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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’

Cholinergic nucleus 4 (Ch4) degeneration is associated with cognitive impairment in Parkinson's disease and dementia with Lewy bodies, but it is unknown if Ch4 degeneration is also present in isolated rapid eye movement sleep behavior disorder (iRBD).The aim was to determine if there is evidence of Ch4 degeneration in patients with iRBD and if it is associated with cognitive impairment.We analyzed the clinical and neuropsychological data of 35 iRBD patients and 35 age- and sex-matched healthy controls. Regional gray matter density (GMD) was calculated for Ch4 using probabilistic maps applied to brain magnetic resonance imaging (MRI).Ch4 GMD was significantly lower in the iRBD group compared to controls (0.417 vs. 0.441, P = 0.02). Ch4 GMD was also found to be a significant predictor of letter number sequencing (β-coefficient = 58.31, P = 0.026, 95% confidence interval [7.47, 109.15]), a measure of working memory.iRBD is associated with Ch4 degeneration, and Ch4 degeneration in iRBD is associated with impairment in working memory. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

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.

Objective/background Adults with multiple sclerosis (MS) often present with conditions that mimic restless legs syndrome (RLS), thereby adding complexity into the assessment of RLS severity. The current gold-standard measures of RLS severity rely on a fixed seven-day time frame, which limits the ability of these measures for studying acute changes in RLS severity. The present study examined if subjective and objective scores from the suggested immobilization test (SIT) provide a valid and reliable acute measure of RLS severity in persons with MS. Patients/methods Participants with MS and RLS (n = 20) and MS without RLS (n = 20) were matched by age, gender, and disability. All participants completed validated questionnaires for RLS severity followed by the SIT, conducted at 18:00 (±15 min) on the same day of the week for two consecutive weeks. Participants wore accelerometer devices for seven nights to capture periodic limb movements (PLMs) during the night. Results Self-reported RLS severity during the SIT had excellent construct validity and convergent validity, but moderate test-retest reliability. Device-measured PLMs, while not themselves a direct measure of RLS severity, were significantly associated with PLMs during the night and had excellent test-retest reliability during the SIT in adults with MS. Conclusions Our results suggest that the SIT represents a valid acute measure for capturing self-reported sensory aspects of RLS severity and should be considered in future research and clinical practice as a standardized acute measure of subjective RLS severity in adults with MS who present with RLS.

Introduction Individuals with idiopathic rapid eye movement sleep behavior disorder (iRBD) are at high risk for a clinical diagnosis of an α‐synucleinopathy (aSN). They could serve as a key population for disease‐modifying trials. Abnormal dopamine transporter (DAT) imaging is a strong candidate biomarker for risk of aSN diagnosis in iRBD. Our primary objective was to identify a quantitative measure of DAT imaging that predicts diagnosis of clinically‐defined aSN in iRBD. Methods The sample included individuals with iRBD, early Parkinson’s Disease (PD), and healthy controls (HC) enrolled in the Parkinson Progression Marker Initiative, a longitudinal, observational, international, multicenter study. The iRBD cohort was enriched with individuals with abnormal DAT binding at baseline. Motor and nonmotor measures were compared across groups. DAT specific binding ratios (SBR) were used to calculate the percent of expected DAT binding for age and sex using normative data from HCs. Receiver operative characteristic analyses identified a baseline DAT binding cutoff that distinguishes iRBD participants diagnosed with an aSN in follow‐up versus those not diagnosed. Results The sample included 38 with iRBD, 205 with PD, and 92 HC who underwent DAT‐SPECT at baseline. Over 4.7 years of mean follow‐up, 14 (36.84%) with iRBD were clinically diagnosed with aSN. Risk of aSN diagnosis was significantly elevated among those with baseline putamen SBR ≤ 48% of that expected for age and sex, relative to those above this cutoff (hazard ratio = 17.8 [95%CI: 3.79–83.3], P = 0.0003). Conclusion We demonstrate the utility of DAT SBR to identify individuals with iRBD with increased short‐term risk of an aSN diagnosis.

