Body fat distribution in Parkinson's disease: An MRI-based body fat quantification study

IntroductionThere is some evidence that Parkinson's Disease (PD) patients have lower body weight and lower fat mass when compared to healthy subjects and that lower body weight and fat mass influence disease risk and progression. It remains unclear, however, if weight loss of fat mass loss occurs only in a subgroup of patients and whether fat distribution is altered during PD. The aim of this study was to prospectively investigate adipose tissue content and distribution in PD patients.MethodsThe body fat composition of PD patients (N = 54) was compared with age matched healthy controls (N = 55) using a magnetic resonance imaging (MRI)-based method. A longitudinal MRI scan was acquired in 25 PD patients after a mean follow up period of 12 months.ResultsThe volume of total body fat as well as of visceral fat showed no difference between PD patients and healthy controls at baseline or at follow up. However, PD patients displayed decreased subcutaneous fat tissue (p = 0.01) and a higher visceral to subcutaneous fat ratio as compared to controls (p = 0.004). After follow up, 16 PD patients did not lose weight, while 9 PD patients lost between 0.5 and 10 kg.ConclusionFat distribution is altered in PD patients, with an increased ratio of visceral to subcutaneous fat.     

Increased all-cause mortality with psychotropic medication in Parkinson's disease and controls: A national register-based study

AimUse of medication and polypharmacy is common as the population ages and its disease burden increases. We evaluated the association of antidepressants, benzodiazepines, antipsychotics and combinations of psychotropic drugs with all-cause mortality in patients with Parkinson's disease (PD) and a matched group without PD.MethodWe identified 5861 PD patients and 31,395 control subjects matched by age, gender and marital status, and obtained register data on medication use and vital status between 1997 and 2007.ResultsAll-cause mortality was significantly higher with the use of most groups of psychotropic medication in PD patients and controls. Hazard ratios were as follows for the medication types: selective serotonin reuptake inhibitors or serotonin-noradrenalin reuptake inhibitors, PD HR = 1.19, 95% CI = 1.04−1.36; Control HR = 1.77, 95% CI = 1.64−1.91; benzodiazepines, PD HR = 1.17, 95% CI = 0.99−1.38; Control HR = 1.39, 95% CI = 1.29−1.51; benzodiazepine-like drugs, PD HR = 1.33, 95% CI = 1.11−1.59; Control HR = 1.27, 95% CI = 1.18−1.37; first-generation antipsychotics, PD HR = 1.89, 95% CI = 1.42−2.53; Control HR = 2.12, 95% CI = 1.82−2.47; second-generation antipsychotics, PD HR = 1.46, 95% CI = 1.20−1.76; Control HR = 2.00, 95% CI 1.66−2.43; and combinations of these drugs compared with non-medicated PD patients and controls. Discontinuation of medication was associated with decreased mortality in both groups.ConclusionsThe use of psychotropic medication in the elderly is associated with increased mortality, independent of concurrent neurodegeneration due to PD. Confounding by indication may partly explain the higher hazard ratios in medicated controls compared with medicated PD patients. Our findings indicate that neurodegeneration should not be a separate contraindication per se for the use of psychotropic drug in patients with PD, but its use should be based on careful clinical evaluation and follow-up.     

Body mass index variations in patients with Parkinson's disease treated with levodopa-carbidopa intestinal gel infusion: A case control study versus standard of care and subthalamic nucleus deep brain stimulation

