The Latest Articles on Sleep in Parkinson’s Disease and Alzheimer's Disease

Our staff editors continue to share exciting, interesting, and thought-provoking reading material in the recommended articles series.

This week, we would like to share several latest articles on sleep in Parkinson’s disease and Alzheimer's disease.

Title: Slow-wave sleep and REM sleep without atonia predict motor progression in Parkinson’s disease
Authors: Meng-Xing Tao, Lin Meng, Wei-Ye Xie, Han-Xing Li, Jin-Ru Zhang, Jia-Hui Yan, Xiao-Yu Cheng, Fen Wang, Cheng-Jie Mao, Yun Shen, Chun-Feng Liu
Type: Research Article

Abstract:

Background
Growing evidence supports the potential role of sleep in the motor progression of Parkinson's disease (PD). Slow-wave sleep (SWS) and rapid eye movement (REM) sleep without atonia (RWA) are important sleep parameters. The association between SWS and RWA with PD motor progression and their predictive value have not yet been elucidated.

Methods    
We retro-prospectively analyzed clinical and polysomnographic data of 136 patients with PD. The motor symptoms were assessed using Unified Parkinson's Disease Rating Scale Part III (UPDRS III) at baseline and follow-up to determine its progression. Partial correlation analysis was used to explore the cross-sectional associations between slow-wave energy (SWE), RWA and clinical symptoms. Longitudinal analyses were performed using Cox regression and linear mixed-effects

Results
Among 136 PD participants, cross-sectional partial correlation analysis showed SWE decreased with the prolongation of the disease course (P = 0.046), RWA density was positively correlated with Hoehn & Yahr (H-Y) stage (tonic RWA, P < 0.001; phasic RWA, P = 0.002). Cox regression analysis confirmed that low SWE (HR = 1.739, 95% CI = 1.038–2.914; P = 0.036; FDR-P = 0.036) and high tonic RWA (HR = 0.575, 95% CI = 0.343–0.963; P = 0.032; FDR-P = 0.036) were predictors of motor symptom progression. Furthermore, we found that lower SWE predicted faster rate of axial motor progression (P < 0.001; FDR-P < 0.001) while higher tonic RWA density was associated with faster rate of rigidity progression (P = 0.006; FDR-P = 0.024) using linear mixed-effects models.

Conclusions  
These findings suggest that SWS and RWA might represent markers of different motor subtypes progression in PD.
Access this article: https://doi.org/10.1016/j.sleep.2024.02.003

Title: Efficacy of biologically-directed daylight therapy on sleep and circadian rhythm in Parkinson's disease: a randomised, double-blind, parallel-group, active-controlled, phase 2 clinical trial
Authors: Beatrix Feigl, Simon J.G. Lewis, Lucy D. Burr, Daniel Schweitzer, Subodh Gnyawali, Dimitrios Vagenas, Drew D. Carter, Andrew J. Zele
Type: Research Article

Summary:

Background
New non-pharmacological treatments for improving non-motor symptoms in Parkinson's disease (PD) are urgently needed. Previous light therapies for modifying sleep behaviour lacked standardised protocols and were not personalised for an individual patient chronotype. We aimed to assess the efficacy of a biologically-directed light therapy in PD that targets retinal inputs to the circadian system on sleep, as well as other non-motor and motor functions.

Methods        
In this randomised, double-blind, parallel-group, active-controlled trial at the Queensland University of Technology, Australia, participants with mild to moderate PD were computer randomised (1:1) to receive one of two light therapies that had the same photometric luminance and visual appearance to allow blinding of investigators and participants to the intervention. One of these biologically-directed lights matched natural daylight (Day Mel), which is known to stimulate melanopsin cells. The light therapy of the other treatment arm of the study, specifically supplemented the stimulation of retinal melanopsin cells (Enhanced Mel), targeting deficits to the circadian system. Both lights were administered 30 min per day over 4-weeks and personalised to an individual patient's chronotype, while monitoring environmental light exposure with actigraphy. Co-primary endpoints were a change from baseline in mean sleep macrostructure (polysomnography, PSG) and an endocrine biomarker of circadian phase (dim light melatonin secretion onset, DLMO) at weeks 4 and 6. Participants data were analysed using an intention to treat principle. All endpoints were evaluated by applying a mixed model analysis. The trial is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12621000077864.

Findings        
Between February 4, 2021 and August 8, 2022, 144 participants with PD were consecutively screened, 60 enrolled and randomly assigned to a light intervention. There was no significant difference in co-primary outcomes between randomised groups overall or at any individual timepoint during follow-up. The mean (95% CI) for PSG, N3% was 24.15 (19.82–28.48) for Day Mel (n = 23) and 19.34 (15.20–23.47) for the Enhanced Mel group (n = 25) in week 4 (p = 0.12); and 21.13 (16.99–25.28) for Day Mel (n = 26) and 18.48 (14.34–22.62) for the Enhanced Mel group (n = 25) in week 6, (p = 0.37). The mean (95% CI) DLMO (decimal time) was 19.82 (19.20–20.44) for Day Mel (n = 22) and 19.44 (18.85–20.04) for the Enhanced Mel group (n = 24) in week 4 (p = 0.38); and 19.90 (19.27–20.53) for Day Mel (n = 23) and 19.04 (18.44–19.64) for the Enhanced Mel group (n = 25) in week 6 (p = 0.05). However, both the controlled daylight (Day Mel) and the enhanced melanopsin (Enhanced Mel) interventions demonstrated significant improvement in primary PSG sleep macrostructure. The restorative deep sleep phase (PSG, N3) significantly improved at week 6 in both groups [model-based mean difference to baseline (95% CI): −3.87 (−6.91 to −0.83), p = 0.04]. There was a phase-advance in DLMO in both groups which did not reach statistical significance between groups at any time-point. There were no safety concerns or severe adverse events related to the intervention.