Background and ObjectivesParkinson’s disease (PD) is associated with a heightened inflammatory state, including activated T cells. However, it is unclear whether these PD T cell responses are antigen specific or more indicative of generalized hyperresponsiveness. Our objective was to measure and compare antigen-specific T cell responses directed towards antigens derived from commonly encountered human pathogens/vaccines in patients with PD and age-matched healthy controls (HC).MethodsPeripheral blood mononuclear cells (PBMCs) from 20 PD patients and 19 age-matched HCs were screened. Antigen specific T cell responses were measured by flow cytometry using a combination of the activation induced marker (AIM) assay and intracellular cytokine staining.ResultsHere we show that both PD patients and HCs show similar T cell activation levels to several antigens derived from commonly encountered human pathogens/vaccines in the general population. Similarly, we also observed no difference between HC and PD in the levels of CD4 and CD8 T cell derived cytokines produced in response to any of the common antigens tested. These antigens encompassed both viral (coronavirus, rhinovirus, respiratory syncytial virus, influenza, cytomegalovirus) and bacterial (pertussis, tetanus) targets.ConclusionsThese results suggest the T cell dysfunction observed in PD may not extend itself to abnormal responses to commonly encountered or vaccine-target antigens. Our study supports the notion that the targets of inflammatory T cell responses in PD may be more directed towards autoantigens like α-synuclein (α-syn) rather than common foreign antigens.

Background Insomnia is one of the most common nonmotor features of Parkinson's disease (PD). However, there are few practical guidelines for providers on how to best evaluate and treat this problem. Methods and Findings This review was developed to provide clinicians with a pragmatic approach to assessing and managing insomnia in PD. Recommendations were based on literature review and expert opinion. We addressed the following topics in this review: prevalence of insomnia in PD, sleep–wake mechanisms, theoretical models of insomnia, risk factors, assessment, pharmacologic and nonpharmacologic treatments. Insomnia treatment choices may be guided by PD severity, comorbidities, and patient preference. However, there is limited evidence supporting pharmacotherapy and nonpharmacologic treatments of insomnia in PD. Conclusions We provide a pragmatic algorithm for evaluating and treating insomnia in PD based on the literature and our clinical experience. We propose personalized insomnia treatment approaches based on age and other issues. Gaps in the existing literature and future directions in the treatment of insomnia in PD are also highlighted.

Background and objectivesParkinson's disease (PD) is associated with a heightened inflammatory state, including activated T cells. However, it is unclear whether these PD T cell responses are antigen specific or more indicative of generalized hyperresponsiveness. Our objective was to measure and compare antigen-specific T cell responses directed towards antigens derived from commonly encountered human pathogens/vaccines in patients with PD and age-matched healthy controls (HC).MethodsPeripheral blood mononuclear cells (PBMCs) from 20 PD patients and 19 age-matched HCs were screened. Antigen specific T cell responses were measured by flow cytometry using a combination of the activation induced marker (AIM) assay and intracellular cytokine staining.ResultsHere we show that both PD patients and HCs show similar T cell activation levels to several antigens derived from commonly encountered human pathogens/vaccines in the general population. Similarly, we also observed no difference between HC and PD in the levels of CD4 and CD8 T cell derived cytokines produced in response to any of the common antigens tested. These antigens encompassed both viral (coronavirus, rhinovirus, respiratory syncytial virus, influenza, cytomegalovirus) and bacterial (pertussis, tetanus) targets.ConclusionsThese results suggest the T cell dysfunction observed in PD may not extend itself to abnormal responses to commonly encountered or vaccine-target antigens. Our study supports the notion that the targets of inflammatory T cell responses in PD may be more directed towards autoantigens like α-synuclein (α-syn) rather than common foreign antigens.

