| Alzheimer’s disease (AD) is a common neurodegenerative disease whichseverely impairs the health of geriatric population. However, because effectivetreatments are still absent presently, this disease is irreversible once the symptomsemerge. Therefore, early diagnosis and intervention in the early stage were thoughtto be the only possible way to delay the progression of AD. Amnestic mild cognitiveimpairment (aMCI) was currently considered as the prodromal stage of AD.Functional connectivity, which mirrors the synchronism of neuronal activity betweendifferent brain regions, is an important analytical method of the resting statefunctional magnetic resonance imaging and has been applied extensively in theresearch on pathophysiological alteration in AD and aMCI. The thalamus is animportant information transmission and processing center and is essential for thecerebral cortex function. However, structural and functional abnormalities of thethalamus in early stage of AD have been repeatedly reported. Therefore, the researchon the changes of thalamic functional connectivity patterns as well as on thelongitudinal changes over time in aMCI and AD will provide us importantinformation for fully understanding of the disease.In this study, patients with AD and aMCI were evaluated by usingneuropsychological assessments and resting state functional magnetic resonancecombined with analysis of functional connectivity. We studied the alteration of thethalamic functional connectivity pattern in AD and aMCI in resting state. In addition,the relationship between the strength of functional connectivity and the cognitivefunction was also explored. The main contents and contributions of the dissertationare as follows: We evaluated the alteration of thalamic functional connectivity pattern in35AD,27aMCI and27normal controls. The results showed that when compared to the NCgroup, the AD group demonstrated decreased functional connectivity between thebilateral thalamus and some brain regions in the default mode network，whichindicates impaired thalamo-default mode network connection. In comparison,increased functional connectivity was observed between the bilateral thalamus andseveral brain regions in the temporal lobe, frontal lobe and sensory-motor cortex，which suggests the presence of some kind of compensation. Further, when the dataof aMCI were introduced to this analysis, our results demonstrated altered functionalconnectivity patterns that correspond to disease progression. More importantly, thestrength of functional connectivity between the thalamus and the identified brainregions were positively correlated with the cognitive assessment scores, whichsuggests that the alteration of thalamic functional connectivity is a possibleimportant pathophysiological mechanism that underlies the cognitive dysfunction inAD and aMCI. This study also provides new functional evidence that aMCI is atransitional stage between normal aging and early AD. In summary, our resultsrevealed disease severity-related alterations of the thalamic functional connectivitypattern in AD and aMCI. These results support the hypothesis of networkdisconnection in AD and aMCI and also provided important information for ourbetter understanding of the pathophysiology of AD as well as the relationshipbetween aMCI and AD. To conclude，our outcomes offers valuable reference forfurther study on early diagnosis and intervention of AD.We investigated the alteration of thalamic functional connectivity in13patientswith aMCI during a one year follow-up. Compared to the baseline, the aMCIpatients showed decreased functional connectivity between the thalamus and theinferior parietal cortex, the putamen and the cerebellum one year later. These brainregions, which are proved to be involved in higher cognitive functions such asepisodic memory, have been repeatedly found to have structural and functionalabnormalities in AD and MCI. Our results indicate that the impaired functional connection between the thalamus and various brain regions may be associated withthe aggravation of cognitive dysfunction over time. The present study also providesnew evidence for the longitudinal alteration of brain function network in aMCI. |
