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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.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.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.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.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.

The late-onset cerebellar ataxias (LOCAs) have largely resisted molecular diagnosis.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.In the six French Canadian patients, we identified a GAA repeat expansion deep in the first intron ofA dominantly inherited deep intronic GAA repeat expansion in

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.

Introduction Rehabilitation therapies are critical for optimizing quality-of-life and daily functions for individuals living with Parkinson's disease (PD). Thus, understanding the patterns of and under what conditions physicians make rehabilitation referrals is important for optimizing care. Method We analyzed data from 5020 participants (4 countries) collected from 1/3/2016 to 4/20/2018 as part of the Parkinson's Foundation Quality Improvement Initiative (PF QII). Data were analyzed for single discipline and multidiscipline referrals to speech language pathology (SLP), physical therapy (PT), and occupational therapy (OT). Group comparisons (referred vs. not-referred) and regression procedures were implemented to determine demographic and clinical variables that were associated with an increased likelihood of rehabilitation referral. Results 35.3% of participants were referred to rehabilitation services. Of these, 25.1% received a multidiscipline referral. There was a statistically significant effect of disease stage on both single discipline (χ2(2) = 45.1, p ≥ 1, Range = 1.08 to 1.62). Conclusions Despite evidence supporting multidiscipline and proactive rehabilitation in PD, the majority of referrals were made to a single service and may be reactions to falls or advancing disease. Data suggest there may be missed opportunities for optimizing care through proactive rehabilitation interventions.

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.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.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- (β = -0.01 vs. 0.61, p = 0.03; p = 0.12 vs. OSA+CPAP- [β = 0.39]) and TUG change was lower compared to OSA+CPAP- (β = -0.01 vs. 0.13, p = 0.002; p = 0.05 vs. OSA- [β = 0.02]).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.

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.

The late-onset cerebellar ataxias (LOCAs) have largely resisted molecular diagnosis.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.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

[See related article at [www.cmaj.ca/lookup/doi/10.1503/cmaj.191089][2]][2] KEY POINTS Parkinson disease is chronic and progressive in nature, decreasing the quality of life for both patients with the disease and their caregivers and placing an onerous economic burden on society.[1][2] The first

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.

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.

Introduction. Parkinson’s disease (PD) affects all aspects of an individual’s life and is heterogeneous across people and time. The Patient Generated Index (PGI) is an individualized measure of quality of life (QOL) that allows patients to identify the areas of life that are important to them. Although the PGI has immense potential for use in clinical and research settings, its validity has not been assessed in PD. The purpose of this study is to estimate how well areas of QOL that patients with PD nominate on the PGI agree with ratings obtained from standard outcome measures. 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.

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.

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.

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.

Objective:To assess the association between obstructive sleep apnea (OSA) and nonmotor symptoms (NMS), including cognitive dysfunction, in patients with Parkinson disease (PD).Methods:Patients with idiopathic PD, recruited from a movement disorder clinic, underwent overnight polysomnography. OSA was defined as an apnea-hypopnea index (AHI) ≥15/h. PD severity was assessed using the Hoehn & Yahr (H&Y) scale and the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS). NMS were assessed using the Montreal Cognitive Assessment (MoCA), Epworth Sleepiness Scale (ESS), Fatigue Severity Scale, Apathy Scale, Beck Depression Inventory, Hospital Depression and Anxiety Scale, and PD sleep Scale.Results:Sixty-seven patients (61.2% male), mean age 64.4 (SD 9.9) years and motor MDS-UPDRS 21.9 (12.6) using levodopa equivalent dose (LED) 752.4 (714.6) mg/d, were studied. OSA occurred in 47 patients (61.6%, mean AHI 27.1/h, SD 20.2/h), and NMS in 57 patients (85%). ESS and MoCA were associated with the AHI (ESS β = 0.0670, p = 0.031; MoCA β = −0.0520, p = 0.043, adjusted for age, sex, body mass index, LED, and H&Y). ESS was associated with respiratory arousals (β = 0.1015, p = 0.011) and intermittent hypoxemia (β = 0.1470, p = 0.006). MoCA was negatively associated with respiratory arousals (β = −0.0596, p = 0.049) but not intermittent hypoxemia.Conclusions:OSA is associated with sleepiness and cognitive dysfunction in PD, suggesting that OSA may be a reversible contributor to these NMS. Further studies will be required to evaluate whether OSA treatment can improve excessive sleepiness and cognitive dysfunction in PD.

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.

