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Outdoor exercise equipment has become popular as important environmental infrastructure to provide opportunities for physical activity and social connectedness in public settings. With higher sedentary behaviour and physical inactivity reported among older people, infrastructure changes and safe environments that promote older peoples' health and mobility are required. Due to ageing-related functional decline and health conditions associated with ageing, older adults may have special physical needs that require careful consideration when choosing outdoor equipment. However, limited information is available regarding the suitability of the types of exercise equipment for older people. This commentary provides further information on the type of equipment available, its functionality and suitability for older age populations and key considerations for the decision-maker involved in selecting, installing and supporting community use of outdoor exercise equipment. Recommendations on what is required to maximise usability from a system or organisational-based approach using research evidence is also discussed. Older people are more susceptible to the negative influences of their local environment and outdoor neighbourhood conditions. Consequently, the age-friendliness and suitability of the outdoor exercise equipment characteristics, location and settings may facilitate older adults' engagement in physical and social activities., (© 2020 The Authors. Health Promotion Journal of Australia published by John Wiley & Sons Australia, Ltd on behalf of Australian Health Promotion Association.)

Background: The physical environment has been shown to have a positive effect on the promotion of physical activity of older people. Outdoor environments that incorporate specialised exercise equipment suitable for older people are uniquely placed to promote physical activity and social connectedness amongst older people. The ENJOY project included the installation of specialised outdoor exercise equipment (the Seniors Exercise Park) and the delivery of a physical and social activity program for older people as part of a prospective pre-post research design. The installation of the specialised equipment in public sites and an aged care facility was also aimed at increasing usage of the equipment by older people from the wider community and to increase physical and social activities., Method: A conceptual framework for implementation and several engagement methods were utilised to guide the research and to support the participating partners throughout the project. This paper is a reflective narrative describing the collaborative process and approach utilised to engage local governments and community, and reports the challenges and the lessons learnt to inform future strategies for implementation., Results: The conceptual framework for the implementation process that guided the conduct and delivery of the ENJOY project included the core elements of the Interactive Systems Framework and the ecologic framework. These models incorporate elements of research-to-practice and community-centred implementation to accommodate the unique perspectives of a range of stakeholders., Conclusion: Partner characteristics such as local governments' structure and policy as well as community factors can impact on implementation. Partnership with local governments with effective communication, strategic planning and community and seniors engagement approaches are recommended for successful implementation. The lessons learnt can further assist public health research design around changes to the built environment to positively impact on older people's physical activity levels., Trial Registration: Trial registration number ACTRN12618001727235. Date of registration 19th October 2018, https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=375979.

