阿尔茨海默病脑血流灌注改变的性别差异及其与认知损害的相关性

Gender difference of cerebral blood flow and its correlation with cognitive impairment in Alzheimer's disease

目的:利用磁共振3D伪连续动脉自旋标记(3D-pcASL)成像,探讨阿尔茨海默病(AD)患者脑血流灌注(CBF)改变是否存在性别差异,及其与认知损害的相关性。方法:招募74例AD患者(男33例、女41例)、74例AD伴遗忘型轻度认知障碍(aMCI)患者(男29例、女45例)及74例健康志愿者(对照组,包括男31例、女43例),所有被试行3D-pcASL成像,获得脑血流量(CBF)图,使用双因素协方差分析获得性别与组别(AD、aMCI及HC组)存在交互作用的脑区,并将这些脑区的CBF值与简易精神状态检查量表(MMSE)及蒙特利尔认知功能评估量表(MoCA)得分进行偏相关分析。结果:对照组和aMCI组中男性组与女性组之间MMSE和MoCA得分的差异均无统计学意义(P>0.05),而AD组中女性组的MMSE和MoCA得分显著低于男性组(P<0.05)。对CBF值的双因素协方差分析结果显示左侧顶下缘角回、缘上回、颞上回及颞中回存在性别与组别(AD、aMCI及HC组)的交互作用,女性AD组中上述脑区的CBF值与MoCA得分均呈显著正相关(r=0.378,P=0.019;r=0.377,P=0.020;r=0.347,P=0.033;r=0.433,P=0.007),而男性AD组中上述脑区的CBF值与MoCA得分均无显著相关性(P>0.05)。结论:在AD进展过程中,男性和女性的脑血流灌注改变存在性别差异,且与认知障碍相关,这提示我们在进行AD进展研究时应充分考虑性别差异,以开发更有效的生物标志物。

Objective:To explore the gender difference of cerebral blood flow(CBF)obtained by 3D pseudo-continuous arterial spin labeling(3D-pcASL)MRI in patients with Alzheimer's disease(AD)and its correlation with cognition impairment.Methods:Seventy-four AD patients(33 males,41 females),74 am-nestic cognitive impairment aMCI patients(29 males,45 females),and 74 healthy controls as HC group(31 males,43 females)were included in this study.All subjects underwent 3D-pcASL imaging to obtain CBF maps.The brain regions with CBF interacting with gender and groups of AD,aMCI and HC were found by two-way analysis of covariance(ANCOVA),and the relation of CBF of such brain regions with scores of Mini-mental State Examination(MMSE)and Montreal Cognitive Assessment(MoCA)was evaluated using partial correlation analysis.Results:The MMSE and MoCA scores of HC group and aMCI groups showed no significant difference between male and female(P>0.05),while in AD group the MMSE and MoCA scores of female group were significantly lower than those of male group(P<0.05).The results of two-way ANCOVA for CBF values showed there were interactions between gender and groups of AD,aMCI and HC in the left inferior parietal gyrus,supramarginal gyrus,superior temporal gyrus and middle temporal gyrus.In addition,significant positive correlations were found between CBF and MoCA in all the brain regions mentioned above in female AD patients(r=0.378,P=0.019;r=0.377,P=0.020;r=0.347,P=0.033;r=0.433,P=0.007),but no correlation was found in male AD patients.Conclusion:During the progression of AD,there existed gender differences of CBF in males and females,which were associated with cognitive im-pairment,suggesting that gender differences should be fully considered in the study of AD progression to deve-lop effective biomarkers.