AI-based differential diagnosis of dementia etiologies on multimodal data.

Differential diagnosis of dementia remains a challenge in neurology due to symptom overlap across etiologies, yet it is crucial for formulating early, personalized management strategies. Here, we present an AI model that harnesses a broad array of data, including demographics, individual and family medical history, medication use, neuropsychological assessments, functional evaluations, and multimodal neuroimaging, to identify the etiologies contributing to dementia in individuals. The study, drawing on 51,269 participants across 9 independent, geographically diverse datasets, facilitated the identification of 10 distinct dementia etiologies. It aligns diagnoses with similar management strategies, ensuring robust predictions even with incomplete data. Our model achieved a micro-averaged area under the receiver operating characteristic curve (AUROC) of 0.94 in classifying individuals with normal cognition, mild cognitive impairment and dementia. Also, the micro-averaged AUROC was 0.96 in differentiating the dementia etiologies. Our model demonstrated proficiency in addressing mixed dementia cases, with a mean AUROC of 0.78 for two co-occurring pathologies. In a randomly selected subset of 100 cases, the AUROC of neurologist assessments augmented by our AI model exceeded neurologist-only evaluations by 26.25%. Furthermore, our model predictions aligned with biomarker evidence and its associations with different proteinopathies were substantiated through postmortem findings. Our framework has the potential to be integrated as a screening tool for dementia in various clinical settings and drug trials, with promising implications for person-level management.

Clinical Use of On-Demand Therapies for Patients with Parkinson's Disease and OFF Periods.

On-demand therapies for Parkinson's disease (PD) provide rapid, reliable relief for patients experiencing OFF periods; however, practical guidelines on the use of these therapies are not generally available. This paper reviews the use of on-demand treatments. Motor fluctuations occur in nearly all patients with PD after long-term use of levodopa. As the goal of PD treatment is to provide good ON time, on-demand treatments that have a more rapid reliable onset than the slower-acting oral medications provide rapid relief for OFF periods. All current on-demand treatments bypass the gastrointestinal tract, providing dopaminergic therapy directly into the blood stream by subcutaneous injection, through the buccal mucosa, or by inhalation into the pulmonary circulation. On-demand treatments are fast acting (10- to 20-min onset), with maximum, reliable, and significant responses reached within 30 min after administration. Oral medications pass through the gastrointestinal tract and thus have slower absorption owing to gastroparesis and competition with food. On-demand therapies, by providing fast-acting relief, can have a positive impact on a patient's quality of life when patients are experiencing OFF periods.

Natural Walking Intensity in Persons With Parkinson Disease.

BACKGROUND AND PURPOSE: Few persons with Parkinson disease (PD) appear to engage in moderate-intensity walking associated with disease-modifying health benefits. How much time is spent walking at lower, yet still potentially beneficial, intensities is poorly understood. The purpose of this exploratory, observational study was to describe natural walking intensity in ambulatory persons with PD. METHODS: Accelerometer-derived real-world walking data were collected for more than 7 days at baseline from 82 participants enrolled in a PD clinical trial. Walking intensity was defined according to the number of steps in each active minute (1-19, 20-39, 40-59, 60-79, 80-99, or ≥100 steps). Daily minutes of walking and duration of the longest sustained walking bout were calculated at each intensity. Number of sustained 10 to 19, 20 to 29, and 30-minute bouts and greater at any intensity also were calculated. Values were analyzed in the context of physical activity guidelines. RESULTS: Most daily walking occurred at lower intensities (157.3 ± 58.1 min of 1-19 steps; 81.3 ± 32.6 min of 20-39 steps; 38.2 ± 21.3 min of 40-59 steps; 15.1 ± 11.5 min of 60-79 steps; 7.4 ± 7.0 min of 80-99 steps; 7.3 ± 9.6 min of ≥100 steps). The longest daily sustained walking bout occurred at the lowest intensity level (15.9 ± 5.2 min of 1-19 steps). Few bouts lasting 20 minutes and greater occurred at any intensity. DISCUSSION AND CONCLUSIONS: Despite relatively high daily step counts, participants tended to walk at remarkably low intensity, in bouts of generally short duration, with relatively few instances of sustained walking. The findings reinforced the need for health promotion interventions designed specifically to increase walking intensity.Video Abstract available for more insight from authors (see the Video, Supplemental Digital Content 1 available at: http://links.lww.com/JNPT/A426 ).

