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Background: Early identification of Parkinson's disease (PD) patients at risk for becoming functionally dependent is important for patient counseling. Several models describing the relationship between predictors and outcome have been reported, however, most of these require computer software for practical use., Objective: Here we report the development of a risk nomogram allowing an approximate graphical computation of the risk of becoming functionally dependent in early PD., Methods: We analyzed data form the Parkinson's Progression Markers Initiative cohort of newly diagnosed PD patients from baseline through the first 5 years of follow-up. Functional dependence was defined as a score < 80 on the Schwab & England Activities of Daily Living scale. A binary logistic model was developed to estimate the risk of functional dependence and based on the results, a nomogram for the prediction of functional dependence was drawn in order to provide an easy-to-use tool in clinical and academic settings as a part of personalized medicine approach to PD treatment., Results: At baseline, three patients and over the five-year follow-up, 85 (22%) out of 395 patients were functionally dependent as scored by the Schwab & England Activities of Daily Living rating scale. The binary logistic model showed that clinical parameters such as MDS-UPDRS I (rater part), MDS-UPDRS II, and MDS-UPDRS axial motor score were significant predictors for functional dependence within 5 years., Conclusion: We here provide an easy-to-use tool to estimate the risk of functional dependence in PD patients based on the MDS-UPDRS part I, II and axial motor score.

Background: Sarcopenia is characterized by a progressive loss of muscle mass, strength, and function resulting in adverse health outcomes. Current assessment strategies are bothersome and means to simplify the diagnosis are an unmet medical need in Parkinson's disease (PD)., Objective: To evaluate temporal muscle thickness (TMT) obtained on routine cranial MRI as a surrogate marker of sarcopenia in PD patients., Methods: We correlated TMT from axial non-contrast-enhanced T1-weighted sequences of MRI close (±12 months) to an outpatient visit including sarcopenia (EWGSOP1, EWGSOP2, SARC-F), frailty (Fried's criteria, clinical frailty scale), and disease characteristics of Parkinson's patients (Hoehn and Yahr-scale, Movement Disorder Society-Unified Parkinson's Disease Rating Scale, quality of life with the Parkinson's Disease Questionnaire-8) assessments., Results: Cranial MRI was available in 32 patients with a mean age of 73.56±5.14 years, mean disease duration of 11.46±5.66 years, and median Hoehn and Yahr stage of 2.5. The mean TMT was 7.49±2.76 (7.15) mm. Mean TMT was significantly associated with sarcopenia (EWGSOP2, p = 0.018; EWGSOP1, p = 0.023) and frailty status (physical phenotype; p = 0.045). Moreover, there were significant moderate to strong correlations between TMT measurement and appendicular skeletal muscle mass index (r: 0.437, p = 0.012), as well as handgrip strength (r: 0.561, p < 0.001)., Conclusion: Reduced TMT seems to be a promising surrogate marker for sarcopenia (EWGSOP2) and muscle strength in this pilot study in PD patients.

