Changes Of Objective Sleep Parameters And Effects Of Light Intervention On Clinical Symptoms Of Parkinson’s Disease

Objective: Parkinson’s disease(PD)is the second most common neurodegenerative disease.The clinical features of PD include motor symptoms such as bradykinesia,tremor,and myotonia,and non-motor symptoms such as sleep disorders,olfactory disorders,and cognitive impairment.As the most common non-motor symptom of PD,there is a bidirectional relationship between sleep disorders and PD,and it will also affect other clinical symptoms of PD.Therefore,exploring the changes of sleep parameters in PD patients and their correlation with the progression of PD clinical symptoms is of great significance for finding clinical intervention targets.In recent years,some studies have found that light can improve the clinical symptoms of neurodegenerative diseases,but systematic and comprehensive clinical studies are still lacking.Therefore,this study aimed to analyze the changes of objective sleep parameters in PD,their correlation with clinical symptoms,and their predictive value for the progression of motor symptoms.A randomized controlled trial was conducted to evaluate the effect of light on motor and non-motor symptoms in patients with Parkinson’s disease(PD),and to observe the electrophysiological and imaging changes of PD patients after light intervention.Method:(1)Clinical data and Polysomnographic(PSG)data of 136 PD patients(PD group)and 140 age-and sexmatched healthy controls(control group)were retrospectively analyzed.PD patients were followed up for 4.63(1-6.5)years to evaluate the progression of motor and non-motor symptoms.The differences in demographic characteristics and objective sleep parameters between PD group and control group were compared.Partial correlation analysis was used to explore the characteristic sleep parameters slow-wave energy(SWE)and rapid eye movement(REM)during Non-rapid eye movement(NREM)sleep.To investigate the correlation between Rapid eye movement sleep without atonia(RWA),a characteristic sleep parameter during REM sleep,and motor and non-motor symptoms in PD.Cox regression model and linear mixed model were used to explore the predictive value of SWE and RWA for the progression of different motor symptom subtypes of PD.In this prospective,randomized,crossover,self-controlled study,33 PD patients were randomly assigned to the bright-dim group and the dim-bright light group.Seventeen patients in the bright-dim light group were first treated with 10000 Lux of bright light for 30 days,and then received 200 Lux of low light for 30 days after a 30-day washout period.The low-bright group(n = 16)had the reverse sequence(30 days 200 Lux low-light intervention,30 days washout period,30 days 10000 Lux bright-light intervention).All patients underwent polysomnography(PSG)and comprehensive clinical assessment at baseline,the first intervention period,the washout period,and the next day after the second intervention(a total of four times).Analysis of variance was used to compare the effects of bright light and low light on objective sleep parameters and clinical symptoms of PD.(3)Twenty-eight PD patients received light intervention(15 cases in the bright-low-light group,15 cases in the dim-light group;Dim-light and bright-light group(n = 13).Four 64-channel high-density electroencephalograms were performed at baseline,the first intervention period,the washout period,and the next day after the second intervention(EEG)and Functional magnetic resonance imaging(f MRI).EEG source analysis,functional connectivity analysis,brain network topology analysis based on graph theory,functional connectivity analysis based on f MRI,and network topology analysis based on graph theory were used to explore the regulatory effect of light intervention on the brain network of PD.Results:(1)PD patients had a higher proportion of NREM stage 1 sleep(P < 0.001)and higher density of tonic RWA(P < 0.001)and phasic RWA(P < 0.001)than controls.The proportion of NREM sleep stage 2(P = 0.027)and SWE level(P = 0.036)were lower.The results of subjective sleep scale showed that ESS score(P < 0.001)and PSQI score(P < 0.001)in PD patients were higher than those in control group.Cross-sectional analysis showed that SWE in PD patients decreased with the prolongation of disease duration(P = 0.046),SWE was negatively correlated with age(P = 0.044),and SWE was higher in female PD patients than in male PD patients(P = 0.011).The density of tonic RWA was significantly associated with Hoehn-Yahr(H-Y)stage(P < 0.001),Levodopa equivalent dose(P < 0.001),and levodopa equivalent dose(P < 0.001).(LEDD)(P = 0.002)and Excessive daytime sleepiness(ESS)(P = 0.010).The density of phasic RWA was positively correlated with LEDD(P = 0.020)and H-Y stage(P = 0.002).Longitudinal analysis showed that low level of SWE(FDR-P =0.036)and high tonic RWA density(FDR-P = 0.036)were predictors of motor symptom progression.A low level of SWE predicted faster progression of axial symptoms(FDR-P <0.001),and a high density of tonic RWA was associated with faster progression of tonic symptoms(FDR-P = 0.024).(2)In the study of light intervention in PD patients,compared with dim light intervention,bright light intervention increased SWE level(P = 0.041),shortened sleep latency(P = 0.031),and decreased ESS score(P = 0.018)in PD patients,but there was no statistical difference in the effect of the two light interventions on RWA(tonic RWA: P = 0.554;Phase RWA: P = 0.696).The Pittsburgh Sleep Quality Index(PSQI)scores decreased after both strong light and dim light intervention(strong light: P = 0.005;Dim light: P = 0.027),but there was no significant difference between the two intervention effects(P = 0.827).(3)Twenty-eight patients underwent high-density EEG and f MRI examination.EEG analysis showed that the Phase Locking Value(PLV)of the α band in the right inferior frontal gyrus and the right superior temporal gyrus(FDR-P = 0.024),the right inferior frontal gyrus and the right middle temporal gyrus(FDR-P = 0.024)in the right orbital inferior frontal gyrus and the right middle temporal gyrus(FDR-P = 0.024)in the bright light intervention group.PLV)increased higher than dim light.In addition,compared with dim light,the global efficiency of α(P = 0.031),β(P = 0.025)and δ(P = 0.029)frequency band in the brain network characteristics of PD patients after bright light intervention was significantly higher than that in the control group(P < 0.05),and the local efficiency of α frequency band(P = 0.043)increased,the characteristic path length of the β(P = 0.046)and α(P = 0.034)bands decreased.The f MRI results showed that sigma(P =0.027)of the small world index of the brain of PD patients increased after bright light intervention compared with dim light intervention.Conclusion:(1)Objective sleep parameters were changed in PD patients and correlated with the progression of motor symptoms.(2)Light intervention can improve the non-motor symptoms of PD patients.Compared with dim light intervention,bright light intervention can improve the symptoms of daytime sleepiness,increase the level of SWE,and shorten the sleep latency of PD patients.(3)Bright light can improve the ability of brain network to transmit information and enhance the flexibility of brain network in PD patients.We speculate that this may be one of the mechanisms of bright light improving the clinical symptoms of PD patients.