Background: Speech impairments are common with Parkinson's disease (reported prevalence 68%), increasing conversational demands, reliance on family and social withdrawal. Objective(s): The PD COMM trial compared the clinical and cost-effectiveness of two speech and language therapy approaches: Lee Silverman Voice Treatment LOUD and National Health Service speech and language therapy for the treatment of speech or voice problems in people with Parkinson's disease to no speech and language therapy (control) and against each other. Design: PD COMM is a phase III, multicentre, three-arm, unblinded, randomised controlled trial. Participants were randomised in a 1 : 1 : 1 ratio to control, National Health Service speech and language therapy or Lee Silverman Voice Treatment LOUD via a central computer-generated programme, using a minimisation procedure with a random element, to ensure allocation concealment. Mixed-methods process and health economic evaluations were conducted. Setting: United Kingdom outpatient and home settings. Participants: People with idiopathic Parkinson's disease, with self-reported or carer-reported speech or voice problems. We excluded people with dementia, laryngeal pathology and those within 24 months of previous speech and language therapy. Interventions: The Lee Silverman Voice Treatment LOUD intervention included maximum effort drills and high-effort speech production tasks delivered over four 50-minute therapist-led personalised sessions per week, for 4 weeks with prescribed daily home practice. National Health Service speech and language therapy content and dosage reflected local non-Lee Silverman Voice Treatment speech and language therapy practices, usually 1 hour, once weekly, for 6 weeks. Trained, experienced speech and language therapists or assistants provided interventions. The control was no speech and language therapy until the trial was completed. Main outcome measures: Primary outcome: Voice Handicap Index total score at 3 months. Secondary outcomes: Voice Handicap Index subscales, Parkinson's Disease Questionnaire-39; Questionnaire on Acquired Speech Disorders; EuroQol-5D-5L; ICEpop Capabilities Measure for Older Adults; Parkinson's Disease Questionnaire - Carers; resource utilisation; and adverse events. Assessments were completed pre-randomisation and at 3, 6 and 12 months post randomisation. Results: Three hundred and eighty-eight participants were randomised to Lee Silverman Voice Treatment LOUD (n = 130), National Health Service speech and language therapy (n = 129) and control (n = 129). The impact of voice problems at 3 months after randomisation was lower for Lee Silverman Voice Treatment LOUD participants than control [-8.0 (99% confidence interval: -13.3, -2.6); p = 0.001]. There was no evidence of improvement for those with access to National Health Service speech and language therapy when compared to control [1.7 (99% confidence interval: -3.8, 7.1); p = 0.4]. Participants randomised to Lee Silverman Voice Treatment LOUD reported a lower impact of their voice problems than participants randomised to National Health Service speech and language therapy [99% confidence interval: -9.6 (-14.9, -4.4); p < 0.0001]. There were no reports of serious adverse events. Staff were confident with the trial interventions; a range of patient and therapist enablers of implementing Lee Silverman Voice Treatment LOUD were identified. The economic evaluation results suggested Lee Silverman Voice Treatment LOUD was more expensive and more effective than control or National Health Service speech and language therapy but was not cost-effective with incremental cost-effectiveness ratios of £197,772 per quality-adjusted life-year gained and £77,017 per quality-adjusted life-year gained, respectively. Limitations: The number of participants recruited to the trial did not meet the pre-specified power. Conclusions: People that had access to Lee Silverman Voice Treatment LOUD described a significantly greater reduction in the impact of their Parkinson's disease-related speech problems 3 months after randomisation compared to people that had no speech and language therapy. There was no evidence of a difference between National Health Service speech and language therapy and those that received no speech and language therapy. Lee Silverman Voice Treatment LOUD resulted in a significantly lower impact of voice problems compared to National Health Service speech and language therapy 3 months after randomisation which was still present after 12 months; however, Lee Silverman Voice Treatment LOUD was not found to be cost-effective. Future work: Implementing Lee Silverman Voice Treatment LOUD in the National Health Service and identifying alternatives to Lee Silverman Voice Treatment LOUD for those who cannot tolerate it. Investigation of less costly alternative options for Lee Silverman Voice Treatment delivery require investigation, with economic evaluation using a preference-based outcome measure that captures improvement in communication. Study registration: This study is registered as ISRCTN12421382.