Delivering a Diagnosis of Parkinson's Disease and Parkinsonism with Wisdom and Sensitivity.

Parkinson's disease (PD) is a chronic, progressive, complex movement disorder. In addition to the motor manifestations, changes in mood and cognition frequently occur. It is understandable that receiving this diagnosis can be difficult for patients and their significant others. For the clinician, delivering a PD diagnosis can be challenging and requires a comprehensive patient assessment followed by a thoughtful treatment plan. How this diagnosis is conveyed can have a long-term impact on patient outcomes such as treatment adherence, participation in decision making, understanding of PD, and satisfaction with care. Because a PD diagnosis is often complicated by uncertainty about the diagnosis itself as well as future prognosis, a sensitive patient-centered approach to care, balanced with realistic expectations, is recommended. Full disclosure, honesty, and empathy on the part of the entire healthcare team are required. This includes relevant information tailored to the patient's unique needs at the time of diagnosis as well as referrals to appropriate rehabilitation and support services. Consistent, timely follow-up of all interventions is essential. It is essential that a diagnosis of PD is properly delivered to optimize understanding of PD, treatment adherence, participation in decision making, and satisfaction with care. In this article, we provide guidance on delivery of this diagnosis based on a growing body of evidence and our >35-year collective clinical experience and work developing and utilizing pertinent, creative educational tools and comprehensive, sensitive support programs for newly diagnosed patients and their significant others. Although most of the evidence we present pertains to PD, our experience suggests it could also apply to other forms of Parkinsonism and other chronic or progressive movement disorders.

Does clinically measured walking capacity contribute to real-world walking performance in Parkinson's disease?

OBJECTIVE: The study examined how clinically measured walking capacity contributes to real-world walking performance in persons with Parkinson's disease (PD). METHODS: Cross-sectional baseline data (n = 82) from a PD clinical trial were analyzed. The 6-Minute Walk Test (6MWT) and 10-Meter Walk Test (10MWT) were used to generate capacity metrics of walking endurance and fast gait speed, respectively. An activity monitor worn for seven days was used to generate performance metrics of mean daily steps and weekly moderate intensity walking minutes. Univariate linear regression analyses were used to examine associations between each capacity and performance measure in the full sample and less and more active subgroups. RESULTS: Walking capacity significantly contributed to daily steps in the full sample (endurance: R2=.13, p < .001; fast gait speed: R2=.07, p = .017) and in the less active subgroup (endurance: R2 =.09, p = .045). Similarly, walking capacity significantly contributed to weekly moderate intensity minutes in the full sample (endurance: R2=.13, p < .001; fast gait speed: R2=.09, p = .007) and less active subgroup (endurance: R2 = .25, p < .001; fast gait speed: R2 =.21, p = .007). Walking capacity did not significantly contribute to daily steps or moderate intensity minutes in the more active subgroup. CONCLUSIONS: Walking capacity contributed to, but explained a relatively small portion of the variance in, real-world walking performance. The contribution was somewhat greater in less active individuals. The study adds support to the idea that clinically measured walking capacity may have limited benefit for understanding real-world walking performance in PD. Factors beyond walking capacity may better account for actual walking behavior.

Multimodal deep learning for Alzheimer's disease dementia assessment.

