Obstructive sleep apnea (OSA) and outcomes from coronavirus disease 2019 (COVID-19) pneumonia: a systematic review and meta-analysis

BackgroundObstructive sleep apnea (OSA) is the most prevalent sleep-related breathing disorder which could impair someone's quality of life and is also associated with poor outcomes from many diseases. Currently, the evidence regarding the link between OSA and coronavirus disease 2019 (COVID-19) is still conflicting. This study aims to analyze the relationship between OSA and poor outcomes of COVID-19.Materials and methodsWe systematically searched the PubMed and Europe PMC database using specific keywords related to our aims until December 10th, 2020. All articles published on COVID-19 and OSA were retrieved. The quality of the study was assessed using the Newcastle–Ottawa Scale (NOS) tool for observational studies. Statistical analysis was done using Review Manager 5.4 software.ResultsA total of 21 studies with 54,276 COVID-19 patients were included in this meta-analysis. This meta-analysis showed that OSA was associated with composite poor outcome [OR 1.72 (95% CI 1.55–1.91), p < 0.00001, I² = 36%, random-effect modeling] and its subgroup which comprised of severe COVID-19 [OR 1.70 (95% CI 1.18–2.45), p = 0.005], ICU admissions [OR 1.76 (95% CI 1.51–2.05), p < 0.00001], the need for mechanical ventilation [OR 1.67 (95% CI 1.48–1.88), p < 0.00001], and mortality [OR 1.74 (95% CI 1.39–2.19), p < 0.00001].ConclusionsExtra care and close monitoring should be provided to patients with OSA to minimize the risk of infections. Simple questionnaires such as STOP-Bang questionnaire can be used for screening patients who may be at risk for severe adverse outcomes.     

A systematic review and meta-analysis of respiratory dysfunction in Parkinson's disease

Introduction

Respiratory dysfunction in Parkinson's disease (PD) is common and associated with increased hospital admission and mortality rates. Central and peripheral mechanisms have been proposed in PD. To date no systematic review identifies the extent and type of respiratory impairments in PD compared with healthy controls.

Methods

PubMed, EMBASE, CINAHL, Web of Science, Pedro, MEDLINE, Cochrane Library and OpenGrey were searched from inception to December 2021 to identify case–control studies reporting respiratory measures in PD and matched controls.

Results

Thirty-nine studies met inclusion criteria, the majority with low risk of bias across Risk of Bias Assessment tool for Non-randomized Studies (RoBANS) domains. Data permitted pooled analysis for 26 distinct respiratory measures. High-to-moderate certainty evidence of impairment in PD was identified for vital capacity (standardised mean difference [SMD] 0.75; 95% CI 0.45–1.05; p < 0.00001; I² = 10%), total chest wall volume (SMD 0.38; 95% CI 0.09–0.68; p = 0.01; I² = 0%), maximum inspiratory pressure (SMD 0.91; 95% CI 0.64–1.19; p < 0.00001; I² = 43%) and sniff nasal inspiratory pressure (SMD 0.58; 95% CI 0.30–0.87; p < 0.00001; I² = 0%). Sensitivity analysis provided high-moderate certainty evidence of impairment for forced vital capacity and forced expiratory volume in 1 s during medication ON phases and increased respiratory rate during OFF phases. Lower certainty evidence identified impairments in PD for maximum expiratory pressure, tidal volume, maximum voluntary ventilation and peak cough flow.

Conclusions

Strong evidence supports a restrictive pattern with inspiratory muscle weakness in PD compared with healthy controls. Limited data for central impairment were identified with inconclusive findings.     

Investigation on sleep and mental health of patients with Parkinson's disease during the Coronavirus disease 2019 pandemic