Interpretation        
Both the controlled daylight and melanopsin booster light showed efficacy in improving measures of restorative deep sleep in people with mild to moderate PD. That there was no significant difference between the two intervention groups may be due to the early disease stage. The findings suggest that controlled indoor daylight that is personalised to the individuals’ chronotype could be effective for improving sleep in early to moderate PD, and further studies evaluating controlled daylight interventions are now required utilising this standardised approach, including in advanced PD.
Access this article: https://doi.org/10.1016/j.eclinm.2024.102474

Title: Circadian regulation of microglia function: Potential targets for treatment of Parkinson’s Disease
Authors: Liang Kou, Xiaosa Chi, Yadi Sun, Sijia Yin, Jiawei Wu, Wenkai Zou, Yiming Wang, Zongjie Jin, Jinsha Huang, Nian Xiong, Yun Xia, Tao Wang
Type: Review Article

Abstract：
Circadian rhythms are involved in the regulation of many aspects of the body, including cell function, physical activity and disease. Circadian disturbance often predates the typical symptoms of neurodegenerative diseases and is not only a non-motor symptom, but also one of the causes of their occurrence and progression. Glial cells possess circadian clocks that regulate their function to maintain brain development and homeostasis. Emerging evidence suggests that the microglial circadian clock is involved in the regulation of many physiological processes, such as cytokine release, phagocytosis, and nutritional and metabolic support, and that disruption of the microglia clock may affect multiple aspects of Parkinson’s disease, especially neuroinflammation and α-synuclein processes. Herein, we review recent advances in the circadian control of microglia function in health and disease, and discuss novel pharmacological interventions for microglial clocks in neurodegenerative disorders.
Access this article: https://doi.org/10.1016/j.arr.2024.102232

Title: Associations of sleep-related variables with reverse dipping patterns of blood pressure in α-synucleinopathies
Authors: Yunchuang Sun, Luhua Wei, Fan Li, Chen Ling, Fei Zhai, Yunfeng Lv, Hong Zhou, Cheng Zhang, Jing Ma, Jing Chen, Wei Sun, Zhaoxia Wang
Type: Research Article

Abstract:

Introduction
The reverse dipping blood pressure (BP) pattern is very common in α-synucleinopathies. We aimed to explore the associations of sleep-related variables with abnormal BP circadian rhythms in Parkinson's disease (PD) and multiple system atrophy (MSA).

Methods
A total of 126 patients, 76 with PD and 50 with MSA, were included. All participants underwent ambulatory BP monitoring and full-night polysomnography (PSG). We analyzed abnormal dipping patterns and sleep-related parameters, including moderate to severe obstructive sleep apnea (OSA), rapid eye movement behavior disorder (RBD), average oxygen saturation (SaO2%), lowest SaO2%, duration of SaO2%<90%, and apnea-hypopnea index (AHI). Binary logistic regression was performed to explore the associations between paraclinical variables, sleep-related variables, and reverse dipping patterns.

Results
Reverse dipping patterns were predominant in patients with PD (58.5 %) and MSA (68.0 %). Patients with MSA had higher AHI, RBD, and lower average SaO2% than those with PD. Taking both diseases together as a whole group of α-synucleinopathies, logistic regression analysis indicates the Hoehn-Yahr stage (odds ratio [OR] = 2.00 for reverse systolic and 2.34 for reverse diastolic dipping patterns), moderate to severe OSA (OR = 2.71 for reverse systolic and 2.53 for reverse diastolic dipping patterns), average SaO2% (OR = 1.35 for reverse systolic dipping patterns), and male sex (OR = 2.70 for reverse diastolic dipping patterns) were independently associated with reverse dipping patterns.

Conclusions
Reverse dipping patterns were common in patients with PD and MSA. Hoehn-Yahr stage, moderate to severe OSA, average SaO2%, and male sex were associated with reverse dipping patterns in α-synucleinopathy.
Access this article: https://doi.org/10.1016/j.parkreldis.2024.106046

Title: Impact of sleep duration and sleep disturbances on the incidence of dementia and Alzheimer's disease: A 10-year follow-up study
Authors: Ying Xiong, Jonas Tvedt, Torbjörn Åkerstedt, Dorina Cadar, Hui-Xin Wang
Type: Research Article

Abstract:

The nature of the relationship between sleep problems and dementia remains unclear. This study investigated the relationship between sleep measures and dementia in older adults (≥ 65) using data from the English Longitudinal Study of Ageing (ELSA) and further investigated the causal association in Mendelian randomization (MR) analysis. In total of 7,223 individuals, 5.7 % developed dementia (1.7 % Alzheimer's disease (AD)) within an average of 8 (± 2.9) years. Cox regression models and MR were employed. Long sleep duration (>8 h) was associated with 64 % increased risk of incident dementia and 2-fold high risk of AD compared to ideal sleep duration (7–8 h). This association was particularly evident in older-older adults (≥70 years) and those who consumed alcohol. Short sleep duration (<7 h) was associated with lower risk of incident dementia among older-older but higher risk among younger-older adults. Sleep disturbances and perceived sleep quality were not associated with dementia or AD. The MR study did not reveal causal associations between sleep duration and dementia. These findings suggest that self-reported short sleep in younger-older and long sleep in older-older adults and those with frequent alcohol consumption are associated with dementia. Early detection of these sleep patterns may help identify individuals at higher dementia risk.    

Access this article: https://doi.org/10.1016/j.psychres.2024.115760