Background: Investigation of sex-related motor and non-motor differences and biological markers in Parkinson’s disease (PD) may improve precision medicine approach. Objective: To examine sex-related longitudinal changes in motor and non-motor features and biologic biomarkers in early PD. Methods: We compared 5-year longitudinal changes in de novo, untreated PD men and women (at baseline N = 423; 65.5%male) of the Parkinson’s Progression Markers Initiative (PPMI), assessing motor and non-motor manifestations of disease; and biologic measures in cerebrospinal fluid (CSF) and dopamine transporter deficit on DaTscanTM uptake. Results: Men experienced greater longitudinal decline in self-reported motor (p

The purpose of this study was to determine the test–retest reliability and construct validity of tools to assess how balance confidence (BC) and state anxiety (SA) change with progressively increasing walking speeds. Sixteen young adults and 15 older adults attended two sessions. Individuals began walking on a treadmill at 0.4 m/s Participants chose to continue increasing the treadmill speed (up to 2.0 m/s) or to discontinue the protocol while rating their BC and SA after completing each speed. BC at participants’ fastest speed attempted demonstrated high and moderate test–retest reliability among young (intraclass correlation coefficient [ICC] = .908) and older adults (ICC = .704). SA for young adults and older adults was good (ICC = .833) and fair (ICC = .490), respectively. Our measures also correlated with measures of dynamic stability while walking for young (r = −.67, p = .008) and older adults (r = .54, p = .046). Our dynamic measures of BC and SA are valid and reliable in young and older adults.

Background Solriamfetol is approved (US and EU) for excessive daytime sleepiness (EDS) in narcolepsy and obstructive sleep apnea. Objectives Evaluate solriamfetol safety/efficacy for EDS in Parkinson's disease (PD). Methods Phase 2, double-blind, 4-week, crossover trial: adults with PD and EDS were randomized to sequence A (placebo, solriamfetol 75, 150, 300 mg/d), B (solriamfetol 75, 150, 300 mg/d, placebo), or C (placebo). Outcomes (safety/tolerability [primary]; Epworth Sleepiness Scale [ESS]; Maintenance of Wakefulness Test [MWT]) were assessed weekly. P values are nominal. Results Common adverse events (n = 66): nausea (10.7%), dizziness (7.1%), dry mouth (7.1%), headache (7.1%), anxiety (5.4%), constipation (5.4%), dyspepsia (5.4%). ESS decreased both placebo (-4.78) and solriamfetol (-4.82 to -5.72; P > 0.05). MWT improved dose-dependently with solriamfetol, increasing by 5.05 minutes with 300 mg relative to placebo (P = 0.0098). Conclusions Safety/tolerability was consistent with solriamfetol's known profile. There were no significant improvements on ESS; MWT results suggest possible benefit with solriamfetol in PD. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Tau protein is found to be aggregated and hyperphosphorylated (p-tau) in many neurologic disorders, including Parkinson disease (PD) and related parkinsonisms, Alzheimer disease, traumatic brain injury, and even in normal aging. Although not known to produce autoimmune responses, we hypothesized that the appearance of aggregated tau and p-tau with disease could activate the immune system. We thus compared T cell responses to tau and p-tau–derived peptides between PD patients, age-matched healthy controls, and young healthy controls (

SummaryParkinson’s disease (PD) is a multi-stage neurodegenerative disorder with largely unknown etiology. Recent findings have identified PD-associated autoimmune features including roles for T cells. To further characterize the role of T cells in PD, we performed RNA sequencing on PBMC and peripheral CD4 and CD8 memory T cell subsets derived from PD patients and age-matched healthy controls. When the groups were stratified by their T cell responsiveness to alpha-synuclein (α-syn) as a proxy for ongoing inflammatory autoimmune response, the study revealed a broad differential gene expression profile in memory T cell subsets and a specific PD associated gene signature. We identified a significant enrichment of transcriptomic signatures previously associated with PD, including for oxidative stress, phosphorylation, autophagy of mitochondria, cholesterol metabolism and inflammation, and the chemokine signaling proteins CX3CR1, CCR5 and CCR1. In addition, we identified genes in these peripheral cells that have previously been shown to be involved in PD pathogenesis and expressed in neurons, such as LRRK2, LAMP3, and aquaporin. Together, these findings suggest that features of circulating T cells with α-syn-specific responses in PD patients provide insights into the interactive processes that occur during PD pathogenesis and suggest potential intervention targets.