BackgroundThe coronavirus disease 2019 (COVID-19) pandemic is adversely affecting sleep quality and mental health, especially in individuals with chronic disease such as Parkinson's disease (PD).MethodsWe conducted a quantitative study, which included 119 Chinese PD patients who had been treated in an outpatient neurology clinic in Wuhan and 169 age- and sex-matched healthy controls. The questionnaire survey focused on the impact of the COVID-19 pandemic on sleep, mental status, symptoms, and daily life and medical treatment of PD patients.ResultsCompared to healthy controls, PD patients had significantly higher scores in both the Pittsburgh Sleep Quality Index (PSQI) (8.13 vs 5.36, p < 0.001) and the Hospital Anxiety and Depression Scale (HADS) -Depression (4.89 vs 3.82, p = 0.022), as well as a higher prevalence of sleep disturbances with PSQI > 5 points (68.9% vs 44.4%, p < 0.001). Sleep disturbance was identified in 68.9% of PD patients. A logistic regression analysis showed that sleep disturbance of PD patients was independently associated with exacerbation of PD symptoms (OR = 3.616, 95%CI= (1.479, 8.844), p = 0.005) and anxiety (OR = 1.379, 95%CI= (1.157, 1.642), p < 0.001). Compared to male PD patients, female ones had higher PSQI scores (9.28 ± 4.41 vs 7.03 ± 4.01, p = 0.009) and anxiety (32.8% vs 0.1%, p = 0.002) and depression prevalence (34.5% vs 11.5%, p = 0.003).ConclusionThe findings of the present study emphasize the importance of mental and sleep health interventions in PD patients during the COVID-19 pandemic. Additional attention should be paid to the difficulty encountered by PD patients in seeking medical treatment.     

Relationships among cognitive impairment,sleep, and fatigue in Parkinson's disease using the MDS-UPDRS

BackgroundNon-motor complications of Parkinson's disease (PD), specifically cognitive impairment, sleep disturbances, and fatigue, are recognized as important contributors to poor patient outcomes and quality of life. How sleep problems and fatigue interrelate and impact cognitive function, however, has not systematically been investigated across the stages of PD. The aim of our study was to investigate the relationships among cognitive impairment, night-time sleep problems, daytime sleepiness, and fatigue across all severities of PD.MethodsWe examined these non-motor problems using the Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) in a study of 1319 PD patients drawn from three large cohort studies: the Parkinson's Progressive Markers Initiative, the Rush University PD Cognitive-Behavioral-Imaging study, and the Movement Disorder Society-Unified Parkinson's Disease Rating Scale Clinimetric testing program study, which spanned the gamut of disease, from early to advanced PD. Generalized linear mixed models with logit linking functions and covariates including study cohort, age, PD duration, and presence/absence of PD medications were used to examine relationships between these three non-motor symptoms and cognitive impairment.ResultsOf these three frequent, and often inter-twined, non-motor complications, greater daytime sleepiness and fatigue were associated with worse cognitive impairment across the full spectrum of PD (F[16,1158] = 2.40 and F[16,1158] = 3.45 respectively, p's < 0.0005), but an association with night-time sleep was not detected (p = 0.83).ConclusionsGiven this association of daytime sleepiness and fatigue with cognitive impairment, clinical monitoring for these problems should be considered across all points in the PD spectrum, from early to more advanced disease.     

Excessive daytime sleepiness in Parkinson's disease: A systematic review and meta-analysis

ObjectiveTo provide a robust estimate of the prevalence of excessive daytime sleepiness (EDS) and its clinical correlates in patients with Parkinson's disease (PD).MethodWe searched the PubMed and Embase databases for studies investigating the prevalence and clinical correlates of EDS from inception to March 01, 2020. Quality assessment was performed using the Newcastle-Ottawa quality assessment scale. Random-effects models were set to pool the risk estimates. Sensitivity analyses were performed to evaluate the stability of the outcomes.ResultsAfter screening 1367 titles and abstracts, 59 studies involving 12,439 participants were included in the systematic review and meta-analysis. The pooled prevalence of EDS in PD was 35.1%, which was higher in South America, North America, Europe, and Australia than that in Asia. Compared to patients without EDS, patients with EDS had higher effect size on disease duration (0.76 years; 95% CI: 0.16–1.37, I² = 68.8%), Hoehn and Yahr (HY) stage (0.23 grade; 95% CI: 0.11–0.34, I² = 69.1%), Unified PD Rating Scale (UPDRS)-III (3.02 points; 95% CI: 1.53–4.51, I²: 61.2%), levodopa equivalent daily dose (LEDD) (141.46 mg; 95% CI: 64.17–218.77, I² = 86.1%), depression symptoms (Hedges’ g = 0.35; 95% CI: 0.15–0.55, I² = 72.0%) and male sex (OR = 1.50; 95% CI: 1.30–1.72, I² = 0).ConclusionOur results showed that approximately one-third of patients with PD had EDS, which may be associated with the severity of the disease, depression, and male sex, or a combination of neurodegeneration and medication.     

