Filley Christopher M, Brown Mark S, Onderko Karen, Ray Megan, Bennett Rachael E, Berry-Kravis Elizabeth, Grigsby Jim
From the Departments of Neurology (C.M.F.), Psychiatry (C.M.F.), Radiology (M.S.B.), and Medicine (R.E.B., J.G.), University of Colorado School of Medicine; Department of Psychology (K.O., M.R., J.G.), University of Colorado Denver; Denver Veterans Affairs Medical Center (C.M.F.), CO; and Departments of Neurological Sciences (E.B.-K.), Pediatrics (E.B.-K.), and Biochemistry (E.B.-K.), Rush University Medical Center, Chicago, IL.
Neurology. 2015 May 26;84(21):2146-52. doi: 10.1212/WNL.0000000000001612. Epub 2015 Apr 29.
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.
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.
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.
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.
本横断面观察性研究探讨了白质受累在脆性X智力低下1（FMR1）前突变个体认知障碍中的作用。
对8名无症状前突变携带者、5名脆性X震颤/共济失调综合征（FXTAS）患者和7名非携带者对照进行了研究。无症状前突变携带者、FXTAS患者和非携带者对照的平均年龄分别为60岁、71岁和67岁。采用磁共振波谱（MRS）和扩散张量成像（DTI）检查小脑中脚（MCP）以及胼胝体膝部和压部与执行功能和处理速度的关系。MRS测量指标为N-乙酰天门冬氨酸/肌酸（NAA/Cr）和胆碱/肌酸，DTI采用分数各向异性（FA）。执行功能通过行为失控量表和受控口语联想测验（COWAT）进行评估，处理速度通过符号数字模式测验进行评估。
在所有13名FMR1前突变携带者中，发现MCP中N-乙酰天门冬氨酸/肌酸和胆碱/肌酸与COWAT评分之间存在显著相关性，胼胝体膝部FA与行为失控量表、COWAT和符号数字模式测验的表现之间存在显著相关性；胼胝体压部FA与COWAT表现之间也存在相关性。在所有研究区域中，FXTAS患者的平均FA最低。
MRS和DTI确定的微观结构白质病变与这些FMR1前突变携带者的执行功能障碍和处理速度减慢相关。胼胝体膝部和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前突变相关的认知障碍中起重要作用。