The self-antigen α-synuclein (α-syn) was recently shown to be associated with Parkinson’s disease (PD). Here we mapped the T cell receptor (TCR) repertoire of α-syn-specific T cells from six PD patients. The self-antigen α-syn-specific repertoire was compared to the repertoire of T cells specific for pertussis (PT), as a representative foreign antigen that most individuals are exposed to, revealing that the repertoire for α-syn was as diverse as the repertoire for PT. The diversity of PT-specific clonotypes was similar between individuals with PD diagnosis and age-matched healthy controls. We found that the TCR repertoire was specific to each PD patient, and no shared TCRs among patients were defined, likely due to differences in HLA expression that select for different subsets of epitope-specific TCR rearrangements. This study provides the first characterization of α-syn-specific TCR clonotypes in individuals with PD. Antigen-specific TCRs can serve as immunotherapeutics and diagnostics, and means to track longitudinal changes in specific T cells, and disease progression.

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.

We conducted a systematic review with meta-analysis to determine the evidence in support of exercise to improve sleep quality assessed subjectively and objectively in Parkinson's Disease (PD). Standardized mean differences (SMD) comparing the effects of exercise and control interventions on sleep quality with 95% confidence intervals (CI) were calculated. Data from 10 randomized and 2 non-randomized controlled trials, including a total of 690 persons with PD were included. Exercise had a significant positive effect on sleep quality assessed subjectively (SMD = 0.53; 95% CI = 0.16-0.90; p = 0.005). However, the methodological quality of the studies showing positive effects on sleep quality was significantly poorer than the studies showing no effects. Only one study assessed the impact of exercise on objective sleep quality, showing improvements in sleep efficiency assessed with polysomnography (SMD = 0.94; 95% CI = 0.38-1.50; p = 0.001). Exercise performed at moderate to maximal intensities (SMD = 0.46; 95% CI = 0.05-0.87; p = 0.03) had significant effects on subjective sleep quality. In contrast, exercise performed at mild to moderate intensities showed non-significant effects (SMD = 0.76; 95% CI = -0.24-1.76; p = 0.14). These results support the use of exercise to improve sleep quality in persons with PD and reinforce the importance of achieving vigorous exercise intensities. Biases, limitations, practice points and directions for future research are discussed.

BACKGROUND Pathologic alterations in resting-state brain activity patterns exist among individuals with Parkinson's disease (PD). Since physical exercise alters resting-state brain activity in non-PD populations and improves PD symptoms, we assessed the acute effect of exercise on resting-state brain activity in exercise-trained individuals with PD. MATERIAL AND METHODS Resting-state functional magnetic resonance imaging (fMRI) was collected twice for 17 PD participants at the conclusion of an exercise intervention. The acute effect of exercise was examined for PD participants using the amplitude of low frequency fluctuation (ALFF) before and after a single bout of exercise. Correlations of clinical variables (i.e., PDQ-39 quality of life and MDS-UPDRS) with ALFF values were examined for the exercise-trained PD participants. RESULTS An effect of acute exercise was observed as an increased ALFF signal within the right ventromedial prefrontal cortex (PFC), left ventrolateral PFC, and bilaterally within the substantia nigra (SN). Quality of life was positively correlated with ALFF values within the vmPFC and vlPFC. CONCLUSIONS Given the role of the SN and PFC in motor and non-motor symptoms in PD, the acute increases in brain activity within these regions, if repeated frequently over time (i.e., exercise training), may serve as a potential mechanism underlying exercise-induced PD-specific clinical benefits.