Obstructive sleep apnea,CPAP therapy and Parkinson's disease motor function: A longitudinal study

IntroductionWe aimed to assess, in patients with Parkinson's disease (PD), the association between obstructive sleep apnea (OSA), progression of motor dysfunction and the effect of OSA treatment.MethodsData were analysed from a prospective cohort study of idiopathic PD patients from a movement disorders clinic. Patients found to have OSA on polysomnography (apnea-hypopnea index [AHI] ≥15 events/h, OSA+) were offered treatment using continuous positive airway pressure (CPAP). CPAP+ was defined as an average ≥ 2 h/night use at each follow-up. Motor symptoms were assessed using the motor section of the Movement Disorder Society Unified Parkinson's Disease Rating Scale (mUPDRS) and the Timed-Up-And-Go (TUG). Follow-up times were 3, 6 and 12 months. Mixed models were constructed, adjusting for age, sex, body mass index, levodopa equivalent dose and comorbidities.ResultsWe studied 67 individuals (61.2% male) of mean age 64.7 years (SD = 10.1). Baseline mUPDRS was higher in OSA+ compared to OSA- (24.5 [13.6] vs. 16.2 [7.2], p < 0.001). Motor dysfunction increased at comparable rates in OSA- and OSA+CPAP-. However, in OSA+CPAP+, mUPDRS change was significantly lower compared to OSA- (β = −0.01 vs. 0.61, p = 0.03; p = 0.12 vs. OSA+CPAP- [β = 0.39]) and TUG change was lower compared to OSA+CPAP- (β = −0.01 vs. 0.13, p = 0.002; p = 0.05 vs. OSA- [β = 0.02]).ConclusionsIn this PD cohort, OSA was associated with higher baseline mUPDRS. In those with OSA, CPAP use was associated with stabilization of motor function (mUPDRS and TUG) over 12 months. These observations support further research to clarify the role of OSA in PD pathophysiology and motor dysfunction.     

Rotigotine for nocturnal hypokinesia in Parkinson's disease: Quantitative analysis of efficacy from a randomized,placebo-controlled trial using an axial inertial sensor

BackgroundNocturnal hypokinesia is a common symptom in Parkinson's disease (PD), negatively affecting quality of life of both patients and caregivers. However, evidence-based treatment strategies are limited.ObjectiveTo evaluate the efficacy of rotigotine transdermal patch, using a wearable sensor, in the management of nocturnal immobility.Methods34 PD subjects with nocturnal immobility were randomized to receive rotigotine transdermal patch (mean ± SD of 10.46 ± 4.63 mg/24 h, n = 17) or placebo patch (n = 17). Treatment was titrated to an optimal dose over 1–8 weeks, then maintained for 4 weeks. Primary endpoints were objective parameters assessing axial rotation measured using an axial inertial sensor (the NIGHT-Recorder) over two nights at the patients' home. Scale-based assessments were also performed.ResultsThere was a significant difference, in favor of rotigotine, in change from baseline score in the number of turns in bed (ANCOVA, p = 0.001), and degree of axial turn (p = 0.042). These objective improvements were mirrored by significantly greater improvements in clinical scale-based assessments, including the Unified Parkinson's Disease Rating Scale (UPDRS) total scores (p = 0.009), UPDRS-motor scores (p < 0.001), UPDRS-axial scores (p = 0.01), the Modified Parkinson's Disease Sleep Scale (p < 0.001), the Nocturnal Akinesia Dystonia and Cramp Scale (p = 0.003) and the eight-item PD Questionnaire (PDQ-8) scores (p = 0.01) from baseline to end of treatment in patients given rotigotine compared to placebo.ConclusionWe show that the rotigotine patch provides a significant improvement in nocturnal symptoms as assessed using both objective measures and clinical rating scales. The study demonstrates the feasibility of using wearable sensors to record objective outcomes in PD-related clinical trials.     