Worldwide, there are nearly 10 million new cases of dementia annually, of which Alzheimer's disease (AD) is the most common. New measures are needed to improve the diagnosis of individuals with cognitive impairment due to various etiologies. Here, we report a deep learning framework that accomplishes multiple diagnostic steps in successive fashion to identify persons with normal cognition (NC), mild cognitive impairment (MCI), AD, and non-AD dementias (nADD). We demonstrate a range of models capable of accepting flexible combinations of routinely collected clinical information, including demographics, medical history, neuropsychological testing, neuroimaging, and functional assessments. We then show that these frameworks compare favorably with the diagnostic accuracy of practicing neurologists and neuroradiologists. Lastly, we apply interpretability methods in computer vision to show that disease-specific patterns detected by our models track distinct patterns of degenerative changes throughout the brain and correspond closely with the presence of neuropathological lesions on autopsy. Our work demonstrates methodologies for validating computational predictions with established standards of medical diagnosis.

Are Mobile Persons With Parkinson Disease Necessarily More Active?

BACKGROUND AND PURPOSE: Walking activity in persons with Parkinson disease (PD) is important for preventing functional decline. The contribution of walking activity to home and community mobility in PD is poorly understood. METHODS: Cross-sectional baseline data (N = 69) were analyzed from a randomized controlled PD trial. The Life-Space Assessment (LSA) quantified the extent, frequency, and independence across 5 expanding levels of home and community mobility, producing individual subscores and a total score. Two additional summed scores were used to represent mobility within (Levels 1-3) and beyond (Levels 4-5) neighborhood limits. An accelerometer measured walking activity for 7 days. Regression and correlation analyses evaluated relationships between daily steps and mobility scores. Mann-Whitney U tests secondarily compared differences in mobility scores between the active and sedentary groups. RESULTS: Walking activity contributed significantly to the summed Level 1-3 score (ß = 0.001, P = 0.004) but not to the summed Level 4-5 (ß = 0.001, P = 0.33) or total (ß = 0.002, P = 0.07) scores. Walking activity was significantly related to Level 1 (ρ = 0.336, P = 0.005), Level 2 (ρ = 0.307, P = 0.010), and Level 3 (ρ = 0.314, P = 0.009) subscores. Only the summed Level 1-3 score (P = 0.030) was significantly different between the active and sedentary groups. DISCUSSION AND CONCLUSIONS: Persons with PD who demonstrated greater mobility beyond the neighborhood were not necessarily more active; walking activity contributed more so to home and neighborhood mobility. Compared with LSA total score, the Level 1-3 summed score may be a more useful participation-level measure for assessing the impact of changes in walking activity.Video Abstract available for more insights from the authors (see the Video, Supplemental Digital Content 1 available at: http://links.lww.com/JNPT/A349).

Profile of social self-management practices in daily life with Parkinson's disease is associated with symptom severity and health quality of life.

PURPOSE: Social participation is a key determinant of healthy aging, yet little is known about how people with Parkinson's disease manage social living. This study describes individual differences in social self-management practices and their association with symptom severity and health quality of life. METHODS: People with Parkinson's disease (N = 90) completed measures of healthy routines, activities and relationships, symptom severity, and health related quality of life. Cluster analysis identified profiles of social self-management practices. Analysis of variance tested differences between profiles in symptom severity and health quality of life. RESULTS: Participants clustered into one of seven groups according to different combinations of three practices: health resources utilization, activities in home and community, and social support relationships. The healthiest cluster engaged equally in all three practices at above sample average degree of engagement. Four clusters that engaged at or above sample average in activities in home and community experienced less health problems than three clusters that engaged below average. Variation in aspects of social lifestyle unrelated to health appeared also to contribute to profile diversity. CONCLUSION: Findings provide insight into similarity and variation in how people with Parkinson's disease engage with social self-management resources and point to person-centered interventions.Implications for RehabilitationSocial self-management is a biopsychosocial construct to identify and describe self-care practices that engage one's social resources for managing healthful daily living.People with Parkinson's disease vary in their profiles of engaging in social self-management practices in daily living, and this variability relates to severity of symptoms and health quality of life.Learning how to identify health-centered social self-management practices may help people with Parkinson's disease to focus on the healthfulness of their own practices.Learning how to strategically engage one's social resources as part of self-care may help people with Parkinson's disease to master managing their health and well-being in daily life.

