Effects of deep brain stimulation on quantitative sleep electroencephalogram during non-rapid eye movement in Parkinson's disease.

Introduction: Sleep dysfunction is frequently experienced by people with Parkinson's disease (PD) and negatively influences quality of life. Although subthalamic nucleus (STN) deep brain stimulation (DBS) can improve sleep in PD, sleep microstructural features such as sleep spindles provide additional insights about healthy sleep. For example, sleep spindles are important for better cognitive performance and for sleep consolidation in healthy adults. We hypothesized that conventional STN DBS settings would yield a greater enhancement in spindle density compared to OFF and low frequency DBS. Methods: In a previous within-subject, cross-sectional study, we evaluated effects of low (60 Hz) and conventional high (≥130 Hz) frequency STN DBS settings on sleep macroarchitectural features in individuals with PD. In this post hoc, exploratory analysis, we conducted polysomnography (PSG)-derived quantitative electroencephalography (qEEG) assessments in a cohort of 15 individuals with PD who had undergone STN DBS treatment a median 13.5 months prior to study participation. Fourteen participants had unilateral DBS and 1 had bilateral DBS. During three nonconsecutive nights of PSG, the participants were assessed under three different DBS conditions: DBS OFF, DBS LOW frequency (60 Hz), and DBS HIGH frequency (≥130 Hz). The primary objective of this study was to investigate the changes in sleep spindle density across the three DBS conditions using repeated-measures analysis of variance. Additionally, we examined various secondary outcomes related to sleep qEEG features. For all participants, PSG-derived EEG data underwent meticulous manual inspection, with the exclusion of any segments affected by movement artifact. Following artifact rejection, sleep qEEG analysis was conducted on frontal and central leads. The measures included slow wave (SW) and spindle density and morphological characteristics, SW-spindle phase-amplitude coupling, and spectral power analysis during non-rapid eye movement (NREM) sleep. Results: The analysis revealed that spindle density was significantly higher in the DBS HIGH condition compared to the DBS LOW condition. Surprisingly, we found that SW amplitude during NREM was significantly higher in the DBS LOW condition compared to DBS OFF and DBS HIGH conditions. However, no significant differences were observed in the other sleep qEEG features during sleep at different DBS conditions. Conclusion: This study presents preliminary evidence suggesting that conventional HIGH frequency DBS settings enhance sleep spindle density in PD. Conversely, LOW frequency settings may have beneficial effects on increasing slow wave amplitude during sleep. These findings may inform mechanisms underlying subjective improvements in sleep quality reported in association with DBS. Moreover, this work supports the need for additional research on the influence of surgical interventions on sleep disorders, which are prevalent and debilitating non-motor symptoms in PD.

Quantitative sleep electroencephalogram and cognitive performance in Parkinson's disease with and without rapid eye movement sleep behavior disorder.

Introduction: Parkinson's disease (PD) patients with REM sleep behavior disorder (RBD) are at greater risk for cognitive decline and RBD has been associated with alterations in sleep-related EEG oscillations. This study evaluates differences in sleep quantitative EEG (qEEG) and cognition in PD participants with (PD-RBD) and without RBD (PD-no-RBD). Methods: In this cross-sectional study, polysomnography (PSG)-derived qEEG and a comprehensive level II neuropsychological assessment were compared between PD-RBD (n = 21) and PD-no-RBD (n = 31). Following artifact rejection, qEEG analysis was performed in the frontal and central leads. Measures included Scalp-slow wave (SW) density, spindle density, morphological properties of SW and sleep spindles, SW-spindle phase-amplitude coupling, and spectral power analysis in NREM and REM. The neurocognitive battery had at least two tests per domain, covering five cognitive domains as recommended by the Movement Disorders Society Task Force for PD-MCI diagnosis. Differences in qEEG features and cognitive performance were compared between the two groups. Stepwise linear regression was performed to evaluate predictors of cognitive performance. Multiple comparisons were corrected using the Benjamini-Hochberg method. Results: Spindle density and SW-spindle co-occurrence percent were lower in participants with PD-RBD compared to PD-no-RBD. The PD-RBD group also demonstrated higher theta spectral power during REM. Sleep spindles and years of education, but not RBD, were predictors of cognitive performance. Conclusion: PD participants with RBD have alterations in sleep-related qEEG compared to PD participants without RBD. Although PD-RBD participants had worse cognitive performance compared to PD-no-RBD, regression models suggest that lower sleep spindle density, rather than presence of RBD, predicts worse comprehensive cognitive score. Future studies should include longitudinal evaluation to determine whether sleep-related qEEG alterations are associated with more rapid cognitive decline in PD-RBD.