Subthalamic nucleus deep brain stimulation improves sleep in Parkinson's disease patients: a retrospective study and a meta-analysis

BackgroundMost Parkinson's patients suffered from sleep problems. There is increasing evidence that Subthalamic Nucleus Deep Brain Stimulation (STN-DBS) has a positive effect on several sleep parameters, improving overall sleep quality in patients with PD. However, the results are controversial.MethodsWe performed a retrospective study and meta-analysis to assess the Parkinson's disease sleep scale (PDSS) in Parkinson's patients.ResultsWe reviewed our data of patients who underwent STN-DBS, and then extracted five other trials to perform a meta-analysis. The pooled results showed an advantage on post-operative PDSS in both our medical center and pooled results (MD = 20.41, 95% CI = [13.03, 27.79], I² = 61%, P < 0.001). There was a significant difference in Unified Parkinson's Disease Rating Scale (UPDRS)-Ⅲ score between pre and post-operation (MD = −12.59, 95% CI = [−14.70, −10.49], I² = 90%, P < 0.001). What's more, Parkinsonian medication was significantly lower in the post-operative groups after DBS (MD = −314.71, 95% CI = [−468.13, −161.28], I² = 53%, P < 0.001).ConclusionIn the retrospective study and meta-analysis of 6 trials, we found that DBS can significantly increase sleep quality. Furthermore, motor function improved and Parkinsonian medication was significantly decreased postoperatively. The sample size was enough and no further investigations would change the conclusion.     

Attentional dysfunction and the punding spectrum in Parkinson's disease

BackgroundPunding is a complication of Parkinson's disease (PD) treatment and stimulant abuse that features excessive preoccupation with repetitive and/or aimless behaviors. We hypothesized that cognitive impairment and functional limitations influence how punding behaviors manifest in PD.MethodsWe extracted data on punding, hobbyism, and cognition from the Parkinson's Progression Marker Initiative (PPMI). Punding and hobbyism were measured with the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease (QUIP) scale. We determined how cognition predicted punding and hobbyism behaviors—adjusting for levodopa dose, Hoehn & Yahr stage, disease duration, and age—using generalized estimating equation (GEE) logistic regression. Activities of daily living (ADL) and motor impairment were measured with the MDS-UPDRS scale.ResultsIn GEE logistic regression models, punding was selectively associated with lower scores on the Letter Number Sequencing test (LNS), the primary attention test in PPMI (Odds ratio: 0.87 (95% CI: 0.79–0.96); p = 0.022). This was corroborated by a subscale-analysis of Montreal Cognitive Assessment (MoCA) scores, as only the attention subscale was significantly associated with punding (OR: 0.59 (0.45–0.77); p < 0.001). Baseline impairment in LNS (Hazard ratio: 2.52 (1.22–5.20); p = 0.012) and MoCA attention (HR: 2.68 (1.32–5.42); p = 0.006) predicted earlier punding in Cox regression. In turn, ADL dysfunction predicted punding (OR: 1.55 (1.20–2.00); p < 0.001), but not hobbyism.ConclusionAttentional dysfunction is a domain-specific cognitive biomarker of punding risk in PD. Further, attentional capacity and functional impairment may determine the complexity of perseverative behaviors on the continuum from rudimentary punding to semi-purposeful hobbyism.     

Motor,behavioural, and cognitive correlates of fatigue in early,de novo Parkinson disease patients

IntroductionFatigue is one of the most common and disabling non-motor symptoms in Parkinson's disease (PD). The objective of this study was to determine prevalence and motor, behavioural, and cognitive correlates of distressing fatigue in early, de novo PD patients.MethodsEighty-one consecutive de novo PD patients (64% men; mean age 65.73 ± 8.26 years) underwent a comprehensive examination, including Parkinson's disease Fatigue Scale (PFS), Epworth Sleepiness Scale (ESS), Parkinson's Disease Sleep Scale (PDSS), Beck Depression Inventory (BDI), Parkinson's Anxiety Scale (PAS), and Apathy Evaluation Scale (AES). Moreover, all patients underwent a detailed neuropsychological evaluation exploring attention and working memory, executive functions, memory, visuospatial abilities and language. Score of patients with or without distressing fatigue (defined as a PFS score ≥ 8) were compared by Student's t-test or Pearson's chi-square test. Logistic regression analyses were performed to search for motor and non-motor features independently associated with presence of distressing fatigue.ResultsTwelve (15%) patients presented distressing fatigue. Logistic regression identified sleepiness (p = 0.04), “episodic anxiety” subscale of PAS (p = 0.005), and “cognitive apathy” subscale of AES (p = 0.017) as the main factors associated with distressing fatigue. No significant association was found between diagnosis of Mild Cognitive Impairment and distressing fatigue (p = 0.745).ConclusionIn a sample of consecutive de novo PD patients, distressing fatigue is associated with episodic anxiety, cognitive apathy and sleepiness, but not with cognitive impairment. Our findings suggest possible shared pathogenic mechanisms underlying these non-motor symptoms and foster development of early combined therapeutic approaches.     

