Follow-up Study Of Non-motor Symptoms And Disease Progression And The Relationship Between Vitamin D And Sleep Disorders In Parkinson’s Disease

Objective: The progression of Parkinson’s disease(PD)varies significantly.Its heterogeneity complicates our prediction of disease and may lead to difficulties in diagnosis.The neurodegenerative characteristics of Parkinson’s disease are extensive and progressive aggregation of alpha-synuclein in specific nuclei of the central and peripheral nervous systems.These pathological changes are not only the causes of motor symptoms,but also a lot of non-motor symptoms(NMS).NMS of PD can develops throughout the course of the disease,even before the clinical diagnosis of PD.NMS are interdependent with the disease progression of PD,and play an important role with the development of the disease.It can affect the motor function and quality of life of patients.It is the main cause of disability of PD and becomes the main disease burden of patients and nurses with PD.Recognition and screening of existing NMS or other clinical features may better predict disease progression.The aim of this study was to explore the role of NMS in disease severity and progression in early drug-naive PD patients.Methods: PD patients who received 3 years follow-up in the movement disorders clinics were enrolled and received Non-motor symptom questions(NMSQ),Mini-mental state examination(MMSE),Montreal cognitive assessment scale(MOCA),Epworth Sleepiness Scale(ESS),fatigue severity scal(FSS),Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Pittsburgh sleep quality index(PSQI).Multiple linear regressions were applied to assess the influence of clinical factors and NMS on Unified Parkinson’s Disease Rating Scale,part Ⅲ(UPDRS Ⅲ).Results: 1.A total of 86 PD patients(mean age 62.31±9.4 years,Hoehn and Yahr stage 1.64±0.62)were included in this study.2.During the follow-up period,UPDRS II(11.54 + 5.47 vs.7.79 + 4.20,P < 0.001),UPDRS III(26.12 + 11.15 vs.18.31 + 9.70,P <0.001)and H-Y staging(2.23 + 0.60 vs.1.64 + 0.62,P < 0.001),ESS(P = 0.002),PSQI(P< 0.001),HAMA(P = 0.013)were significantly higher than those at baseline.During the follow-up period,the scores of fall and frozen gait(P = 0.045,P < 0.001),symptomsfluctuation(P < 0.001)and MMSE(P = 0.005)and Mo CA(P < 0.001)in PD patients were significantly lower than those at baseline(72.1%,70.7% and 70.7% respectively).The most prevalent symptom was constipation(72.1%),followed by RBD(70.7%),memory(62.8%)and hyposmia(61.4%);the incidence of olfactory changes,coughing,nausea and vomiting,incomplete defecation,urgency,pain,memory loss,hallucination or hallucination,diplopia increased significantly at follow-up(P < 0.05);4.The regression model for UPDRSⅢ indicated that rigidity subtype,falls,RBD and sweating were major predictors of disease severity.Conclusion: NMS are common in early PD patients,with a high prevalence,and gradually increase with the progress of the disease.Falls,p RBD and autonomic dysfunction are risk factor for disease severity in PD.Early recognition and management of NMS may well predict the disease severity and development.Objective: Sleep disorders are common and important non-motor symptoms in Parkinson’s Disease(PD).The prevalence of sleep disorders is 40-98% in PD patients,which have a serious impact on the quality of life in PD patients.Vitamin D deficiency is widespread in patients with PD.Immunohistochemical results confirm that the human brain contains a large number of vitamin D receptors(VDR)and 1α-hydroxylase,a enzymes that produce vitamin D3,especially in substantia nigra dopaminergic neurons and hypothalamus.It is speculated that vitamin D may be involved in the mechanism of sleep regulation,although there are limited studies in PD.The incidence of insomnia is higher in PD patients with vitamin D deficiency,and the quality of sleep is poor.Video polysomnography(v PSG)is the most commonly used method for the diagnosis of sleep disorders,which can objectively and completely record sleep conditions.Our aim was to determine whether serum vitamin D levels correlated with sleep disorders and problems in patients with PD by using v PSG.Methods: 86 patients with PD were enrolled in the Department of Neurology and Sleep Center of the Second Affiliated Hospital of Suzhou University from November 2013 to April 2017.Serum vitamin D and video-polysomnography(v PSG)were examined for65 PD patients.Measures of global non-motor symptoms(Non-motor symptom questions,NMSQ),cognitive function [Minimum Mental State Examination(MMSE),Montreal Cognitive Assessment(MOCA)],excessive daytime sleepiness(Epworth Sleepiness Scale,ESS),fatigue(Fatigue Severity Scale,FSS),sleep quality(Pittsburgh sleep quality index,PSQI),quality of life(the 39-item Parkinson’s Disease Questionnaire,PDQ-39)and PD motor symptom’s severity [Hoehn & Yahr stage(H-Y)and Unified Parkinson’s Disease Rating Scale(UPDRS)] were administered.Associations between serum vitamin D levels,v PSG and clinical data were evaluated using partial correlation analysis.Levels of serum vitamin D were divided into tertiles: 1st tertile,<32.7 nmol/L;2nd tertile,32.7 ~ 45.2nmol/L;and 3rd tertile,>45.2 nmol/L.Results: 1.The average serum vitamin D level of PD patients was 42.17 ± 17.16nmol/L.There was a difference in ESS among the three groups(P = 0.014).PD patients with lower vitamin D levels had a significantly higher scores for the ESS(P = 0.014),use of sleeping medication(P = 0.044)and lower scores for sleep duration(P = 0.033).The sleep time of group 1 was higher than that of group 3(P = 0.044).In group 2(P = 0.033),the score of hypnotic drugs was higher than that in group 3(P = 0.042).3.There were significant differences in sleep time(P = 0.004),sleep efficiency(P = 0.002)and sleep latency(P = 0.038)among the three groups,and the sleep time(P = 0.001)and sleep efficiency(P < 0.001)of the first group were lower than those of the third group,while the sleep latency(P = 0.045)was higher than those of the third group.4.Univariate correlation analysis showed that serum vitamin D level was negatively correlated with ESS score(r =0.177,P = 0.025),use of sleeping medication scores(r = 0.257,P = 0.040),spontaneous arousal index(r = 0.254,P = 0.041),and significantly correlated with total sleep time(r =0.361,P = 0.003),sleep efficiency(r = 0.349,P = 0.004),N3(r = 0.254,P = 0.042).Conclusion: In patients with PD,vitamin D levels significantly correlated with some sleep problems.Thus,vitamin D supplementation is a potential therapeutic for sleep problems in PD patients.