Objective: The objective of this study was to assess the efficacy and safety of nabilone, a synthetic tetrahydrocannabinol analogue, as a treatment for non-motor symptoms (NMS) in Parkinson's disease (PD)., Methods: This was a phase II placebo-controlled, double-blind, parallel-group, enriched enrollment randomized withdrawal trial conducted at the Medical University Innsbruck. A random sample of 47 patients with PD with stable motor disease and disturbing NMS defined by a score of ≥4 points on the Movement Disorder Society - Unified PD Rating Scale-I (MDS-UPDRS-I) underwent open-label nabilone titration (0.25 mg once daily to 1 mg twice daily, phase I). Responders were randomized 1:1 to continue with nabilone or switch to placebo for 4 weeks (phase II). The primary efficacy criterion was the change of the MDS-UPDRS-I between randomization and week 4. Safety was analyzed in all patients who received at least one nabilone dose., Results: Between October 2017 and July 2019, 19 patients received either nabilone (median dose = 0.75 mg) or placebo. At week 4, mean change of the MDS-UPDRS-I was 2.63 (95% confidence interval [CI] 1.53 to 3.74, p = 0.002, effect size = 1.15) in the placebo versus 1.00 (95% CI -0.16 to 2.16, p = 0.280, effect size = 0.42) in the nabilone-group (difference: 1.63, 95% CI 0.09 to 3.18, p = 0.030, effect size = 0.66). Seventy-seven percent of patients had adverse events (AEs) during open-label titration, most of them were transient. In the double-blind phase, similar proportions of patients in each group had AEs (42% in the placebo group and 32% in the nabilone group). There were no serious AEs., Interpretation: Our results highlight the potential efficacy of nabilone for patients with PD with disturbing NMS, which appears to be driven by positive effects on anxious mood and night-time sleep problems., Trial Registry: ClinicalTrials.gov (NCT03769896) and EudraCT (2017-000192-86). ANN NEUROL 2020;88:712-722., (© 2020 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Although open-label observations report a positive effect of cannabinoids on non-motor symptoms (NMS) in Parkinson's disease (PD) patients, these effects remain to be investigated in a controlled trial for a broader use in NMS in PD patients. Therefore, we decided to design a proof-of-concept study to assess the synthetic cannabinoid nabilone for the treatment of NMS. We hypothesize that nabilone will improve NMS in patients with PD and have a favorable safety profile. The NMS-Nab Study is as a mono-centric phase II, randomized, placebo-controlled, double-blind, parallel-group, enriched enrollment withdrawal study. The primary efficacy criterion will be the change in Movement Disorders Society-Unified Parkinson's Disease-Rating Scale Part I score between baseline (i.e. randomization) and week 4. A total of 38 patients will have 80% power to detect a probability of 0.231 that an observation in the treatment group is less than an observation in the placebo group using a Wilcoxon rank-sum test with a 0.050 two-sided significance level assuming a true difference of 2.5 points between nabilone and placebo in the primary outcome measure and a standard deviation of the change of 2.4 points. The reduction of harm through an ineffective treatment, the possibility of individualized dosing, the reduction of sample size, and the possible evaluation of the influence of the placebo effect on efficacy outcomes justify this design for a single-centered placebo-controlled investigator-initiated trial of nabilone. This study should be the basis for further evaluations of long-term efficacy and safety of the use of cannabinoids in PD patients.

Background: Sarcopenia and frailty are found in up to one-third of the general elderly population. Both are associated with major adverse health outcomes such as nursing home placement, disability, decreased quality of life, and death. Data on the frequency of both syndromes in Parkinson's disease (PD), however, are very limited., Objective: We aimed to screen for sarcopenia and frailty in PD patients and to assess potential associations of both geriatric syndromes with demographic and clinical parameters as well as quality of life., Methods: In this observational, cross-sectional study, we included 104 PD patients from a tertiary center and 330 non-PD controls from a population-based cohort aged > 65 years. All groups were screened for sarcopenia using the SARC-F score and for frailty using the Clinical Frailty Scale of the Canadian Study of Health and Aging (CSHA CFS). Prevalence rates of sarcopenia and frailty were also assessed in 18 PD patients from a population-based cohort aged > 65 years. Moreover, PD patients from the tertiary center were evaluated for motor and non-motor symptoms, quality of life, and dependency., Results: The prevalence of sarcopenia was 55.8% (95% CI: 46.2-64.9%) in PD patients from the tertiary center and 8.2% (5.7-11.7%; p < 0.001) in non-PD controls. Frailty was detected in 35.6% (27.0-45.2%) and 5.2% (3.2-8.1%; p < 0.001). Prevalence rates for sarcopenia and frailty were 33.3% (16.1-56.4%; p = 0.004) and 22.2% (8.5-45.8%; p = 0.017) in the community-based PD sample. Both sarcopenia and frailty were significantly associated with longer disease duration, higher motor impairment, higher Hoehn and Yahr stages, decreased quality of life, higher frequency of falls, a higher non-motor symptom burden, institutionalization, and higher care levels in PD patients from a tertiary center compared to not affected PD patients (all p < 0.05)., Conclusions: Both frailty and sarcopenia are more common in PD patients than in the general community and are associated with a more adverse course of the disease. Future studies should look into underlying risk factors for the occurrence of sarcopenia and frailty in PD patients and into adequate management to prevent and mitigate them., (© 2018 S. Karger AG, Basel.)