Deep Intronic FGF14 GAA Repeat Expansion in Late-Onset Cerebellar Ataxia.

BACKGROUND: The late-onset cerebellar ataxias (LOCAs) have largely resisted molecular diagnosis. METHODS: We sequenced the genomes of six persons with autosomal dominant LOCA who were members of three French Canadian families and identified a candidate pathogenic repeat expansion. We then tested for association between the repeat expansion and disease in two independent case-control series - one French Canadian (66 patients and 209 controls) and the other German (228 patients and 199 controls). We also genotyped the repeat in 20 Australian and 31 Indian index patients. We assayed gene and protein expression in two postmortem cerebellum specimens and two induced pluripotent stem-cell (iPSC)-derived motor-neuron cell lines. RESULTS: In the six French Canadian patients, we identified a GAA repeat expansion deep in the first intron of FGF14, which encodes fibroblast growth factor 14. Cosegregation of the repeat expansion with disease in the families supported a pathogenic threshold of at least 250 GAA repeats ([GAA]≥250). There was significant association between FGF14 (GAA)≥250 expansions and LOCA in the French Canadian series (odds ratio, 105.60; 95% confidence interval [CI], 31.09 to 334.20; P<0.001) and in the German series (odds ratio, 8.76; 95% CI, 3.45 to 20.84; P<0.001). The repeat expansion was present in 61%, 18%, 15%, and 10% of French Canadian, German, Australian, and Indian index patients, respectively. In total, we identified 128 patients with LOCA who carried an FGF14 (GAA)≥250 expansion. Postmortem cerebellum specimens and iPSC-derived motor neurons from patients showed reduced expression of FGF14 RNA and protein. CONCLUSIONS: A dominantly inherited deep intronic GAA repeat expansion in FGF14 was found to be associated with LOCA. (Funded by Fondation Groupe Monaco and others.).

White matter degeneration profile in the cognitive cortico-subcortical tracts in Parkinson's disease.

BACKGROUND: In Parkinson's disease cognitive impairment is an early nonmotor feature, but it is still unclear why some patients are able to maintain their cognitive performance at normal levels, as quantified by neuropsychological tests, whereas others cannot. The objectives of this study were to perform a cross-sectional study and analyze the white matter changes in the cognitive and motor bundles in patients with Parkinson's disease. METHODS: Sixteen Parkinson's disease patients with normal cognitive performance, 19 with mild cognitive impairment (based on their performance of 1.5 standard deviations below the healthy population mean), and 16 healthy controls were compared with respect to their tractography patterns between the cortical cognitive / motor regions and subcortical structures, using high angular resolution diffusion imaging and constrained spherical deconvolution computation. RESULTS: Motor bundles showed decreased apparent fiber density in both PD groups, associated with a significant increase in diffusivity metrics, number of reconstructed streamlines, and track volumes, compared with healthy controls. By contrast, in the cognitive bundles, decreased fiber density in both Parkinson's groups was compounded by the absence of changes in diffusivity in patients with normal cognition, whereas patients with cognitive impairment had increased diffusivity metrics, lower numbers of reconstructed streamlines, and lower track volumes. CONCLUSIONS: Both PD groups showed similar patterns of white matter neurodegeneration in the motor bundles, whereas cognitive bundles showed a distinct pattern: Parkinson's patients with normal cognition had white matter diffusivity metrics similar to healthy controls, whereas in patients with cognitive impairment white matter showed a neurodegeneration pattern. © 2018 International Parkinson and Movement Disorder Society.

Depressive symptoms in Parkinson's disease correlate with cortical atrophy over time.

INTRODUCTION: Depressive symptoms are very common in patients with Parkinson's disease (PD) and have a significant impact on the quality of life. METHODS: The present study analyzed the correlations between over-time changes in depressive symptoms and gray matter parameters of cortical thickness and subcortical volumes in non-demented PD patients. RESULTS: A significant correlation was observed, between increased scores for depression over time and lower cortical thickness over time in the right temporo-parietal junction, right occipital medial region, right dorsolateral prefrontal cortex, right posterior cingulate region, left middle temporal as well as left supplementary motor area. Furthermore, the presence of depressive symptoms at baseline predicted increased cortical thinning over time in the left middle temporal, left anterior cingulate, right posterior cingulate and right parahippocampal cortices. Finally, a statistically significant negative correlation has been revealed between the thalamus' volume changes over time and the change in depressive symptoms scores. All other analyzed subcortical structures didn't reveal any significant correlations. CONCLUSION: These results suggest that depressive symptoms in PD patients are associated with gray matter cortical thinning and thalamus volume shrinkage over time and higher scores of depressive symptoms at baseline correlate with a higher rate of cortical thinning longitudinally. The present study highlights the importance of addressing depressive symptoms in PD patients early in the disease.