Quantitative Sleep Electroencephalogram in Parkinson's Disease: A Case-Control Study.

BACKGROUND: Sleep disorders are common in Parkinson's disease (PD) and include alterations in sleep-related EEG oscillations. OBJECTIVE: This case-control study tested the hypothesis that patients with PD would have a lower density of Scalp-Slow Wave (SW) oscillations and higher slow-to-fast frequencies ratio in rapid eye movement (REM) sleep than non-PD controls. Other sleep-related quantitative EEG (qEEG) features were also examined, including SW morphology, sleep spindles, and Scalp-SW spindle phase-amplitude coupling. METHODS: Polysomnography (PSG)-derived sleep EEG was compared between PD participants (n = 56) and non-PD controls (n = 30). Following artifact rejection, sleep qEEG analysis was performed in frontal and central leads. Measures included SW density and morphological features of SW and sleep spindles, SW-spindle phase-amplitude coupling, and spectral power analysis in Non-REM (NREM) and REM. Differences in qEEG features between PD and non-PD controls were compared using two-tailed Welch's t-tests, and correction for multiple comparisons was performed per the Benjamini-Hochberg method. RESULTS: SW density was lower in PD than in non-PD controls (F = 13.5, p' = 0.003). The PD group also exhibited higher ratio of slow REM EEG frequencies (F = 4.23, p' = 0.013), higher slow spindle peak frequency (F = 24.7, p' < 0.002), and greater SW-spindle coupling angle distribution non-uniformity (strength) (F = 7.30, p' = 0.034). CONCLUSION: This study comprehensively evaluates sleep qEEG including SW-spindle phase amplitude coupling in PD compared to non-PD controls. These findings provide novel insights into how neurodegenerative disease disrupts electrophysiological sleep rhythms. Considering the role of sleep oscillatory activity on neural plasticity, future studies should investigate the influence of these qEEG markers on cognition in PD.

Effects of exercise on sleep spindles in Parkinson's disease.

Background: In a randomized, controlled trial, we showed that high-intensity rehabilitation, combining resistance training and body-weight interval training, improves sleep efficiency in Parkinson's disease (PD). Quantitative sleep EEG (sleep qEEG) features, including sleep spindles, are altered in aging and in neurodegenerative disease. Objective: The objective of this post-hoc analysis was to determine the effects of exercise, in comparison to a sleep hygiene, no-exercise control group, on the quantitative characteristics of sleep spindle morphology in PD. Methods: We conducted an exploratory post-hoc analysis of 24 PD participants who were randomized to exercise (supervised 3 times/week for 16 weeks) versus 26 PD participants who were assigned to a sleep hygiene, no-exercise control group. At baseline and post-intervention, all participants completed memory testing and underwent polysomnography (PSG). PSG-derived sleep EEG central leads (C3 and C4) were manually inspected, with rejection of movement and electrical artifacts. Sleep spindle events were detected based on the following parameters: (1) frequency filter = 11-16 Hz, (2) event duration = 0.5-3 s, and (3) amplitude threshold 75% percentile. We then calculated spindle morphological features, including density and amplitude. These characteristics were computed and averaged over non-rapid eye movement (NREM) sleep stages N2 and N3 for the full night and separately for the first and second halves of the recording. Intervention effects on these features were analyzed using general linear models with group x time interaction. Significant interaction effects were evaluated for correlations with changes in performance in the memory domain. Results: A significant group x time interaction effect was observed for changes in sleep spindle density due to exercise compared to sleep hygiene control during N2 and N3 during the first half of the night, with a moderate effect size. This change in spindle density was positively correlated with changes in performance on memory testing in the exercise group. Conclusions: This study is the first to demonstrate that high-intensity exercise rehabilitation has a potential role in improving sleep spindle density in PD and leading to better cognitive performance in the memory domain. These findings represent a promising advance in the search for non-pharmacological treatments for this common and debilitating non-motor symptom.

Taking the Time to Assess Cognition in Parkinson's Disease: The Clock Drawing Test.

