脑白质疏松症患者执行功能障碍的弥散张量成像研究

Association of diffusion tensor imaging abnormalities with executive dysfunction in patients with leukoaraiosis

目的拟采用弥散张量成像（DTI）技术探讨脑白质疏松症（LA）患者脑白质超微结构的改变与认知功能，尤其是执行功能障碍的关系。方法研究对象来源于自2010年7月至2011年6月就诊于首都医科大学附属北京朝阳医院神经内科的44例LA患者（脑白质疏松组），和36名年龄、性别、受教育程度相匹配的健康对照组，进行神经心理测评包括简易智力状态量表（MMSE）、蒙特利尔认知评估和4项执行功能测验（Stroop色词干扰测验、连线测验、数字符号测验、言语流畅性测验），并行DTI扫描，测量LA患者的脑白质损伤区（WML）、LA患者的形似正常脑白质区（NAWM）、对照组的正常脑白质区在半卵圆中心、侧脑室前部、侧脑室后部3个感兴趣区的各向异向性（FA）和平均扩散率（MD），并对LA患者的DTI参数与认知功能进行相关性分析。结果（1）与健康对照组相比，脑白质疏松组患者存在显著的认知功能损害，表现为MMSE[（24．4±3．2）分比（28．3±1．2）分]、MoCA[（21．2±3．4）分比（25．7±1．7）分]显著低于对照组（P〈0．05）。在执行功能测验中，脑白质疏松组患者存在更为显著的执行功能障碍，表现为在StroopB[（69．2±13．5）s比（43．3±5．0）S]、StroopC[（141．2±42．6）s比（64．8±10．0）Sf、Stroop（C—B）[（72．0±41．9）S比（21．5±9．4）SI、TMT-A[（73．d±15．d）s比（31．1±7．1）S]、TMT．B[（126．2±17．5）S比（81．4±5．7）S]、数字符号测验[（25．2±5．4）分比（36．7±5．1）分]上存在组别上的差异（P〈0．05）。（2）DTI研究发现脑白质疏松组患者在半卵圆中心、侧脑室前部、侧脑室后部的WML区的FA值显著低于NAWM和健康对照组（P〈0．05），MD值显著高于NAWM和健康对照组（P〈0．05）；脑白质疏松组患者在半卵圆中心、侧脑室后部NAWM区的FA值显著低于健康对照组（P〈0．05），而在侧脑室前部NAWM区的MD值显著高于健康对照组（P〈0．05）。（3）脑白质疏松组患者在侧脑室前部NAWM区的FA值与执行功能的Z评分呈负相关（r=-0．311，P=0．04）。结论LA患者存在显著的认知功能障碍，尤其是执行功能障碍；DTI技术能够准确显示LA患者特征性脑白质微结构的改变。

Objective To explore abnormal microstructural changes of white matter using diffusion tensor imaging （DTI） in patients with leukoaraiosis （LA）, and to determine the association of such abnormalities of DTI parameters with cognitive function, especially executive function. Methods A total of 44 patients with LA and 36 healthy controls were recruited from the department of Neurology, Beijing Chaoyang Hospital, Capital Medical University between July 2010 and June 2011. The two groups were matched for age, sex, education, and vascular risk factors. All the subjects underwent the scans of conventional magnetic resonance imaging （MRI）, DTI and neuropsychological assessment. The values of mean diffusivity （MD） and fractional anisotropy （FA） were measured within white matter lesions （WML） and normal appearing white matter （NAWM）. Three regions of interest （ROIs） were located in tha white matter of centrum semiovale, anterior periventricular white matter and posterior periventricular white matter. The relationships between the cognitive function and the abnormalities of DTI parameters were analyzed. Results （1） Patients with LA performed significantly worse cognitive function, especially in the fields of executive function. The results of our study showed that patients with LA were associated with comprehensive cognitive function deficits, including mini mental state examination （MMSE） （24.4 ± 3.2 vs 28.3 ±1.2）, montreal cognitive assessment （MoCA） （21.2±3.4 vs 25.7± 1.7）, Stroop B （69.2± 13.5 vs 43.3 ± 5.0）, StroopC （141.2 ±42.6 vs64.8 ±10.0）, Stroop （C-B） （72.0±41.9 vs 21.5 ±9.4）, trail making test （TMT） -A （73.4 ±15.4 vs 31.1 ±7.1 ）, TMT-B （ 126.2± 17.5 vs 81.4 ± 5.7 ）, digit symbol test （ 25.2± 5.4 vs 36.7± 5.1 ） （ all P 〈 0.05 ）. （2） The values of FA were lower, and MD were higher in WML than NAWM and controls in all the three ROIs （ P 〈 0.05 ）. The values of FA in NAWM located in centrum semiovale and posterior periventricular white matter were lower than controls （ P 〈 0.05 ）. The values of MD in NAWM located in anterior periventricular white matter were higher than controls （ P 〈 0. 05 ）. （3） The values of FA of NAWM located in anterior periventricular correlated inversely with the Z scores of executive function （ r = - 0.311, P = 0. 04 ）. Conclusions Patients with LA are related with significant cognitive impairment, especially in the domains of executive dysfunction. Mierostruetural integrity of both white matter lesions and NAWM is associated with executive function. The underlying executive dysfunction in LA may attribute to the damage of the prefrontal-subeortical circle.