Examining chronic care patient preferences for involvement in health-care decision making: the case of Parkinson's disease patients in a patient-centred clinic.

BACKGROUND: Patient-centred care is a recommended model of care for Parkinson's disease (PD). It aims to provide care that is respectful and responsive to patient preferences, values and perspectives. Provision of patient-centred care should entail considering how patients want to be involved in their care. OBJECTIVE: To understand the participation preferences of patients with PD from a patient-centred care clinic in health-care decision-making processes. DESIGN, SETTING AND PARTICIPANTS: Mixed-methods study with early-stage Parkinson's disease patients from a patient-centred care clinic. Study involved a modified Autonomy Preference Index survey (N=65) and qualitative, semi-structured in-depth interviews, analysed using thematic qualitative content analysis (N=20, purposefully selected from survey participants). Interviews examined (i) the patient preferences for involvement in health-care decision making; (ii) patient perspectives on the patient-physician relationship; and (iii) patient preferences for communication of information relevant to decision making. RESULTS: Preferences for participation in decision making varied between individuals and also within individuals depending on decision type, relational and contextual factors. Patients had high preferences for communication of information, but with acknowledged limits. The importance of communication in the patient-physician relationship was emphasized. DISCUSSION: Patient preferences for involvement in decision making are dynamic and support shared decision making. Relational autonomy corresponds to how patients envision their participation in decision making. Clinicians may need to assess patient preferences on an on-going basis. CONCLUSION: Our results highlight the complexities of decision-making processes. Improved understanding of individual preferences could enhance respect for persons and make for patient-centred care that is truly respectful of individual patients' wants, needs and values.

Obstructive sleep apnea in Parkinson's disease patients: effect of Sinemet CR taken at bedtime.

PURPOSE: Obstructive sleep apnea (OSA) results from upper airway (UA) obstruction. In Parkinson's disease (PD), levodopa improves UA obstruction during wakefulness. We hypothesized that bedtime controlled-release levodopa (Sinemet CR) is associated with less severe OSA (lower apnea-hypopnea index [AHI]) in PD patients. METHODS: Idiopathic PD subjects underwent nocturnal polysomnography (PSG) and were divided into those taking bedtime Sinemet CR (SinCR+) and those not taking Sinemet CR (SinCR-). Outcomes were compared between groups for PSG recordings analyzed in whole and split at their mid-point with each half analyzed separately, using linear regression. RESULTS: Fifty-seven subjects were studied, eight SinCR+, and 49 SinCR-. They were 65 % male, aged 64.4 ± 10.3 years (mean ± SD), with body mass index 27.26 ± 3.98 kg/m(2). The whole night AHI was 15.6 ± 13.3 and 29.1 ± 20.8 in SinCR+ and SinCR-, respectively (p = 0.07 unadjusted, p = 0.11 adjusted for confounders). A similar trend was observed in the first half of the night. In the second half, the SinCR+ group had significantly lower AHI (beta = -18.8; p = 0.01 adjusted) and respiratory arousal index (beta = -14.2; p = 0.02 adjusted) than the SinCR- group. CONCLUSIONS: Bedtime Sinemet CR appears to reduce OSA in PD patients. There were no significant differences between groups in the first half of the night likely because of residual effects of short-acting levodopa in both groups, while Sinemet CR had residual effect in the second half. These results possibly provide an alternative to help manage OSA and improve sleep quality in PD patients.

Dopamine transporter SLC6A3 genotype affects cortico-striatal activity of set-shifts in Parkinson's disease.