BACKGROUND: Cognitive impairment is common and disabling in Parkinson's disease (PD). Cognitive testing can be time consuming in the clinical setting. One rapid test to detect cognitive impairment in non-PD populations is the Clock Drawing Test (CDT), which calls upon the brain's executive and visuospatial abilities to draw a clock designating a certain time. OBJECTIVE: Test the hypothesis that PD participants would perform worse on CDT compared to controls and that CDT would correlate with other measures of cognition. METHODS: This study evaluated two independent CDT scoring systems and differences in CDT performance between PD (N = 97) and control (N = 54) participants using a two-sample t-test. Pearson's correlations were conducted between the CDT and tests of sleepiness (Epworth Sleepiness Scale) and vigilance (Psychomotor Vigilance Test); executive function (Trails B-A); and global cognition (Montreal Cognitive Assessment). Receiver operating characteristic curves were used to determine cut points on the CDT that identify individuals who need additional cognitive testing. RESULTS: PD participants had worse performance on CDT compared to controls. The CDT was correlated with executive function (Trails B-A) and global cognition (Montreal Cognitive Assessment). The CDT correlated with vigilance (Psychomotor Vigilance Task) only in healthy controls. However, the CDT was not correlated with measures of sleepiness (Epworth Sleepiness Scale) in either group. A cut point of 9 on the Rouleau scale and 18 on the Mendez scale identified PD participants with cognitive impairment. CONCLUSION: The CDT is a rapid clinical cognitive assessment that is feasible in PD and correlates with other measures of cognition.

Slow Wave Sleep and EEG Delta Spectral Power are Associated with Cognitive Function in Parkinson's Disease.

BACKGROUND: Cognitive and sleep dysfunction are common non-motor symptoms in Parkinson's disease (PD). OBJECTIVE: Determine the relationship between slow wave sleep (SWS) and cognitive performance in PD. METHODS: Thirty-two PD participants were evaluated with polysomnography and a comprehensive level II neurocognitive battery, as defined by the Movement Disorders Society Task Force for diagnosis of PD-mild cognitive impairment. Raw scores for each test were transformed into z-scores using normative data. Z-scores were averaged to obtain domain scores, and domain scores were averaged to determine the Composite Cognitive Score (CCS), the primary outcome. Participants were grouped by percent of SWS into High SWS and Low SWS groups and compared on CCS and other outcomes using 2-sided t-tests or Mann-Whitney U. Correlations of cognitive outcomes with sleep architecture and EEG spectral power were performed. RESULTS: Participants in the High SWS group demonstrated better global cognitive function (CCS) (p = 0.01, effect size: r = 0.45). In exploratory analyses, the High SWS group showed better performance in domains of executive function (effect size: Cohen's d = 1.05), language (d = 0.95), and processing speed (d = 1.12). Percentage of SWS was correlated with global cognition and executive function, language, and processing speed. Frontal EEG delta power during N3 was correlated with the CCS and executive function. Cognition was not correlated with subjective sleep quality. CONCLUSION: Increased SWS and higher delta spectral power are associated with better cognitive performance in PD. This demonstrates the significant relationship between sleep and cognitive function and suggests that interventions to improve sleep might improve cognition in individuals with PD.

Randomized, Controlled Trial of Exercise on Objective and Subjective Sleep in Parkinson's Disease.

BACKGROUND: Sleep dysfunction is common and disabling in persons with Parkinson's Disease (PD). Exercise improves motor symptoms and subjective sleep quality in PD, but there are no published studies evaluating the impact of exercise on objective sleep outcomes. The goal of this study was to to determine if high-intensity exercise rehabilitation combining resistance training and body-weight interval training, compared with a sleep hygiene control improved objective sleep outcomes in PD. METHODS: Persons with PD (Hoehn & Yahr stages 2-3; aged ≥45 years, not in a regular exercise program) were randomized to exercise (supervised 3 times a week for 16 weeks; n = 27) or a sleep hygiene, no-exercise control (in-person discussion and monthly phone calls; n = 28). Participants underwent polysomnography at baseline and post-intervention. Change in sleep efficiency was the primary outcome, measured from baseline to post-intervention. Intervention effects were evaluated with general linear models with measurement of group × time interaction. As secondary outcomes, we evaluated changes in other aspects of sleep architecture and compared the effects of acute and chronic training on objective sleep outcomes. RESULTS: The exercise group showed significant improvement in sleep efficiency compared with the sleep hygiene group (group × time interaction: F = 16.0, P < 0.001, d = 1.08). Other parameters of sleep architecture also improved in exercise compared with sleep hygiene, including total sleep time, wake after sleep onset, and slow-wave sleep. Chronic but not acute exercise improved sleep efficiency compared with baseline. CONCLUSIONS: High-intensity exercise rehabilitation improves objective sleep outcomes in PD. Exercise is an effective nonpharmacological intervention to improve this disabling nonmotor symptom in PD. © 2020 International Parkinson and Movement Disorder Society.

Pedestrian safety in patients with Parkinson's disease: A case-control study.