Background Aerobic exercise training (AET) has been shown to provide general health benefits, and to improve motor behaviours in particular, in individuals with Parkinson's disease (PD). However, the influence of AET on their motor learning capacities, as well as the change in neural substrates mediating this effect remains to be explored. Objective In the current study, we employed functional Magnetic Resonance Imaging (fMRI) to assess the effect of a 3-month AET program on the neural correlates of implicit motor sequence learning (MSL). Methods 20 healthy controls (HC) and 19 early PD individuals participated in a supervised, high-intensity, stationary recumbent bike training program (3 times/week for 12 weeks). Exercise prescription started at 20 min (+ 5 min/week up to 40 min) based on participant's maximal aerobic power. Before and after the AET program, participants' brain was scanned while performing an implicit version of the serial reaction time task. Results Brain data revealed pre-post MSL-related increases in functional activity in the hippocampus, striatum and cerebellum in PD patients, as well as in the striatum in HC individuals. Importantly, the functional brain changes in PD individuals correlated with changes in aerobic fitness: a positive relationship was found with increased activity in the hippocampus and striatum, while a negative relationship was observed with the cerebellar activity. Conclusion Our results reveal, for the first time, that exercise training produces functional changes in known motor learning related brain structures that are consistent with improved behavioural performance observed in PD patients. As such, AET can be a valuable non-pharmacological intervention to promote, not only physical fitness in early PD, but also better motor learning capacity useful in day-to-day activities through increased plasticity in motor related structures., Highlights • Three months of aerobic exercise training (AET) improves fitness in PD patients. • Effects of AET on cognitive and motor skills in PD were evaluated concurrently. • Some executive functions and procedural learning capacity improved after AET. • Striatum, hippocampus and cerebellar brain plasticity was observed after AET. • AET can be used as a non-pharmacological intervention to improve functioning in PD.

Using resting-state functional MRI (rsfMRI) data of younger and older healthy volunteers and patients with Parkinson's disease (PD) with and without mild cognitive impairment (MCI) and applying two different analytic approaches, we investigated the effects of age, pathology, and cognition on brain connectivity. When comparing rsfMRI connectivity strength of PD patients and older healthy volunteers, reduction between multiple brain regions in PD patients with MCI (PD-MCI) compared with PD patients without MCI (PD-non-MCI) was observed. This group difference was not affected by the number and location of clusters but was reduced when age was included as a covariate. Next, we applied a graph-theory method with a cost-threshold approach to the rsfMRI data from patients with PD with and without MCI as well as groups of younger and older healthy volunteers. We observed decreased hub function (measured by degree and betweenness centrality) mainly in the medial prefrontal cortex (mPFC) in older healthy volunteers compared with younger healthy volunteers. We also found increased hub function in the posterior medial structure (precuneus and the cingulate cortex) in PD-non-MCI patients compared with older healthy volunteers and PD-MCI patients. Hub function in these posterior medial structures was positively correlated with cognitive function in all PD patients. Together these data suggest that overlapping patterns of hub modifications could mediate the effect of age as a risk factor for cognitive decline in PD, including age-related reduction of hub function in the mPFC, and recruitment availability of the posterior medial structure, possibly to compensate for impaired basal ganglia function.

Background Generic preference-based measures are used to assess the cost-utility of different interventions in Parkinson's disease (PD). However, the difficulty of using them in people with a particular health condition is that these measures may not encapsulate all of the domains that are impacted by the disease. Objective To contribute evidence towards the content validity of generic preference-based measures in people with PD. Methods Participants with PD were interviewed on a personalized measure of quality of life, the Patient Generated Index (PGI). The domains identified with the PGI were then categorized using the WHO's International Classification of Functioning, Disability and Health. The extent to which the generic measures (EQ-5D-5L, SF-6D, HUI II, and HUI III) included domains important to persons with PD was qualitatively evaluated. Results The study included seventy-six participants with PD (mean age 69 years). Dexterity, the top domain nominated by participants, was only included in 1 out of 4 of the generic measures. Fatigue, another commonly reported problem, was not included in 3 out of 4 measures. Sleep, dyskinesia and bowel/bladder problems were not included in any of the measures. Conclusion Content validity is an essential step in the evaluation of whether a questionnaire truly measures the construct it purports to measure, in this case the construct being health related quality of life (HRQL). This study evaluated the content validity of the EQ-5D-5L, SF-6D, HUI II and HUI III in people with PD, and demonstrated that several important PD specific domains are missing from these measures.