Antagonising the serotonin 2A (5-HT 2A ) receptor is an efficacious way to alleviate dyskinesia and psychosis in Parkinson's disease (PD). However, previous research indicates that there might be a limit to the effects conferred by this approach. 5-HT 2A receptors were shown to form hetero-dimers with metabotropic glutamate 2 (mGlu 2 ) receptors, in which 5-HT 2A blockade and mGlu 2 activation elicit equivalent effects at the downstream signalling level. We have previously shown that mGlu 2 activation reduces both dyskinesia and psychosis-like behaviours (PLBs) induced by L-3,4-dihydroxyphenylalanine (l-DOPA), in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned primate. Here, we hypothesised that concurrent 5-HT 2A antagonism and mGlu 2 activation would provide greater anti-dyskinetic and anti-psychotic benefits than either approach alone. We conducted 3 series of experiments in the MPTP-lesioned marmoset. In the first series of experiments, the mGlu 2 positive allosteric modulator LY-487,379 and the 5-HT 2A antagonist EMD-281,014, either alone or in combination, were added to l-DOPA. In the second series of experiments, the mGlu 2/3 orthosteric agonist LY-354,740 and EMD-281,014, either alone or in combination, were added to l-DOPA. In the last series of experiments, we investigated whether mGlu 2 blockade would diminish the effects of antagonising 5-HT 2A receptors. To this end, the mGlu 2/3 orthosteric antagonist LY-341,495 and EMD-281,014, either alone or in combination, were added to l-DOPA. We found that the anti-dyskinetic effect of the combination LY-487,379/EMD-281,014 was greater than the ones conferred by LY-487,379 (by 35%, P < 0.05) and EMD-281,014 (by 38%, P < 0.01). The anti-dyskinetic and anti-psychotic effects of the combination LY-354,740/EMD-281,014 were also greater than the ones conferred by LY-354,740 (by 57% for dyskinesia and 54% for PLBs, both P < 0.001) and EMD-281,014 (by 61% for dyskinesia and 53% for PLBs, both P < 0.001). The anti-parkinsonian action of l-DOPA was maintained with all treatments. Lastly, the addition of LY-341,495 abolished the therapeutic effects of EMD-281,014 on dyskinesia and PLBs. Our results suggest that mGlu 2 activation may enhance the anti-dyskinetic and anti-psychotic effects of 5-HT 2A blockade and could provide relief to PD patients with dyskinesia and psychotic symptoms beyond what can be achieved with current therapies., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Modelling and remodelling adapt bone morphology to accommodate strains commonly encountered during loading. If strains exceed a threshold threatening fracture, modelling-based bone formation increases bone volume reducing these strains. If unloading reduces strains below a threshold that inhibits resorption, increased remodelling-based bone resorption reduces bone volume restoring strains, but at the price of compromised bone volume and microstructure. As weight-bearing regions are adapted to greater strains, we hypothesized that microstructural deterioration will be more severe than at regions commonly adapted to low strains following spinal cord injury., Methods: We quantified distal tibial, fibula and radius volumetric bone mineral density (vBMD) using high-resolution peripheral quantitative computed tomography in 31 men, mean age 43.5 years (range 23.5-75.0), 12 with tetraplegia and 19 with paraplegia of 0.7 to 18.6 years duration, and 102 healthy age- and sex-matched controls. Differences in morphology relative to controls were expressed as standardized deviation (SD) scores (mean ± SD). Standardized between-region differences in vBMD were expressed as SDs (95% confidence intervals, CI)., Results: Relative to controls, men with tetraplegia had deficits in total vBMD of -1.72 ± 1.38 SD at the distal tibia (p < 0.001) and - 0.68 ± 0.69 SD at distal fibula (p = 0.041), but not at the distal radius, despite paralysis. Deficits in men with paraplegia were -2.14 ± 1.50 SD (p < 0.001) at the distal tibia and -0.83 ± 0.98 SD (p = 0.005) at the distal fibula while distal radial total vBMD was 0.23 ± 1.02 (p = 0.371), not significantly increased, despite upper limb mobility. Comparing regions, in men with tetraplegia, distal tibial total vBMD was 1.04 SD (95%CI 0.07, 2.01) lower than at the distal fibula (p = 0.037) and 1.51 SD (95%CI 0.45, 2.57) lower than at the distal radius (p = 0.007); the latter two sites did not differ from each other. Results were similar in men with paraplegia, but total vBMD at the distal fibula was 1.06 SD (95%CI 0.35, 1.77) lower than at the distal radius (p = 0.004)., Conclusion: Microarchitectural deterioration following spinal cord injury is heterogeneous, perhaps partly because strain thresholds regulating the cellular activity of mechano-transduction are region specific., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Many research studies evaluate physical activity interventions for older people in the community, however relatively few successfully promote maintenance of physical activity beyond the completion of the intervention. This study aimed to implement and evaluate the effects of sustained engagement in physical activity on mental, social and physical health outcomes through the use of the Seniors Exercise Park physical activity program for older people (the ENJOY project)., Method: People aged ≥60 years underwent a 12-week structured supervised physical activity program using outdoor exercise park equipment followed by 6 months unstructured independent use of the exercise park. Participants were assessed at baseline, 3 months and 9 months and completed a test battery evaluating physical activity, physical function and health related quality of life measures. Repeated measures ANOVA was used to compare differences between baseline, 3 and 9 months., Results: Of the 95 participants, 80 (84.2%) completed the 3 months supervised program, and 58 (61%) completed the 9 month assessment (the latter impacted by COVID-19 restrictions). A significant increase in physical activity level was demonstrated following the 12 weeks intervention (p < 0.01). Significant improvements were also demonstrated in all physical function measures (p < 0.01), self-rated quality of life (p < 0.05), wellbeing (p < 0.01), fear of falls (p < 0.01), falls risk (p < 0.01), depressive symptoms (p = 0.01) and loneliness (p = 0.03) at 3 months. At the 9 months follow up, significant improvements from baseline were demonstrated in the frequency, duration and total of physical activity level (p < 0.05), and all physical function measures (p < 0.05), with no decline in these measures from 3 to 9 months. At 9 months, significant changes were observed in the health related quality of life mobility and self care domains with reductions in both fear of falls and falls risk (p < 0.05)., Conclusion: The Seniors Exercise Park may be an effective modality for improving and sustaining older people's physical function and wellbeing and can be an important public health infrastructure investment in promoting physical activity for older people. Future work should focus on wider implementation of the program and on scaling up this initiative to achieve public health benefit for the community., Trial Registration: Trial registration number ACTRN12618001727235, Date of registration 19th October 2018, https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=375979.

