Neuroimaging Research For Early Recognition Of Alzheimer’s Disease Based On Hippocampal Subfield Volume And Regional Cerebral Blood Flow

Background: Existing studies have shown that Alzheimer’s disease(AD)has continuous pathological and clinical processes.Mild cognitive impairment(MCI)is considered as a transition stage of normal aging and AD,which contains multiple pathophysiological changes.Magnetic resonance imaging(MRI)has wide application in AD research with its unique advantages.For early recognition of AD,we can start with structure and function of brain.Structural Magnetic Resonance Imaging(sMRI)is recommended to describe the atrophy of brain structures.Arterial spin labeling(ASL)has capacity to assess the changes of cerebral blood flow(CBF)to reflect brain function.Hippocampal atrophy is commonly found in high-risk individuals of AD.The hippocampus can be divided into several subfields which have different sensitivity to the occurence and development of AD.Also,CBF has unique changes in multiple brain regions at different stages of AD.Therefore,apart from providing methods for further discussing pathophysiological mechanism,the combination of sMRI and ASL-MRI may offer new help to early diagnosis as well as long-term follow-up of AD.Objectives: The aim of this neuroimaging study was to describe the reduction of hippocampal subfields volume as well as the changes of regional CBF in individuals at the risk of AD.It was assumed that combination of hippocampal subfields volumes and regional CBF can acquire higher accuracy than either method alone in discriminating high-risk individuals of AD from cognitively normal elderly adults.Methods: 44 early mild cognitive impairment(EMCI)patients,50 late mild cognitive impairment(LMCI)patients and 40 healthy controls(HC)underwent sMRI and ASL-MRI scan along with a battery of neuropsychological tests.Hippocampal subfields volume was acquired by voxel-based morphometry(VBM)software,with total intracranial volume normalization.Normalized regional and whole-brain voxel-based CBF differences were calculated using voxel-based analysis software.We compared the differences in hippocampal subfields volumes and regional CBF among the three groups.Combined with the results of multidimensional cognitive psychology evaluation,we analyzed the significant correlation between hippocampal subfield volumes and regional CBF with behavioral performance.Finally,Various combinations of these parameters were used to create the Receiver Operating Characteristic curves(ROC)in distinguishing MCI patients from the controls.Results: 1.Episodic memory score and executive function score gradually declined by the order of HC,LMCI patients and EMCI patients,and the difference was statistically significant.2.The normalized volume of multiple subfields in bilateral hippocampus was significantly lower in LMCI patients than in HC(P<0.05)and there was no significant difference in hippocampal subfield volume between EMCI patients and HC.3.The normalized volumes of each hippocampus,left dentate gyrus(DG)subfield,right CA2 subfield,right CA3 subfield and right DG subfield were significantly positive correlated with performance in episodic memory(P<0.001)and Logical Memory Test-Delay recall(LMT-DR)(P<0.001)in all subjects.4.Left medial frontal gyrus CBF was significantly higher in the EMCI patients than the controls(P<0.01).Right anterior/meddle cingulate gyrus CBF was significantly lower in LMCI patients than the EMCI patients(P<0.01).5.Right anterior cingulate gyrus CBF was significantly positive correlated with performance in visuospatial function and Clock Drawing Test(CDT)(P<0.005)in the controls.6.For predicting the LMCI patients,the highest area under curve value was 0.857,by combining normalized right CA3 subfield volume,normalized CBF in the right anterior/middle cingulate gyrus and Left medial frontal gyrus.Conclusion: Among high-risk individuals of AD,gray matter volume decreases in the hippocampus and its subfields with CBF changing in multiple brain regions.Moreover,regional CBF changes precede the hippocampal subfields atrophy in EMCI patients.Both them reflect the cognitive function status of patients at an early stage of AD.Furthermore,they can be used as important biomarkers to evaluate the cognitive impairment.Combination of hippocampal subfield volume and regional CBF could improve the efficacy in early recognition of individuals in high risk of AD.