BackgroundLevodopa-carbidopa intestinal gel (LCIG) is an advanced therapy for patients with Parkinson Disease (PD). Weight loss has been pointed out as an adverse event of LCIG infusion.Aims of the studyTo compare weight changes between three groups of PD patients: patients treated with LCIG, patients within the first year of subthalamic deep brain stimulation (STN-DBS) and patients treated exclusively with oral treatment during 1 year of follow up.MethodsPatients treated with LCIG were retrospectively matched by age, gender, disease duration and Hoehn and Yahr to patients undergoing STN-DBS and to patients both receiving the standard of care treatment and unwilling advanced therapies (SOC). Clinical features and weight were collected at baseline, and 12 months after introducing the treatment (LCIG and STN-DBS groups) or for one year of treatment (SOC).ResultsEighteen patients were included in each group. They had no differences in clinical and demographic features, except for cognitive impairment. There was a mean weight (−5.8 kg ±6.8) and BMI (−2.1 kg/m² ± 2.6) reduction in the LCIG group after 12 months, while there was a slight weight loss in the SOC (−1.4 kg ±3.1) and a weight increase in the STN-DBS group (5.4 kg ±4.7). Differences of weight were statistically different between, LCIG and STN-DBS (P < 0.001), LCIG and SOC (P = 0.002) and STN-DBS and SOC (P < 0.001).ConclusionsThe study shows a significant weight reduction after starting LCIG infusion compared to the other groups. Weight loss should be closely monitored in patients treated with LCIG.     

Longitudinal association between dopamine agonists and weight in Parkinson's disease

ObjectiveTo examine the longitudinal relation of dopamine agonists (DA) use with body mass index (BMI) change and weight gain in Parkinson's disease (PD).MethodsIn a cohort of 356 patients with PD annually followed up to 6 years, BMI, antiparkinsonian drugs use, and impulse control disorders (ICDs) were assessed at each visit. DA dose trajectories were estimated using latent class mixed models. The association of DA use with BMI change and weight gain was examined using latent-process mixed models and time-dependent Cox models respectively, while adjusting for disease severity and levodopa (LD) use.ResultsIn the mixed model, BMI (kg/m²) increased over the follow-up in DA users (beta_DA×time = 0.13, 95% CI = 0.02, 0.24) compared to non-users, while it decreased in LD users (beta_LD×time = −0.26, 95% CI = −0.38, −0.13). We identified three trajectories of average daily DA dose over the follow-up. Patients in the high trajectory gained more weight than patients who never used DA (P = .001) and in the low (P = .02) or moderate (P = .04) trajectories. The incidence of weight gain of ≥6 kg was 2.10-fold (95% CI = 1.03, 4.28) higher in DA users compared to non-users, while LD users were less likely to gain weight (HR = 0.60, 95% CI = 0.33, 1.11). Associations decreased in analyses adjusted for compulsive eating or ICDs.ConclusionWeight increased in DA users over 6 years, and DA use was associated with increased incidence of weight gain. These associations were partially explained by compulsive eating. Alternatively, weight decreased in LD users. These findings warrant careful monitoring of compulsive eating and weight in PD patients.     

Machine learning for automated EEG-based biomarkers of cognitive impairment during Deep Brain Stimulation screening in patients with Parkinson’s Disease

ObjectiveA downside of Deep Brain Stimulation (DBS) for Parkinson’s Disease (PD) is that cognitive function may deteriorate postoperatively. Electroencephalography (EEG) was explored as biomarker of cognition using a Machine Learning (ML) pipeline.MethodsA fully automated ML pipeline was applied to 112 PD patients, taking EEG time-series as input and predicted class-labels as output. The most extreme cognitive scores were selected for class differentiation, i.e. best vs. worst cognitive performance (n = 20 per group). 16,674 features were extracted per patient; feature-selection was performed using a Boruta algorithm. A random forest classifier was modelled; 10-fold cross-validation with Bayesian optimization was performed to ensure generalizability. The predicted class-probabilities of the entire cohort were compared to actual cognitive performance.ResultsBoth groups were differentiated with a mean accuracy of 0.92; using only occipital peak frequency yielded an accuracy of 0.67. Class-probabilities and actual cognitive performance were negatively linearly correlated (β = −0.23 (95% confidence interval (−0.29, −0.18))).ConclusionsParticularly high accuracies were achieved using a compound of automatically extracted EEG biomarkers to classify PD patients according to cognition, rather than a single spectral EEG feature.SignificanceAutomated EEG assessment may have utility for cognitive profiling of PD patients during the DBS screening.     