Parkinson's disease is a neurodegenerative condition that affects motor function along with a wide range of cognitive domains, including executive function. The hallmark of the pathology is its significant loss of nigrostriatal dopamine, which is necessary for the cortico-striatal interactions that underlie executive control. Striatal dopamine reuptake is mediated by the SLC6A3 gene (formerly named DAT1) and its polymorphisms, which have been largely overlooked in Parkinson's disease. Thirty patients (ages 53-68 years; 19 males, 11 females) at early stages of Parkinson's disease, were genotyped according to a 9-repeat (9R) or 10-repeat (10R) allele on the SLC6A3/DAT1 gene. They underwent neuropsychological assessment and functional magnetic resonance imaging while performing a set-shifting task (a computerized Wisconsin Card Sorting Task) that relies on fronto-striatal interactions. Patients homozygous on the 10R allele performed significantly better on working memory tasks than 9R-carrier patients. Most importantly, patients carrying a 9R allele exhibited less activation than their 10R homozygous counterparts in the prefrontal cortex, premotor cortex and caudate nucleus, when planning and executing a set-shift. This pattern was exacerbated for conditions that usually recruit the striatum compared to those that do not. This is the first study indicating that the SLC6A3/DAT1 genotype has a significant effect on fronto-striatal activation and performance in Parkinson's disease. This effect is stronger for conditions that engage the striatum. Longitudinal studies are warranted to assess this polymorphism's effect on the clinical evolution of patients with Parkinson's disease, especially with cognitive decline.

Mild cognitive impairment is linked with faster rate of cortical thinning in patients with Parkinson's disease longitudinally.

Previous studies have shown greater atrophy in grey and white matter of various brain regions in patients with Parkinson's disease with mild cognitive impairment than in those without. These anatomical differences likely account for the distinct clinical profiles observed between those groups, but do not account for the evolution of regional brain degradation observed as the disease evolves. Although we have shown recently that cortical thinning correlates significantly more with disease duration in Parkinson's patients with mild cognitive impairment than in those without, to the best of our knowledge no study to date has explored this longitudinally. The present study investigated the longitudinal changes of the cortical and subcortical grey matter in patients with Parkinson's disease with and without mild cognitive impairment. Additionally, these two groups were compared with healthy controls. We found a higher rate of cortical thinning in the temporal, occipital, parietal and supplementary motor area, in patients with Parkinson's disease with mild cognitive impairment compared with both cognitively stable patients and healthy controls. On the other hand cognitively stable patients had only one lateral occipital and one fusiform cluster with increased rate of thinning compared with healthy individuals. Correlating the rate of change of cortical thickness with the results of Montreal Cognitive Assessment scores revealed significant thinning associated with cognitive decline in the group of all patients, in similar regions including temporal and medial occipital lobe. Finally, a significant decrease in the volume of the amygdala and nucleus accumbens was observed specifically in patients with Parkinson's disease with mild cognitive impairment. These results indicate that the early presence of mild cognitive impairment in patients with Parkinson's disease is associated with a faster rate of grey matter thinning in various cortical regions as well as a significant diminishment of limbic subcortical structures. This specific pattern of brain degradation associated with the early presence of mild cognitive impairment might serve as a marker of development toward dementia.

Exploring obstructive sleep apnea and sleep architecture in Parkinson's disease motor subtypes.

INTRODUCTION: Parkinson's disease (PD) can be divided into motor subtypes: postural instability/gait difficulty (PIGD), tremor dominant, and indeterminate. This study aimed to assess differences in sleep structure and obstructive sleep apnea (OSA) between the PIGD and non-PIGD subtypes. METHODS: PD participants with or without OSA (defined as apnea-hypopnea index (AHI) ≥ 15 events/hour on overnight polysomnography) were included. Patients were separated into two groups: PIGD and non-PIGD. Linear regression was used to explore differences in sleep, AHI, and other respiratory parameters between groups (adjusted for variables determined a priori). Logistic regression adjusted for the same variables was used to determine if the proportion of patients with OSA differed across groups. Subset analyses were performed: subset 1 excluding patients on psychoactive medication; subset 2 excluding patients taking levodopa or dopaminergic agonists (DAs) at nighttime and subset 3 excluding patients on either of the abovementioned drugs. RESULTS: 146 participants were studied. The non-PIGD group had less N3 sleep compared to the PIGD group (12.4% vs 16.9% p = 0.06), reaching significance in subsets 1 and 3. The AHI was significantly lower in the PIGD group (p = 0.047), including when medication effects were removed (p < 0.05). OSA was more frequent in the non-PIGD group, but only significantly in subset 3 (adjusted OR 0.3, p = 0.04). CONCLUSION: OSA may be more severe in non-PIGD subtypes, and more frequent, in a subset free of psychoactive medication, and of levodopa and DAs, possibly owing to motor complications and dyskinesia. Future studies are required to confirm this.

