The Brain Network Balance Mechanism Of Patients In Alzheimer’s Disease Spectrum

Alzheimer’s disease(AD)is a progressive neurodegenerative disease characterized by slow cognitive loss and accompanied with other functional decline in executive,attentional visualspace etc.The clinical diagnosis bases on biomarkers,neuroimaging,and symptoms above.The ultra-early stage,subjective cognitive decline(SCD),and the preclinical stage,mild cognitive impairment(MCI),have gained much attention in clinic and research in current.There are five chapters in this study.The first chapter,given a comprehensive description on the clinical diagnosis,treatment and research of the AD spectrum with deep investigated researches of neuropathology and the characteristics of neuro network damages in imaging analysis.Chapter two,aiming to improve the application of individualized information in current clinic,a deep research has conducted from AD guidelines to analyze and explore the assessment methods of patients of the AD spectrum.A new scale,the Brief Risk Rating Scale System,has carried out to assist the deficiencies in current guidelines without additional burden to clinical diagnosis process.It contributes to enhance the clinical attention to individual differences.Not only helps to assess the progression risk of individuals objectively,but to identify the high-risks among the patients immediately.It as a guide to provide individualized diagnosis and treatment precisely and promote the further research of disease prevention and control strategies.In chapter three,the research aims to reveal the mechanism of network damages and compensation occurred in patients of the AD spectrum based on the imbalance of network function which leads to disease progression.The study has conducted with comprehensively logical analysis to investigate the mechanism through biological level and neuroimage analysis.According to the normal regulation mechanism between task-positive and task-negative networks in brain,research puts forward the hypothesis,the Network Balance Path.It is capable of a benchmark and a center hub for brain to measure functional balance and maintain the operation between two-state networks,respectively.The similar benchmarks among individuals,specificity of functional damage,and the compensatory potentiality within the path jointly affect the prognosis.Chapter four,the main purpose is to verify the quality and research potential of clinical database collected by the Neurology department of affiliated Drum Towel hospital of Nanjing University medical school.The experiment was performed with neuropsychological assessment scales recognized internationally to analyze the functional relation and verify the protection of cognitive reserve and the interaction of emotion respectively to brain functions between stages of the disease.Results showed most functions close-related in between and to the disease,which significant different between the healthy control(HC),MCI and AD groups,except subjects’ emotion scales and performance in silhouette test.The characteristics of cognitive reserve which affected by the disease has revealed.Feasibility analysis of present database recommended to expand the sample size as prior issue,and therefore the international imaging database,ADNI(Alzheimer’s Disease Neuroimaging Initiative),was used to systematically analyze the effect of self-reference network(SRN)interaction with other networks on clinical symptoms.Chapter five,the project focuses on the importance of SRN in AD progression.Functional connectivity of resting state network is analyzed,and discloses the manifestation of SRN modulation,its damage patterns and the relations between cognitive functions in the disease progression.There are interactions between SRN and attentional system networks,and all affected by the diseases.The mechanisms of SRN regulating attention system networks in the left and right hemispheres are different,while all functions of networks were damaged in MCI.Within above,the function of the SRN decreased the most,the salience network(SN)the least,and the dorsal attention network(DAN)in between.Further investigation found the visual spatial,executive and memory functions correlated to the functional integrity of SRN.To conclude,the study researches on the diagnosis and treatment of AD spectrum and the characteristics of network functional impairment,and put forwards the application of individualized recognition and the assessment of patients in AD spectrum.Furthermore,the balance mechanism of neural network functional impairment and the patterns of SRN functional characteristics damaged and compensated in the progress of the AD spectrum have revealed.