Efficacy and Safety of Esketamine Nasal Spray Plus an Oral Antidepressant in Elderly Patients With Treatment-Resistant Depression—TRANSFORM-3

BackgroundElderly patients with major depression have a poorer prognosis, are less responsive to treatment, and show greater functional decline compared with younger patients, highlighting the need for effective treatment.MethodsThis phase 3 double-blind study randomized patients with treatment-resistant depression (TRD) ≥65 years (1:1) to flexibly dosed esketamine nasal spray and new oral antidepressant (esketamine/antidepressant) or new oral antidepressant and placebo nasal spray (antidepressant/placebo). The primary endpoint was change in the Montgomery-Åsberg Depression Rating Scale (MADRS) from baseline to day 28. Analyses included a preplanned analysis by age (65–74 versus ≥75 years) and post-hoc analyses including age at depression onset.ResultsFor the primary endpoint, the median-unbiased estimate of the treatment difference (95% CI) was −3.6 (−7.20, 0.07); weighted combination test using MMRM analyses z = 1.89, two-sided p = 0.059. Adjusted mean (95% CI) difference for change in MADRS score between treatment groups was −4.9 (−8.96, −0.89; t = −2.4, df = 127; two-sided nominal p = 0.017) for patients 65 to 74 years versus −0.4 (−10.38, 9.50; t = −0.09, two-sided nominal p = 0.930) for those ≥75 years, and −6.1 (−10.33, −1.81; t = −2.8, df = 127; two-sided nominal p = 0.006) for patients with depression onset <55 years and 3.1 (−4.51, 10.80; t = 0.8, two-sided nominal p = 0.407) for those ≥55 years. Patients who rolled over into the long-term open-label study showed continued improvement with esketamine following 4 additional treatment weeks.ConclusionsEsketamine/antidepressant did not achieve statistical significance for the primary endpoint. Greater differences between treatment arms were seen for younger patients (65–74 years) and patients with earlier onset of depression (<55 years).     

Effect of exercise training on body composition in patients with obstructive sleep apnea: a systematic review and meta-analysis

Reduction in adiposity is considered a cornerstone in the treatment of obstructive sleep apnea (OSA). Exercise training is one of the interventions used in the treatment of OSA. However, it remains unclear whether exercise training alleviates OSA by improving body composition. This study aimed to verify the effect of exercise training on body composition and the apnea-hypopnea index (AHI) in patients with OSA. This study adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and was registered in PROSPERO. PubMed/Medline, Scopus, and Cochrane databases were used for systematic review. Analyses were performed using Review Manager software (version 5.3; R Foundation for Statistical Computing, Vienna, Austria). Exercise training significantly reduced body mass index (mean difference = −0.55 kg/m²; 95% CI = −0.95 to −0.15), body fat percentage (mean difference = −1.19%; 95% CI = −2.03 to −0.35), neck circumference (mean difference = −0.55 cm; 95% CI = −1.08 to −0.02), total body weight (mean difference = −2.13 kg; 95% CI = −4.30 to 0.04), and AHI -8.06 events/hour; 95% CI = −10.47 to −5.66). Although body composition was improved by exercise, this improvement was clinically small. Moreover, improvement in AHI by exercise may not be entirely due to improvements in adiposity.Prospero #CRD42020210509.     

Weight changes associated with unilateral STN DBS and advanced PD

Weight gain following bilateral subthalamic nucleus deep brain stimulation (STN DBS) in Parkinson disease (PD) has been characterized previously, but little is known about changes in weight following unilateral STN DBS. Weight gain of approximately 10 kg at one year after bilateral STN DBS for PD has been noted in previous studies, and PD in the absence of DBS has been associated with weight loss. A case-control comparison evaluated the change in weight following unilateral STN DBS in PD. In 39 patients who underwent unilateral STN DBS for PD, we measured the weight change over 1 year versus both preoperative weight change and the weight change in 40 age- and disease severity-matched PD controls without DBS. Regression analyses incorporating age, gender, baseline weight in case or control were conducted to assess weight changes. At 12 months following surgery, the mean weight of unilateral STN DBS patients increased by 4.3 ± 7.2 kg versus the preoperative baseline weight (p < 0.001) and this increase was 4.8 kg compared with the controls (p = 0.015). Over a 1 year time interval, weight gain occurred in 41% of the preoperative unilateral STN DBS patients and 45% of the PD controls, while 85% of the unilateral STN DBS patients had gained weight at 12 months after surgery (p < 0.0001, respectively, chi square test). We conclude that unilateral STN DBS in PD is associated with weight gain, which offsets weight loss associated with advanced PD.     