Cognitive impairment in Parkinson's disease: Associations between subjective and objective cognitive decline in a large longitudinal study.

BACKGROUND: Cognitive decline creates substantial morbidity and cost in Parkinson's disease (PD) and clinicians have limited tools for counseling patients on prognosis. We aimed to use data from a randomized, controlled trial of isradipine in Parkinson's disease (STEADY-PD III) to determine which objective cognitive domain deficits drive patient complaints of cognitive symptoms. METHODS: Neuro-Quality of Life (Neuro-QoL) Cognition: General Concerns (GC), and Cognition: Executive Function (EF) (subjective measures), were administered at baseline, 1, 2, and 3 years in 324 people with PD. Baseline Montreal Cognitive Assessment (MoCA) was divided into 4 domains: visuospatial/executive, memory, attention, and language (objective measures). Spearman rank correlations and multiple regression models adjusted for other clinical variables evaluated associations between baseline Neuro-QoL domains and individual MoCA domains. Multiple regression models evaluated the association between baseline MoCA domain performance and Neuro-QoL change over three years. Cox proportional hazards predicted development of PD-MCI based on baseline and time-varying Neuro-QoL reporting. RESULTS: Higher MoCA memory performance was associated with better Neuro-QoL-GC (ß = 0.75, SE = 0.391, p = 0.05) and Neuro-QoL-EF (ß = 0.81, SE = 0.36, p = 0.02) at baseline. There was a trend for baseline MoCA memory to predict the degree of subjective cognitive decline on the Neuro-QoL-EF (ß = 0.70, SE = 0.42, p = 0.09). Baseline depression and anticholinergic use were associated with worsened Neuro-QoL-EF and Neuro-QoL-GC. Increasing subjective cognitive complaints in Neuro-QoL-EF were associated with development of PD-MCI over 3 years of follow-up (HR = 0.95, CI = 0.90-1.0, p = 0.039). CONCLUSIONS: Objective memory impairment may be a stronger predictor than executive or visuospatial dysfunction for the presence of subjective cognitive complaints in early PD.

Development and validation of an interpretable deep learning framework for Alzheimer's disease classification.

Alzheimer's disease is the primary cause of dementia worldwide, with an increasing morbidity burden that may outstrip diagnosis and management capacity as the population ages. Current methods integrate patient history, neuropsychological testing and MRI to identify likely cases, yet effective practices remain variably applied and lacking in sensitivity and specificity. Here we report an interpretable deep learning strategy that delineates unique Alzheimer's disease signatures from multimodal inputs of MRI, age, gender, and Mini-Mental State Examination score. Our framework linked a fully convolutional network, which constructs high resolution maps of disease probability from local brain structure to a multilayer perceptron and generates precise, intuitive visualization of individual Alzheimer's disease risk en route to accurate diagnosis. The model was trained using clinically diagnosed Alzheimer's disease and cognitively normal subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset (n = 417) and validated on three independent cohorts: the Australian Imaging, Biomarker and Lifestyle Flagship Study of Ageing (AIBL) (n = 382), the Framingham Heart Study (n = 102), and the National Alzheimer's Coordinating Center (NACC) (n = 582). Performance of the model that used the multimodal inputs was consistent across datasets, with mean area under curve values of 0.996, 0.974, 0.876 and 0.954 for the ADNI study, AIBL, Framingham Heart Study and NACC datasets, respectively. Moreover, our approach exceeded the diagnostic performance of a multi-institutional team of practicing neurologists (n = 11), and high-risk cerebral regions predicted by the model closely tracked post-mortem histopathological findings. This framework provides a clinically adaptable strategy for using routinely available imaging techniques such as MRI to generate nuanced neuroimaging signatures for Alzheimer's disease diagnosis, as well as a generalizable approach for linking deep learning to pathophysiological processes in human disease.

