Associations Between Cognitive Impairment And Malnutrition In An Elderly Population And Identification The Key Genes In Alzheimer’s Disease

PART ONE: ASSOCIATIONS BETWEEN MALNUTRITION AND COGNITIVE IMPAIRMENT IN AN ELDERLY POPULATIONBackground: In recent years,there is an increasing interest in the risk factors of cognition impairment in older people.There is still uncertainty,however,whether nutritional status is associated with increased risk of cognition decline.Aim: This study aimed to elucidate whether malnutrition is associated with cognitive impairment in an older Chinese population.Methods: A cross-sectional study was conducted in 2365 participants aged 60 years or older from January 2013 to September 2019.Nutritional status was measured by using the Mini Nutritional Assessment Short Form(MNA-SF).Cognitive function was assessed with the Mini-Mental State Examination(MMSE).The relationship between malnutrition or each Mini Nutritional Assessment Short Form domain and cognitive impairment was examined with univariate and multivariate logistic regression analysis.Results: The prevalence of malnutrition,risk of malnutrition,and cognitive impairment was 5.54%,33.45%,and 36.74%,respectively.The prevalence was higher in those 80 years and older: 7.88%,40.75%,and53.65%,respectively.The Mini-Mental State Examination score was positively correlated with the Mini Nutritional Assessment Short Form score(r = 0.364,P < 0.001).After adjustment for age,gender,education,marital status,and living alone,malnutrition(odds ratio(OR)= 3.927,95%confidence interval(CI): 2.650–5.819),anorexia(OR = 1.454,95%CI:1.192–1.774),weight loss(OR = 1.697,95%CI: 1.406–2.047),impaired mobility(OR = 4.156,95% CI: 3.311–5.218),and psychological stress(OR= 1.414,95% CI: 1.070–1.869)were significantly associated with an increased risk of cognitive impairment.Conclusions: Our results suggest that the prevalence of malnutrition and cognitive impairment is relatively high and increases with age.Malnutrition,anorexia,weight loss,impaired mobility,and psychological stress are significantly associated with an increased risk of cognitive impairment.Therefore,clinicians should assess the nutritional and cognitive status of the elderly regularly to improve early detection and timely intervention.PART TWO: IDENTIFICATION THE KEY GENES IN ALZHEIMER’S DISEASEBackground Alzheimer’s disease(AD)is one of the major threats of the twenty-first century and lacks available therapy.Identification of novel molecular markers for diagnosis and treatment of AD is urgently demanded,and genetic biomarkers show potential prospects.Method We identify and intersected differentially expressed genes(DEGs)from five microarray datasets to detect consensus DEGs.Based on these DEGs,we conducted the Gene Ontology(GO),performed the Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis,constructed protein-protein interaction(PPI)network and utilized Cytoscape to identify hub genes.The LASSO logistic regression was applied to identify potential diagnostic biomarkers.Gene set enrichment analysis(GSEA)was performed to investigate the biological functions of the key genes.Result We identified 608 consensus DEGs,several dysregulated pathways and 18 hub genes.Sixteen hub genes dysregulated as AD progressed.The diagnostic model of 35 genes was constructed,which has a high AUC value in both the validation dataset and combined dataset(AUC=0.992 and AUC=0.985,respectively).The model can also differentiate mild cognitive impairment and AD patients from controls in two blood datasets.BDNF and WWTR1,which are associated with the Braak stage,Aβ42 levels and β-secretase activity,were identified as critical genes of AD.Conclusion Our study identified 16 hub genes correlated to the neuropathological stage and 35 potential biomarkers for the diagnosis of AD.WWTR1 were identified as candidate genes for future studies.This study deepens our understanding of the transcriptomic and functional features and provides new potential diagnostic biomarkers and therapeutic targets for AD.