BACKGROUND Research indicates intermittent theta burst stimulation (iTBS) is a potential treatment of post-stroke aphasia. MATERIAL AND METHODS In this double-blind, sham-controlled trial (NCT01512264) participants were randomized to receive 3 weeks of sham (G₀), 1 week of iTBS/2 weeks of sham (G₁), 2 weeks of iTBS/1 week of sham (G₂), or 3 weeks of iTBS (G₃). FMRI localized residual language function in the left hemisphere; iTBS was applied to the maximum fMRI activation in the residual language cortex in the left frontal lobe. FMRI and aphasia testing were conducted pre-treatment, at ≤1 week after completing treatment, and at 3 months follow-up. RESULTS 27/36 participants completed the trial. We compared G0 to each of the individual treatment group and to all iTBS treatment groups combined (G₁₋₃). In individual groups, participants gained (of moderate or large effect sizes; some significant at P

Signal transforms are very important tools to extract useful information from scientific, engineering, or medical raw data. Unfortunately, traditional transform techniques impose unrealistic assumptions on the signal, often producing erroneous interpretation of results. Well-known integral transforms, such as short-time Fourier transform, though have fast implementation algorithms (e.g., FFT), are still computationally expensive. They have multiple parameters that should be tuned, and it is not readily clear how to tune them for long-duration non-stationary signals. To solve these problems, one needs a computationally inexpensive transform with no parameters that will highlight important data aspects. We propose a simple transform based on extrema points of the signal. The transform value at a given point is calculated based on the distance and magnitude difference of two extrema points it lies between, rather than considering every point around it. We discuss implementation of the developed algorithm and show examples of successfully applying the transform to noise-corrupted synthetic signals and to sleep studies detecting delta wave in brain EEG signal. Ideas for improvement and further research are discussed.

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

Sleep disorders are among the most common non-motor manifestations in Parkinson's disease (PD) and have a significant negative impact on quality of life. While sleep disorders in PD share most characteristics with those that occur in the general population, there are several considerations specific to this patient population regarding diagnosis, management, and implications. The available research on these disorders is expanding rapidly, but many questions remain unanswered. We thus conducted a systematic review of the literature published from 2005 to 2015 on the following disorders of sleep and wakefulness in PD: REM sleep behavior disorder, insomnia, nocturia, restless legs syndrome and periodic limb movements, sleep disordered breathing, excessive daytime sleepiness, and circadian rhythm disorders. We discuss the epidemiology, etiology, clinical implications, associated features, evaluation measures, and management of these disorders. The influence on sleep of medications used in the treatment of motor and non-motor symptoms of PD is detailed. Additionally, we suggest areas in need of further research.

BACKGROUND: Excessive daytime sleepiness (EDS) is common and disabling in Parkinson’s disease (PD). Predictors of EDS are unclear, and data on biological correlates of EDS in PD are limited. We investigated clinical, imaging and biological variables associated with longitudinal changes in sleepiness in early PD. METHODS: The Parkinson’s Progression Markers Initiative is a prospective cohort study evaluating progression markers in participants with PD who are unmedicated at baseline (n=423) and healthy controls (HC; n=196). EDS was measured with the Epworth Sleepiness Scale (ESS). Clinical, biological and imaging variables were assessed for associations with EDS for up to 3 years. A machine learning approach (random survival forests) was used to investigate baseline predictors of incident EDS. RESULTS: ESS increased in PD from baseline to year 3 (mean±SD 5.8±3.5 to 7.55±4.6, p

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

PURPOSE: Restless legs syndrome (RLS) is a sleep disorder that results in sleep dysfunction. Sleep disruption can have profound negative consequences in adults with Parkinson’s disease (PD), potentially including cognitive dysfunction. This study examined the relationships among RLS, cognition, and sleep quality in persons with PD. MATERIALS AND METHODS: Participants (N=79) with idiopathic PD completed six questionnaires evaluating RLS, sleep quality, daytime sleepiness, global cognitive function, sleep apnea risk, and depression. Participants were further examined for body composition (BMI) and motor symptom severity (MDS-UPDRS Part III). RESULTS: Persons with RLS (n = 25) had significantly worse cognitive function (p = 0.035, d = − 0.56) and sleep quality (p < 0.0001, d= −1.19), and more daytime sleepiness (p = 0.009, d = 0.67) than those without RLS (n = 54). Cognitive function was not significantly correlated with sleep quality (r(s) = 0.113) or daytime sleepiness (r(s) = −0.001). The association between RLS and cognition was not attenuated by controlling for sleep quality or daytime sleepiness. CONCLUSIONS: This study is unique as it is the first to consider the possibility that RLS in PD may be associated with cognitive deficits through a pathway involving sleep quality. Persons with RLS and PD have greater deficits in both sleep quality and cognitive function than individuals without RLS; however, cognitive dysfunction among those with PD and RLS in this sample is not accounted for by sleep quality.

