Sleep In Parkinson's Disease Patients Research Articles

Deep brain stimulation of the subthalamic nucleus improves sleep in Parkinson disease patients: A systematic review and meta-analysis.

Sleep disorders significantly affect the quality of life in Parkinson disease (PD) patients. Deep brain stimulation of the subthalamic nucleus has been reported to improve motor symptoms and decrease medication usage. However, the impact of subthalamic nucleus deep brain stimulation (STN-DBS) on sleep quality in PD patients remains to be definitively determined. This systematic review and meta-analysis, conducted following the preferred reporting items for systematic reviews and meta-analyses guidelines, aimed to clarify the effect of STN-DBS on sleep quality in PD patients. A rigorous literature search identified 6 studies, including 1 randomized controlled trial and 5 self-controlled trials, totaling 154 patients who underwent deep brain stimulation, providing 308 pairs of data for analysis. Parkinson disease sleep scale was the primary measure of interest, while the Movement Disorder Society-sponsored revision of the unified Parkinson disease rating scale was documented in all trials. Study quality was assessed using the Newcastle-Ottawa scale. STN-DBS significantly improved Parkinson disease sleep scale scores (mean difference = 20.41, 95% CI: [13.03, 27.79], I² = 60.8%, P < .001), indicating enhanced sleep quality. Furthermore, a significant reduction in movement disorder society unified Parkinson disease rating scale part III scores postoperatively (mean difference = -12.59, 95% CI: [-14.70, -10.49], I² = 89.9%, P < .001) suggested improved motor function. PD medication usage was also significantly reduced postoperatively (mean difference = -314.71, 95% CI: [-468.13, -161.28], I² = 52.9%, P < .001). A sensitivity analysis confirmed the robustness of the main findings. The sample size was adequate, allowing for conclusive inferences. The present study, which comprises a comprehensive systematic review and meta-analysis, offers compelling evidence that STN-DBS can ameliorate sleep quality, augment motor function, and curtail medication consumption among individuals afflicted with PD.

Telehealth for Parkinson disease patients during the COVID-19 pandemic: the TeleParkinson study.

Telemedicine allows Parkinson disease (PD) patients to overcome physical barriers to access health care services and increases accessibility for people with mobility impairments. To investigate the feasibility indicators of a telehealth intervention for PD patients, including patient recruitment, attendance, technical issues, satisfaction, and benefits on levels of physical activity and sleep. We conducted a single-center, single-arm study of telehealth video consultations using WhatsApp (Meta Platforms, Inc., Menlo Park, CA, USA). Also, we collected the feasibility indicators as the primary endpoints. All the patients in the study were previously evaluated in person by the same team. Patient recruitment, attendance, and technical issues rates were 61.3%, 90.5%, and 13.3%, respectively, with good scores of patient acceptance and satisfaction with the study intervention. The telehealth intervention improved physical activity, including the number of walks for at least 10 continuous minutes (p = 0.009) and the number of moderate-intensity activities lasting at least 10 continuous minutes (p = 0.001). The Pittsburgh sleep quality index (PSQI) scores also improved for one of its components: perceived sleep duration (p < 0.001) and for total Pittsburgh score (p < 0,001). The average travel time saving was 289.6 minutes, and money-saving was R$106.67 (around USD 18; almost 10% of the current minimum wage in Brazil). Direct-to-patient telehealth video consultations proved to be feasible and effective and had a positive impact on physical activity levels and sleep in PD patients.

Narcolepsy genetic marker HLA DQB1*06:02 and excessive daytime sleepiness in Parkinson disease patients treated with dopaminergic agents.