No abstract available

Background: The PD MED study reported small but persistent benefits in patient-rated mobility scores and quality of life from initiating therapy with levodopa compared with levodopa-sparing therapies in early Parkinson's disease (PD). Objectives: The objective was to estimate the cost-effectiveness of levodopa-sparing therapy (dopamine agonists or monoamine oxidase type B inhibitors compared with levodopa alone. Methods: PD MED is a pragmatic, open-label randomized, controlled trial in which patients newly diagnosed with PD were randomly assigned between levodopa-sparing therapy (dopamine agonists or monoamine oxidase type B inhibitors ) and levodopa alone. Mean quality-adjusted life-years and costs were calculated for each participant. Differences in mean quality-adjusted life-years and costs between levodopa and levodopa-sparing therapies and between dopamine agonists and monoamine oxidase type B inhibitors were estimated using linear regression. Results: Over a mean observation period of 4 years, levodopa was associated with significantly higher quality-adjusted life-years (difference, 0.18; 95% CI, 0.05-0.30; P < 0.01) and lower mean costs (£3390; £2671-£4109; P < 0.01) than levodopa-sparing therapies, the difference in costs driven by the higher costs of levodopa-sparing therapies. There were no significant differences in the costs of inpatient, social care, and institutional care between arms. There was no significant difference in quality-adjusted life-years between those allocated dopamine agonists and monoamine oxidase type B inhibitors (0.02; -0.17 to 0.13 in favor of dopamine agonists; P = 0.81); however costs were significantly lower for those allocated monoamine oxidase type B inhibitors (£2321; £1628-£3015; P < 0.01) because of the higher costs of dopamine agonists. There were no significant differences between arms for other costs. Conclusions: Initial treatment with levodopa is highly cost-effective compared with levodopa-sparing therapies. Monoamine oxidase type B inhibitors, as initial levodopa-sparing therapy was more cost-effective, with similar quality-adjusted life-years but lower costs than dopamine agonists. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Background: Previous studies showed that lifestyle behaviors (cigarette smoking, alcohol, coffee) are inversely associated with Parkinson's disease (PD). The prodromal phase of PD raises the possibility that these associations may be explained by reverse causation. Objective: To examine associations of lifestyle behaviors with PD using two-sample Mendelian randomisation (MR) and the potential for survival and incidence-prevalence biases. Methods: We used summary statistics from publicly available studies to estimate the association of genetic polymorphisms with lifestyle behaviors, and from Courage-PD (7,369 cases, 7,018 controls; European ancestry) to estimate the association of these variants with PD. We used the inverse-variance weighted method to compute odds ratios (ORIVW) of PD and 95%confidence intervals (CI). Significance was determined using a Bonferroni-corrected significance threshold (p = 0.017). Results: We found a significant inverse association between smoking initiation and PD (ORIVW per 1-SD increase in the prevalence of ever smoking = 0.74, 95%CI = 0.60-0.93, p = 0.009) without significant directional pleiotropy. Associations in participants ≤67 years old and cases with disease duration ≤7 years were of a similar size. No significant associations were observed for alcohol and coffee drinking. In reverse MR, genetic liability toward PD was not associated with smoking or coffee drinking but was positively associated with alcohol drinking. Conclusion: Our findings are in favor of an inverse association between smoking and PD that is not explained by reverse causation, confounding, and survival or incidence-prevalence biases. Genetic liability toward PD was positively associated with alcohol drinking. Conclusions on the association of alcohol and coffee drinking with PD are hampered by insufficient statistical power.

