Clinical Characteristics And HD-tDCS Intervention Of Parkinson’s Disease With REM Sleep Behavior Disorder

Background Parkinson’s disease(PD)is a relatively common disease with chronic neurodegenerative changes.It includes motional symptoms such as static tremor,muscle stiffness,motor retardation,abnormal body posture and gait,and non-motional symptoms such as cognitive decline,sleep disorders,anxiety and depression,olfactory disorders,autonomic nervous system symptoms,mental and behavioral abnormalities.Rapid eye movement sleep behavior disorder(RBD)is a kind of abnormal sleep,and also a kind of dyskinesia.RBD refers to the abnormal muscle tone during REM sleep,and the behavior that the body performs the dream.The most accurate diagnostic method is that in the polysomnography(PSG)of patients all night long,the phenomenon of muscle dystonia(RSWA)appears during rapid eye movement(REM)sleep.Research shows that RBD is known so far α Synucleoprotein disease is the strongest clinical predictor.More than 80% of RBD patients may develop into Synucleoprotein disease such as PD or other degenerative diseases of the nervous system in the later stage of the disease.Moreover,the appearance of RBD in patients with PD often marks the concomitant occurrence of more serious clinical symptoms and cognitive impairment.The first-line treatment drugs for RBD are clonazepam and melatonin.Previous studies have shown that drug treatment can only control the symptoms of RBD,and cannot delay the progress of RBD,nor can it reverse the conversion of RBD to neurodegenerative diseases such as PD.In recent years,the use of repetitive transcranial direct current stimulation(t DCS)to treat patients with PD has been more and more widely used in the world,but at present there is no international study on the use of high-precision transcranial direct current stimulation(HD-TDCS)to treat patients with PD and RBD.The Parkinson’s Progression Markers Initiative(PPMI)provides conditions for longitudinal study of imaging and clinical progress of PD with RBD through a prospective cohort study.Objective Based on different experimental hypotheses,this study aims to analyze the clinical characteristics,progress and outcome of PD with RBD,and explore the efficacy of HD-t DCS in the treatment of PD with RBD.(1)Study 1: This study intends to explore the different clinical characteristics of patients with PD with RBD and patients without RBD through scale analysis.(2)Study 2: This study intends to use PPMI database to explore which factors can predict the progress and outcome of RBD in PD.(3)Study 3: Up to now,there is no uniform treatment plan and exact effect of t DCS intervention on PD with RBD.This study intends to use HD-t DCS to intervene PD patients with RBD,explore new targets,and observe the changes of clinical scales and PSG indicators before and after their own.Methods(1)Study 1: According to the RBD Screening Questionnaire(RBDSQ),62 PD patients were divided into PD with possible RBD group(PD-pRBD)and PD without possible RBD group(PD-npRBD).The sleep,motor symptoms,severity of illness,cognition and olfaction of patients with Parkinson’s disease were evaluated by using the third part of the unified Parkinson’s disease assessment scale(MDS-UPDRS-Ⅲ),Hoehn-Yahr scale(H-Y scale),the simple mental state scale(MMSE),the Montreal Cognitive Assessment Scale(MOCA),Beijing version,and the Chinese Smell Recognition Test(CSIT).The correlation analysis and regression analysis with clinical symptoms were performed.(2)Study 2: The study subjects were 405 newly diagnosed PD patients who did not take drugs from the PPMI database.According to the baseline RBDSQ,PD patients were divided into PD-pRBD group and PD-npRBD group.They were followed up for 5 years.Prospective cohort study was used to analyze the progress and outcome of clinical symptoms of PD with RBD,and a generalized estimation equation model was established for the baseline PD-npRBD group to explore the predictive factors of the progress of RBD symptoms.