To determine whether narcolepsy Human Leukocyte Antigen (HLA) risk allele DQB1*0602 is associated with excessive daytime sleepiness (EDS) and inappropriate sleep in patients with Parkinson disease (PD). EDS is a common and disabling non-motor manifestation of PD, affecting quality of life and driving performance. DQB1*0602 is an HLA risk allele for narcolepsy. It is present in 12-30% of the general population. We hypothesize that DQB1*0602 is associated with an increased risk of EDS and inappropriate sleep in PD patients. This was a cross-sectional observational study of 150 PD individuals on dopaminergic agents. Main outcome measures were DQB1*0602 status and the modified Epworth Sleepiness Scale. Individuals with dementia, loss of independence, narcolepsy and untreated sleep apnea were excluded. Confounding variables for EDS were assessed using Parkinson Disease Sleep Scale, Mayo Sleep Questionnaire, Unified PD Rating Scale, Hoehn and Yahr scale. DQB1*06:02 positive PD patients were approximately three times more likely to experience EDS and fall asleep inappropriately during activities that required sustained alertness (e.g. driving, eating, attending work etc.). Exploratory post hoc analysis showed a dopaminergic drug dose- and type- dependent effect on daytime sleepiness in DQB1*06:02 positive individuals. No significant differences were found in confounding variables. PD individuals are more likely to experience EDS and fall asleep inappropriately during activities if DQB1*0602 positive. Genetic vulnerability may explain EDS risk in PD.

Clinical characteristics of sleep disorders in patients with Parkinson's disease.

In order to investigate the sleep quality and influencing factors in patients with Parkinson's disease (PD), 201 PD patients were enrolled and underwent extensive clinical evaluations. Subjective sleep evaluation was assessed using the Pittsburgh Sleep Quality Index (PSQI), and the Epworth Sleepiness Scale (ESS). It was found that poor sleep quality (77.11%) and excessive daytime sleepiness (32.34%) were commonly seen in PD patients and positively correlated with disease severity. Then 70 out of the 201 PD patients and 70 age- and sex-matched controls underwent a polysomnographic recording. The parameters were compared between PD group and control group and the influencing factors of sleep in PD patients were analyzed. The results showed that sleep efficiency (SE) was significantly decreased (P<0.01), and sleep latency (SL) and the arousal index (AI) were increased (P<0.05) in the PD group as compared with those in the control group. SE and total sleep time (TST) were positively correlated with the Hoehn and Yahr (H&Y) stage. There was significant difference in the extent of hypopnea and hypoxemia between the PD group and the control group (P<0.05). Our results indicate that PD patients have an overall poor sleep quality and a high prevalence of sleep disorder, which may be correlated with the disease severity. Respiratory function and oxygen supply are also affected to a certain degree in PD patients.

An observational clinical and video-polysomnographic study of the effects of rotigotine in sleep disorder in Parkinson's disease.

Sleep disturbance is common in Parkinson's disease (PD) and negatively impacts quality of life. There is little data on how dopamine agonists influence nocturnal sleep in PD, particularly in sleep laboratory data to measure sleep parameters and their changes objectively. The goal of this open-label study was to objectively evaluate the effect of rotigotine on sleep in PD patients by video-polysomnographic methods. A total of 25 PD patients with complaints of nocturnal sleep impairment were enrolled. The sleep quality before and after stable rotigotine therapy was evaluated subjectively through questionnaire assessments and objectively measured by video-polysomnographic methods. The Parkinsonism, depression, anxiety, and quality of life of PD patients were also evaluated through questionnaire assessments. At the end of rotigotine treatment, the PD daytime functioning, motor performance, depression, subjective quality of sleep, and the quality of life improved. Video-polysomnographic analysis showed that the sleep efficiency and stage N1% were increased, while the sleep latency, wake after sleep onset, and the periodic leg movements in sleep index were decreased after rotigotine treatment. Video-polysomnographic analysis confirmed the subjective improvement of sleep after rotigotine treatment. This observation suggests that in PD rotigotine is a treatment option for patients complaining from sleep disturbances.

The Evolution of REM Sleep Behavior Disorder in Early Parkinson Disease.