Subjectively impaired bed mobility in Parkinson disease affects sleep efficiency

BackgroundImpaired bed mobility (IBM) may be an important reason for the high prevalence of sleep insomnia in Parkinson disease (PD). Here we assessed the influence of subjectively IBM on both subjective and objective sleep parameters in insomnia PD patients with (PD+IBM) and without (PD−IBM) concerns of IBM and controls with primary insomnia.MethodsWe included 44 PD patients with sleep initiation or maintenance concerns and 44 control subjects with primary insomnia. Sleep questionnaires, polysomnographic sleep parameters, activity data, and the number of body position changes were compared between PD patients and controls as well as within the PD group between PD+IBM vs PD−IBM subjects.ResultsThere were 54.5% of PD subjects who reported having IBM. In the PD+IBM group, the number of body position changes was significantly lower than in PD−IBM (0.4/h [0.0–1.8] vs 1.4/h [0.0–4.6], P = .015). Sleep efficiency (SE) was lower in PD+IBM patients (63.5; 26.2–85.6) compared to PD−IBM patients (78.4; 54.8–92.6; P < .001).ConclusionPD patients who report IBM have fewer sleep-related body position changes (i.e., nocturnal hypokinesia) than PD patients without such concerns. Furthermore, objective SE is significantly diminished in these patients.     

Impacto de la estimulación subtalámica a largo plazo sobre la situación cognitiva de los pacientes con enfermedad de Parkinson avanzada

ObjectiveThe aim of this study was to evaluate the effects of deep brain stimulation of the subthalamic nucleus (DBS-SN) on cognitive function in patients with Parkinson's disease (PD) 5 years after surgery.Material and methodsWe conducted a prospective study including 50 patients with PD who underwent DBS-SN (62.5% were men; mean age of 62.2 ± 8.2 years; mean progression time of 14.1 ± 6.3 years). All patients were assessed before the procedure and at one year after surgery; 40 patients were further followed up until the 5-year mark. Follow-up assessments included the following neuropsychological tests: Mini–Mental State Examination (MMSE), Mattis Dementia Rating Scale (MDRS), letter-number sequencing of the WAIS-III (WAIS-III-LN), clock-drawing test, Rey auditory verbal learning test (RAVLT), Benton Visual Retention Test (BVRT), Judgment of Line Orientation (JLO) test, FAS Phonemic Verbal Fluency Test, Stroop test, and the Montgomery-Asberg Depression Rating Scale (MADRS).ResultsPatients were found to score lower on the MMSE (−0.89%), clock-drawing test (−2.61%), MDRS (−1.72%), and especially phonemic (−13.28%) and sematic verbal fluency tests (−12.40%) at one year after surgery. Delayed recall on the RAVLT worsened one year after the procedure (−10.12%). At 5 years, impairment affected mainly verbal fluency; scores decreased an additional 16.10% and 16.60% in semantic and phonemic verbal fluency, respectively. Moderate decreases were observed in immediate recall (−16.87%), WAIS-III-LN (−16.67%), and JLO test (−11.56%).DiscussionIn our sample, DBS-SN did not result in global cognitive impairment 5 years after surgery. Verbal function was found to be significantly impaired one year after the procedure. Impaired learning and visuospatial function may be attributed to degeneration associated with PD.     