Objectives: The treatment of Parkinson disease (PD) psychosis remains a challenge. Only a few treatments eliciting significant relief of psychotic symptoms have passed the test of randomized controlled trials., Methods: Here, we conducted a review of the literature on the effect of antidepressants on PD psychosis. Because there is no randomized controlled trial that assessed the antipsychotic effects of antidepressants in PD, only case reports, case series, and open-label trials were available to review. Because of the scarce literature, statistical analysis could not be performed., Results: The following antidepressants alleviated hallucinations in PD: amoxapine, citalopram, clomipramine, escitalopram, mianserin, mirtazapine, and venlafaxine. The antidepressants were generally well tolerated, with the exception of amoxapine, which exacerbated parkinsonism., Conclusions: Whereas the conclusions that can be drawn on the efficacy of antidepressants at reducing PD psychosis are limited because of the poor quality of the reported studies, it is encouraging to notice that there are positive anecdotal reports. Further studies are needed to confirm the potential of these drugs and also to determine if a subtype of patients or of psychotic features may be more likely to be improved by antidepressants.

Psychosis and dyskinesia significantly diminish the quality of life of patients with advanced Parkinson's disease (PD). Available treatment options are unfortunately few and their use is limited by adverse effects. We have recently shown that activation of metabotropic glutamate 2 and 3 (mGlu2/3) receptors produced significant relief of L-3,4-dihydroxyphenylalanine (L-DOPA)-induced psychosis-like behaviours (PLBs) and dyskinesia in experimental models of PD. Here, using the highly-selective mGlu2 positive allosteric modulator (PAM) LY-487,379, we seek to determine the contribution of selective mGlu2 activation on both L-DOPA-induced PLBs and dyskinesia, in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned primate. We first determined the pharmacokinetic (PK) profile of LY-487,379 in the common marmoset, following which we administered it (0.1, 1 and 10 mg/kg) or its vehicle to 6 MPTP-lesioned marmosets previously exposed to L-DOPA to elicit stable PLBs and dyskinesia. We found that LY-487,379 provided a ≈45% reduction of the global PLBs observed and reduced global dyskinesia score by ≈ 55%. Moreover, LY-487,379 enhanced the anti-parkinsonian effect of L-DOPA, by reducing global parkinsonian score by ≈ 15%. Our data suggest that selective mGlu2 positive allosteric modulation with LY-487,379 may represent a potential therapeutic approach to alleviate both L-DOPA-induced PLBs and dyskinesia in PD., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: More than 75% of Parkinson's disease (PD) patients will develop dementia. Previous studies on the cognitive predictors of dementia in PD had some methodological limitations and the cognitive tests identified as good predictors vary greatly., Objective: This prospective cohort study aims to identify the optimal cognitive predictors of dementia in PD using complementary statistical methods., Methods: Eighty PD patients without dementia underwent polysomnographic recording, a neurological examination, and a complete neuropsychological assessment at baseline. They were then followed for a mean of 4.3 years. Baseline group comparisons and survival analyses were used to identify optimal cognitive predictors. Moreover, patients who developed dementia were pair-matched at baseline according to age, sex, and education to healthy controls (2 : 1), and receiver operating characteristic curves were calculated for cognitive tests., Results: At follow-up, 23 patients (29%) developed dementia. PD patients who developed dementia had poorer baseline performance and a higher proportion of clinically impaired performance on several cognitive tests. Impaired baseline performance on the Block Design subtest was the best independent predictor of dementia (HR = 8). Moreover, the Trail Making Test part B (time) and Verbal Fluency (semantic) had the best psychometric properties (area under the curve >0.90) for identifying PD patients at risk of dementia., Conclusion: The present study identified three cognitive tests as the most accurate to detect individuals with PD at high risk of developing dementia.