BACKGROUND: Patients with Parkinson's disease experience debilitating motor symptoms as well as nonmotor symptoms, such as cognitive dysfunction and sleep disorders. This constellation of symptoms has the potential to negatively influence pedestrian safety. The objective of this study was to investigate the association of motor symptoms, daytime sleepiness, impaired vigilance, and cognitive dysfunction with pedestrian behavior in patients with Parkinson's disease and healthy older adults. METHODS: Fifty Parkinson's disease and 25 control participants were evaluated within a virtual reality pedestrian environment and completed assessments of motor performance, daytime sleepiness (Epworth Sleepiness Scale), vigilance (psychomotor vigilance task), and visual processing speed (Useful Field of View) outside the virtual reality environment. The primary outcome measure was time to contact, defined as the time remaining until a participant would have been hit by an approaching vehicle while crossing the virtual street. RESULTS: The virtual reality pedestrian environment was feasible in all participants. Patients with Parkinson's disease demonstrated riskier pedestrian behavior compared with controls. Among Parkinson's disease participants, walking speed, objective measures of vigilance, and visual processing speed were correlated with pedestrian behavior, with walking speed the strongest predictor of time to contact, explaining 48% of the variance. Vigilance explained an additional 8% of the variance. In controls, vigilance was also important for street-crossing safety, but older age was the most robust predictor of pedestrian safety. CONCLUSIONS: Walking speed is associated with unsafe pedestrian behavior in patients with Parkinson's disease. In contrast, age was the strongest predictor of pedestrian safety in healthy older adults. © 2017 International Parkinson and Movement Disorder Society.

Effects of subthalamic nucleus deep brain stimulation on objective sleep outcomes in Parkinson's disease.

BACKGROUND: Sleep dysfunction is a common and disabling non-motor symptom in Parkinson's disease. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) improves motor symptoms and subjective sleep in PD, but alternative stimulation parameters to optimize sleep have not been explored. We hypothesized that low frequency STN DBS would improve objective sleep more than conventional settings. METHODS: Twenty PD subjects with STN DBS (18 unilateral, 2 bilateral) underwent 3 non-consecutive nights of polysomnography: DBS off; DBS high frequency (≥130 Hz); and DBS low frequency (60 Hz). Motor symptom tolerability was assessed 30 minutes after resumption of baseline settings the morning following polysomnography. The primary outcome was change in sleep efficiency between high and low frequency nights measured with repeated measures ANOVA. RESULTS: There was no difference in sleep efficiency between nights at high frequency (82.1% (72.6-90.1)) (median (IQR)), low frequency (81.2% (56.2-88.8)), or DBS off (82.8% (75.7-87.4)), p=0.241. Additionally, there was no difference in sleep stage percent, arousals, limb movements, subjective sleep quality, or objective vigilance measures. These outcomes did not change after adjusting for age, sex, disease duration, or side of surgery. No residual adverse motor effects were noted. CONCLUSIONS: Although well tolerated, low frequency STN DBS did not improve objective sleep in PD. Remarkably, objective measures of sleep were not worse with DBS off. These observations point to the potential for adaptive stimulation approaches, through which DBS settings could be optimized during sleep to meet individual needs. Additionally, these changes could preserve battery life without compromising patient outcomes.

The effect of unilateral subthalamic nucleus deep brain stimulation on depression in Parkinson's disease.

BACKGROUND: Depression is common in Parkinson's disease (PD) and adversely affects quality of life. Both unilateral and bilateral subthalamic (STN) deep brain stimulation (DBS) effectively treat the motor symptoms of PD, but questions remain regarding the impact of unilateral STN DBS on non-motor symptoms, such as depression. METHODS: We report changes in depression, as measured by the Hamilton Depression Rating Scale (HAMD-17), in 50 consecutive PD patients who underwent unilateral STN DBS. Participants were also evaluated with UPDRS part III, Parkinson's Disease Questionnaire-39, and Pittsburgh Sleep Quality Index. The primary outcome was change in HAMD-17 at 6 months versus pre-operative baseline, using repeated measures analysis of variance (ANOVA). Secondary outcomes included the change in HAMD-17 at 3, 12, 18, and 24 months post-operatively and correlations amongst outcome variables using Pearson correlation coefficients. As a control, we also evaluated changes in HAMD-17 in 25 advanced PD patients who did not undergo DBS. RESULTS: Participants with unilateral STN DBS experienced significant improvement in depression 6 months post-operatively (4.94 ± 4.02) compared to preoperative baseline (7.90 ± 4.44) (mean ± SD) (p = <0.0001). HAMD-17 scores did not correlate with UPDRS part III at any time-point. Interestingly, the HAMD-17 was significantly correlated with sleep quality and quality of life at baseline, 3 months, and 6 months post-operatively. Participants without DBS experienced no significant change in HAMD-17 over the same interval. CONCLUSION: Unilateral STN DBS improves depression 6 months post-operatively in patients with PD. Improvement in depression is maintained over time and correlates with improvement in sleep quality and quality of life.