Study On The Related Predictors Of Post-ischemic Stroke Apathy And Preventive Effect Of Early Stroke Rehabilitation On Post-ischemic Stroke Apathy

Part Ⅰ:The related predictors of post-ischemic stroke apathy.Objective: Cerebral infarction is one of the major diseases that endanger the physical health and life of middle-aged and elderly people.It not only affects the speech function and body movement of patients,but also leads to the occurrence of anxiety,depression and apathy of patients.At present,many studies have found that apathy is a common symptom after stroke,and even the core symptom of some stroke patients.Post-ischemic stroke apathy is a disorder of motivation,characterized by reduced initiative,difficulty in initiating,difficulty in maintaining or completing assigned tasks,decreased self-activation or self-priming,and indifference to emotion.There are relatively few researches on stroke patients at home and abroad,but the incidence of post-ischemic stroke apathy is very high.In recent years,researches on risk factors and structural basis of apathy have become hot spots.Related studies have shown that the incidence of apathy after stroke varies with different study design and evaluation methods.As a kind of emotional disorder after stroke,post-stroke apathy may be affected by multiple factors.It has been found that post-stroke apathy is significantly correlated with such factors as old age,cognitive dysfunction,activities of daily living function impairment and posterior limb injury of internal capsule.In elderly patients,inflammatory markers are associated with depression,but whether they are associated with apathy remains unclear.C-reactive protein(CRP)is an acute phase reaction protein synthesized by the liver,is the biological markers of inflammation.It is also extremely sensitive to the coronary heart disease events and it is one of the predicting factors of occurrence of future ischemic stroke.Besides,it is also a new marker of atherosclerosis diseases,it can reflect the artery atheromatous plaque in inflammatory activity.What more,it is a direct regulator of atherosclerotic plaque formation.Cheng et al.found that CRP was related to the outcome of stroke and the occurrence of future vascular events.Wysokiński A et al.found that the higher the CRP,the more severe the depressive symptoms.In Alzheimer’s patients,the higher the CRP level,the higher the apathy score.However,in patients withischemic stroke,the relationship between CRP level and apathy has not been studied.Therefore,it is urgent to explored the association between the biochemical factors and post-ischemic stroke apathy.Between June 2016 and June 2017,584 patients with ischemic stroke who were consecutively admitted to the stroke unit of the Department of Neurology at Ji’an Central People’s Hospital were recruited.We investigated the incidence rate of apathy in patients with ischemic stroke and its related influencing factors.The aim was to reveal the early predictive factors of some biochemical indicators(e.g.,CRP)on post-ischemic stroke apathy.Methods:Peripheral venous blood was extracted in the morning of the next day after admission,and levels of CRP,plasma homocysteine(Hcy),blood glucose,blood lipid series,fibrinogen(Fib)were measured.Within 7 days after stroke,apathy symptoms were assessed using the Apathy Evaluation Scale-Clinical(AES-C).Demographic and clinical information were obtained using the National Institutes of Health Stroke Scale(NIHSS)scores,Barthel Index(BI)scores,Mini-Mental State Examination(MMSE)scores,Hamilton Depression Scale(HAMD)scores,and Hamilton Anxiety Scale(HAMA)scores.The serum levels of C-reactive protein(CRP),homocysteine(Hcy),blood sugar,lipid spectrum,and fibrinogen of patients were determined at admission.The factors that were statistically significant(P < 0.05)were analyzed,and multivariate logistic regression model was used to analyze the related factors of post-stroke apathy during the acute stage of ischemic stroke.Patients were followed up via telephone,home visit or outpatient follow-up(1 month,3 months and 6 months after stroke)after discharge,and the follow-up content was mainly AES-C.Results:During the follow-up period,432 patients were followed up and the final data were analyzed.1.We found that 35.27% of patients(206 patients for apathy in 584 patients)with acute ischemic stroke experienced apathy at admission,39.49% of patients(216 patients for apathy in 547 patients)with acute ischemic stroke experienced apathy at 1 month,42.45% of patients(211patients for apathy in 497 patients)with acute ischemic stroke experienced apathy at 3 month,34.95% of patients(151 patients for apathy in 432patients)with acute ischemic stroke experienced apathy at 6 month.2.When the confounders affecting of post-stroke apathy are not considered,based onunivariate logistic regression(enter)analysis,we showed that age,hours of sleep,level of education,body mass index(BMI),HAMD score,NIHSS score,MMSE score,BI score,HCY,HbA1,CRP,frontal lobe,basal ganglia,and pontine significantly related to post-stroke apathy at baseline(P < 0.05).3.The education duration,MMSE and BI scores of patients in the acute PSA group were lower than those in the non-apathy group(P < 0.05).4.Thus,for post-stroke apathy at baseline,these independent variables were entered into the multivariate logistic regression model.These analyses were conducted using only baseline variables.Multivariate logistic regression(stepwise forward)analysis demonstrated that low MMSE score(OR=0.715,95% CI: 0.564-0.844,P =0.001),and low BI score(OR=0.865,95% CI: 0.779-0.960,P =0.006),high BMI(OR=1.420,95%CI: 1.094-1.843,P=0.008),high HAMD score(OR=1.226,95% CI: 1.050-1.432,P=0.010),and high NIHSS score(OR=1.483,95% CI: 1.126-1.953,P=0.005)were associated with post-stroke apathy at baseline.5.Multivariate logistic regression(stepwise forward)analysis found that the level of CRP(OR =3.889,95% confidence interval: 2.111-7.164,P < 0.001)on admission was most closely related to the post-stroke apathy at baseline,and it was the related risk factor for the onset of post-stroke apathy in the acute phase.6.The incidence of post-stroke apathy was significantly different at different