Based On ¹⁸F-AV-1451PET/MR To Explore The Relationship Between Tau Protein,brain Atrophy And Cognitive Function In Alzheimer’s Disease

Objective:Despite the associations of Aβdeposition with connectivity alterations,atrophy,and cognition,the exact role of tau and regional atrophy on cognition in Alzheimer’s disease remains unclear.This study aimed to investigate the relationship between regional tau pathology,gray matter volume in vivo and their effects on cognitive function in AD continuum,improving effective clinical trials and future therapeutic strategies for AD.Methods:A total of 34 patients with positive ¹¹C-PIB were prospectively recruited from hospital and were diagnosed by neurologists.Another 23 subjects of the normal cognitive（NC）group were enrolled.All patients underwent ¹⁸F-AV-1451 PET/MR Brain imaging and completed neuropsychological assessments（including MOCA,MMSE,ADAS-COG and ADL）,and statistical cognitive function scores.Voxel-based method was used to explore the brain regions with differences in tau deposition between AD/MCI group and the control group,and VBM was used to explore the brain regions with differences in gray matter volume between AD/MCI group and the control group.The entorhinal cortex,hippocampus,medial temporal lobe,medial parietal lobe,lateral temporal lobe,lateral parietal lobe,occipital lobe,whole brain gray matter volume was selected as regions of interest（ROI）,and ¹⁸F-AV-1451 standardized uptake ratio（SUVR）and gray matter volume（GMV）were extracted from the ROI.Two-sample t test was used to compare the GMV and SUVR between groups to verify the results of voxels.Spearman correlation analysis was used to analyze the correlation between GMV and SUVR in each ROI,and the correlation between the average GMV of each ROI,the average SUVR of each ROI and the scores of cognitive domains.Using ¹⁸F-AV-1451 SUVR in each region of interest as an independent variable,gray matter volume as a mediator variable,and cognitive function scores in each domain as a dependent variable,mediation was used to test whether the association between tau PET and cognitive change was mediated by gray matter volume measured on MRI,and Whether age,sex,education modifies these associations.Results:Compared with the control group,¹⁸F-AV-1451 radiation uptake in bilateral hippocampus,parahippocampal gyrus,precuneus,posterior cingulate gyrus,left parietal lobule and bilateral frontotemporal lobule in AD/MCI group was significantly increased（FDR corrected,P<0.05）.In AD/MCI group,gray matter volume decreased in most areas of bilateral frontotemporal lobe,including hippocampus,parahippocampal gyrus,and right precuneus（FDR corrected,P<0.05）.At the ROI level of the lobe,a local and distant spatial correlation was observed between ¹⁸F-AV-1451 SUVR and gray matter volume in the AD/MCI group（r=-0.43～-0.77,P<0.05,FDR corrected）,and no significant correlation was found between gray matter volume and ¹⁸F-AV-1451 SUVR in the control group(except for a weak correlation between gray matter volume in the medial temporal lobe and ¹⁸F-AV-1451 SUVR in the medial parietal lobe（r=-0.42）.Spearman correlation analysis showed that there was a strong negative correlation between the ¹⁸F-AV-1451SUVR and the overall cognitive function in the medial temporal lobe and the medial parietal lobe.The gray matter volume of medial temporal lobe,lateral temporal lobe,medial parietal lobe,lateral parietal lobe,occipital lobe and whole brain showed a strong positive correlation with the overall cognitive level.The ROI-based mediation analysis showed that tau pathology had no direct impact on the overall cognitive impairment,and local and distant gray matter atrophy was one of the mediating factors in the relationship between the two.Gray matter atrophy in the entorhinal cortex,medial temporal lobe and parietal lobe mediated the effect of abnormal deposition of tau protein in local brain regions on cognitive impairment.Gray matter atrophy in medial temporal lobe,lateral temporal lobe and medial parietal lobe mediates tau pathology in distant space to cognitive impairment.Conclusions:In AD/MCI patients,gray matter atrophy is mainly concentrated in the entorhinal cortex and temporal cortex,and tau deposition is mainly concentrated in the medial temporal lobe and medial parietal cortex,which may be the pathological and structural basis of brain memory and cognitive impairment.AD/MCI patients,Entorhinal cortex,Limbic region,there was a significant correlation between ¹⁸F-AV-1451 binding values in neocortical regions and cortical atrophy.The atrophy of gray matter volume in local and distant brain regions is one of the mediating factors of clinical cognitive impairment caused by tau pathology.