Background: Genetic, biologic and clinical data suggest that Parkinson's disease (PD) is an umbrella for multiple disorders with clinical and pathological overlap, yet with different underlying mechanisms. To better understand these and to move towards neuroprotective treatment, we have established the Quebec Parkinson Network (QPN), an open-access patient registry, and data and bio-samples repository., Objective: To present the QPN and to perform preliminary analysis of the QPN data., Methods: A total of 1,070 consecutively recruited PD patients were included in the analysis. Demographic and clinical data were analyzed, including comparisons between males and females, PD patients with and without RBD, and stratified analyses comparing early and late-onset PD and different age groups., Results: QPN patients exhibit a male:female ratio of 1.8:1, an average age-at-onset of 58.6 years, an age-at-diagnosis of 60.4 years, and average disease duration of 8.9 years. REM-sleep behavior disorder (RBD) was more common among men, and RBD was associated with other motor and non-motor symptoms including dyskinesia, fluctuations, postural hypotension and hallucinations. Older patients had significantly higher rates of constipation and cognitive impairment, and longer disease duration was associated with higher rates of dyskinesia, fluctuations, freezing of gait, falls, hallucinations and cognitive impairment. Since QPN's creation, over 60 studies and 30 publications have included patients and data from the QPN., Conclusions: The QPN cohort displays typical PD demographics and clinical features. These data are open-access upon application (http://rpq-qpn.ca/en/), and will soon include genetic, imaging and bio-samples. We encourage clinicians and researchers to perform studies using these resources.

Background: Creating inclusive and accessible outdoor environments that provide and encourage opportunities for older adults to engage in physical activity and social interaction is important for healthy ageing. The Senior Exercise Park is outdoor exercise equipment designed specifically for use by older people that provides physical and social benefits for older people in the community, and has the potential to be used widely as a sustainable mode of physical activity. The aim of this study is to implement and evaluate the effects of sustained engagement through the use of a community-based novel outdoor physical activity program (purpose-built exercise park) for older people on physical, mental and social health and physical activity outcomes (the ENJOY project)., Methods: This is a prospective pre-post design study with 12 months follow up. Adults aged ≥60 years will be recruited from the general community from the suburbs close to the Senior Exercise Parks locations in Melbourne. Participants will undergo a 12 week structured supervised physical activity program using the outdoor Senior Exercise Park equipment followed by 6 months unstructured physical activity program. Participants will be assessed at baseline, 3, 9, and 12 months. The following outcomes will be assessed: physical activity, physical function, psychosocial and mental health outcomes, falls risk and falls occurrence, participants' feedback and satisfaction, and health care resource use., Discussion: The ENJOY trial is designed to operate in a community setting with local government engagement to maximise the usage of the exercise park and provide an outdoor space for older people to be physically active. This project will evaluate the effectiveness and sustainability of the outdoor exercise park on a range of health outcomes and its long-term usability in the community., Trial Registration: This trial is prospectively registered with the Australian New Zealand Clinical Trials Registry. Trial registration number ACTRN12618001727235 registered 18th of October 2018.

We aimed to investigate cortical and subcortical brain alterations in people with Parkinson's disease with polysomnography-confirmed rapid eye movement (REM) sleep behavior disorder (RBD). Thirty people with Parkinson's disease, including 15 people with RBD, were recruited and compared with 41 healthy controls. Surface-based cortical and subcortical analyses were performed on T1-weighted images to investigate thickness and shape abnormalities between groups, and voxel-based and deformation-based morphometry were performed to investigate local volume. Correlations were performed in patients to investigate the structural correlates of motor activity during REM sleep. People with RBD showed cortical thinning in the right perisylvian and inferior temporal cortices and shape contraction in the putamen compared with people without RBD. Compared with controls, people with RBD had extensive cortical thinning and volume loss, brainstem volume was reduced, and shape contraction was found in the basal ganglia and hippocampus. In comparison to controls, people without RBD showed more restricted thinning in the sensorimotor, parietal, and occipital cortices, reduced volume in the brainstem, temporal and more posterior areas, and shape contraction in the pallidum and hippocampus. In Parkinson's disease, higher tonic and phasic REM sleep motor activity was associated with contraction of the thalamic surface, extensive cortical thinning, and subtle volume reduction in the middle temporal gyrus. In Parkinson's disease, the presence of RBD is associated with extensive cortical and subcortical abnormalities, suggesting more severe neurodegeneration in people with RBD. This provides potential neuroanatomical correlates for the more severe clinical phenotype reported in people with Parkinson's disease with RBD., (© Sleep Research Society 2019. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.)

