A Study On Early Diagnosis Of Alzheimer's Disease Based On Arterial Spin Labeling MRI

Part 1 The pattern of cerebral blood flow in Alzheimer's disease and its association with cognitive functionAim:To compare cerebral blood flow(CBF)values in patients with Alzheimer's disease(AD),patients with mild cognitive impairment(MCI),and healthy control(HC)by using an arterial spin-labeling(ASL)technique and analyze the association with cognitive function.Method:This study included 49 AD patients,60 MCI patients,and 55 healthy controls.ASL was adopted to detect the whole-brain CBF.Neuropsychological assessment covered global cognition and five cognitive domains,including memory,language function,executive function,attention and visuospatial function.Differences of CBF were analyzed using a voxel-wise approach.Linear regression model was used to determine the correlation between CBF and cognitive function.Results:There were significant differences of CBF between groups in the medial temporal gyrus,posterior cingulate gyrus,precuneus and parietal cortex.In the whole sample,reductions of CBF in the whole brain and differential brain regions were associated with cognitive impairment in all cognitive domains.Decreased CBF was significantly associated with poorer cognitive function in the AD group,but not in the MCI and HC groups.Conclusion:This study showed the changes of ASL-CBF in the spectrum of AD(i.e.from HC to AD).and our research demonstrated the associations between CBF and cognitive function.Notably,these associations were strongest in patients with AD.This study suggests that ASL-CBF may serve as a functional marker for AD disease severity.Part 2 Regulating Effect of CBF on Memory in cognitively normal older adults with different ApoE GenotypesAim:CBF changes and apolipoprotein E(ApoE)status have been independently related to the cognitive impairment in older adults at risk for AD.However,much less attention is given to how CBF and ApoE genotype may interact to affect cognitive performance in cognitively normal older adults.This study investigated potential statistical interactions between CBF and ApoE genotype in regions typically affected in Alzheimer's disease(AD)within a sample of cognitively normal older adults from the Alzheimer's Disease Neuroimaging Initiative(ADNI)study.Method:62 participants,including 23 ApoE ?4 allele carriers and 39 noncarriers,underwent resting CBF measurement and memory testing.CBF was measured by arterial spin labeling magnetic resonance imaging and memory performance was assessed by the Rey Auditory Verbal Learning Test.Results:Linear regression models showed that,among ApoE ?4 allele carries,there were significant negative associations between higher CBF in hippocampus,posterior cingulate,and precuneus and worse memory function.In contrast,among s4 non-carries,there were positive significant associations between CBF and cognition.Conclusion:This study suggests that in cognitively normal ?4 allele carriers,increased CBF is incapable of compensating memory deficit,perhaps reflecting dysregulation within the neurovascular unit.Part 3 Altered Coupling Between Cerebral Blood Flow and Functional Connectivity in Mild Cognitive ImpairmentAim:Previous studies mainly focused on the changes of resting CBF and functional connectivity in MCI patients,while the studies on the coupling changes of the two parameters were insufficient.This study intends to explore the characteristics of the coupling changes of CBF and functional connectivity in MCI patients.Method:75 patients with MCI and 61 patients with HC matched by gender and age were selected for undergoing ASL sequence and resting state Functional magnetic resonance scanning.CBF and Functional Connectivity Strength(FCS)were calculated respectively.CBF-FCS Coupling was assessed using CBF-FCS correlation and CBF/FCS ratio(blood supply per unit of functional connection strength).The correlation between CBF and FCS was analyzed by linear regression method,and the differences in CBF-FCS correlation and CBF/FCS ratio were compared by 2-sample t test.Results:Both in MCI patients and HC patients,there was a significant correlation between CBF and FCS:MCI(r=0.40,p<0.0001),HC(r=0.49,p<0.0001).Compared with HC,the correlation of CBF-FCS in MCI patients was reduced(t=2.332,p=0.023,reduced by 15%).The decrease of CBF/FCS ratio in MCI patients was mainly concentrated in brain areas related to memory function,such as precuneus and posterior cingulate gyrus.Conclusion:This study showed a disrupted coupling between cerebral blood flow and functional connectivity in mild cognitive impairment by using a combination of blood oxygenation level dependent and arterial spin labeling techniques.In addition,this study demonstrated a decreased CBF/FCS ratio in regions involved in episodic memory.These findings indicate that the neurovascular decoupling in the brain may be a potential neural mechanism involved in the pathophysiology of MCI.