Reduced muscle power is associated with slower walking velocity and falls in people with Parkinson's disease

PurposeMuscle strength (force) and power (force × velocity) are reduced in Parkinson's disease (PD). Reduced muscle power is associated with slower walking velocity and falls in the older population, but these associations in people with PD have not previously been investigated. This study investigated the relationships between leg extensor muscle power and strength with walking speed and past falls in people with PD.Participants and MethodsForty people with mild to moderate PD were assessed. Walking velocity was measured over 10 m and the number of falls the participant reported having in the past 12 months was recorded. Leg extensor muscle power and strength were measured using a Keiser leg press machine.ResultsMuscle power explained more than half of the variance (R² = 0.54) in walking velocity and remained significantly (p < 0.05) associated with walking velocity in models which included Unified Parkinson's Disease Rating Scale (UPDRS) motor scores. Participants with low muscle power were 6 times more likely to report multiple falls in the past year than those with high muscle power (OR = 6.0, 95% CI 1.1 to 33.3), though this association between falls and power was no longer significant in models which included UPDRS motor scores (p = 0.09).ConclusionMuscle power is a significant determinant of walking velocity in PD even after adjusting for UPDRS motor score. Muscle power training warrants investigation in people with PD.     

Timing matters: Otological symptoms and Parkinson's disease

IntroductionOtological symptoms contribute to the disability of established Parkinson's disease (PD). We sought to evaluate whether prodromal onset may affect PD progression.MethodsA retrospective cohort design was used to compare time to advanced disease, defined as a Hoehn & Yahr stage ≥3 in consecutive PD patients with history of auditory and/or vestibular symptoms appearing before versus after PD onset. Time from PD onset to H&Y ≥ 3 was determined using Cox proportional hazards, with adjusted results summarized as hazards ratio (HR).ResultsAfter adjusting for age at PD onset, there was a lower risk of progression to advanced disease in patients with prodromal otological symptoms compared to those with otological symptoms after PD onset (HR = 0.34; 95%CI: 0.15–0.75, p = 0.008). This association remained significant after adjusting for age at PD onset and MDS-UPDRS III (HR = 0.25; 95% CI: 0.10–0.63, p = 0.003) and propensity score-adjusted analysis (HR = 0.46; 95% CI: 0.24–0.91, p = 0.025).ConclusionProdromal otological symptoms might be associated with a reduced risk of motor progression in PD.     

Visual complaints and visual hallucinations in Parkinson's disease

BackgroundVisual symptoms are common in Parkinson's disease (PD) and are frequently under-diagnosed. The detection of visual symptoms is important for differential diagnosis and patient management.AimTo establish the prevalence of recurrent visual complaints (RVC) and recurrent visual hallucinations (RVH) and to investigate their interaction in PD patients and controls.MethodsThis cross-sectional study included 88 PD patients and 90 controls. RVC and RVH were assessed with a visual symptom questionnaire and the North-East-Visual-Hallucinations-Interview (NEVHI).ResultsDouble vision (PD vs. Controls: 18.2% vs. 1.3%; p < 0.001), misjudging objects when walking (PD vs. Controls: 12.5% vs. 1.3%; p < 0.01), words moving whilst reading (PD vs. Controls: 17.0% vs. 1.3%; p < 0.001) and freezing in narrow spaces (PD vs. Controls: 30.7% vs. 0%; p < 0.001) were almost exclusively found in PD patients. The same was true for recurrent complex visual hallucinations and illusions (PD vs. Controls: both 17.0% vs. 0%; p < 0.001). Multiple RVC (43.2% vs. 15.8%) and multiple RVH (29.5% vs. 5.6%) were also more common in PD patients (both p < 0.001). RVC did not predict recurrent complex visual hallucinations; but double vision (p = 0.018, R² = 0.302) and misjudging objects (p = 0.002, R² = 0.302) predicted passage hallucinations. Misjudging objects also predicted the feeling of presence (p = 0.010, R² = 0.321).ConclusionsMultiple and recurrent visual symptoms are common in PD. RVC emerged as risk factors predictive of the minor forms of hallucinations, but not recurrent complex visual hallucinations.     

