White matter disease and cognitive impairment in FMR1 premutation carriers
White matter disease and cognitive impairment in FMR1 premutation carriers
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DOI：
10.1212/wnl.0000000000001612
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发表时间：
2015-05-26
期刊：
影响因子：
9.9
通讯作者：
Grigsby, Jim
中科院分区：
文献类型：
--
作者：
Filley, Christopher M.;Brown, Mark S.;Grigsby, Jim
目的：本横断面观察性研究探讨了白质参与脆性X智力发育迟滞1 （FMR1）前兆突变个体认知障碍的作用。方法：8名无症状突变前携带者，5名脆性X震颤/共济失调综合征（FXTAS）患者，7名非携带者对照。无症状突变前携带者、FXTAS患者和非携带者对照组的平均年龄分别为60岁、71岁和67岁。采用磁共振波谱（MRS）和弥散张量成像（DTI）检测小脑中脚（MCP）和胼胝体膝、脾对执行功能和处理速度的影响。MRS测量为n -乙酰天冬氨酸/肌酸（NAA/Cr）和胆碱/肌酸，DTI采用分数各向异性（FA）。用行为控制障碍量表和对照口语单词联想测验（COWAT）评估执行功能，用符号数字模态测验评估处理速度。结果：在所有13名FMR1预突变携带者中，n -乙酰天冬氨酸/肌酸和胆碱/肌酸在MCP和COWAT评分中存在显著相关性，膝内FA与行为控制障碍量表、COWAT和符号数字模式测试中的表现存在显著相关性；脾脏FA与奶牛奶牛奶牛的生产性能也存在相关性。在所有被研究的地区，FXTAS患者的平均FA最低。结论：MRS和DTI检测的微结构白质疾病与FMR1预突变携带者的执行功能障碍和处理速度减慢有关。膝和MCP的神经影像学异常表明，额小脑网络内白质的破坏在与FMR1预突变相关的认知障碍中起重要作用。
Objective:This cross-sectional, observational study examined the role of white matter involvement in the cognitive impairment of individuals with the fragile X mental retardation 1 (FMR1) premutation.Methods:Eight asymptomatic premutation carriers, 5 participants with fragile X tremor/ataxia syndrome (FXTAS), and 7 noncarrier controls were studied. The mean age of the asymptomatic premutation carriers, participants with FXTAS, and noncarrier controls was 60, 71, and 67 years, respectively. Magnetic resonance spectroscopy (MRS) and diffusion tensor imaging (DTI) were used to examine the middle cerebellar peduncles (MCP) and the genu and splenium of the corpus callosum in relation to executive function and processing speed. MRS measures were N-acetyl aspartate/creatine (NAA/Cr) and choline/creatine, and fractional anisotropy (FA) was used for DTI. Executive function was assessed with the Behavioral Dyscontrol Scale and the Controlled Oral Word Association Test (COWAT), and processing speed with the Symbol Digit Modalities Test.Results:Among all 13 FMR1 premutation carriers, significant correlations were found between N-acetyl aspartate/creatine and choline/creatine in the MCP and COWAT scores, and between FA in the genu and performance on the Behavioral Dyscontrol Scale, COWAT, and Symbol Digit Modalities Test; a correlation was also found between FA in the splenium and COWAT performance. In all regions studied, participants with FXTAS had the lowest mean FA.Conclusion:Microstructural white matter disease as determined by MRS and DTI correlated with executive dysfunction and slowed processing speed in these FMR1 premutation carriers. Neuroimaging abnormalities in the genu and MCP suggest that disruption of white matter within frontocerebellar networks has an important role in the cognitive impairment associated with the FMR1 premutation.