Essential Tremor is a prevalent neurological disorder of unknown etiology. Studies suggest that genetic factors contribute to this pathology. To date, no causative mutations in a gene have been reproducibly reported. All three structures of the olivocerebellar motor circuitry have been linked to Essential Tremor. We postulated that genes enriched for their expression in the olivocerebellar circuitry would be more susceptible to harbor mutations in Essential Tremor patients. A list of 11 candidate genes, enriched for their expression in the olivocerebellar circuitry, was assessed for their variation spectrum and frequency in a cohort of Canadian Essential Tremor cases. Our results from this list of 11 candidate genes do not support an association for Essential Tremor in our cohort of Canadian cases. The heterogenic nature of ET and modest size of the cohort used in this study are two confounding factors that could explain these results.

The production of extracellular vesicles (EV) is a ubiquitous feature of eukaryotic cells but pathological events can affect their formation and constituents. We sought to characterize the nature, profile and protein signature of EV in the plasma of Parkinson's disease (PD) patients and how they correlate to clinical measures of the disease. EV were initially collected from cohorts of PD (n = 60; Controls, n = 37) and Huntington's disease (HD) patients (Pre-manifest, n = 11; manifest, n = 52; Controls, n = 55) - for comparative purposes in individuals with another chronic neurodegenerative condition - and exhaustively analyzed using flow cytometry, electron microscopy and proteomics. We then collected 42 samples from an additional independent cohort of PD patients to confirm our initial results. Through a series of iterative steps, we optimized an approach for defining the EV signature in PD. We found that the number of EV derived specifically from erythrocytes segregated with UPDRS scores corresponding to different disease stages. Proteomic analysis further revealed that there is a specific signature of proteins that could reliably differentiate control subjects from mild and moderate PD patients. Taken together, we have developed/identified an EV blood-based assay that has the potential to be used as a biomarker for PD., (Copyright © 2018. Published by Elsevier Inc.)

Objective: To assess the contribution of variants in STK32B , PPARGC1A , and CTNNA3 as essential tremor (ET) predisposing factors following their association in a 2-stage genome-wide association study (GWAS)., Methods: The coding regions of these genes was examined for the presence of rare variants using two approaches: (1) Looking at whole-exome and whole-genome sequencing data of 14 autosomal dominant multiplex ET families. (2) Conducting a targeted massive parallel sequencing to examine the three genes in cohorts of 269 ET cases and 287 control individuals. The cumulative impact of rare variants was assessed using SKAT-O analyses using (1) all variants, (2) only rare variants, and (3) only the rare variants altering the mRNA., Results: Thirty-four variants were identified. No difference emerged regarding the distributions of individual variants (or gene) between cases and controls., Conclusion: No rare exonic variants further validated one of these genes as a risk factor for ET. The recent GWAS offers promising avenues, but the genetic heterogeneity of ET is nonetheless challenging for the validation of risk factors, and ultimately larger cohorts of cases should help to overcome this task.

Background: Individuals with Parkinson's disease (PD) often present with visual symptoms (e.g., difficulty in reading, double vision) that can also be found in convergence insufficiency (CI). Our objective was to estimate the prevalence of CI-type visual symptomatology in individuals with PD, in comparison with controls., Methods: Participants ≥50 years with (n=300) and without (n=300) PD were recruited. They were administered the Convergence Insufficiency Symptom Survey (CISS-15) over the phone. A score of ≥21 on the CISS-15, considered positive for CI-type symptomatology, served as the cutoff. Data from individuals (n=87 with, n=94 without PD) who were approached but who reported having a known oculovisual condition were analysed separately. Student's t test and chi-square at the 0.05 level were employed for statistical significance., Results: A total of 29.3% of participants with versus 7.3% without PD presented with a score of ≥21 on the CISS-15 (p=0.001). Of the participants having a known oculovisual condition, 39.1% with versus 19.1% without PD presented with a score of ≥21 on the CISS-15 (p=0.01)., Conclusions: The prevalence of CI-type visual symptoms is higher in individuals with versus without PD whether or not they have a coexisting oculovisual condition. These results suggest that PD per se places individuals with the disease at greater risk of visual symptomatology. These results further underline the importance of providing regular eye exams for individuals with PD.