The impact of weight reduction in the prevention of the progression of obstructive sleep apnea: an explanatory analysis of a 5-year observational follow-up trial

BackgroundObstructive sleep apnea (OSA) is a chronic progressive disease, and it is well-documented that severe OSA is associated with an increased cardiovascular morbidity and mortality. Weight reduction has been shown to improve OSA; however, we need further evidence to determine if it may prevent the progression of OSA in the long term. The aim of our study was to assess the impact of weight change during a 5-year observational follow-up of an original 1-year randomized controlled trial.MethodsThe participants were divided into the two groups according to the weight change at 5-year follow-up using the 5% weight loss as a cutoff point, which was later referred to as the successful (n = 20) or unsuccessful groups (n = 27). The change in apnea–hypopnea index (AHI) was the main objective outcome variable.ResultsFifty-seven patients participated in the 5-year follow-up. At 5 years from the baseline, the change in AHI between the groups was significant in the successful group (−3.5 [95% confidence interval {CI}, −6.1 to −0.9]) compared with the unsuccessful group (5.0 [95% CI, 2.0–8.5]) (P = .002). Successful weight reduction achieved an 80% reduction in the incidence of progression of OSA compared to the unsuccessful group (log-rank test, P = .016).ConclusionsA moderate but sustained weight reduction can prevent the progression of the disease or even cure mild OSA in obese patients.     

Early mobilisation is associated with lower subacute blood pressure and variability in ICH: A retrospective cohort study✰

BackgroundVery early rehabilitation after stroke appears to worsen outcome, particularly in intracerebral haemorrhage (ICH). Plausible mechanisms include increased mean blood pressure (BP) and BP variability.AimsTo test associations between early mobilisation, subacute BP and survival, in observational data of ICH patients during routine clinical care.MethodsWe collected demographic, clinical and imaging data from 1372 consecutive spontaneous ICH patients admitted between 2 June 2013 and 28 September 2018. Time to first mobilisation (defined as walking, standing, or sitting out-of-bed) was extracted from electronic records. We evaluated associations between early mobilisation (within 24 h of onset) and both subacute BP and death by 30 days using multifactorial linear and logistic regression analyses respectively.ResultsMobilisation at 24 h was not associated with increased odds of death by 30 days when adjusting for key prognostic factors (OR 0.4, 95% CI 0.2 to 1.1, p = 0.07). Mobilisation at 24 h was independently associated with both lower mean systolic BP (−4.5 mmHg, 95% CI −7.5 to −1.5 mmHg, p = 0.003) and lower diastolic BP variability (−1.3 mmHg, 95% CI −2.4 to −0.2 mg, p = 0.02) during the first 72 h after admission.ConclusionsAdjusted analysis in this observational dataset did not find an association between early mobilisation and death by 30 days. We found early mobilisation at 24 h to be independently associated with lower mean systolic BP and lower diastolic BP variability over 72 h. Further work is needed to establish mechanisms for the possible detrimental effect of early mobilisation in ICH.     

Prenatal phthalate,triclosan, and bisphenol A exposures and child visual-spatial abilities

