Relationship between sleep, physical fitness, brain microstructure, and cognition in healthy older adults: A pilot study.

BACKGROUND: There is a critical need for neuroimaging markers of brain integrity to monitor effects of modifiable lifestyle factors on brain health. This observational, cross-sectional study assessed relationships between brain microstructure and sleep, physical fitness, and cognition in healthy older adults. METHODS: Twenty-three adults aged 60 and older underwent whole-brain multi-shell diffusion imaging, comprehensive cognitive testing, polysomnography, and exercise testing. Neurite Orientation Dispersion and Density Imaging (NODDI) was used to quantify neurite density (NDI) and orientation dispersion (ODI). Diffusion tensor imaging (DTI) was used to quantify axial diffusivity (AxD), fractional anisotropy (FA), mean diffusivity (MD), and radial diffusivity (RD). Relationships between sleep efficiency (SE), time and percent in N3 sleep, cognitive function, physical fitness (VO2 peak) and the diffusion metrics in regions of interest and the whole brain were evaluated. RESULTS: Higher NDI in bilateral white and gray matter was associated with better executive functioning. NDI in the right anterior cingulate and adjacent white matter was positively associated with language skills. Higher NDI in the left posterior corona radiata was associated with faster processing speed. Physical fitness was positively associated with NDI in the left precentral gyrus and corticospinal tract. N3 % was positively associated with NDI in the left caudate and right pre- and postcentral gyri. Higher ODI in the left putamen and adjacent white matter was associated with better executive function. CONCLUSION: NDI and ODI derived from NODDI are potential neuroimaging markers for associations between brain microstructure and modifiable risk factors in aging. If these associations are observable in clinical samples, NODDI could be incorporated into clinical trials assessing the effects of modifiable risk factors on brain integrity in aging and neurodegenerative diseases.

A systematic review of health disparities research in deep brain stimulation surgery for Parkinson's disease.

Background: Deep brain stimulation (DBS) is the primary surgical intervention for Parkinson's disease (PD) patients with insufficient response to medication, significantly improving motor symptoms and quality of life. Despite FDA approval for over two decades, access to this therapy remains limited. This systematic review aims to evaluate the influence of gender, race/ethnicity, socioeconomic status, and age on health disparities associated with DBS for PD, providing an overview of current research in this field. Methods: A systematic literature search was conducted in PubMed/MEDLINE, Embase, Web of Science and Cochrane databases from 1960 to September 12th, 2023, following Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Studies that examine the disparities in accessing DBS among patients with PD were included, comparing different demographic factors. Findings were synthesized and presented narratively to identify and understand DBS disparities. Results: After screening for relevance, 25 studies published between 1960 and 2023 were included, with 16 studies meeting full-text review criteria. While reviewing the references of the 16 articles, two additional studies were included, bringing the total number of included studies to 18. Most studies originated from the United States (44%). The identified studies were categorized as identifying disparities, understanding disparities, or reducing disparities. The majority focused on identifying disparities (72%), while fewer studies delved into understanding the underlying factors (28%). No studies evaluated strategies for reducing disparities. The findings indicate that elderly, female, and Black people, as well as those from low socioeconomic backgrounds and developing countries face greater obstacles in accessing DBS for PD. Conclusion: This study highlights factors contributing to disparities in DBS utilization for PD, including race, gender, and socioeconomic status. Public health policymakers, practitioners, and clinicians should recognize these inequalities and work toward reducing disparities, particularly among vulnerable populations.

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.

Heart rate variability during sleep in synucleinopathies: a review.

Synucleinopathies are a group of neurodegenerative diseases characterized by abnormal accumulations of insoluble alpha-synuclein in neurons or glial cells. These consist of Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). Moreover, idiopathic REM sleep behavior disorder (iRBD) is often the first manifestation of synucleinopathies, demonstrating a pathophysiological continuum. While these disorders vary in prevalence, symptom patterns, and severity, they can all include autonomic nervous system (ANS) dysfunction, which significantly reduces quality of life and worsens prognosis. Consequently, identifying abnormalities of the ANS can provide opportunities for improving quality of life through symptomatic treatments that are tailored to the individual's symptoms. An exciting development is using heart rate variability (HRV) as a non-invasive research tool for analyzing how the ANS regulates physiological processes. HRV during sleep, however, may provide a more accurate and reliable measure of ANS activity than during wakefulness, as during awake time, ANS activity is influenced by a variety of factors, including physical activity, stress, and emotions, which may mask or confound the underlying patterns of ANS activity. This review aims to provide an overview of the current knowledge regarding sleep-related HRV in synucleinopathies and to discuss contributing mechanisms. Evidence suggests that iRBD, PD, and MSA are associated with nocturnal ANS dysfunction. Further, comparative studies indicate that the presence of RBD could exacerbate this abnormality. In contrast, no studies have been conducted in patients with DLB. Overall, this review provides new insight into the complex interplay between the ANS and synucleinopathies and underscores the need for further research in this area to develop effective therapies to improve sleep and overall quality of life in patients with synucleinopathies.

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.

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.