To investigate the development of REM sleep behavior disorder (RBD) and REM sleep behavioral events (RBE) not yet fulfilling diagnostic criteria for RBD as markers for neurodegeneration in a cohort of Parkinson disease (PD) patients between their de novo baseline assessment and two-year follow-up in comparison to healthy controls (HC). Clinically confirmed PD patients and HC with video-supported polysomnography (vPSG) data at baseline were re-investigated after two years. Diagnostic scoring for RBE and RBD was performed in both groups and related to baseline findings. One hundred thirteen PD patients and 102 healthy controls (HC) were included in the study. Within two years, the overall occurrence of behaviors during REM sleep in PD patients increased from 50% to 63% (P = 0.02). RBD increased from 25% to 43% (P < 0.001). Eleven of 29 (38%) RBE positive PD patients and 10/56 (18%) patients with normal REM sleep at baseline converted to RBD. In HC, the occurrence of any REM behavior increased from 17% to 20% (n.s.). RBD increased from 2% to 4% (n.s.). One of 15 (7%) RBE positive HC and 1/85 (1%) HC with normal REM at baseline converted to RBD. RBD increased significantly in PD patients from the de novo state to two-year follow-up. We propose RBE being named "prodromal RBD" as it may follow a continuous evolution in PD possibly similar to the spreading of Lewy bodies in PD patients. RBD itself was shown as a robust and stable marker of early PD.

Sleep correlates of trait executive function and memory in Parkinson's disease.

Sleep disturbance and cognitive impairment are correlated in non-diseased populations, but their association in Parkinson's disease (PD) is uncertain. Prior studies examining measures of cognition in relation to sleep have used either self-report or actigraphically measured sleep and have produced conflicting findings. In this descriptive study, we correlated measurements of sleep in PD patients derived from the gold-standard measurement, in-lab polysomnography, with an extensive battery of cognitive measures. We hypothesized that poorer sleep would be related to relatively more impaired cognition. Idiopathic PD patients (n = 34) completed a cognitive battery encompassing three broad domains (executive function, immediate memory and delayed memory), and underwent PSG for two nights. Scores for each domain from individual cognitive measures were converted to z-scores and then averaged to produce a composite score. We used second night PSG data and quantified measures of sleep architecture, sleep continuity, sleep apnea and nocturnal movement (periodic leg movements, PLMS). Lower executive function was associated with higher PLMS after controlling for chronological age, mini-mental state examination scores, and UPDRS motor subscale scores. These results were independent from psychomotor speed. There was a marginally significant positive correlation between the proportion of time spent in REM and immediate recall ability. Measures of sleep continuity and sleep apnea were unrelated to cognition in these patients. PLMS, known to be a frequent feature of PSG-measured sleep in PD, may be an important correlate of impaired executive function in PD. Whether treating this disorder of sleep results in improvement in cognition remains to be determined.

Sleep Disorders in Parkinson’s Disease: Clinical Features, Iron Metabolism and Related Mechanism

ObjectiveTo investigate clinical features, iron metabolism and neuroinflammation in Parkinson’s disease (PD) patients with sleep disorders (SD).Methods211 PD patients were evaluated by Pittsburgh Sleep Quality Index (PSQI) and a body of scales for motor symptoms and non-motor symptoms. 94 blood and 38 cerebral spinal fluid (CSF) samples were collected and iron and its metabolism-relating proteins, neuroinflammatory factors were detected and analyzed.Results136 cases (64.5%) of PD patients were accompanied by SD. Factor with the highest score in PSQI was daytime dysfunction. Depression, restless leg syndrome, autonomic symptoms and fatigue contributed 68.6% of the variance of PSQI score. Transferrin level in serum and tumor necrosis factor–α level in CSF decreased, and the levels of iron, transferrin, lactoferrin and prostaglandin E2 in CSF increased in PD patients with SD compared with those without SD. In CSF, prostaglandin E2 level was positively correlated with the levels of transferrin and lactoferrin, and tumor necrosis factor–α level was negatively correlated with the levels of iron, transferrin and lactoferrin in CSF.ConclusionsDepression, restless leg syndrome, autonomic disorders and fatigue are the important contributors for the poor sleep in PD patients. Abnormal iron metabolism may cause excessive iron deposition in brain and be related to SD in PD patients through dual potential mechanisms, including neuroinflammation by activating microglia and neurotoxicity by targeting neurons. Hence, inhibition of iron deposition-related neuroinflammation and neurotoxicity may cast a new light for drug development for SD in PD patients.