Background: Aerobic exercise training (AET) has been shown to provide health benefits in individuals with Parkinson’s disease (PD). However, it is yet unknown to what extent AET also improves cognitive and procedural learning capacities, which ensure an optimal daily functioning. Objective: In the current study, we assessed the effects of a 3-month AET program on executive functions (EF), implicit motor sequence learning (MSL) capacity, as well as on different health-related outcome indicators. Methods: Twenty healthy controls (HC) and 19 early PD individuals participated in a supervised, high-intensity, stationary recumbent bike-training program (3 times/week for 12 weeks). Exercise prescription started at 20 min (+5 min/week up to 40 min) based on participant’s maximal aerobic power. Before and after AET, EF tests assessed participants’ inhibition and flexibility functions, whereas implicit MSL capacity was evaluated using a version of the Serial Reaction Time Task. Results: The AET program was effective as indicated by significant improvement in aerobic capacity in all participants. Most importantly, AET improved inhibition but not flexibility, and motor learning skill, in both groups. Conclusion: Our results suggest that AET can be a valuable non-pharmacological intervention to promote physical fitness in early PD, but also better cognitive and procedural functioning.

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. 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. 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/m2. 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. 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.

Purpose.Obstructive sleep apnea (OSA) is frequent in Parkinson’s disease (PD) and may contribute to nonmotor symptoms. Polysomnography (PSG) is the gold standard for OSA diagnosis. Unattended portable monitoring (PM) may improve access to diagnosis but has not been studied in PD. We assessed feasibility and diagnostic accuracy in PD.Methods.Selected PD patients without known OSA underwent home PM and laboratory PSG. The quality of PM signals (n= 28) was compared with matched controls. PM accuracy was calculated compared with PSG for standard apnea hypopnea index (AHI) thresholds.Results.Technical failure rate was 27.0% and airflow signal quality was lower than in controls. Sensitivity of PM was 84.0%, 36.4%, and 50.0% for AHI cut-offs of 5/h, 15/h, and 30/h, respectively, using the same cut-offs on PM. Specificity was 66.7%, 83.3%, and 100%, respectively. PM underestimated the AHI with a mean bias of 12.4/h. Discrepancy between PM and PSG was greater in those with more motor dysfunction.Conclusion.PM was adequate to “rule in” moderate or severe OSA in PD patients, but the failure rate was relatively high and signal quality poorer than in controls. PM overall underestimated the severity of OSA in PD patients, especially those with greater motor dysfunction.

Parkinson disease (PD) non-motor symptoms are associated with sleep disorders and impair quality of life. Our objective was to assess the effect of obstructive sleep apnea (OSA) treatment using continuous positive airway pressure (CPAP) on PD non-motor symptoms.In this prospective observational study, 67 patients with idiopathic PD underwent polysomnography. Those with moderate-severe OSA were offered CPAP therapy. Subjects were divided into those without OSA (OSA-), and those with OSA (OSA+). Analyses were conducted for 6 and 12 months' follow-up data. At 6 months, those who had used CPAP at home for at least 1 month were considered CPAP users (OSA+CPAP+), whereas those who did not try it, or declined further treatment following a short trial were considered non-users (OSA+CPAP-). For the 12-month analysis, only those still actively using CPAP at 12 months were included in the OSA+CPAP+ group. Non-motor symptom measurements were: Epworth Sleepiness Scale, Montreal Cognitive Assessment (MoCA), Unified Parkinson's Disease Rating Scale part 1 (UPDRS1), Parkinson's Disease Sleep Scale (PDSS), Fatigue Severity Scale, Apathy Scale, Beck Depression Inventory, and Hospital Anxiety and Depression Scale (HADS).Sixty-five participants were re-assessed at least once. At 6 months, 30 participants were categorized as OSA+CPAP+, 11 OSA+CPAP-, and 18 OSA-. At 12 months, 21 were categorized as OSA+CPAP+, 21 OSA+CPAP-, and 17 OSA-. The UPDRS1 and PDSS improved from baseline in OSA+CPAP+ at 6 months (-2.7, standard deviation [SD] 4.0,CPAP treatment of OSA in PD is associated with improved overall non-motor symptoms, sleep quality, anxiety, and global cognitive function over a 12-month period.

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.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.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.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.