Design of the WHIP-PD study: a phase II, twelve-month, dual-site, randomized controlled trial evaluating the effects of a cognitive-behavioral approach for promoting enhanced walking activity using mobile health technology in people with Parkinson-disease.

BACKGROUND: Parkinson disease (PD) is a debilitating and chronic neurodegenerative disease resulting in ambulation difficulties. Natural walking activity often declines early in disease progression despite the relative stability of motor impairments. In this study, we propose a paradigm shift with a "connected behavioral approach" that targets real-world walking using cognitive-behavioral training and mobile health (mHealth) technology. METHODS/DESIGN: The Walking and mHealth to Increase Participation in Parkinson Disease (WHIP-PD) study is a twelve-month, dual site, two-arm, randomized controlled trial recruiting 148 participants with early to mid-stage PD. Participants will be randomly assigned to connected behavioral or active control conditions. Both conditions will include a customized program of goal-oriented walking, walking-enhancing strengthening exercises, and eight in-person visits with a physical therapist. Participants in the connected behavioral condition also will (1) receive cognitive-behavioral training to promote self-efficacy for routine walking behavior and (2) use a mHealth software application to manage their program and communicate remotely with their physical therapist. Active control participants will receive no cognitive-behavioral training and manage their program on paper. Evaluations will occur at baseline, three-, six-, and twelve-months and include walking assessments, self-efficacy questionnaires, and seven days of activity monitoring. Primary outcomes will include the change between baseline and twelve months in overall amount of walking activity (mean number of steps per day) and amount of moderate intensity walking activity (mean number of minutes per day in which > 100 steps were accumulated). Secondary outcomes will include change in walking capacity as measured by the six-minute walk test and ten-meter walk test. We also will examine if self-efficacy mediates change in amount of walking activity and if change in amount of walking activity mediates change in walking capacity. DISCUSSION: We expect this study to show the connected behavioral approach will be more effective than the active control condition in increasing the amount and intensity of real-world walking activity and improving walking capacity. Determining effective physical activity interventions for persons with PD is important for preserving mobility and essential for maintaining quality of life. Clinical trials registration NCT03517371, May 7, 2018. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03517371. Date of registration: May 7, 2018. Protocol version: Original.

Cognitive-Behavioral Therapy for Anxiety in Parkinson's Disease.

Parkinson's disease (PD) is characterized by motor symptoms, but nonmotor symptoms also significantly impair daily functioning and reduce quality of life. Anxiety is prevalent and debilitating in PD, but remains understudied and undertreated. Much affective research in PD focuses on depression rather than anxiety, and as such, there are no evidence-based treatments for anxiety in this population. Cognitive-behavioral therapy (CBT) has shown promise for treating depression in PD and may be efficacious for anxiety. This exploratory study implemented a multiple-baseline single-case experimental design to evaluate the utility and feasibility of CBT for individuals with PD who also met criteria for a DSM-5 anxiety disorder (n = 9). Participants were randomized to a 2-, 4-, or 6-week baseline phase, followed by 12 CBT sessions, and two post treatment assessments (immediately post treatment and 6-week follow-up). Multiple outcome measures of anxiety and depression were administered weekly during baseline and intervention. Weekly CBT sessions were conducted in-person (n = 5) or via secure videoconferencing (n = 4). At post treatment, seven of the nine participants showed significant reductions in anxiety and/or depression, with changes functionally related to treatment and most improvements maintained at 6-week follow-up. Effects of CBT on secondary outcomes varied across participants, with preliminary evidence for reduction in fear of falling. Adherence and retention were high, as were treatment satisfaction and acceptability. The findings of this pilot study provide preliminary evidence for the utility of CBT as a feasible treatment for anxiety and comorbid depressive symptoms in PD and highlight the potential of telehealth interventions for mood in this population.

Sex differences by design and outcome in the Safety of Urate Elevation in PD (SURE-PD) trial.