BDNF levels and nigrostriatal degeneration in “drug naïve” Parkinson's disease patients. An “in vivo” study using I-123-FP-CIT SPECT

IntroductionParkinson's Disease (PD) is a common neurodegenerative disorder, characterized by a progressive loss of dopaminergic neurons and whose cause remains unclear. Brain-Derived Neurotrophic factor (BDNF) is a protein involved in dopaminergic cells survival. Previous studies have shown decreased serum BDNF levels in PD patients.Aim and objectivesThe aim of the study was to evaluate serum BDNF levels in a group of recently diagnosed non-medicated PD patients and its relationship with the nigrostriatal system degeneration using I-123-FP-CIT.Methods30 recently diagnosed, unmedicated PD patients were included in this study. Serum BDNF levels were measured twice using a sandwich enzyme linked immunoabsorbent assay and compared with levels of 27 unrelated Caucasian healthy adults.A I-123-FP-CIT SPECT was performed in all PD Patients in order to assess the association between serum BDNF levels and I-123-FP CIT uptake in several brain areas using a volumetric semi-automatic method.ResultsPD patients showed lower serum BDNF levels (Median = 49.61, IQ range: 43.55 to 61.82) than the controls (Median = 68.82, IQ range: 51.87 to 88.14) (U = 211.00, z = -3.10, p = 0.002). BDNF levels in PD patients correlated with both caudate (Spearman r = 0.58, p = 0.001 for ispilateral and r 0.55, p = 0.002 for contralateral) and putamen (Spearman r = 0.68, p < 0.001 for ipsilateral and r = 0.80, p < 0.001 for contralateral) I-123-FP-CIT uptake ratios.ConclusionsSerum BDNF levels were lower in recently diagnosed, untreated PD patients compared to controls. These lower levels were significantly correlated with the I-123-FP-CIT uptake ratios.     

Sexual and relationship dysfunction in people with Parkinson's disease

ObjectivesTo quantify the extent of self-reported sexual and relationship problems in people with Parkinson's disease (PD).MethodsA cross-sectional correlation design was used. All people with idiopathic PD, according to the UK Brain Bank criteria, who were known to the Northumbria Healthcare NHS Trust PD service, were asked to participate. Those who consented were assessed by a research nurse during a six month period using a series of rating scales, including the Unified Parkinson's Disease Rating Scale (UPDRS), the PD Questionnaire-39, the Mini Mental State Examination (MMSE), the Szasz sexual functioning scale and, for those in long-term relationships, the Golombok Rust Inventory of Marital State.ResultsConcern over sexual function was reported in 22 (25%) of the 88 participants in the study. Males (p = 0.001) and younger people with PD (p = 0.001) were significantly more likely to report problems with sexual function. Gender (p = 0.007) and UPDRS score (p = 0.045) were significant independent predictors of relationship problems. Males with PD and those with increasing functional problems (UPDRS score) were more likely to report problems in their relationship. Disease duration and levels of anxiety and depression (Hospital Anxiety and Depression scale) were not associated with sexual or relationship problems.ConclusionsSexual and relationship dysfunction was a problem for many people in this study, but these problems were unlikely to be volunteered unless specifically enquired about. Problems were apparent across all age groups and genders.     