IntroductionDuring fetal development, sex steroids influence sexually dimorphic behaviors, such as visual-spatial abilities. Thus, endocrine disrupting chemicals that impact sex steroids during gestation may affect these behaviors.ObjectiveWe investigated the relationship between prenatal urinary phthalate metabolite, triclosan, and BPA concentrations and visual-spatial abilities in a prospective cohort of 198 mother-child dyads.MethodsData are from a prospective cohort in Cincinnati, OH (HOME Study). We measured nine phthalate metabolites, triclosan, and BPA in maternal urine samples collected at 16 and 26 weeks of gestation. We assessed children’s visual-spatial abilities at 8 years of age using the Virtual Morris Water Maze (VMWM), a computerized version of the rodent Morris Water Maze. We quantified the covariate-adjusted change in the time or distance to complete the VMWM and time spent in the correct quadrant during a probe trial with an interquartile range increase in chemical concentrations using linear mixed models and linear regression, respectively.ResultsBoys completed the VMWM faster (4.1 s; 95% CI:−7.1, −1.2) and in less distance (1.4 units; 95% CI:−2.8, 0) than girls. Overall, children with higher mono-n-butyl (MnBP), mono-benzyl (MBzP), and mono-carboxypropyl phthalate concentrations completed the VMWM in less time and distance than children with lower concentrations. For example, children with higher MnBP concentrations completed the VMWM in 0.9 less distance units (95% CI:−1.8, −0.0). Child sex modified the association between MnBP and VMWM performance. In girls, higher MnBP concentrations were associated with longer time (1.7 s; 95% CI: −0.7, 4.1) and shorter distance (−1.7 units; 95% CI: −2.8, −0.5), whereas in boys, it was associated with shorter time (-3.0 s; 95% CI:−5.6, −0.4), but not distance (−0.1 units; 95% CI:1.4, 1.0). Other phthalate metabolites, triclosan, and BPA were not associated with VMWM performance, and sex did not consistently modify these associations.ConclusionsIn this cohort, greater prenatal urinary concentrations of some phthalate metabolites were associated with improved VMWM performance, particularly among boys. Future studies should confirm these findings and determine if phthalates affect other hormonally sensitive aspects of child neurobehavior.     

Impact of carbidopa-levodopa enteral suspension on quality of life and activities of daily living in patients with advanced Parkinson's disease: Results from a pooled meta-analysis

IntroductionTo estimate the impact of carbidopa/levodopa enteral suspension (CLES) on key patient-centered outcomes in patients with advanced Parkinson's disease (PD).MethodsA comprehensive literature review identified relevant studies, from which data were meta-analyzed over 3-month intervals up to 24 months. Patient-centered outcomes of interest included mean (95% CI) changes from baseline (Δ) in quality of life (QoL), measured using PD-specific (PDQ-8, PDQ-39) and generic (EQ-5D) instruments; activities of daily living (ADL), measured in On and Off states using UPDRS Part II; and motor symptoms (i.e., Off time/day and motor examination [measured in On and Off states using UPDRS Part III]).ResultsThe pooled meta-analysis included data from 26 studies evaluating 1556 patients on CLES. At 3 months, all outcomes showed significant improvement: QoL (ΔPDQ-39 = −10.26 [-11.54, −8.97], ΔEQ-5D_VAS = 15.42 [12.58, 18.26]); ADL (ΔUPDRS II_ON = −4.32 [-5.63, −3.01]); motor symptoms (ΔOff time hours/day = −3.48 [-4.15, −2.82], ΔUPDRS III_ON = −6.20 [-9.88, −2.51]). At 24 months, there were statistically significant mean improvements in QoL (ΔPDQ-39 = −7.74 [-12.40, −3.07], ΔEQ-5D_VAS = 11.18 [6.90, 15.45]) and ADL (ΔUPDRS II_OFF = −3.88 [-5.34, −2.42]), and Off time (−4.21 [-5.16, −3.26] hours/day).ConclusionsImpact of CLES on significantly reducing Off time/day was observed to be rapid and durable (i.e., remained consistent across 24 months). Most QoL and ADL measures showed a consistent pattern of improvement with initiation of treatment and remained significantly improved from baseline at 24 months.     

Effect of adenotonsillectomy on blood pressure in children with obstructive sleep apnea: a meta-analysis