No abstract available

Background: Distressing dreams in middle-aged and older adults have been associated with an increased risk of developing cognitive impairment (including dementia) and Parkinson's disease (PD). Whether distressing dreams in younger people might be associated with an increased risk of developing these conditions is unknown. This study investigated the association between distressing dreams in childhood and the risk of developing cognitive impairment or PD by age 50. Methods: Data from the 1958 British Birth Cohort Study - a prospective birth cohort which included all people born in Britain during a single week in 1958, were used in this longitudinal analysis. Information on distressing dreams were obtained prospectively from the children's mothers at ages 7 (1965) and 11 (1969). Cognitive impairment and PD at age 50 (2008) were determined by cognitive assessment and doctor-diagnosis respectively. The association between distressing dreams at ages 7 and 11 (no time point, 1 time point, 2 time points) and cognitive impairment or PD at age 50, was evaluated using multivariable Firth logistic regression, with adjustment for potential confounders. Findings: Among 6991 children (50.6% female) with follow-up available at age 50, 267 (3.8%) developed cognitive impairment or PD. After adjustment for all covariates, having more regular distressing dreams during childhood was linearly and statistically significantly associated with higher risk of developing cognitive impairment or PD by age 50 (P for trend = 0.037). Compared with children who never had distressing dreams (no time point), children who had persistent distressing dreams (2 time points) had an 85% increased risk of developing cognitive impairment or PD by age 50 (adjusted odds ratio = 1.85; 95% CI: 1.10, 3.11). Interpretation: Having persistent distressing dreams during childhood may be associated with an increased risk of developing cognitive impairment or PD in adulthood. Future studies are needed to confirm these findings and to determine whether treating distressing dreams during early life may lower the risk of dementia and PD.

Objectives This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To evaluate the effectiveness of speech and language therapy (SLT) interventions on speech and voice problems in people with Parkinson’s disease. We will investigate whether: SLT is more effective than no SLT; SLT is more effective than placebo or attention control interventions; one SLT intervention is more effective than another SLT intervention (including standard care). Background

After adjustment for all covariates, a higher frequency of distressing dreams was linearly and statistically significantly associated with higher risk of cognitive decline amongst middle-aged adults (P for trend = 0·016), and higher risk of incident all-cause dementia amongst older adults (P for trend <0·001). Compared with middle-aged adults who reported having no distressing dreams at baseline, those who reported having weekly distressing dreams had a 4-fold risk of experiencing cognitive decline (adjusted odds ratio [aOR] = 3·99; 95% CI: 1·07, 14·85). Amongst older adults, the difference in dementia risk was 2·2-fold (aOR = 2·21; 95% CI: 1·35, 3·62). In sex-stratified analyses, the associations between distressing dreams and both cognitive outcomes were only statistically significant amongst men.

During a mean follow-up of 7·3 years, 91 (2·4%) cases of incident PD were identified. Participants with frequent distressing dreams at baseline had a 2-fold risk for incident PD (OR, 2·01; 95% CI, 1·1-3·6, P = 0.02). When stratified by follow-up time, frequent distressing dreams were associated with a greater than 3-fold risk for incident PD during the first 5 years after baseline (OR, 3·38; 95% CI, 1·3-8·7; P = 0·01), however no effect was found during the subsequent 7 years (OR, 1·55; 95% CI, 0·7-3·3; P = 0·26).

Parkinson's disease (PD) is associated with low religiosity cross-sectionally. Whether low religiosity might be associated with an increased risk for developing PD is unknown. This study investigated whether low religiosity in adulthood is associated with increased risk for developing PD. A population-based prospective cohort study was conducted. Participants from the English Longitudinal Study of Aging and the Midlife in the United States study who were free from PD at baseline (2004-2011) and completed questionnaires on self-reported religiosity, were included in a pooled analysis. Incident PD was based on self-report. Multivariable logistic regression was used to estimate odds ratios (OR) for developing PD according to baseline religiosity, with adjustment for sociodemographic characteristics, health and lifestyle factors and engagement in religious practices. Among 9,796 participants in the pooled dataset, 74 (0.8%) cases of incident PD were identified during a median follow-up of 8.1 years. In the fully adjusted model, compared with participants who considered religion very important in their lives at baseline, it was found that participants who considered religion "not at all important" in their lives had a tenfold risk of developing PD during follow-up (OR, 9.99; 95% CI 3.28-30.36). Moreover, there was a dose-response relationship between decreasing religiosity and increasing PD risk (P < 0.001 for trend). These associations were similar when adjusting for religious upbringing and when cases occurring within the first two years of follow-up were excluded from the analysis. The association was somewhat attenuated when religious practices were removed from the model as covariates, though it remained statistically significant (OR for "not at all important" vs. "very important", 2.26; 95% CI 1.03-4.95) (P < 0.029 for trend). This longitudinal study provides evidence for the first time that low religiosity in adulthood may be a strong risk factor for developing PD.