How well do Parkinson's disease patients turn in bed? Quantitative analysis of nocturnal hypokinesia using multisite wearable inertial sensors

BackgroundNocturnal hypokinesia/akinesia is a distressing symptom in patients with Parkinson's disease (PD). However, it is difficult to accurately monitor these symptoms based on clinical interviews alone.ObjectivesTo quantitatively compare nocturnal movements of PD patients with their spouses by using multisite inertial sensors and to correlate these parameters with disease severity scores.MethodsNocturnal movements in 19 PD couples (mild-moderate stage) were assessed and compared using wearable sensors (limbs and trunk) for one night at their homes. Nocturnal parameters included number, velocity, acceleration, degree, and duration of rolling over, number of getting out of bed, and limb movements. Each activity was compared to sleep diary, and video recording for accuracy.ResultsPD patients significantly had fewer rolling over (p = 0.048), turned with smaller degree (p = 0.007), less velocity (p = 0.011), and acceleration (p < 0.001), but had more episodes of getting out of bed (p = 0.03, nocturia) when compared to their spouses. Moderate and significant correlations were observed between the mean duration of rolling over and the Unified Parkinson's Disease Rating Scale-Axial score, and Nocturnal Akinesia Dystonia and Cramp Score. The number of leg movements (predominant side) significantly correlated with REM behavior disorder single-question screen. Episodes of nocturia correlated with total and bedtime levodopa equivalent dose. Several other correlations were also observed.ConclusionOur study was able to demonstrate quantitatively the presence of nocturnal hypokinesia in PD patients. This problem correlated with daytime axial motor and nonmotor symptoms. Treatment strategy for PD should be based on a comprehensive review of both day- and nighttime symptoms.     

NREM sleep arousal-related disorders reflect cognitive impairment in Parkinson's disease

BackgroundSleep disorders and cognitive impairment are frequently reported in Parkinson's disease (PD) as non-motor disabling symptoms. While it is known that REM sleep Behaviour Disorder (RBD) in PD is associated with motor and cognitive decline, little is known about the neurobiological significance of NREM sleep arousal-related disorders.Objectives: to evaluate the cognitive and clinical correlates of arousal-related disorders in PD.MethodsClinical data and video-polysomnography were analysed from one hundred-seventy consecutive subjects with PD. Based on the neuropsychological assessment, the subjects were divided into three groups: no cognitive impairment (PD; n = 58), mild cognitive impairment (PD-MCI; n = 58) and overt dementia (PDD; n = 54).ResultsArousal-related disorders by history were reported in 32.9% of the subjects: 10.3% PD, 31.6% PD-MCI and 59.3% PDD (p = 0.001). Video-PSG captured arousal-related disorders in 1.7% PD, 21.2% MCI-PD and 35.6% PDD (p = 0.001). Arousal-related disorders and RBD were recorded in the same night in 7.7% PD, 9.8% MCI-PD and 15.6% PDD (p = 0.04). Patients with arousal-related disorders captured at V-PSG have a longer disease duration (p = 0.003), higher UPDRS score (p = 0.039), longer duration of treatment with levodopa (p = 0.017) and dopamine agonists (p = 0.018), worse H&Y staging (p = 0.001), lower MMSE score (p = 0.019) and more frequently hallucinations (p = 0.004). In multivariate analysis, cognitive impairment significantly increases the risk of arousal-related disorders (OR 3.387–95% CI 1.395–8.220, p = 0.007).ConclusionArousal-related disorders appear to be a marker of cognitive decline in PD. Recognizing arousal-related disorders should make clinicians aware of a possible cognitive decline in PD and eventually modify the therapeutic approach.     

Cognitive disorders associated with hospitalization of COVID-19: Results from an observational cohort study

IntroductionOur understanding of risk factors for COVID‑19, including pre-existing medical conditions and genetic variations, is limited. To what extent the pre-existing clinical condition and genetic background have implications for COVID-19 still needs to be explored.MethodsOur study included 389,620 participants of European descent from the UK Biobank, of whom 3,884 received the COVID-19 test and 1,091 were tested positive for COVID-19. We examined the association of COVID-19 status with an extensive list of 974 medical conditions and 30 blood biomarkers. Additionally, we tested the association of genetic variants in two key genes related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2), with COVID-19 or any other phenotypes.ResultsThe most significant risk factors for COVID-19 include Alzheimer’s disease (OR = 2.29, 95% CI: 1.25–4.16), dementia (OR = 2.16, 95% CI: 1.36–3.42), and the overall category of delirium, dementia, amnestic and other cognitive disorders (OR = 1.90, 95% CI: 1.24–2.90). Evidence suggesting associations of genetic variants in SARS-CoV-2 infection-related genes with COVID-19 (rs7282236, OR = 1.33, 95% CI: 1.14–1.54, p = 2.31 × 10⁻⁴) and other phenotypes, such as an immune deficiency (p = 5.65 × 10⁻⁵) and prostate cancer (p = 1.1 × 10⁻⁵), was obtained.ConclusionsOur unbiased and extensive search identified pre-existing Alzheimer’s disease and dementia as top risk factors for hospital admission due to COVID-19, highlighting the importance of providing special protective care for patients with cognitive disorders during this pandemic. We also obtained evidence suggesting a direct association of genetic variants with COVID-19.     

