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Microribonucleic Acid-132 (miR-132) Improves The Basic And Clinical Research Of Alzheimer's Disease

Posted on:2020-06-17Degree:DoctorType:Dissertation
Country:ChinaCandidate:L QianFull Text:PDF
GTID:1364330614959149Subject:Neurology
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ObjectiveAlzheimer's disease(AD)is the most common neurodegenerative disease,and its main clinical manifestation is irreversible progressive memory impairment and other cognitive dysfunction.At present,there are more than 8.6 million AD patients in the elderly population over the age of 60 in China,which brings a heavy burden to the patients' families and society.The pathogenesis of amyloid cascade hypothesis,cholinergic hypothesis,inflammatory mechanism hypothesis,free radical injury hypothesis,etc.At present,the diagnosis of AD often depends on the clinical examination of clinicians,magnetic resonance imaging,positron emission tomography,cerebrospinal fluid testing and neuropsychological evaluation.These methods are not sensitive at the early stage,so in recent years,more and more researchers have turned their attention to looking for biomarkers for the early recognition of AD.Some researchers have proposed imaging markers based on magnetic resonance imaging to improve the accuracy of early diagnosis.Many studies on structural mri have confirmed that it can be used as a prognostic indicator for patients with MCI and AD.Previous studies have found that in most MCI and early AD patients,gray matter and cortical atrophy can be observed in different brain areas,such as the hippocampus,the olfactory cortex and the medial temporal cortex.In addition to changes in imaging parameters,many markers related to cerebrospinal fluid and blood neurochemistry have been found,such as cerebrospinal fluid A?42 and tau protein.However,due to the simple,cheap and traumatic detection of cerebrospinal fluid,many biomarker detection has not been widely used in clinical practice.Therefore,it is of great significance to search for biomarkers for early diagnosis of non-invasive or minor trauma.In view of the above,this study will explore the correlation between the changes of subcortical structures and cognitive domains in patients with mild cognitive impairment in the early stage of alzheimer's disease,in order to find the imagingmarkers of MCI progression to dementia.These research results may contribute to the early diagnosis of AD and provide effective means and methods for clinicians to take early intervention to delay the progression of the disease.MethodA total of 59 subjects were recruited.All subjects were examined using a standardized protocol,including a set of neuropsychological assessments of all cognitive domains,high-resolution magnetic resonance imaging and Free Surfer(v6.0.0),subcortical structural volume analysis,and detailed medical and neurological physical examinations.According to the results of cognitive evaluation,the patients were divided into 12 cases in the cognitively normal group,35 cases in the mild cognitive impairment group and 12 cases in the Alzheimer's disease group.ResultsThere was no significant difference in gender ratio,hypertension ratio,diabetes ratio,hyperlipidemia ratio,smoking ratio,alcohol consumption ratio and age of the subjects.However,the educational years of subjects in the Alzheimer's disease group were significantly lower than those in the cognitively normal group.Subjects in the dementia group scored lower on memory,language,attention,executive function and visuospatial ability than subjects in the cognitively normal group,while subjects in the mild cognitive impairment group scored lower on memory and visuospatial ability.Subjects in the Alzheimer's disease group scored lower on memory and visual-spatial abilities than those in the mild cognitive impairment group.The plasma mir-132 content of the subjects was sampled and detected,and no significant difference was found.One-way analysis of variance suggested that there were significant differences in the structural volume of left thalamus,right thalamus,left hippocampus,right hippocampus,left amygdala,right amygdala,left nucleus accumbens,right nucleus accumbens and brainstem among the three groups.Partial correlation analysissuggested that memory function scores were significantly correlated with left thalamic volume and bilateral hippocampal volume.Language function scores were significantly correlated with bilateral thalamic volume and left hippocampal volume.Executive function scores were significantly correlated with left thalamic volume and right amygdala.Visual spatial function scores were significantly correlated with bilateral thalamic volume and bilateral hippocampal volume.There was no significant correlation between attention score and subcortical structural volume.General linear regression analysis suggests that left hippocampal volume may be a predictor of memory function,and left thalamic volume may be a predictor of language function,executive function and visuospatial ability.ConclusionThere were differences in subcortical structural volume in subjects with normal cognition,mild cognitive impairment and Alzheimer's disease,and this difference atrophy was closely related to cognitive dysfunction.In all subcortical structures,left hippocampal volume may be a predictor of memory function,and left thalamic volume may be a predictor of language function,executive function,and visuospatial ability.These findings suggest that these brain regions may be important in predicting small changes in cognitive domains in patients with mild cognitive impairment and Alzheimer's disease or evaluating the effectiveness of interventions and treatments in patients with mild cognitive impairment and Alzheimer's disease.
Keywords/Search Tags:Alzheimer's disease, sub-cortical structures, cognitive domain, Plasma miR-132
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