Mild cognitive impairment in patients with Parkinson's disease is associated with increased cortical degeneration.

Mild cognitive impairment (MCI) can occur early in the course of Parkinson's disease (PD), and its presence increases the risk of developing dementia. Determining the cortical changes associated with MCI in PD, thus, may be useful in predicting the future development of dementia. To address this objective, 37 patients with PD, divided into 2 groups according to the presence or absence MCI (18 with and 19 without) and 16 matched controls, underwent anatomic magnetic resonance imaging. Corticometry analyses were performed to measure the changes in cortical thickness and surface area as well as their correlation with disease duration. Compared with healthy controls, the PD-MCI group exhibited increased atrophy and changes of local surface area in the bilateral occipital, left temporal, and frontal cortices; whereas the PD non-MCI group exhibited only unilateral thinning and decreased surface area in the occipital lobe and in the frontal cortex. In addition, a comparison between the PD-MCI and PD non-MCI groups revealed increased local surface area in the occipital lobe, temporal lobe, and postcentral gyrus for the cognitively impaired patients. It is noteworthy that, in the PD-MCI group, cortical thickness had a significant negative correlation with disease duration in the precentral, supramarginal, occipital, and superior temporal cortices; whereas, in the PD non-MCI group, such a correlation was absent. The findings from this study reveal that, at the same stage of PD evolution, the presence of MCI is associated with a higher level of cortical changes, suggesting that cortical degeneration is increased in patients with PD because of the presence of MCI.

An overview of the effects of levodopa and dopaminergic agonists on sleep disorders in Parkinson's disease.

Sleep disorders are among the most common nonmotor symptoms in Parkinson's disease and are associated with reduced cognition and health-related quality of life. Disturbed sleep can often present in the prodromal or early stages of this neurodegenerative disease, rendering it crucial to manage and treat these symptoms. Levodopa and dopaminergic agonists are frequently prescribed to treat motor symptoms in Parkinson's disease, and there is increasing interest in how these pharmacological agents affect sleep and their effect on concomitant sleep disturbances and disorders. In this review, we discuss the role of dopamine in regulating the sleep-wake state and the impact of neurodegeneration on sleep. We provide an overview of the effects of levodopa and dopaminergic agonists on sleep architecture, insomnia, excessive daytime sleepiness, sleep-disordered breathing, rapid eye movement sleep behavior disorder, and restless legs syndrome in Parkinson's disease. Levodopa and dopaminergic drugs may have different effects, beneficial or adverse, depending on dosing, method of administration, and differential effects on the different dopamine receptors. Future research in this area should focus on elucidating the specific mechanisms by which these drugs affect sleep in order to better understand the pathophysiology of sleep disorders in Parkinson's disease and aid in developing suitable therapies and treatment regimens. CITATION: Scanga A, Lafontaine A-L, Kaminska M. An overview of the effects of levodopa and dopaminergic agonists on sleep disorders in Parkinson's disease. J Clin Sleep Med. 2023;19(6):1133-1144.