OBJECTIVE: To investigate whether women and men with Parkinson disease (PD) differ in their biochemical and clinical responses to long-term treatment with inosine. METHODS: The Safety of Urate Elevation in Parkinson's Disease (SURE-PD) trial enrolled 75 people with early PD and baseline serum urate below 6 mg/dL and randomized them to 3 double-blinded treatment arms: oral placebo or inosine titrated to produce mild (6.1-7.0 mg/dL) or moderate (7.1-8.0 mg/dL) serum urate elevation for up to 2 years. Parkinsonism, serum urate, and plasma antioxidant capacity were measured at baseline and repeatedly on treatment; CSF urate was assessed once, at 3 months. Here in secondary analyses results are stratified by sex. RESULTS: Inosine produced an absolute increase in average serum urate from baseline that was 50% greater in women (3.0 mg/dL) than in men (2.0 mg/dL), consistent with expected lower baseline levels in women. Similarly, only among women was CSF urate significantly greater on mild or moderate inosine (+87% [p < 0.001] and +98% [p < 0.001], respectively) than on placebo (in contrast to men: +10% [p = 0.6] and +14% [p = 0.4], respectively). Women in the higher inosine dosing group showed a 7.0 Unified Parkinson's Disease Rating Scale (UPDRS) points/year lower rate of decline vs placebo (p = 0.01). In women, slower rates of UPDRS change were associated with greater increases in serum urate (r = -0.52; p = 0.001), and with greater increases in plasma antioxidant capacity (r = -0.44; p = 0.006). No significant associations were observed in men. CONCLUSIONS: Inosine produced greater increases in serum and CSF urate in women compared to men in the SURE-PD trial, consistent with the study's design and with preliminary evidence for slower clinical decline in early PD among women treated with urate-elevating doses of inosine. CLINICALTRIALSGOV IDENTIFIER: NCT00833690. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that inosine produced greater urate elevation in women than men and may slow PD progression in women.

Comparative Effectiveness of mHealth-Supported Exercise Compared With Exercise Alone for People With Parkinson Disease: Randomized Controlled Pilot Study.

Background: Declining physical activity commonly occurs in people with Parkinson disease (PD) and contributes to reduced functional capacity and quality of life. Objective: The purpose of this study was to explore the preliminary effectiveness, safety, and acceptability of a mobile health (mHealth)-mediated exercise program designed to promote sustained physical activity in people with PD. Design: This was a 12-month single-blind (assessor), pilot, comparative-effectiveness, randomized controlled study. Methods: An mHealth-mediated exercise program (walking with a pedometer plus engagement in planned exercise supported by a mobile health application) was compared over 1 year with an active control condition (walking with a pedometer and exercise only). There were 51 participants in a community setting with mild-to-moderately severe (Hoehn and Yahr stages 1-3) idiopathic PD. Daily steps and moderate-intensity minutes were measured using a step activity monitor for 1 week at baseline and again at 12 months. Secondary outcomes included the 6-Minute Walk Test, Parkinson Disease Questionnaire 39 mobility domain, safety, acceptability, and adherence. Results: Both groups increased daily steps, moderate-intensity minutes, and 6-Minute Walk Test, with no statistically significant between-group differences observed. In the less active subgroup, changes in daily steps and moderate-intensity minutes were clinically meaningful. An improvement in the Parkinson Disease Questionnaire 39 mobility score favored mHealth in the overall comparison and was statistically and clinically meaningful in the less active subgroup. Limitations: The limitation of the current study was the small sample size. Conclusions: Both groups improved physical activity compared with expected activity decline over 1 year. The addition of the mHealth app to the exercise intervention appeared to differentially benefit the more sedentary participants. Further study in a larger group of people with low activity at baseline is needed.

Self-Reported Exercise Trends in Parkinson's Disease Patients.