Study Objectives: REM sleep behavior disorder (RBD) is a parasomnia affecting 33% to 46% of patients with Parkinson's disease (PD). The existence of a unique and specific impaired cognitive profile in PD patients with RBD is still controversial. We extensively assessed cognitive functions to identify whether RBD is associated with more severe cognitive deficits in nondemented patients with PD., Methods: One hundred sixty-two participants, including 53 PD patients with RBD, 40 PD patients without RBD, and 69 healthy subjects, underwent polysomnography, a neurological assessment and an extensive neuropsychological exam to assess attention, executive functions, episodic learning and memory, visuospatial abilities, and language., Results: PD patients with RBD had poorer and clinically impaired performance in several cognitive tests compared to PD patients without RBD and healthy subjects. These two latter groups were similar on all cognitive measures. Mild cognitive impairment (MCI) diagnosis frequency was almost threefold higher in PD patients with RBD compared to PD patients without RBD (66% vs. 23%, p < .001). Moreover, subjective cognitive decline was reported in 89% of PD patients with RBD compared to 58% of PD patients without RBD (p = .024)., Conclusions: RBD in PD is associated with a more impaired cognitive profile and higher MCI diagnosis frequency, suggesting more severe and widespread neurodegeneration. This patient subgroup and their caregivers should receive targeted medical attention to better detect and monitor impairment and to enable the development of management interventions for cognitive decline and its consequences., (© Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.)

Introduction: This study reports a case series of orthoptic treatment (OT) for convergence insufficiency (CI) in individuals with Parkinson's disease (PD). Method: We are reporting two cases of individuals with PD who completed OT for CI. Both had a confirmed diagnosis of CI, accompanied by CI-type symptomatology. They each underwent an OT program consisting of three office-based visits and 8 weeks of home-based exercises. Treatment outcome was based on the changes measured pre- versus post-OT on the near point of convergence, positive fusional vergences, and symptomatology score. Results: The two participants successfully completed therapy, gained ability to converge, had fewer symptoms, and were satisfied with the OT-induced changes they felt in their day-to-day lives. Conclusion: This case series show that OT for CI in PD is possible. Further research is required as these results demonstrate that OT has the potential to improve symptomatic CI in these patients. In the meantime, the positive results obtained in these two cases should encourage clinicians to consider OT (a therapy with no/minimal risk) for CI in patients with PD whose quality of life is affected by this binocular dysfunction., Competing Interests: Declaration of Conflicting Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

During the "DBS Canada Day" symposium held in Toronto July 4-5, 2014, the scientific committee invited experts to share their knowledge regarding deep brain stimulation (DBS) management of movement disorders in three domains: (1) the programming algorithms, (2) the necessary team to run a neurosurgery program, and (3) the appropriate scales to better define in a more comprehensive fashion the effect of the brain surgery. Each presentation was followed by an open discussion, and this article reports on the conclusions of this meeting on these three questions. Concerning programming, the role of the pulse width and the switching off of the stimulation at night for thalamic stimulation for the control of tremor have been discussed. The algorithms proposed in the literature for programming in Parkinson's disease (PD) need validation. In dystonia, the use of monopolar vs bipolar parameters, the use of low vs high frequencies and the use of smaller versus larger pulse widths all need to be examined properly. Concerning the necessary team to run a neurosurgical program, recommendations will follow the suggestions for standardized outcome measures. Regarding the outcome measures for DBS in PD, investigations need to focus on the non-motor aspects of PD. Identifying which nonmotor symptoms respond to DBS would allow a better screening before and satisfaction postoperatively. There is an important need for more data to determine the optimal programming protocol and the standard measures that should be performed routinely by all centers.

Introduction: Mutations in teneurin transmembrane protein 4 were reported to be a risk factor for essential tremor, but the relevance of this across different population remains to be examined. The aim of this study was to determine the frequency and spectrum of variations in teneurin transmembrane protein 4 in a cohort of Canadian essential tremor cases., Methods: The coding portion of teneurin transmembrane protein 4 was sequenced in 269 unrelated essential tremor cases and 288 matched control individuals using a targeted and high-throughput sequencing approach., Results: A total of 157 single nucleotide variations were identified, and from these 99 were a missense or nonsense mutation. A total of 68 cases were carriers of ≥1 rare missense or nonsense mutations, and 39 control individuals were carriers of the same types of variations. Gene-based association tests were used to jointly analyze the single nucleotide variations., Conclusions: Our results do not support a positive association between teneurin transmembrane protein 4 and the Canadian population. © 2017 International Parkinson and Movement Disorder Society., (© 2017 International Parkinson and Movement Disorder Society.)

