基于^(18)F-THK5317 PET/MR对阿尔茨海默病患者脑tau蛋白与脑萎缩的研究

Relationships between tau and brain atrophy in Alzheimer′s disease based on ^(18)F-THK5317 PET/MR

目的探讨阿尔茨海默病(AD)患者脑内tau蛋白沉积和脑萎缩情况并探索二者之间及其与认知功能障碍的关系。方法回顾性分析2017年4月至2019年10月间在解放军总医院就诊的26例AD患者[男12例,女14例,年龄(70.7±12.2)岁]和19名认知功能正常的健康对照(CN)者[男9名,女10名,年龄(65.6±8.1)岁]。所有受试者均行^(18)F-(S)-6-[(3-氟-2-羟基)丙氧基]-2-(4-甲基氨基苯基)喹啉(THK5317)PET/MR显像,计算每个受试者标准摄取值比值(SUVR)和灰质体积(GMV)。使用一般线性模型进行GMV和SUVR的组间比较,应用Pearson相关分析逐体素分析GMV与SUVR的相关性以及大脑皮质平均GMV、平均SUVR与简易精神状态检查量表(MMSE)评分之间的相关性。结果与CN者相比,AD患者在外侧颞叶、额叶、后扣带回/楔前叶及枕叶存在^(18)F-THK5317异常摄取,2组间SUVR差异有统计学意义(2.18±0.54和1.78±0.09、2.13±0.50和1.82±0.06、2.03±0.45和1.69±0.08、2.18±0.57和1.76±0.10;t值:2.58~6.57,均P<0.001);在内侧颞叶、后扣带回/楔前叶及眶额部存在GMV显著缩小(t值:3.67~8.85,均P<0.001)。相关分析显示,在AD患者中,SUVR与GMV在双侧外侧颞叶、前额叶中线区及眶额叶存在显著负相关(r值:-0.52~-0.43,均P<0.05);大脑皮质平均SUVR(r=-0.599,P=0.001)、平均GMV(r=0.443,P=0.023)均与MMSE评分有显著相关性。结论AD患者存在大脑皮质^(18)F-THK5317异常摄取及GMV缩小,两者与认知功能的减退存在显著相关性。

Objective To investigate the neuroimaging relationship between tau protein deposition and brain atrophy,and assess their relationships with cognitive decline in Alzheimer′s disease(AD)patients.Methods From April 2017 to October 2019,26 AD patients(12 males,14 females,age(70.7±12.2)years)and 19 cognitively normal controls(CN;9 males,10 females,age(65.6±8.1)years)in Chinese PLA General Hospital were retrospectively enrolled.All subjects received(S)-6-[(3-^(18)F-fluoro-2-hydroxy)propoxy]-2-(4-methylaminophenyl)quinoline(^(18)F-THK5317)PET/MR and the standardized uptake value ratio(SUVR)and gray matter volume(GMV)were measured.General linear model(GLM)was used to evaluate the differences of SUVR and GMV between two groups.Pearson correlation analysis was used to assess the relationships between SUVR and GMV,and relationships of SUVR and GMV with Mini-Mental State Examination(MMSE)scores in AD patients.Results Compared with CN,the AD patients showed significantly increased ^(18)F-THK5317 retention in lateral temporal,frontal,posterior cingulated/precuneus and occipital cortex with significant differences of SUVR between two groups(2.18±0.54 vs 1.78±0.09,2.13±0.50 vs 1.82±0.06,2.03±0.45 vs 1.69±0.08,2.18±0.57 vs 1.76±0.10,t values:2.58-6.57,all P<0.001).The AD patients also showed decreased GMV in medial temporal,posterior cingulated/precuneus and orbitofrontal cortex(t values:3.67-8.85,all P<0.001).In AD patients,SUVR was negatively associated with GMV in bilateral lateral temporal cortex,pre-frontal cortex and orbital frontal cortex(r values:from-0.52 to-0.43,all P<0.05).Both SUVR(r=-0.599,P=0.001)and GMV(r=0.443,P=0.023)were significantly correlated with MMSE scores in AD patients.Conclusion AD patients have neocortical ^(18)F-THK5317 abnormal uptake and GMV reduction,which are significantly correlated with cognitive decline.