Application Of Longitudinal Mediation Analysis In The Occurrence Of Depression And Anxiety In Parkinson's Patients

Objective:As a chronic disease,the incidence of Parkinson's disease continues to increase with the increase in the elderly population,which has a significant impact on patients'motor and non-motor functions,and increases the economic burden on society.The autonomic nerve function of Parkinson's patients begins to decline in the early stages of the disease,and the ability of daily activities gradually declines in the course of the disease,which has a great impact on the quality of life of patients.At the same time,the incidence of depression and anxiety is also higher in patients with Parkinson's disease,and these two non-motor symptoms usually exist in the same patient with Parkinson's disease.In this study we included autonomic nerve function,daily activity ability,anxiety,and depression in patients with Parkinson's disease into a longitudinal mediation analysis.We aimed to explore the interaction mechanism of these symptoms in the progression of Parkinson's patients and then provides some suggestions for the prevention and treatment of anxiety and depression in Parkinson's patients.Methods:The subjects of this study were sampled from the Parkinson's Progression Markers Initiative?PPMI?database,and 338 subjects who were diagnosed with Parkinson's disease at baseline were included.The Scales for Outcomes in Parkinson's disease-Autonomic?SCOPA-AUT?was used to evaluate the autonomic nerve function of PD patients.Patients'daily activities were evaluated using Modified Schwab and England ADL scale.The State-Trait Anxiety Inventory?STAI?and the Brief of Geriatric Depression Scale?GDS-15?were used to evaluate patients'anxiety and depression.In this study,three kinds of models of autoregressive mediation analysis were used for longitudinal mediation analysis.Using a data set uploaded in the 2018.07.02 of the PPMI and followed up for three years at a year,the patient's autonomic function,daily ability,anxiety and depression were used as independent,mediating and dependent variables.The parameter estimation method applied maximum likelihood estimation,and the biased Bootstrap method was used to test the mediated effects.Results:Parkinson's demographic information such as age(r_anxiety=0.056,p_anxiety=0.322,rdepression=0.056,pdepression=0.322),gender?ranxiety=-0.029,panxiety=0.602,rdepression=0.005,pdepression=0.933?,education level(ranxiety=0.068,panxiety=0.229,rdepression=-0.036,p_depression=0.528)and other demographic data were not significantly correlated with the patient's level of anxiety and depression in this study.In autoregressive mediation model?,the longitudinal autoregressive mediated effects of autonomic nerve function of patients on Parkinson's anxiety level through daily activities is partly significant?a₁b₁=-0.003,95%CI?-0.026,0.018?;a₂b₂=0.014,95%CI?0.002,0.039??,the longitudinal mediation effect was significant?a₁b₂=0.027,95%CI?0.005,0.067??,and the total mediating effect was also significant and equals0.039?95%CI?0.005,0.091??.The longitudinal autoregressive mediated effects of autonomic nerve function on patients'depression level through daily activities is also partially significant?a₁b₁=-0.006,95%CI?-0.053,0.036?;a₂b₂=0.014,95%CI?0.002,0.039??,the longitudinal mediation effect and total mediating effect were significant?a₁b₂=0.055,95%CI?0.010,0.134?;total mediating effects=0.077,95%CI?0.010,0.083??.In autoregressive mediation model?,the longitudinal autoregressive mediation effects and longitudinal mediation effect of autonomic nerve function affecting patients'anxiety level through daily activities are not significant?a₁b₁=-0.003,95%CI?-0.033,0.026?;a₂b₂=0.001,95%CI?-0.006,0.023?;a₁b₂=0.000,95%CI?0.020,0.010??;both the contemporaneous mediated effects and the total mediating effect were significant?a₃b₃=0.038,95%CI?0.003,0.106?;a₄b₄=0.048,95%CI?0.009,0.114?;total mediating effect=0.084,95%CI?0.015,0.184??.The longitudinal autoregressive and longitudinal mediation effects of autonomic nerve function on patients'depression level through daily activity ability were also not significant?a₁b₁=-0.005,95%CI?-0.066,0.051?;a₂b₂=0.002,95%CI?-0.012,0.045?;a₁b₂=-0.001,95%CI?-0.039,0.019??;the contemporaneous mediated effects and the total mediating effect were significant in this mediation chain?a₃b₃=0.077,95%CI?0.007,0.213?;a₄b₄=0.096,95%CI?0.015,0.227?;total mediating effect=0.169,95%CI?0.030,0.367??.The results of the autoregressive mediation model III were similar to those in model II.The longitudinal autoregressive mediation effects and longitudinal mediation effect of autonomic nerve function on patients'anxiety level through daily activities were not significant?a₁b₁=-0.002,95%CI?-0.031,0.024?;a₂b₂=0.001,95%CI?-0.006,0.022?;a₁b₂=0.000,95%CI?0.018,0.011??;both the contemporaneous mediated effects and the total mediating effect were significant?a₃b₃=0.032,95%CI?0.003,0.091?;a₄b₄=0.046,95%CI?0.008,0.108?;total mediating effect=0.078,95%CI?0.015,0.172??.The longitudinal autoregressive and longitudinal mediating effects of autonomic nerve function affecting patients'depression level through daily activity ability were also not significant?a₁b₁=-0.003,95%CI?-0.062,0.048?;a₂b₂=0.002,95%CI?-0.013,0.044?;a₁b₂=-0.001,95%CI?-0.035,0.021??;the contemporaneous mediated effects and total mediating effect were all significant too?a₃b₃=0.065,95%CI?0.005,0.182?;a₄b₄=0.092,95%CI?0.016,0.215?;total mediating effect=0.156,95%CI?0.030,0.344??.Through a comprehensive comparison of model fitting results:the autonomic function of Parkinson's patients affects the level of anxiety of patients through their daily activities:Model??AIC=12689.929,BIC=12793.151?,model??AIC=12677.427,BIC=12784.472?,model III?AIC=12669.894,BIC=12796.055?;the autonomic function of Parkinson's patients affects the level of depression in patients through their daily activities:model I?AIC=12689.929,BIC=12793.151?,model II?AIC=13614.562,BIC=13721.607?,model III?AIC=13607.029,BIC=13733.190?.In the above two mediation chains,model II has lower AIC and BIC values than model I,model III has a lower AIC and a higher BIC than model II and there is no statistically significant of the cross-lagged relations of model III added to model II.Therefore,it is considered that the fitting result of model II is relatively good.Conclusion:There is a relationship between the decline in daily activities and the occurrence and exacerbation of anxiety and depression in patients with Parkinson's disease and the autonomic nerve function in patients with Parkinson's disease.Patients'autonomic nerve function has a longitudinal mediating effect on their anxiety and depression through daily activity ability,and interactions among variables differ at different time points.In clinical work and preventive care for Parkinson's disease,we should take targeted preventive and intervention measures to improve the patient's mental life according to the characteristics of the variables among different stages.The analysis of autoregressive mediating model has a comprehensive analysis of the longitudinal interaction between variables,and can provide some methodological references for the study of the mechanism of other diseases.