BackgroundWhile adenotonsillectomy (T&A) is widely recognized as the first-line therapy for pediatric obstructive sleep apnea (OSA), effects of T&A on blood pressure (BP) remain unclear. This meta-analysis evaluates the associations between T&A and BP in children with OSA.MethodsThe study protocol was registered on PROSPERO (CRD42020154425). Two authors independently searched the PubMed, Medline, EMBASE, and Cochrane databases. The keywords used were “sleep apnea syndromes,” “adenotonsillectomy,” and “child.” A random-effects model was applied to determine office systolic BP (SBP), diastolic BP (DBP), and ambulatory BP changes.ResultTwelve studies with 1193 children were analyzed (mean age: 7.6 y; 54% boys). The apnea-hypopnea index significantly reduced of 9.4 events/h (95% CI, −12.0 to −6.8) after T&A. Office SBP (−0.24 mmHg; 95% CI, −1.64 to 1.16) and DBP (−1.65 mmHg; 95% CI, −3.47 to 0.17) did not decrease significantly after surgery. No significant decreases were observed in 24-h ambulatory BP after T&A. Subgroup analysis showed a significant postoperative decrease in office SBP (−6.23 mmHg; 95% CI, −7.78 to −4.67) and DBP (−7.93 mmHg; 95% CI, −10.37 to −5.48) among children with hypertension but a slight increase in office SBP (2.50 mmHg; 95% CI, 1.14 to 3.86) and DBP (1.98 mmHg; 95% CI, −0.02 to 3.98) in those without (P for heterogeneity < 0.001).ConclusionThis meta-analysis suggests the office and ambulatory BP changes after T&A in children with OSA are trivial. Moreover, children with hypertension experience a significantly greater decrease in office BP than children without hypertension.     

Comparative efficacy of CPAP,MADs, exercise-training,and dietary weight loss for sleep apnea: a network meta-analysis

Study objectiveTo synthesize evidence from available studies on the relative efficacies of continuous positive airway pressure (CPAP), mandibular advancement device (MAD), supervised aerobic exercise training, and dietary weight loss in patients with obstructive sleep apnea (OSA).DesignNetwork meta-analysis of 80 randomized controlled trials (RCTs) short-listed from PubMed, SCOPUS, Web of science, and Cochrane register (inception – September 8, 2015).PatientsIndividuals with OSA.InterventionsCPAP, MADs, exercise training, and dietary weight loss.ResultsCPAP decreased apnea–hypopnea index (AHI) the most [by 25.27 events/hour (22.03–28.52)] followed by exercise training, MADs, and dietary weight loss. While the difference between exercise training and CPAP was non-significant [−8.04 (−17.00 to 0.92), a significant difference was found between CPAP and MADs on AHI and oxygen desaturation index (ODI) [−10.06 (−14.21 to −5.91) and −7.82 (−13.04 to −2.59), respectively]. Exercise training significantly improved Epworth sleepiness scores (ESS) [by 3.08 (0.68–5.48)], albeit with a non-significant difference compared to MADs and CPAP.ConclusionsCPAP is the most efficacious in complete resolution of sleep apnea and in improving the indices of saturation during sleep. While MADs offer a reasonable alternative to CPAP, exercise training which significantly improved daytime sleepiness (ESS) could be used as adjunctive to the former two.     

Advanced therapies in Parkinson’s disease: Long-term retrospective study

BackgroundLevodopa/carbidopa intestinal gel infusion (LCIG) and subthalamic nucleus deep brain stimulation (STN-DBS) are approved therapies for advanced Parkinson’s disease (PD) whose long-term comparability remains unclear.MethodsWe reviewed the 5-year data on activities of daily living (ADL) and motor complications (OFF time, dyskinesia duration, and dyskinesia severity), as measured by the Unified Parkinson Disease Rating Scale (UPDRS) section-II and section-IV (items 39, 32, and 33, respectively) in 60 PD patients exposed to STN-DBS (n = 20), LCIG (n = 20), and oral medical therapy (OMT) (n = 20) at similar baseline disability and cognitive state.ResultsSTN-DBS and LCIG showed a similar magnitude of deterioration in ADL (+6.1 vs. +5.7 UPDRS-II; p = 0.709), but lesser than with OMT (+13.7 UPDRS-II; p = 0.005). OFF time also improved to the same extent in STN-DBS and LCIG (−62% vs. −54.5%; p = 0.830), while worsened with OMT (+78.6%; p < 0.001). STN-DBS and LCIG yielded greater improvement on dyskinesia compared to OMT (dyskinesia duration: −66.1% vs. −9.0% vs. +24.2% [p = 0.001]; dyskinesia severity: −68.8% vs. −18.0% vs. +16.2% [p = 0.002]), with relative superiority of STN-DBS over LCIG (p = 0.004 for duration; p = 0.014 for severity). The annualized rate of complication was lower in STN-DBS vs. LCIG (0.13 vs. 0.68; p < 0.001) but not different between STN-DBS and OMT (0.13 vs. 0.10; p = 0.795).ConclusionsSTN-DBS and LCIG showed comparable efficacy in ADL and OFF time, superior to OMT. STN-DBS yielded greater improvement in dyskinesia and lower long-term rate of complications than LCIG.     