OBJECTIVE: To examine trends in type, frequency, and effectiveness of different modes of exercise in patients with Parkinson's Disease (PD). BACKGROUND: Exercise has been shown to improve symptoms in PD patients. Recent studies suggest that dance may be a particularly helpful exercise option. However, it remains unclear how the benefits of various forms of exercise compare to dance and to each other. Information on these trends can help inform future exercise programs for PD patients. METHOD: 55 PD patients completed a survey on their exercise frequency, the impact of exercise on their symptoms, and whether they exercise alone or in groups. 9 PD patients who attend dance therapy classes completed an extended survey with additional questions comparing the benefit of dance therapy to traditional forms of exercise. RESULTS: Of the 64 patients surveyed, 67% of patients exercised at least twice a week for at least 30 minutes at a time, and 28% of patients exercised alone only. Walking was most commonly reported (77%), followed by stretching (52%), and weights (28%). 97% of patients who exercised noted mitigation of their PD symptoms. Additionally, a significantly greater percentage of patients who exercised in groups reported symptomatic improvements compared to patients who only exercised alone (p = 0.03). CONCLUSION: More patients who participated in group exercise reported symptomatic improvement compared to those who exercised strictly alone. This suggests that the psychosocial and cognitive component of group therapy, such as dance, may confer additional benefits to PD patients.

Safety and efficacy of CVT-301 (levodopa inhalation powder) on motor function during off periods in patients with Parkinson's disease: a randomised, double-blind, placebo-controlled phase 3 trial.

BACKGROUND: Patients with Parkinson's disease chronically treated with levodopa commonly have delayed or unpredictable onset of its benefits after oral intake. In this study, we assessed the safety and efficacy of CVT-301, a self-administered levodopa oral inhalation powder, for the treatment of patients with Parkinson's disease during off periods. METHODS: In this randomised, double-blind, placebo-controlled, phase 3 trial, patients were recruited at 65 sites in Canada, Poland, Spain, and the USA. Eligible participants were patients with Parkinson's disease aged 30-85 years, who had daily off periods of 2 h or longer and showed an improvement of 25% or greater in the Unified Parkinson's Disease Rating Scale (UPDRS) motor score from off to on state after use of an oral levodopa plus a dopa-decarboxylase inhibitor combination. Patients were assigned (1:1:1) with a computer-generated randomisation code, in fixed blocks of six, to either CVT-301 60 mg, CVT-301 84 mg, or placebo. Spirometry results and modified Hoehn and Yahr disease stage at screening were used for stratification of treatment groups. Patients, the sponsor, and site personnel were masked to treatment assignment. Each study dose consisted of two capsules administered with an inhaler. Patients were instructed to use the study drug as needed for off periods, and could self-administer up to five doses per day. The primary endpoint was the change in UPDRS motor score from predose to 30 min postdose, assessed at week 12 during an in-clinic off period, in the CVT-301 84 mg group compared with the placebo group. Analysis was by intention to treat. Safety was assessed in all patients who received at least one dose of experimental treatment. This trial is registered with ClinicalTrials.gov, number NCT02240030. FINDINGS: Between Dec 4, 2014, and Aug 26, 2016, 351 patients were enrolled and randomly assigned to receive CVT-301 60 mg (115 patients), CVT-301 84 mg (120 patients), or placebo (116 patients). Of these, 339 received the assigned study treatment (CVT-301 60 mg, n=113; CVT-301 84 mg, n=114; placebo, n=112) and 290 completed the study (CVT-301 60 mg, n=96; CVT-301 84 mg, n=97; placebo, n=97). The least-squares mean difference in UPDRS motor score change from predose to 30 min postdose was -5·91 (SE 1·50, 95% CI -8·86 to -2·96) for the placebo group and -9·83 (1·51; -12·79 to -6·87) for the CVT-301 84 mg group (between-group difference -3·92 [-6·84 to -1·00]; p=0·0088). Treatments were safe and well tolerated. Severe adverse events were reported by 2 (2%) of 112 patients in the placebo group, 7 (6%) of 113 in the CVT-301 60 mg group, and 5 (4%) of 114 in the CVT-301 84 mg group, with no severe adverse event occurring in more than one patient in any treatment group. 11 (3%) of 339 patients had 19 serious adverse events (three [3%] of 112 patients in placebo, six [5%] of 113 in CVT-301 60 mg, and two [2%] of 114 in CVT-301 84 mg). Of these, hypotension and atrial fibrillation were assessed by investigators to be possibly related to the study drug. INTERPRETATION: CVT-301 can improve UPDRS motor scores of patients with Parkinson's disease during in-clinic off periods, with few severe or serious adverse events. The long-term safety and efficacy of CVT-301 need to be investigated in future studies. FUNDING: Acorda Therapeutics.