During the "DBS Canada Day" symposium held in Toronto July 4-5, 2014, the scientific committee invited experts to discuss three main questions on target selection for deep brain stimulation (DBS) of patients with Parkinson's disease (PD). First, is the subthalamic nucleus (STN) or the globus pallidus internus (GPi) the ideal target? In summary, both targets are equally effective in improving the motor symptoms of PD. STN allows a greater medications reduction, while GPi exerts a direct antidyskinetic effect. Second, are there further potential targets? Ventral intermediate nucleus DBS has significant long-term benefit for tremor control but insufficiently addresses other motor features of PD. DBS in the posterior subthalamic area also reduces tremor. The pedunculopontine nucleus remains an investigational target. Third, should DBS for PD be performed unilaterally, bilaterally or staged? Unilateral STN DBS can be proposed to asymmetric patients. There is no evidence that a staged bilateral approach reduces the incidence of DBS-related adverse events.

We conducted a genome-wide association study of essential tremor, a common movement disorder characterized mainly by a postural and kinetic tremor of the upper extremities. Twin and family history studies show a high heritability for essential tremor. The molecular genetic determinants of essential tremor are unknown. We included 2807 patients and 6441 controls of European descent in our two-stage genome-wide association study. The 59 most significantly disease-associated markers of the discovery stage were genotyped in the replication stage. After Bonferroni correction two markers, one (rs10937625) located in the serine/threonine kinase STK32B and one (rs17590046) in the transcriptional coactivator PPARGC1A were associated with essential tremor. Three markers (rs12764057, rs10822974, rs7903491) in the cell-adhesion molecule CTNNA3 were significant in the combined analysis of both stages. The expression of STK32B was increased in the cerebellar cortex of patients and expression quantitative trait loci database mining showed association between the protective minor allele of rs10937625 and reduced expression in cerebellar cortex. We found no expression differences related to disease status or marker genotype for the other two genes. Replication of two lead single nucleotide polymorphisms of previous small genome-wide association studies (rs3794087 in SLC1A2, rs9652490 in LINGO1) did not confirm the association with essential tremor., (© The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain.)

Background: We recently reported that convergence insufficiency (CI)-type visual symptomatology was more prevalent in participants with Parkinson's disease (PD), compared to controls. The objective of this work was to determine the prevalence of a confirmed clinical diagnosis of CI in PD, compared to controls., Methods: Participants with (n = 80) and without (n = 80) PD were recruited and received an eye exam. Published criteria were used to arrive at a clinical diagnosis of CI. The Convergence Insufficiency Symptom Survey (CISS-15) questionnaire was administered to each participant, with a score of ≥21 being considered positive for CI symptomatology. Student t test, chi-square, or nonparametric tests at the 0.05 level were used for statistical significance., Results: A total of 43.8% of participants with versus 16.3% without PD had a clinical diagnosis of CI ( P ≤ 0.001). A total of 53.8% of participants with versus 18.8% without PD had scores on the CISS-15 of ≥21 ( P ≤ 0.001)., Conclusions: These results indicate that individuals with PD have a higher prevalence of CI and CI symptomatology than controls. These data provide evidence supporting the notion that treatment for symptomatic CI should be investigated in individuals with PD.

Background: The prevalence of sleep disturbances among patients with Parkinson's disease (PD) is estimated to occur in 37% to 98% of patients. Sleep disturbances have been associated with a reduced quality of life for patients with PD. The objective of this study was to assess the impact of rasagiline treatment on the severity of sleep disturbances among patients with idiopathic PD., Methods: In this open-label, multicentre study, 110 adult patients with idiopathic PD were treated with rasagiline either as monotherapy or as adjunct therapy. The primary endpoint was the change in severity of sleep disturbances, assessed with the PD Sleep Scale from baseline to month 2. Exploratory endpoints included change in daytime sleepiness, assessed with the Epworth Sleep Scale, treatment satisfaction measured with the Treatment Satisfaction Questionnaire for Medication, patient's overall improvement or deterioration over time measured with the Clinical Global Impression of Improvement, tolerability, and safety., Findings: Patients treated with rasagiline as mono- or adjunct therapy showed a statistically significant improvement in sleep quality after 2 months. There was no change in daytime sleepiness. Overall, patients were satisfied with rasagiline treatment with a mean Treatment Satisfaction Questionnaire for Medication [standard deviation] total score at month 2 of 68% [16.1]. At the end of study, 64 patients (65.9%) were judged, by the investigator, as being at least minimally improved from baseline on the Clinical Global Impression of Improvement. Rasagiline was safe and well-tolerated., Interpretation: Rasagiline as mono- or adjunct-therapy may improve sleep experience in patients with PD in the short term.