Validation of STOP, STOP-BANG, STOP-BAG, STOP-B28, and GOAL screening tools for identification of obstructive sleep apnea in patients with Parkinson disease.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is common in Parkinson disease (PD). Questionnaires can be used as screening tools and have been used as a surrogate definition of OSA in large-scale research. This study aimed to validate the performance of STOP, STOP-BANG, STOP-BAG, STOP-B28, and GOAL and OSA predictors as tools to identify OSA in PD. METHODS: Data were analyzed from a PD cohort study in which OSA was diagnosed using laboratory polysomnography. We calculated sensitivity and specificity of each questionnaire for OSA using different definitions and performed receiver operating characteristics curve analysis. Linear regression was used to assess adjusted associations between questionnaires and outcomes: Montreal Cognitive Assessment, Epworth Sleepiness Scale, and Movement Disorder Society revision of the Unified Parkinson Disease Rating Scale. RESULTS: Questionnaire data were available for 68 PD patients (61.8% male, mean age 64.5 [standard deviation 9.9] years, and Hoehn and Yahr score 2.1 [0.8]). OSA (apnea-hypopnea index ≥ 15 events/h) occurred in 69.4% of participants. STOP-B28 ≥ 2 presented a higher sensitivity for OSA than STOP ≥ 2 (0.76 vs 0.65, respectively) and slightly lower specificity (0.65 vs 0.70, respectively). GOAL ≥ 2 had the highest sensitivity but poor specificity. Loud snoring had sensitivity 0.63 and specificity 0.65. STOP and snoring were significantly associated with Montreal Cognitive Assessment, Epworth Sleepiness Scale, and Movement Disorder Society revision of the Unified Parkinson Disease Rating Scale (total, motor, and nonmotor); STOP-BANG, STOP-BAG, and STOP-B28 showed associations with most outcomes, but the GOAL showed none. CONCLUSIONS: The STOP-B28 followed by STOP and presence of loud snoring alone seem to have the best overall properties to identify PD patients with OSA, whose clinical characteristics differ from the general population with OSA. CITATION: Gomes T, Benedetti A, Lafontaine A-L, Kimoff RJ Robinson A, Kaminska M. Validation of STOP, STOP-BANG, STOP-BAG, STOP-B28, and GOAL screening tools for identification of obstructive sleep apnea in patients with Parkinson disease. J Clin Sleep Med. 2023;19(1):45-54.

Patterns of cortical thickness and surface area in early Parkinson's disease.

Idiopathic Parkinson's disease (PD) is a neurodegenerative disorder diagnosed on the basis of motor symptoms, but that also includes cognitive and visuo-spatial deficits. Though PD is known to initially affect subcortical regions, the cortex also exhibits neuronal loss in the course of the disease as post mortem studies have shown. So far, PD-related pattern of cortical damage remains unclear, because of disease-caused heterogeneity, and also in part because of methodological issues such as the limitations of Voxel Based Morphometry. Here corticometry was used, a technique that decouples local surface from thickness, to obtain a better picture of PD corticomorphometric patterns. We acquired MRI volumes for 33 healthy controls (HC) and 49 PD patients, extracted local cortical thickness and surface area and modeled both of them as a function of group and age for each participant. Cortical thickness averaged on the whole cortex did not differ between the two groups while mean surface area was significantly larger in the PD group. The bilateral parietal lobule, the right superior frontal gyrus, the left cingulate cortex and the left insular cortex exhibited larger local surface area in the PD group. The right precuneus exhibited cortical thinning associated with age in the PD group and not in the HC group. Furthermore, cortical thinning was observed in the PD group compared with the control group in the left medial supplementary motor area (SMA) and in the right dorsal pre-SMA. Finally, we found the left temporal pole thickness to correlate with disease duration, as well as the bilateral occipital cortex and Broca's area. These results suggest that PD etiology is associated with specific cortical alterations, which could account for cognitive deficits that arise as the disease evolves. Finally, our results observed in the occipital cortex as a function of disease duration may indicate the increase in PD-related visuo-spatial deficits, which can sometimes result in hallucinations later on in the disease. In the future, MRI-generated corticometry, combined with additional behavioral markers, may prove to be a useful diagnosis tool to characterize the evolution of motor and cognitive deficits in PD.

The Spectrum of Sleep Disorders in Parkinson Disease: A Review.

There is increasing interest in the effects of sleep and sleep disturbances on the brain, particularly in relation to aging and neurodegenerative processes. Parkinson disease (PD) is the second most common neurodegenerative disorder, with growing prevalence worldwide. Sleep disorders, including sleep-disordered breathing (SDB), are among the most frequent non-motor manifestations of PD. They can substantially impair quality of life and possibly affect the course of the disease. This article reviews the etiology, implications, and management of sleep disturbances in PD, such as excessive daytime sleepiness, insomnia, restless legs syndrome, rapid eye movement sleep behavior disorder, and SDB. Also briefly explored is the potential role of sleep disorders, including SDB, in the progression of neurodegeneration.