Levodopa-carbidopa intestinal gel in advanced Parkinson's: Final results of the GLORIA registry

IntroductionThis registry evaluated the 24-month safety and efficacy of levodopa-carbidopa intestinal gel (LCIG) treatment in advanced Parkinson's disease (PD) patients under routine clinical care.MethodsMotor fluctuations, dyskinesia, non-motor symptoms, quality of life, and safety were evaluated. Observations were fully prospective for treatment-naïve patients (60% of patients) and partially retrospective for patients with ≤12 months of pre-treatment with LCIG (40% of patients). Hours of “On” and “Off” time were assessed with a modified version of the Unified Parkinson's Disease Rating Scale part IV items 32 and 39.ResultsOverall, 375 patients were enrolled by 75 movement disorder centers in 18 countries and 258 patients completed the registry. At 24 months LCIG treatment led to significant reductions from baseline in “Off” time (hours/day) (mean ± SD = −4.1 ± 3.5, P < 0.001), “On” time with dyskinesia (hours/day) (−1.1 ± 4.8, P = 0.006), Non-Motor Symptom Scale total (−16.7 ± 43.2, P < 0.001) and individual domains scores, and Parkinson's Disease Questionnaire-8 item total score (−7.1 ± 21.0, P < 0.001). Adverse events deemed to have a possible/probable causal relationship to treatment drug/device were reported in 194 (54%) patients; the most frequently reported were decreased weight (6.7%), device related infections (5.9%), device dislocations (4.8%), device issues (4.8%), and polyneuropathy (4.5%).ConclusionsLCIG treatment led to sustained improvements in motor fluctuations, non-motor symptoms particularly sleep/fatigue, mood/cognition and gastrointestinal domains, as well as quality of life in advanced PD patients over 24 months. Safety events were consistent with the established safety profile of LCIG.     

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.     

Pilot data on the association between social jetlag and obesity-related characteristics in Dutch adolescents over one year

ObjectiveSocial jetlag, a form of chronic circadian misalignment, has previously been associated with obesity in adults. We aimed to investigate the association between social jetlag and obesity-related characteristics in Dutch adolescents over a 1-year period.MethodsWe analysed data of 83 adolescents, who were recruited from a Dutch cohort born between the years 1990 and 1993. At the age of 16 and 17y, we determined anthropometric measurements, body composition, physical activity, hours of television use, and self-reported sleep duration. Using linear regression models, we assessed the association between social jetlag, defined as more than a 1-hour difference between the midpoint of sleep during weekdays and weekend days, and body mass index (BMI), body fat percentage, and waist circumference at baseline and after one year. We corrected the analysis for sex, sleep, physical activity, and hours of television use.ResultsAt age 16y, we observed that social jetlag was highly prevalent, with only 13% of the adolescents reporting no social jetlag (≤1 h), whereas 29% and 58% reported a social jetlag of >1–2 h and ≥2 h. In a cross-sectional analysis, we observed at age 16y a significant higher BMI in the group with no social jetlag, compared to the group with >1- to 2-hour and ≥2-hour social jetlag after adjustment for sex (−0.81 kg/m², 95% confidence interval = −3.1 to 1.4; and −2.09 kg/m², 95% confidence interval = −4.1 to −0.1). This association remained significant after correction for the other possible confounders. No significant associations were observed between social jetlag at age 16y and changes in obesity-related characteristics over one year.ConclusionOur pilot data showed that social jetlag is highly prevalent in adolescents, with social jetlag associated with a lower BMI; however, in this small group, social jetlag was not associated with changes in obesity-related characteristics over time.