Establishment Of A Diagnostic Model Of Alzheimer's Disease With Olfaction,visionand Plasma Inflammatory Cytokines

With the aging population,the incidence of Alzheimer's disease(AD)is increasing year by year.The question of how to early diagnose Alzheimer's disease is getting more and more attention from researchers and clinicians.Driven by the aging society in our country,the number of AD patients in China will increase even more rapidly in the next 20 years.AD is a neurodegenerative disease in the elderly population over the age of 65.AD is a progressive memory-related disorder,presenting with memory impairment,aphasia,apraxia,agnosia,visual skills impairment,executive dysfunction and personality and behavioral changes.The long courseand high morbidity feartures of AD bring huge economic burden on society and families.Early recognition and intervention of AD can delay progression of cognitive decline,reduce the disability rate and greatly ease the burden of AD treatment.As the pathogenesis of AD is still not fully elucidated,there is a lack of effective treatment that can block the progress of the disease.How to early detectand diagnose AD is particularly important for the control of disease progressionPart?.Olfactory identification deficit in Chinese patients with Alzheimer's disease and mild cognitive impairment:a case-control studyBackground:As one of the early symptoms in Alzheimer's disease(AD),hyposmia is of great significance for prediction and diagnosis of AD.So far,there has been no study on the application of olfactory identification tests for Chinese patients with AD and mild cognitive impairment(MCI).The goal of this study was to validate the possibility of Sniffin sticks(SS-16)in evaluating cognitive ability in patients with AD and MCI in a case-control study.This study also explored the related factors of olfactory function in AD and MCI patients.Methods:In this study,the olfactory function of 50 healthy people,75 patients with MCI,and 75 patients with AD were evaluated with the 16-item odor identification test.Results:Mean odor identification scores in patients with AD were significantly lower than that in patients with MCI and healthy subjects,while mean scores in patients with MCI were lower than those of healthy controls.Comparing the AD and MCI groups,the ROC curve showed 56%sensitivity and 90%specificity with a cut-off value of 8 in the SS-16.Multiple linear regression analysis revealed that lower Mini-Mental State Examination(MMSE)score was a significant influential factor of odor identification scores.SS-16 showed almost the same higher diagnostic efficiency in patients with low and high education levels.Conclusion:Odor identification test is a validated biomarker for the diagnosis of AD.SS-16 is a useful tool for olfactory assessment in Chinese patients with AD and MCIPart?.The visual impairment in Alzheimer‘s disease correlated with the hippocampus volumeBackground:Visual biomarkershave been proved as non-invasive and indirect indicators for assessing brain pathophysiology.Visual disturbance can be one of the symptoms in AD.This study was conducted to determine whether AD alters the visual function and the relationships between hippocampal changes and visual system.Method:23 individuals with mild cognitive impairment and 17 age-and sex-matched AD patients were included in the investigation.Optical coherence tomography(OCT),pattern visual evoked potentials(PVEP)and flash electroretinograms(FERG)recordings were obtained from all participants with the use of a clinical electrodiagnostic system.Results:OCT showed decreased RNFL thickness in AD patients compared to MCI patients.There was significant difference between left eye P100-wave latency in PVEP.In FERG examination,increased implicit time of rod response and 3.0 flicker and amplitudes reductions in cone rod response and cone response were observed.RNFL thickness,rod cone response amplitude,cone response amplitude and 30Hz flicker latency were significantly correlated tohippocampal volume with a moderate correlation coefficient Multiple stepwise linear regression analysis indicated that MMSE scores were strongly related to the hippocampal volume and retinal nerve fiber layer(RNFL)thickness.And the combined diagnostic model of the hippocampal volume and RNFL thickness reached the sensitivity of 0.943 and the specificity of 0.773.Conclusion:Our results revealed that compared to MCI patients,AD patients showed significant difference in RNFL thickness,VEP and ERG responses,and the changes were related to hippocampus volumes.RNFL thickness was related to MMSE scores,which could also be a diagnostic indicator for ADPart?.Detection of inflammatory biomarkers for the early diagnosis of Alzheimer's disease and mild cognitive disorderBackground:The diagnosis of Alzheimer's disease(AD)and mild cognitive impairment(MCI)mainly depends on the combination of clinical symptoms,neuropsychological assessment and neuroimaging examination.The related biomarkers are still under research.The purpose of this study was to screen the potential biomarkers of AD and MCI for early diagnosis through plasma protein of peripheral blood.Methods:The peripheral blood samples of 30 MCI patients,30 AD patients and 25 healthy controls were collected and 40 plasma proteins were measured with Luminex.Plasma protein levels in different groups were screened by t test and Mann-Whitney U test,and partial correlation analysis was used to explore whether the plasma protein was related to cognitive abilities.The receiver operating characteristic curve(ROC)was established to evaluate the diagnostic efficacy of single plasma protein or a combined diagnostic model.Results:There were 10 elevated proteins of the 40 plasma proteins both in MCI and AD patients.Partial correlation analysis showed that 8 plasma proteins(EGF,GRO,MDC,IL-8,IL-17A,IP-10,MIP-1?,MIP-1?)were associated with MMSE scores.The ROC curves proved that the combined diagnostic model of 8 plasma protein were better than single factor diagnostic models in the diagnosis of AD and MCI.Conclusion:The biomarker model consisting of 8 plasma protein(EGF,GRO,MDC,IL-8,IL-17A,IP-10,MIP-1?,MIP-1?)has the potential for the early diagnosis of MCI and AD.Part IV.Establishment of a diagnostic model of olfaction,vision and plasma inflammatory cytokines in Alzheimer s diseaseBackground:The aim of this study was to screen the olfaction,vision and plasma inflammatory proteins in AD patients to determine AD associated biomarkers for the early diagnosis or prediction models of AD with high sensitivity and specificity.Methods:In this study,we usedthe objective and method of the first to the third part in the above researches to select the subjects that met all requirement.We used the ttest and Mann-Whitney U test to screenthe different indicators in AD and MCI groups,and the Wilks'lambda stepwise analysis to establish a diagnostic equationmodel of AD with ROC curves to verify the diagnostic efficiency of the equation.Results:The SS-16 scores,RNFL thickness,plasma EGF,GRO,MDC,IL-8,IL-17A and MIP-1? levels between AD and MCI groups were included in the diagnostic medel.The equation and ROC curve show that the diagnostic efficiency of the equation is 0.990 and the cut-off value is 0.015 with 100%sensitivity and 90%specificity,which indicated the better diagnostic of the equation.Conclusion:This study screened the diagnostic indicators of AD,namely SS-16 score,RNFL thickness,plasma protein EGF,GRO,MDC,IL-8,IL-17A and MIP-1?levels,and established a diagnostic equation model,with a good diagnostic efficacy,which required the long-term research in the future.