轻度认知障碍患者认知储备、神经血管耦合及认知功能的相关性研究

Correlation of cognitive reserve,neurovascular coupling and cognitive function in patients with mild cognitive impairment

目的采用动脉自旋标记(arterial spin labeling,ASL)、静息态功能磁共振成像(resting-state functional MRI,rs-fMRI)方法,探究认知储备(cognitive reserve,CR)在轻度认知障碍(mlid cognitive impairment,MCI)患者中影响认知功能的神经血管耦合机制。材料与方法本研究前瞻性收集40例MCI患者和26例性别、年龄相匹配的健康对照(healthy controls,HC),所有受试者均在3.0 T MRI机器采集ASL、rs-fMRI图像,所有受试者接受标准化神经心理学评估,包括蒙特利尔认知评估(Montreal Cognitive Assessment,MoCA)、简易精神状态检查(Mini-Mental State Examination,MMSE)、日常生活能力量表(Activity of Daily Living Scale,ADL)、听觉言语学习测验(Auditory Verbal Learning Test,AVLT)(中文版)、言语流畅性测验(Verbal Fluency Test,VFT)。所有受试者接受CR评估,根据两组受试者的教育程度、业余活动时间和工作经历生成认知储备指数问卷(Cognitive Reserve Index questionnaire,CRIq)评分。基于体素水平获取低频振幅(amplitude of low frequency fluctuations,ALFF)、比率低频振幅(fractionalALFF,fALFF)及脑血流量(cerebral blood flow,CBF),计算CBF/ALFF及CBF/fALFF比值,以评估神经血管耦合,并选择CBF/ALFF和CBF/fALFF存在显著组间差异的脑区作为ROI,进一步提取ROI平均值,与各认知功能及认知储备量表间进行相关性分析,以阐明CR、神经血管耦合和认知表现之间的关系。结果MCI组CRIq得分明显低于HC组(89.23±11.03 vs.98.70±12.75);在MCI及HC组中,CRIq得分与MoCA和AVLT得分均呈正相关(r=0.447,P=0.004;r=0.344,P=0.030;r=0.245,P=0.050;r=0.900,P<0.001);与HC相比,MCI患者双侧颞中回CBF/ALFF比值显著升高(双尾检验P<0.005,alphsim校正,团块大小>39),双侧眶部额下回、额中回CBF/ALFF比值显著降低(双尾检验P<0.005,alphsim校正,团块大小>93);双侧颞下回CBF/fALFF比值升高(双尾检验P<0.005,alphsim校正,团块大小>53)。此外,MCI组中,左侧眶部额下回CBF/ALFF比值与CRIq得分及MoCA、AVLT得分均呈负相关(r=-0.417,P=0.007;r=-0.336,P=0.034;r=-0.378,P=0.016)。结论CR较高的人群表现出更好的认知功能水平,且CR越高的MCI患者左侧眶部额下回CBF/ALFF比值越低,即出现了神经血管解耦合现象,表现出更严重的脑病理,但其尚能保持良好的认知功能,提示大脑的神经血管耦合和解耦合可能是CR在MCI患者中影响认知功能的一种潜在的神经机制。

Objective:To investigate the neural vascular coupling mechanisms of cognitive reserve(CR)influencing cognitive function in patients with mild cognitive impairment(MCI)using arterial spin labeling(ASL)and resting-state functional MRI(rs-fMRI)methods.Materials and Methods:This study prospectively recruited 40 MCI patients and 26 age-and gender-matched healthy controls(HC).All participants underwent ASL and rs-fMRI imaging on a 3.0 T MRI scanner and standardized neuropsychological assessments,including the Montreal Cognitive Assessment(MoCA),Mini-Mental State Examination(MMSE),Activity of Daily Living Scale(ADL),Auditory Verbal Learning Test(AVLT),and Verbal Fluency Test(VFT).Cognitive Reserve Index questionnaire(CRIq)scores were generated based on education level,leisure activities,and work experience ratings for both groups to assess CR.Amplitude of low frequency fluctuations(ALFF),fractional ALFF(fALFF),and cerebral blood flow(CBF)were obtained at the voxel level,and CBF/ALFF and CBF/fALFF values were calculated to assess neural vascular coupling.Regions of interest(ROIs)with significant between-group differences in CBF/ALFF and CBF/fALFF were selected for further correlation analysis with cognitive function and CR scales to elucidate the relationship between cognitive reserve,neural vascular coupling,and cognitive performance.Results:CRIq scores were significantly lower in the MCI group compared to the HC group(89.23±11.03 vs.98.70±12.75).In MCI and HC,CRIq scores were positively correlated with MoCA and AVLT scores(r=0.447,P=0.004;r=0.344,P=0.030;r=0.245,P=0.050;r=0.900,P<0.001).Compared to HC,MCI patients showed significantly increased CBF/ALFF ratios in bilateral temporal middle gyrus(bilateral,two-tailed P<0.005,alphsim corrected,cluster size>39),and significantly decreased CBF/ALFF ratios in bilateral orbital inferior frontal gyrus and frontal middle gyrus(bilateral,two-tailed P<0.005,alphsim corrected,cluster size>93).Additionally,CBF/fALFF ratios were increased in bilateral temporal fusiform gyrus(bilateral,two-tailed P<0.005,alphsim corrected,cluster size>53)in MCI.Furthermore,in the MCI group,the left orbital inferior frontal gyrus CBF/ALFF ratio was negatively correlated with CRIq,MoCA,and AVLT scores(r=-0.417,P=0.007;r=-0.336,P=0.034;r=-0.378,P=0.016).Conclusions:Individuals with higher cognitive reserve(CR)exhibit better cognitive function.Among patients with mild cognitive impairment(MCI),those with higher CR show a lower left orbitofrontal cortex CBF/ALFF ratio,indicating neurovascular uncoupling.This uncoupling is associated with more severe brain pathology,yet these individuals maintain good cognitive function.This suggests that neurovascular coupling and uncoupling might be potential neural mechanisms through which CR influences cognitive function in MCI patients.