Amygdala Subfield Volume And Functional Connectivity Changes And The Relationship To Cognitive Function In Neurodegeneration

With the growth of age,the aging of the brain leads to the decline of cognitive function of the elderly,and is also one of the main factors of dementia,especially Alzheimer’s disease(AD).The increasing incidence of AD has become an important social problem worldwide.Finding neuroimage biomarkers for the diagnosis of brain aging,amnestic mild cognitive impairment(aMCI)and AD,as well as for the related cognitive function decline,has important scientific and clinical significance.The amygdala is a key structure of the limbic system and widely connected with the cerebral cortex,subcortical structure,and brain stem.The amygdala is also involved in cognitive functions such as attention and alertness,working memory,and episodic memory.Research showed that the amygdala is significantly affected in brain aging,and is also one of the medial temporal lobe structures affected earliest by AD pathology.Therefore,the impairment of amygdala might be one of the reasons for the clinical cognitive function decline in brain aging,aMCI and AD.The neuroimaging characteristics of the amygdala or its subregions may be used as biomarkers for brain aging,aMCI and AD.Based on above objectives,this dissertation utilized multimodal imaging methods to study the neuroimage characteristics changes of the amygdala and its subregions,in the brain aging as well as in aMCI and AD.We also analyzed the correlation between neuroimage characteristics changes and the cognitive function decline.Firstly,in order to explore the volumetric changes of the amygdala and subregions in brain aging,we grouped cognitively normal subjects carrying APOE ε3/ε3 alleles into yong,middle-early,middle-late and old groups.We then segmented the amygdala into nine subregions,namely,the lateral nucleus(La),basal nucleus(Ba),accessory nucleus(AB),central nucleus(Ce),medial nucleus(Me),cortical nucleus(Co),anterior amygdala area(AAA),Cortico-amygdala transition(CAT)and paralaminar nucleus(PL)to study the volumetric group differences of the whole amygdala(Whole)as well as amygdala subregions.Study results revealed that volume of all subregions except Me,as well as the whole amygdala,declined significantly in the old group.Left AB,CAT volumes declined already in middle-late group.At the same time,the analysis of the relationship between the volume of amygdala and its subregions and cognitive function showed that the volume of amygdala as a whole and some subregions is significantly correlated with the decline of overall cognitive function,memory function and executive function.The results indicate that volumes of the whole amygdala and its subregions except Me,may be used as imaging biomarkers of brain aging,especially the left AB and CAT volumes.Subsequently,we studied the volumetric changes of amygdala and its subregion in aMCI and AD compared with normal control(NC),and the relationship with clinical cognitive decline.The results showed that volumes of the whole amygdala as well as amygdala subregions except bilateral PL,decreased significantly in AD,and the volume of bilateral AAA decreased significantly in aMCI.The correlation analysis showed that the volumes of the whole amygdala and some subregions significantly related to the overall cognitive function,memory function and visual spatial function,the volume of some subregions also significantly related to the decline of executive function and language function.The results demonstrate that volume of the amygdala subregion except PL,as well as the whole amygdala,may be used as the neuroimage biomarkers of AD,and the bilateral AAA volumes may be used as the imaging biomarker of aMCI.Finally,we studied the functional connectivity changes of the amygdala and its subregions in aMCI and AD compared with NC,and the relation to clinical cognitive function decline.The results showed that the functional connectivity of bilateral La,left Ba,CAT,Whole decreased significantly in AD.The functional connectivity between right La,left Ba,and right superior temporal gyrus decreased significantly in aMCI.The correlation analysis results demonstrated that the functional connections of bilateral La and left whole significantly related to overall cognitive and executive functions.The functional connectivity between left CAT and right superior temporal pole/amygdala is related to the overall cognitive function.The functional connection between the left La and right angular gyrus also related to the visuospatial function.The research results indicate that changes in functional connectivity between bilateral La,left Ba,CAT,and Whole may serve as neuroimaging biomarkers for AD.Decreased functional connectivity between right La,left Ba,and right superior temporal gyrus may serve as diagnostic markers for distinguishing aMCI from NC.In addition,the results of the analysis suggest that the decline of cognitive functions such as overall cognition,memory and execution may be related to the weakening of the regulation between the amygdala and the dorsal attention network,the somatomotor network,and the frontoparietal control network.In summary,this study provides new potential biomarkers for brain aging,aMCI,and AD.