In this review, we have gathered all the available evidence to guide medication management after deep brain stimulation (DBS) in Parkinson's disease (PD). Surprisingly, we found that almost no study addressed drug-based management in the postoperative period. Dopaminergic medications are usually reduced, but whether the levodopa or dopamine agonist is to be reduced is left to the personal preference of the treating physician. We have summarized the pros and cons of both approaches. No study on the management of cognitive problems after DBS has been done, and only a few studies have explored the pharmacological management of such DBS-resistant symptoms as voice (amantadine), balance (donepezil) or gait disorders (amantadine, methylphenidate). As for the psychiatric problems so frequently reported in PD patients, researchers have directed their attention to the complex interplay between stimulation and reduction of dopaminergic drugs only recently. In conclusion, studies addressing medical management following DBS are still needed and will certainly contribute to the ultimate success of DBS procedures.

In this review, the available evidence to guide clinicians regarding eligibility for deep brain stimulation (DBS) in the main conditions in which these forms of therapy are generally indicated-Parkinson's disease (PD), tremor, and dystonia-is presented. In general, the literature shows that DBS is effective for PD, essential tremor, and idiopathic dystonia. In these cases, key points in patient selection must include the level of disability and inability to manage symptoms using the best available medical therapy. Results are, however, still not optimal when dealing with other aetiologies, such as secondary tremors and symptomatic dystonia. Also, in PD, issues such as age and neuropsychiatric profile are still debatable parameters. Overall, currently available literature is able to guide physicians on basic aspects of patient selection and indications for DBS; however, a few points are still debatable and controversial. These issues should be refined and clarified in future studies.

In Parkinson's disease, electroencephalographic abnormalities during wakefulness and non-rapid eye movement sleep (spindles) were found to be predictive biomarkers of dementia. Because rapid eye movement sleep is regulated by the cholinergic system, which shows early degeneration in Parkinson's disease with cognitive impairment, anomalies during this sleep stage might mirror dementia development. In this prospective study, we examined baseline electroencephalographic absolute spectral power across three states of consciousness (non-rapid eye movement sleep, rapid eye movement sleep, and wakefulness) in 68 non-demented patients with Parkinson's disease and 44 healthy controls. All participants underwent baseline polysomnographic recordings and a comprehensive neuropsychological assessment. Power spectral analyses were performed on standard frequency bands. Dominant occipital frequency during wakefulness and ratios of slow-to-fast frequencies during rapid eye movement sleep and wakefulness were also computed. At follow-up (an average 4.5 years after baseline), 18 patients with Parkinson's disease had developed dementia and 50 patients remained dementia-free. In rapid eye movement sleep, patients with Parkinson's disease who later developed dementia showed, at baseline, higher absolute power in delta and theta bands and a higher slowing ratio, especially in temporal, parietal, and occipital regions, compared to patients who remained dementia-free and controls. In non-rapid eye movement sleep, lower baseline sigma power in parietal cortical regions also predicted development of dementia. During wakefulness, patients with Parkinson's disease who later developed dementia showed lower dominant occipital frequency as well as higher delta and slowing ratio compared to patients who remained dementia-free and controls. At baseline, higher slowing ratios in temporo-occipital regions during rapid eye movement sleep were associated with poor performance on visuospatial tests in patients with Parkinson's disease. Using receiver operating characteristic curves, we found that best predictors of dementia in Parkinson's disease were rapid eye movement sleep slowing ratios in posterior regions, wakefulness slowing ratios in temporal areas, and lower dominant occipital frequency. These results suggest that electroencephalographic slowing during sleep is a new promising predictive biomarker for Parkinson's disease dementia, perhaps as a marker of cholinergic denervation., (© The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)