Feasibility of remote neurocognitive assessment: pandemic adaptations for a clinical trial, the Cognition and Obstructive Sleep Apnea in Parkinson's Disease, Effect of Positive Airway Pressure Therapy (COPE-PAP) study.

BACKGROUND: The COVID-19 pandemic poses challenges for timely outcome assessment in randomized clinical trials (RCT). Our aim was to describe our remote neurocognitive testing (NCT) protocol administered by telephone in patients with Parkinson's disease (PD) and obstructive sleep apnea (OSA). METHODS: We studied PD patients with OSA and Montreal Cognitive Assessment (MoCA) score ≤ 27 participating in a RCT assessing OSA treatment impact on cognition. Trial outcomes included change in MoCA and specific cognitive domains from baseline to 3 and 6 months. With COVID19 pandemic-related restrictions, 3-month visits were converted from in-person to telephone administration with materials mailed to participants for compatible tests and retrieved by courier the same day. In exploratory analyses, we compared baseline vs. 3-month results in the control arm, which were not expected to change significantly (test-re-test), using a paired t-test and assessed agreement with the intraclass correlation coefficient (ICC). RESULTS: Seven participants were approached and agreed to remote NCT at 3-month follow-up. Compared to the in-person NCT control arm group, they were younger (60.6 versus 70.6 years) and had a shorter disease course (3.9 versus 9.2 years). Remote NCT data were complete. The mean test-retest difference in MoCA was similar for in-person and remote NCT control-arm groups (between group difference - 0.69; 95%CI - 3.67, 2.29). Agreement was good for MOCA and varied for specific neurocognitive tests. CONCLUSION: Telephone administration of the MoCA and a modified neurocognitive battery is feasible in patients with PD and OSA. Further validation will require a larger sample size.

Validation of an Individualized Measure of Quality of Life, Patient Generated Index, for Use with People with Parkinson's Disease.

METHODS: Patients with PD completed the PGI and various standard patient-reported outcome (PRO) measures. The PGI and standard PRO measures were compared at the total score, domain, and item levels. Pearson's correlations and independent t-tests were used, as well as positive and negative predictive values. RESULTS: The sample (n = 76) had a mean age of 69 (standard deviation 9) and were predominantly men (59%). The PGI was moderately correlated (r = -0.35) with the standardized disease-specific QOL measure Parkinson's Disease Questionnaire (PDQ-8). Within one severity rating, agreement between the PGI and different standard outcome measures ranged from 85 to 100% for walking, 69 to 100% for fatigue, 38 to 75% for depression, and 20 to 80% for memory/concentration. CONCLUSION: This study demonstrates that nominated areas of QOL on the PGI provide comparable results to standard PRO measures, and provides evidence in support of the validity of this individualized measure in PD.

Obstructive Sleep Apnea in Neurodegenerative Disorders: Current Evidence in Support of Benefit from Sleep Apnea Treatment.

Obstructive sleep apnea (OSA) is a prevalent disorder characterized by recurrent upper airway obstruction during sleep resulting in intermittent hypoxemia and sleep fragmentation. Research has recently increasingly focused on the impact of OSA on the brain's structure and function, in particular as this relates to neurodegenerative diseases. This article reviews the links between OSA and neurodegenerative disease, focusing on Parkinson's disease, including proposed pathogenic mechanisms and current knowledge on the effects of treatment.

A new approach toward gait training in patients with Parkinson's Disease.

BACKGROUND: Typically, people with Parkinson's Disease (PD) progress to develop a gait pattern that is characterized by quick, short and shuffling steps. Gait cycle is altered and lacks definition and fluidity. Gait training combined with a variety of feedback modalities for PD are usually based on non-immediate and externally-based cues but none of these provide real-time feedback on gait quality and acquired gains tend to abate shortly after rehabilitation. Based on principals of motor learning, our team has developed the Heel2Toe sensor to provide real-time auditory feedback during gait training. RESEARCH QUESTION: Is a short-term training using the Heel2Toe sensor feasible and efficient to improve gait in people with PD? Our objectives are to identify the extent of the immediate response to the feedback within the same session and the carry-over response to training and; 2) to identify patients' perceived effects, pleasures and challenges of using the Heel2Toe. METHODS: Single-arm, proof-of-concept study. Six people received five sessions of gait training over a 2-3-week period using the Heel2Toe augmented with mobility exercises as an adjunct to gait training. The main outcomes were technically assessed gait parameters collected over a 2-minute walk test, without and with feedback. Heel2Toe signals were analyzed to extract angular velocity(AV), percentage of good steps, average cadence, and AV coefficient of variation(CV). RESULTS: An immediate response to the Heel2Toe use and a carry-over response to the short-term training with the sensor were observed: an increase in AV with a reduction in CV (better heel strike and gait regularity); an increase in %good steps; and a near-optimal and homogeneous cadence (∼100 steps/min), which is equivalent to a moderate-intensity walking. SIGNIFICANCE: Gait training using the Heel2Toe sensor is feasible and potentially effective for improving gait quality in people with PD. A definitive trial is a logical next step.