A diagnosis of motor Parkinson's disease (PD) is preceded by a prolonged premotor phase with accumulating neuronal damage. Here we examined the temporal relation between α-synuclein (α-syn) T cell reactivity and PD. A longitudinal case study revealed that elevated α-syn-specific T cell responses were detected prior to the diagnosis of motor PD, and declined after. The relationship between T cell reactivity and early PD in two independent cohorts showed that α-syn-specific T cell responses were highest shortly after diagnosis of motor PD and then decreased. Additional analysis revealed significant association of α-syn-specific T cell responses with age and lower levodopa equivalent dose. These results confirm the presence of α-syn-reactive T cells in PD and show that they are most abundant immediately after diagnosis of motor PD. These cells may be present years before the diagnosis of motor PD, suggesting avenues of investigation into PD pathogenesis and potential early diagnosis.

Mobile and wearable device-captured data have the potential to inform Parkinson’s disease (PD) care. The objective of the Clinician Input Study was to assess the feasibility and clinical utility of data obtained using a mobile health technology from PD patients. In this observational, exploratory study, PD participants wore a smartwatch and used the Fox Wearable Companion mobile phone app to stream movement data and report symptom severity and medication intake for 6 months. Data were analyzed using the Intel® Pharma Analytics Platform. Clinicians reviewed participants’ data in a dashboard during in-office visits at 2 weeks, 1, 3, and 6 months. Clinicians provided feedback in focus groups leading to dashboard updates. Between June and August 2017, 51 PD patients were recruited at four US sites, and 39 (76%) completed the 6-month study. Patients streamed 83,432 h of movement data from their smartwatches (91% of expected). Reporting of symptoms and medication intake using the app was lower than expected, 44% and 60%, respectively, but did not differ according to baseline characteristics. Clinicians’ feedback resulted in ten updates to the dashboard during the study period. Clinicians reported that medications and patient reported outcomes were generally discernable in the dashboard and complementary to clinical assessments. Movement, symptoms, and medication intake data were feasibly translated from the app into a clinician dashboard but there was substantial attrition rate over 6 months. Further enhancements are needed to ensure long-term patient adherence to portable technologies and optimal digital data transfer to clinicians caring for PD patients.

Background Three motor phenotypes have been described in PD: postural instability and gait difficulty (PIGD) dominant, tremor-dominant (TD), and indeterminate (IND) subtype. These phenotypes have been associated with different cognitive trajectories, motor outcomes, and biomarkers profiles. However, whether motor subtype classifications change with treatment and disease progression is not well established. Methods To evaluate motor subtype ratio changes, we used the chi-square test for the off and on state motor subtypes for 115 PD participants in the BioFIND study and used repeated-measures analyses to evaluate longitudinal changes in 162 PD participants with five-year follow-up in the PPMI study. Results PIGD and TD subtypes in moderate to advanced PD participants change with dopaminergic agents. For those who shifted subtypes, improvement in tremor accounted for the transition of 15 (25.4%) TD participants, while the lack of tremor improvement along with minimal changes in PIGD score resulted in changes for eight (19.0%) PIGD individuals. Analyses of PPMI data revealed that all three subgroups had a significant decrease in subtype ratio with disease progression and a significant decline in subtype ratio occurred only in the TD subgroup with dopaminergic agents. The impact of dopaminergic medication effect on subtype shift for each visit was also more notable with disease advancement. Conclusions Motor subtypes are not fixed but change with progression of the disease and with treatment. Improvement in tremor was the main contributor to motor phenotype transitions in the BioFIND cohort. A more stable classification system for subtypes based on underlying biological differences is desirable.