Background: There is increasing evidence that executive functions and attention are associated with gait and balance, and that this link is especially prominent in older individuals or those who are afflicted by neurodegenerative diseases that affect cognition and/or motor functions. People with Parkinsons disease (PD) often present gait disturbances, which can be reduced when PD patients engage in different types of physical exercise (PE), such as walking on a treadmill. Similarly, PE has also been found to improve executive functions in this population. Yet, no exercise intervention investigated simultaneously gait and non-motor symptoms (executive functions, motor learning) in PD patients. Objective: To assess the impact of aerobic exercise training (AET) using a stationary bicycle on a set of gait parameters (walking speed, cadence, step length, step width, single and double support time, as well as variability of step length, step width and double support time) and executive functions (cognitive inhibition and flexibility) in sedentary PD patients and healthy controls. Methods: Two groups, 19 PD patients (Hoehn and Yahr =2) and 20 healthy adults, matched on age and sedentary level, followed a 3-month stationary bicycle AET regimen. Results: Aerobic capacity, as well as performance of motor learning and on cognitive inhibition, increased significantly in both groups after the training regimen, but only PD patients improved their walking speed and cadence (all p < 0.05; with no change in the step length). Moreover, in PD patients, training-related improvements in aerobic capacity correlated positively with improvements in walking speed (r = 0.461, p < 0.05). Conclusion: AET using stationary bicycle can independently improve gait and cognitive inhibition in sedentary PD patients. Given that increases in walking speed were obtained through increases in cadence, with no change in step length, our findings suggest that gait improvements are specific to the type of motor activity practiced during exercise (i.e., pedaling). In contrast, the improvements seen in cognitive inhibition were, most likely, not specific to the type of training and they could be due to indirect action mechanisms (i.e., improvement of cardiovascular capacity). These results are also relevant for the development of targeted AET interventions to improve functional autonomy in PD patients

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.

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. * Abbreviation : MCI : mild cognitive impairment

We have previously observed decreased activation of corticostriatal loops involved in planning (cognitive loop) and execution (motor loop) of a set shift in patients with early Parkinson's disease (PD) compared with control subjects. Here, we aimed to assess whether cognitive impairment in PD could drive these differences. Nondemented patients underwent a comprehensive neuropsychological evaluation and participated in our Wisconsin Card Sorting task functional magnetic resonance imaging protocol. Patients were separated into 2 groups according to the presence of mild cognitive impairment (MCI). Patients with MCI displayed reduced activity in the cognitive corticostriatal loop, which includes the caudate nucleus and prefrontal cortex while planning a set shift, whereas non-MCI patients exhibited activation patterns similar to those of healthy participants from our previous studies. Furthermore, reduced activation was observed in the premotor cortex of the MCI patients. Finally, hippocampal activity, correlated with individual memory scores, suggesting a compensatory mechanism in patients with preserved memory. These results suggest that the presence of MCI in PD affects activity in the prefrontal cortex and caudate nucleus as well as motor-related regions.

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. © 2013 International Parkinson and Movement Disorder Society

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.

As with other neurodegenerative disorders, research into the group of diseases known under the umbrella term of "neuroacanthocytosis" has greatly benefited from the identification of causative genes. The distinct and unifying aspect of these disorders is the presence of thorny deformations of circulating erythrocytes. This may be due to abnormal properties of red cell membranes, which could lead to insights into mechanisms of neurodegeneration. Research approaches in this field, in addition to examining functions and protein interactions of the affected proteins with particular respect to neurons, have also drawn upon the expertise of hematologists and red cell membrane biologists. In this article, recent developments in the field are presented.

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.

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.

Background The goal of this study was to evaluate the effects of L-Dopa medication in Parkinson's disease (PD) on brain activation during the performance of a set-shifting task. Using fMRI, we have previously studied the patterns of activity observed in patients with PD after overnight removal of dopaminergic medication compared with control participants during the performance of different stages of the Wisconsin Card Sorting Task (WCST). The results revealed decreased cortical activity in the PD group compared to controls in the conditions that significantly required striatum, while increased cortical activity was observed when striatum was not involved. However, the effect of dopaminergic medication in PD patients on those patterns of activity has not yet been studied. Methodology/Principal Findings Here, eleven PD patients at early stage of the disease taking L-Dopa medication were recruited and underwent two fMRI sessions while performing the WCST: one session while taking their normal dose of medication and the other following overnight dopaminergic medication withdrawal. We found that L-dopa medication helped restoring a normal pattern of activity when matching and not planning was required, by increasing cortical activity in the premotor cortex. This effect was even stronger in the motor loop, i.e. when the putamen was required for controls, when matching following negative feedback. However, the medication did not change the pattern of activity in conditions relying primarily on a cognitive loop, i.e. when the caudate nucleus was required. Conclusions/Significance These studies provide explanation at the neural level regarding the relatively poor effects of L-Dopa on the cognitive deficits observed in PD.