An 8-weeks exercise muscle training improves subjective fatigue and quality of sleep in Parkinson Disease’s patients

Numerous studies have previously shown that physical activity improves quality of life in patients with Parkinson Disease (PD) in several areas. Between non-motor difficulties, PD patients develop sleep disturbances. Poor reported sleep quality is very common in this condition and it is important to be taken into account because it impacts seriously on daily function. The objective of this study was to assess the effectiveness of an eight weeks exercise program with elastic bands on the subjective quality of sleep in PD patients. A sample including 23 PD patients with more than 21 punctuation in the MiniMental State Examination were recruited from a local association. Each participant underwent an individual assessment. Anthropometric data were measured. Outcomes measures were perceived sleep quality measured with the Pittsburgh Sleep Quality Index (PSQI) and perceived fatigue evaluated with the Piper Questionnaire. The participants were included in an eight weeks-physical activity program with elastic bands during an hour three times per week. The majority of the participants were men (74%) with a mean age of 74.12 ± 6.11 years old. The Geriatric Functional Rating Scale (GFRS) showed a 70% value of functionality. Their Hoen & Yahr score in off condition was I in the 4.3% of participants, II in 17.4%, III in 52.2% and IV in the 26.1%. Pre-to-postintervention significant improvements ( p = 0.011) are important to consider regarding to perceived quality of sleep in total punctuation of PSQI. Significant differences ( p = 0.005) were found in the sleep disturbances subscale, that appear to be reduced after the 8 weeks training program. Perceived fatigue was also significantly better ( p < 0.05) after the exercise program. The participants reported improvements in the areas of behavioural, affective and sensorial fatigue. The exercise program used in this study was safe and effective in order to improve perceived fatigue and quality of sleep in PD patients.

Deep Brain Stimulation of Pedunculopontine Tegmental Nucleus: Role in Sleep Modulation in Advanced Parkinson Disease Patients—One-Year Follow-Up

Sleep disorders are frequent non-motor symptoms in Parkinson disease (PD), probably due to multifactorial pathogeneses including disease progression, dopaminergic drugs, or concomitant illness. In recent years, the pedunculopontine tegmental (PPTg) nucleus has been considered a surgical target for deep brain stimulation (DBS) in advanced PD patients. As it is involved in controlling the sleep-wake cycle, we investigated the long-lasting effects of PPTg-DBS on the sleep of five PD patients implanted in both the PPTg and the subthalamic nucleus (STN) by rating two subjective clinical scales for sleep: the Parkinson's Disease Sleep Scale (PDSS), and the Epworth Sleepiness Scale (ESS). Sleep scales were administered a week before surgery (T0), three months after DBS (T1), and one year later (T2). In this study, STN-DBS was kept constantly in ON, and three different patterns of PPTg-DBS were investigated: STN-ON (PPTg switched off); PPTg-ON (PPTg stimulated 24 h/day); PPTg-cycle (PPTg stimulated only at night). In post-surgery follow-up, PD patients reported a marked improvement of sleep quality in all DBS conditions. In particular, stimulation of the PPTg nucleus produced not only a remarkable long-term improvement of nighttime sleep, but unlike STN-DBS, also produced significant amelioration of daytime sleepiness. Our study suggests that PPTg-DBS plays an important role in reorganizing regular sleep in PD patients.

Case control polysomnographic studies of sleep disorders in Parkinson's disease.