Obstructive sleep apnea, CPAP therapy and Parkinson's disease motor function: A longitudinal study.

INTRODUCTION: We aimed to assess, in patients with Parkinson's disease (PD), the association between obstructive sleep apnea (OSA), progression of motor dysfunction and the effect of OSA treatment. METHODS: Data were analysed from a prospective cohort study of idiopathic PD patients from a movement disorders clinic. Patients found to have OSA on polysomnography (apnea-hypopnea index [AHI] ≥15 events/h, OSA+) were offered treatment using continuous positive airway pressure (CPAP). CPAP+ was defined as an average ≥ 2 h/night use at each follow-up. Motor symptoms were assessed using the motor section of the Movement Disorder Society Unified Parkinson's Disease Rating Scale (mUPDRS) and the Timed-Up-And-Go (TUG). Follow-up times were 3, 6 and 12 months. Mixed models were constructed, adjusting for age, sex, body mass index, levodopa equivalent dose and comorbidities. RESULTS: We studied 67 individuals (61.2% male) of mean age 64.7 years (SD = 10.1). Baseline mUPDRS was higher in OSA+ compared to OSA- (24.5 [13.6] vs. 16.2 [7.2], p < 0.001). Motor dysfunction increased at comparable rates in OSA- and OSA+CPAP-. However, in OSA+CPAP+, mUPDRS change was significantly lower compared to OSA- (ß = -0.01 vs. 0.61, p = 0.03; p = 0.12 vs. OSA+CPAP- [ß = 0.39]) and TUG change was lower compared to OSA+CPAP- (ß = -0.01 vs. 0.13, p = 0.002; p = 0.05 vs. OSA- [ß = 0.02]). CONCLUSIONS: In this PD cohort, OSA was associated with higher baseline mUPDRS. In those with OSA, CPAP use was associated with stabilization of motor function (mUPDRS and TUG) over 12 months. These observations support further research to clarify the role of OSA in PD pathophysiology and motor dysfunction.

Recommendations for the Organization of Multidisciplinary Clinical Care Teams in Parkinson's Disease.

BACKGROUND: Optimal management in expert centers for Parkinson's disease (PD) usually involves pharmacological and non-pharmacological interventions, delivered by a multidisciplinary approach. However, there is no guideline specifying how this model should be organized. Consequently, the nature of multidisciplinary care varies widely. OBJECTIVE: To optimize care delivery, we aimed to provide recommendations for the organization of multidisciplinary care in PD. METHODS: Twenty expert centers in the field of multidisciplinary PD care participated. Their leading neurologists completed a survey covering eight themes: elements for optimal multidisciplinary care; team members; role of patients and care partners; team coordination; team meetings; inpatient versus outpatient care; telehealth; and challenges towards multidisciplinary care. During a consensus meeting, outcomes were incorporated into concept recommendations that were reviewed by each center's multidisciplinary team. Three patient organizations rated the recommendations according to patient priorities. Based on this feedback, a final set of recommendations (essential elements for delivery of multidisciplinary care) and considerations (desirable elements) was developed. RESULTS: We developed 30 recommendations and 10 considerations. The patient organizations rated the following recommendations as most important: care is organized in a patient-centered way; every newly diagnosed patient has access to a core multidisciplinary team; and each team has a coordinator. A checklist was created to further facilitate its implementation. CONCLUSION: We provide a practical tool to improve multidisciplinary care for persons with PD at the organizational level. Future studies should focus on implementing these recommendations in clinical practice, evaluating their potential applicability and effectiveness, and comparing alternative models of PD care.