Background Identifying PD‐specific biomarkers in biofluids will greatly aid in diagnosis, monitoring progression, and therapeutic interventions. PD biomarkers have been limited by poor discriminatory power, partly driven by heterogeneity of the disease, variability of collection protocols, and focus on de novo, unmedicated patients. Thus, a platform for biomarker discovery and validation in well‐characterized, clinically typical, moderate to advanced PD cohorts is critically needed. Methods BioFIND (Fox Investigation for New Discovery of Biomarkers in Parkinson's Disease) is a cross‐sectional, multicenter biomarker study that established a repository of clinical data, blood, DNA, RNA, CSF, saliva, and urine samples from 118 moderate to advanced PD and 88 healthy control subjects. Inclusion criteria were designed to maximize diagnostic specificity by selecting participants with clinically typical PD symptoms, and clinical data and biospecimen collection utilized standardized procedures to minimize variability across sites. Results We present the study methodology and data on the cohort's clinical characteristics. Motor scores and biospecimen samples including plasma are available for practically defined off and on states and thus enable testing the effects of PD medications on biomarkers. Other biospecimens are available from off state PD assessments and from controls. Conclusion Our cohort provides a valuable resource for biomarker discovery and validation in PD. Clinical data and biospecimens, available through The Michael J. Fox Foundation for Parkinson's Research and the National Institute of Neurological Disorders and Stroke, can serve as a platform for discovering biomarkers in clinically typical PD and comparisons across PD's broad and heterogeneous spectrum. © 2016 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society

As the population ages, the incidence and prevalence of neurodegenerative disorders will continue to increase. Persons with neurodegenerative disease frequently experience sleep disorders, which not only affect quality of life, but potentially accelerate progression of the disease. Unfortunately, pharmacological interventions are often futile or have adverse effects. Therefore, investigation of non-pharmacological interventions has the potential to expand the treatment landscape for these disorders. The last decade has observed increasing recognition of the beneficial role of exercise in brain diseases, and neurodegenerative disorders in particular. In this review, we will focus on the therapeutic role of exercise for sleep dysfunction in four neurodegenerative diseases, namely Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. Available data suggest that exercise may have the potential to improve sleep disorders and attenuate neurodegeneration, particularly in Alzheimer's disease and Parkinson's disease. However, additional research is required in order to understand the most effective exercise therapy for these indications; the best way to monitor the response to interventions; the influence of exercise on sleep dysfunction in Huntington's disease and amyotrophic lateral sclerosis; and the mechanisms underlying exercise-induced sleep modifications.

A clinical diagnosis of motor Parkinson’s disease (PD) is preceded by a prolonged premotor phase with accumulating neuronal damage. α-Synuclein (α-syn)-specific T cell reactivity is preferentially associated with PD patients. Here we examined the temporal relation between α-syn T cell reactivity and PD. Analysis of PBMCs from a longitudinal case study revealed that elevated α-syn-specific T cell responses were detected prior to the diagnosis of motor PD, and declined after. These results suggest that α-syn-specific proinflammatory T cell reactivity could serve as an early predictor of PD. The relationship between T cell reactivity and early PD was further examined in two independent cohorts, which showed that α-syn-specific T cell responses were highest shortly after diagnosis of motor PD and then decreased. Additional analysis of clinical variables revealed significant association of α-syn-specific T cell responses with age and lower levodopa equivalent dose, and no correlation with motor and cognitive deficits. These results confirm the presence of α-syn-reactive T cells in PD and show that they are most abundant immediately after diagnosis of motor PD. Our single case study suggests that these cells may be present years before the diagnosis of motor PD, suggesting new avenues of investigation into PD pathogenesis, potential early diagnosis, and treatment options.