BackgroundThe relationship between a number of primary sleep disorders and Parkinson's disease (PD) is still debated. There are limited case control polysomnographic studies in PD and most of these study sample sizes are small.Methodology/FindingsWe conducted one of the largest case-control studies involving overnight polysomnographic evaluation, with prospective recruitment of unselected Parkinson's disease patients and healthy controls from an Asian population. The cases were recruited from the specialized movement disorder outpatient clinics in a tertiary referral center, and controls from the same geographical locations. All subjects underwent an overnight polysomnographic study and a multiple sleep latency test.A total of 124 subjects including 56 patients and 68 controls frequency-matched for age and sex were included. Multivariate analysis revealed that patients had significantly shorter total sleep time than controls (p = 0.01), lower sleep efficiency (p = 0.001) and increased REM latency (p = 0.007). In patients, multivariate analysis showed that reduced total sleep time was significantly associated with increased age (p = 0.001) and increased levodopa dose (p = 0.032). The mean Insomnia Severity Index was higher in PD patients (9.0±7.1) compared to controls (3.3±3.9, p<0.001). The mean Epworth Sleepiness Scale score was higher in PD patients (9.3±5.9 vs. 5.7±4.8, p<0.001). Nocturnal arousals, obstructive sleep apnea, periodic leg movements and objective abnormal sleepiness were not increased in our patients.Conclusions/SignificanceOur case-control polysomnographic study, the first-ever performed in an Asian population, revealed altered sleep architecture and reduced sleep in PD patients compared to controls. Reduced total sleep time was associated with increased age and levodopa dose. However, nocturnal arousals, primary sleep disorders and abnormal sleepiness were not increased in our PD patients suggesting that ethnic/genetic differences may be a factor in the pathophysiology of these conditions.

Beneficial effect of transcranial magnetic stimulation on sleep in Parkinson's disease

Sleep disorders are common in Parkinson's disease (PD) and have profound negative influences on quality of life. Sleep structure in healthy participants can be changed by repetitive transcranial magnetic stimulation (rTMS), but this has never been studied systematically in PD. Therefore, we characterized sleep in PD patients and examined effects of rTMS using a combination of actigraphy and a pressure sensitive pad. Thirteen PD patients received 5 Hz rTMS over the motor or parietal cortex. Actigraphic sleep estimates were obtained before, during and after rTMS, as well as compared with 8 healthy, age-matched controls. Motor symptoms and mood were evaluated before and after rTMS. Mixed-model regression analyses indicated that PD patients slept shorter (350 +/- 17 vs. 419 +/- 24 min., P = 0.02), more fragmented (fragmentation index 41 +/- 4 vs. 22 +/- 2, P = 0.0004) and had a lower sleep efficiency (77 +/- 2 vs. 86 +/- 2%, P = 0.002) and longer nocturnal awakenings (3.4 +/- 0.2 vs. 2.3 +/- 0.2 min., P = 0.003) than healthy controls. rTMS over the parietal, but not over the motor cortex improved sleep fragmentation (P = 0.0002) and sleep efficiency (P = 0.0002) and reduced the average duration of nocturnal awakenings (P = 0.02). No change of motor symptoms or mood was observed. Disturbed sleep in PD patients may partly be reversed by parietal rTMS, without affecting motor symptoms or mood.

Sleep disorders in Parkinson's disease: facts and new perspectives

Awareness of the clinical and pathophysiological importance of sleep disorders in Parkinson's disease (PD) has been growing in recent years. Sleep disorders are now regarded as important among non-motor symptoms in PD and as a significant variable of PD-related quality of life. Furthermore, some sleep disorders, namely REM behaviour disorder (RBD), has been hypothesised to herald PD by years. Subjective reports of disrupted nocturnal sleep and daytime sleepiness appear to be supported by descriptions of several sleep alterations at nocturnal polysomnographic investigation and Multiple Sleep Latency Test findings. Sleep alterations in PD are to be viewed from the multifactorial perspective of a framework of reciprocally interacting factors: pathophysiology of the disease itself, sleep-related motor symptoms, dopaminergic treatments, ageing, depression, restless legs, periodic limb movements (PMLs) and sleep-disordered breathing. Ad hoc questionnaires and scales such as the Parkinson's Disease Sleep Scale and the Short and Practical (SCOPA) Sleep Scale are now available for the evaluation of disordered sleep in PD patients and have been proved to be useful for preliminary screening of sleep disorders in PD. However in a few cases a video-polysomnography (V-PSG) is needed in order to confirm a diagnosis of sleep disorder in PD, particularly in diagnosing RBD. As for treatment of sleep disorders, combined pharmacological and non-pharmacological protocols appear to be particularly suitable in their treatment in PD.

