶记录到异常的 ERPs，其中 FXTAS 患者表现出 P300 振幅减小和潜伏期延长，而无 FXTAS 的携带者仅表现出额叶 P300 振幅降低。这些额叶 P300 指标与执行功能和信息处理速度相关。
本研究的神经心理学测试和 ERP 结果支持这样一种假说，即执行功能障碍是老年女性脆性 X 前突变携带者伴或不伴 FXTAS 的主要认知障碍，尽管与 FXTAS 男性相比，这些缺陷相对较轻。这些发现与前突变和衰老对老年女性脆性 X 前突变携带者认知障碍的协同作用一致，即使在无 FXTAS 症状的携带者中也是如此。