Experienced facial masking indirectly compromises quality of life through stigmatization of women and men with Parkinson's disease.

This study examined the relationship between self-reported facial masking and quality of life (QoL) in people with Parkinson's disease (PD), and tested experienced stigma as a mediator and gender as a moderator of this relationship. The strength of stigma as a mediator was compared against an alternative mediator, depression. Ninety people with PD (34 women) rated difficulty showing facial expression (masking), and completed the Stigma Scale for Chronic Illness, Geriatric Depression Scale (15-item), and Parkinson's Disease Questionnaire-39. A conditional process model tested the indirect effect of facial masking on QoL through stigma, separately for women and men. A parallel indirect model included both stigma and depression to compare their statistical and clinical significance as mediators. Gender-moderated mediation of stigma reduced the association between facial masking and QoL to non-significance, suggesting stigma explained the association between facial masking and QoL. While facial masking was more stigmatizing for women than for men, stigma mediated the facial masking-QoL association for both women and men. Stigma (controlling for depression) reached a statistically and clinically significant level of mediation, whereas depression (controlling for stigma) reached a statistically yet not clinically significant level of mediation. People with PD who experience more severe facial masking feel more stigmatized, especially women. Regardless of gender, an increase in stigma from facial masking increases the likelihood of compromised QoL that reaches both statistical and clinical levels of significance.

Can patients be trained to expect shared decision making in clinical consultations? Feasibility study of a public library program to raise patient awareness.

INTRODUCTION: Shared decision making (SDM) is a process whereby decisions are made together by patients and/or families and clinicians. Nevertheless, few patients are aware of its proven benefits. This study investigated the feasibility, acceptability and impact of an intervention to raise public awareness of SDM in public libraries. MATERIALS AND METHODS: A 1.5 hour interactive workshop to be presented in public libraries was co-designed with Quebec City public library network officials, a science communication specialist and physicians. A clinical topic of maximum reach was chosen: antibiotic overuse in treatment of acute respiratory tract infections. The workshop content was designed and a format, whereby a physician presents the information and the science communication specialist invites questions and participation, was devised. The event was advertised to the general public. An evaluation form was used to collect data on participants' sociodemographics, feasibility and acceptability components and assess a potential impact of the intervention. Facilitators held a post-workshop focus group to qualitatively assess feasibility, acceptability and impact. RESULTS: All 10 planned workshops were held. Out of 106 eligible public participants, 89 were included in the analysis. Most participants were women (77.6%), retired (46.1%) and over 45 (59.5%). Over 90% of participants considered the workshop content to be relevant, accessible, and clear. They reported substantial average knowledge gain about antibiotics (2.4, 95% Confidence Interval (CI): 2.0-2.8; P < .001) and about SDM (4.0, 95% CI: 3.4-4.5; P < .001). Self-reported knowledge gain about SDM was significantly higher than about antibiotics (4.0 versus 2.4; P < .001). Knowledge gain did not vary by sociodemographic characteristics. The focus group confirmed feasibility and suggested improvements. CONCLUSIONS: A public library intervention is feasible and effective way to increase public awareness of SDM and could be a new approach to implementing SDM by preparing potential patients to ask for it in the consulting room.