time periods(at admission,1 month,3 months and 6 months after stroke).AES-C score was highest at 3 months after stroke,but lower than that at admission(P <0.05).7.At 6 months after stroke,AES-C score was significantly correlated with high CRP,high AES-C score and low BI score on admission(P <0.05).Conclusion:1.The incidence of post-stroke apathy was highest at 3 months after stroke,lowest at 6months after stroke,and lower than the incidence of apathy after admission.2.Higher BMI score,HAMD score,NIHSS score,and CRP at admission were closely related to the apathy in the acute phase of ischemic stroke,of which the CRP level at admission is most closely related to the apathy in the acute phase of ischemic stroke.3.Low MMSE and BI scores on admission may be risk factors for apathy in acute phase of ischemic stroke.4.Low BI scores,high CRP and high AES-C scores on admission were risk factors for post-stroke apathy at 6 months after ischemic stroke.5.AES-C score was highest at 3 months after ischemic stroke,but lowest at 6 months after ischemic stroke and below the level at admission.Part Ⅱ: Preventive effect of early stroke rehabilitation on post-ischemic stroke apathy.Objective:Apathy refers to the emotional response to the external stimuli corresponding and inner experience,characterized by loss of motivation,interest,attention and emotional response.Its core is characterized by patients in the purposeful activity behavior,cognitive and purpose about the lack of emotional behavior,lead to lose initiative,reduce contact with environment,the loss of interest in social life activities.Many diseases such as stroke,Alzheimer’s disease,Parkinson’s disease and schizophrenia can lead to apathy.Post-stroke apathy(PSA)is a common post-stroke emotional disorder,characterized by reduced initiative,difficulty in initiating,difficulty in maintaining or completing assigned tasks,and indifference to emotion.As post-stroke apathy can seriously affect the patient’s daily living ability,functional recovery,rehabilitation exercise,quality of life,and so on,it brings serious economic burden to the patient’s family and society,which is increasingly concerned by people.However,there are few reports on the post-stoke apathy.Now,dopamine receptor agonist and central nervous system stimulant were often used in clinical treatment of apathy,but the treatment effect was not ideal.Therefore,early prevention of apathy after ischemic stroke is of vital importance.A prospective cohort study was undertaken in the stroke unit of the Department of Neurology at Ji’an Central People’s Hospital from June 2016 to January2018 involving 518 ischemic stroke patients.We followed up these patients who had received rehabilitation therapy within 1 month after stroke,to explore the apathy preventive effects of early rehabilitation therapy in different time periods and the possible reasons.Methods:A total of 436 patients were selected according to the inclusion and exclusion criteria.Patients were followed up 1 month,3 months,6 months,9 months and 12 months after stroke by telephone,home visit or outpatient follow-up.The Apathy Evaluation scale-clinical(AES-C)and Hamilton Depression Scale(HAMD)were used in the follow-up process until 12 months after stroke.According to the rehabilitation treatment methods of Motor Relearning Programme(MRP)and Bobath therapy or not in our hospital for 3 weeks within 1 month after ischemic stroke,the patients were divided into rehabilitation treatment group or non-rehabilitation treatment group.The follow-upoutcome event was the first diagnosis of PSA.Results:1.Baseline characteristics of the subjects were: age mean 65.1(SD 10.9);47.1%female.2.Apathy Evaluation Scale-Clinical mean 24.9(SD 4.7);National Institutes of Health Stroke Scale mean 3.9(SD 3.8);Barthel Index mean 87.9(SD 8.7);Mini-Mental State Examination mean 23.3(SD 4.5);Hamilton Depression Scale mean 17.5(SD 6.6);Hamilton Anxiety Scale mean 14.4(SD 6.2).3.Participants in both groups had similar levels of apathy symptoms at study admission(rehabilitation treatment group,mean=24.78,standard deviation=4.62;non-rehabilitation treatment group,mean=25.07,standard deviation=4.75).4.The Apathy Evaluation Scale scores of participants in both groups demonstrated to decline gradually from month 1 to month 12.5.Rehabilitation treatment participants had significantly less apathy severity compared to Bobath participants with respect to each time point(P<0.05).6.In the 12 months follow-up,a total of 78 patients(35.78%)in the rehabilitation treatment group were first diagnosed with PSA.Among them,30 patients(14.85%)at 1month after stroke,19 patients(11.52%)at 3 months after stroke,15 patients(11.03%)at6 months after stroke,10 patients(8.70%)at 9 months after stroke and 4 patients(4.30%)at 12 months after stroke were first diagnosed with PSA.7.In the 12 months follow-up,a total of 144 patients(66.67%)in the non-rehabilitation treatment group were first diagnosed with PSA.Among them,62 patients(30.39%)at 1month after stroke,37 patients(28.68%)at 3 months after stroke,25patients(30.49%)at6 months after stroke,14patients(28.57%)at 9 months after stroke and 6 patients(20.69%)at 12 months after stroke were first diagnosed with PSA.8.Participants not given rehabilitation treatment were 2.198 times more likely to develop post-stroke apathy than patients given rehabilitation treatment over 12 months.9.After excluding the depression patients,participants not given rehabilitation treatment were 2.494 times more likely to develop post-stroke apathy than patients given rehabilitation treatment over 12 months.Conclusion:1.The Apathy Evaluation Scale scores of participants in both groups demonstrated to decline gradually from month 1 to month 12.2.Rehabilitation treatment participants had significantly less apathy severity compared to non-rehabilitation treatment participants with respect to each time point.3.Over time,the ratio of patients with first diagnosed with PSA decreased gradually in both groups.4.Compared with non-rehabilitation therapy,rehabilitation treatment within 1 month after stroke was more effective in preventing the first occurrence of post-stroke apathy in1 year’s follow-up after stroke.