(3)Study 3: The subjects were PD patients with RBD.All subjects were diagnosed as PD with RBD(PD-RBD)by RBDSQ or polysomnography.Based on the 10-20 EEG system,the brain area is located by wearing a 64-channel high-precision electrode cap.The negative electrode is placed in the left primary motor area(M1),and the anode is located in FC5,FC1,CP5 and CP1 respectively.Subjects received electrical stimulation once a day for a total of 10 treatments,and were evaluated for RBD clinical symptoms before and after treatment.Results(1)Study 1: There was no significant difference between PD-pRBD group and PD-npRBD group in age,sex,education level,course of disease,severity of disease and cognitive ability,but PD-pRBD group showed more severe olfactory dysfunction than PD-npRBD group(t=2.44,P=0.018).Rank correlation analysis showed that there was a negative correlation between olfactory recognition score and RBDSQ score(rs=-0.413,P=0.001).The score of olfactory recognition was positively correlated with the score of Mo CA and MMSE(rp=0.274,P=0.031;rs=0.266,P=0.036).Bivariate logistic regression analysis found that the higher the olfactory recognition score,the lower the risk of RBD outcome(OR=0.87,P=0.027).(2)Study 2: At baseline,all patients did not receive dopamine replacement therapy(DRT);The prevalence of PD-pRBD was 24.7%,and the average score of RBDSQ was4.07 ± 2.66.After 5 years,the proportion of patients using DRT was 96.2%,the prevalence of PD-pRBD was 36.9%,and the average score of RBDSQ in the fifth year was 4.86 ± 3.19.For PD patients with baseline PD-npRBD,there was a significant difference in the change of RBDSQ score between patients with different treatments(P<0.001).Specifically,the RBDSQ score of patients receiving levodopa treatment was significantly higher than that of patients not receiving DRT and dopamine agonist treatment(P<0.001;P=0.006).In addition,the RBDSQ score of patients treated with levodopa and dopamine agonist was significantly higher than that of patients not treated with DRT and dopamine agonist(P<0.001;P=0.005).In addition,except for the second year,the increase of RBDSQ score was significantly correlated with the equivalent dose of levodopa,but not with the equivalent dose of dopamine agonists.For PD patients with baseline PD-npRBD,the change of RBDSQ score at follow-up was significantly related to the use of levodopa alone(OR=1.875(1.176 to 2.991),P=0.008)and the combination of levodopa and dopamine agonists(OR=2.188(1.190 to 4.023),P=0.012)and the amount of levodopa equivalent(OR=1.001(1.000 to 1.001),P=0.005).Similarly,in the Logit model(QIC=1310.61),the conversion from PD-npRBD to PDpRBD was significantly correlated with the equivalent dose of levodopa(OR=1.001(1.000 to 1.001),P=0.014),but not with the equivalent dose of dopamine agonist(OR=1.001(0.999 to 1.002),P=0.574).(3)Study 3: 11 patients with PD-RBD were finally included.After 10 times of HDt DCS treatment,the clinical symptoms after stimulation were significantly improved.It is mainly reflected in the scores of RBDSQ and RBD Screening Questionnaire Hong Kong(RBDSQ-HK)(Z=2.232,P=0.026;Z=2.852,P=0.004),the total score of MDS-UPDRS and the third part(Z=2.940,P=0.003;Z=2.941,P=0.003),and the score of Parkinson’s disease sleep scale(PDSS)(Z=2.499,P=0.012).Conclusions(1)Study 1: The olfactory recognition ability of patients in PDpRBDgroup was significantly lower than that in PD-npRBD group,and there was a negative correlation between olfactory recognition ability and RBDSQ score.The stronger the ability of odor recognition,the lower the probability of RBD.(2)Study 2: The use of levodopa can predict the clinical progress of RBD symptoms,and may also be an important promoter of RBD after the onset of PD.It is suggested that there may be two different pathogenesis of RBD occurring at different time in PD patients,and dopamine drugs may play a more important role in the occurrence and development of post-PD RBD.(3)Study 3: This study is the first time to explore the movement symptoms and RBD clinical symptoms of PD-RBD patients treated with HD-t DCS for 10 consecutive times,affirming that HD-t DCS as a non-invasive auxiliary treatment can alleviate RBD symptoms,improve movement function and improve sleep quality.