Nocturnal sleep disturbances and daytime dysfunction in patients with Parkinson's disease and in their caregivers

Background. The role of aging, disease, medications, and mood disturbances in sleep disturbances (SD) in patients with Parkinson's disease (PD) is poorly understood, and the impact of SD on the quality of life of their caregivers (CG) largely undocumented. Objectives. To evaluate the pattern and determinants of disturbed sleep in PD patients complaining of SD, and in their primary CG. Methods. A prospective evaluation of 40 non-demented patients with PD complaining of SD and 23 of their primary CG (all were spouses) was conducted using Pittsburgh Sleep Quality Index, Zung's self-rating depression and anxiety scales, Parkinson's Impact Scale (PIMS) (only for PD), and an additional sleep questionnaire. Results: Eighty-four percent of patients were ‘poor sleepers’ with global sleep scores (GLSc)>5. Other abnormalities were: excessive daytime sleepiness-57.5%, excessive daytime fatigue-72.5%, depression-51.5%, anxiety-63.1%, and abnormal PIMS score-83.8%. There was no correlation between the degree of sleep dysfunction and the age, severity, duration of PD or its treatment. Several component sleep scores correlated with anxiety scores, PIMS score with depression, and, subjects with GLSc≥10 had higher mean anxiety index. Daytime dysfunction (97.5%) was mainly associated with reduced enthusiasm, rather than excessive sleepiness. Among CG, 40% had a GLSc>5, 21% had depression, and 10.5% had anxiety. Their depression, anxiety and sleep scores correlated with those of their spouses. Conclusions. PD patients with significant SD may represent a subset of patients with early, progressive degeneration of sleep centres, rather than an enhanced aging process. They are more susceptible mood disturbances, which correlate with the severity of sleep dysfunction. Sleep and mood disturbances also adversely affect the quality of life of spousal caregivers.

Evaluation of sleep and driving performance in six patients with Parkinson's disease reporting sudden onset of sleep under dopaminergic medication: a pilot study.

Six patients with Parkinson's disease (PD) reporting unusually fast or sudden onset of sleep under the addition of dopamine agonists to a previous levodopa-containing therapy were examined using a sleep-wake diary, the Epworth sleepiness scale (ESS), polysomnography, multiple sleep latency tests (MSLT), a standardized vigilance test, and driving simulation. In all patients, ESS scores were increased and polysomnography showed disruption of the sleep pattern, a tendency towards poor sleep efficiency, and reduced proportions of slow- wave and rapid eye movement sleep. Pathological results in the MSLT or the vigilance test were obtained in five cases. For evaluation of driving performance, the standard deviation from the mean lane position during driving simulation was calculated. Three of five patients had clearly increased mean SDLP values. With respect to the measurement of daytime sleepiness (ESS, MSLT, vigilance test, and driving simulation), each patient had pathological results in at least two of these examinations. However, only a limited transfer of the routine vigilance assessment to driving performance was possible. In summary, this pilot study indicates that unusually fast or sudden onset of sleep in PD patients is a phenomenon of daytime sleepiness.

Sleep in Parkinson's Disease: The Role of Depression and Anxiety

Sleep disorders are frequent and well documented in patients with Parkinson's disease (PD). The effect of depression and anxiety on sleep in PD patients has not been carefully studied however, despite the fact that both depression and anxiety are common in PD and well known to affect sleep in patients without PD. In this questionnaire study, sleep, anxiety, and depression were evaluated in 99 patients with PD and 47 control subjects. PD patients had significantly higher scores on a variety of sleep variables as well as on measures of anxiety and depression. While anxiety and depression were correlated with some sleep measures, neither contributed significantly to overall variance in sleep quality. The effect on sleep variables was dominated by on-off symptom phenomena, levodopa dose, and age.