Trends of inpatient palliative care use among hospitalized patients with Parkinson's disease

IntroductionPalliative care in Parkinson's Disease (PD) is an effective intervention to improve quality of life, although historically, access and availability have been very restricted.MethodsWe performed a retrospective cohort study using the National Inpatient Sample (NIS) data from 2007 to 2014. Diagnostic codes were used to identify patients with PD and palliative care referral. Trends were calculated and logistic analysis performed to identify predictors of palliative care use.ResultsWe identified 397,963 hospitalizations from 2007 to 2014 for patients with PD. Of these, 10,639 (2.67%) were referred to palliative care. The rate of consultation increased from 0.85% in 2007 to 4.49% in 2014. For 1 unit in year increase, there was 1.23 time the odds of receiving palliative consultation (OR 1.23, CI 1.21–1.25, p < 0.0001). Hispanics (OR 0.90, CI 0.81–1.01, p = 0.0550), Black (OR 0.90, CI 0.81–1.01, p = 0.0747) and White patients had similar rates of referral after adjustment. Women were less likely to be referred to palliative care (OR 0.90, CI 0.87–0.94, p < 0.0001). Other factors strongly associated with a higher rate of referrals included private insurance when compared to Medicare (OR 2.14, CI 1.89–2.41, p < 0.0001) and higher income (OR 1.41, CI 1.30–1.53, p < 0.0001).ConclusionThere has been a significant increase in palliative care referrals among hospitalized patients with PD in the US, although the overall rate remains low. After controlling for confounders, racial and ethnic disparities were not found. Women, patients with Medicare/Medicaid, and those with lower income were less likely to be referred to palliative care.     

Dopa-decarboxylase gene polymorphisms affect the motor response to l-dopa in Parkinson's disease

BackgroundIn Parkinson's disease (PD), the response to l-dopa is highly variable and unpredictable. The major pathway for dopamine synthesis from l-dopa is decarboxylation by aromatic l-amino acid decarboxylase (AAAD, encoded by the DDC gene).ObjectiveTo determine the motor response to l-dopa in PD patients as a function of the DDC gene promoter polymorphisms (rs921451 T > C polymorphism (DDC^T/C) and rs3837091 AGAG del (DDC^AGAG/−)).MethodsThirty-three Caucasian PD patients underwent an acute l-dopa challenge together with the peripheral AAAD inhibitor benserazide and were genotyped for rs921451 and rs3837091. The primary efficacy criterion was the motor response to l-dopa, as estimated by the area under the curve for the change in the Unified Parkinson's Disease Rating Scale part III (UPDRS) score relative to baseline (AUC_ΔUPDRS) in the 4 h following l-dopa administration. Secondary endpoints were pharmacokinetic parameters for plasma levels of l-dopa and dopamine. Investigators and patients were blinded to genotypes data throughout the study.ResultsWhen adjusted for the l-dopa dose, the AUC_ΔUPDRS was significantly lower in DDC^CC/CT patients (n = 14) than in DDC^TT patients (n = 19) and significantly lower in DDC^{−/− or AGAG/−} patients (n = 8) than in DDC^AGAG/AGAG patients (n = 25). There were no significant intergroup differences in plasma pharmacokinetic parameters for l-dopa and dopamine.DiscussionThe rs921451 and rs3837091 polymorphisms of the DDC gene promoter influence the motor response to l-dopa but do not significantly change peripheral pharmacokinetic parameters for l-dopa and dopamine. Our results suggest that DDC may be a genetic modifier of the l-dopa response in Parkinson's disease.