Quebec Memory and Motor Skills Disorders Research Center

Sainte-Anne-de-Bellevue, Canada

Quebec Memory and Motor Skills Disorders Research Center

Sainte-Anne-de-Bellevue, Canada

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Dubois B.,University Pierre and Marie Curie | Tolosa E.,University of Barcelona | Tolosa E.,French Institute of Health and Medical Research | Katzenschlager R.,Donauspital SMZ Ost | And 9 more authors.
Movement Disorders | Year: 2012

Parkinson's disease dementia (PDD) is associated with cholinergic deficits. This report presents an efficacy and safety study of the acetylcholinesterase inhibitor donepezil hydrochloride in PDD. PDD patients (n = 550) were randomized to donepezil (5 or 10 mg) or placebo for 24 weeks. Coprimary end points were the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) and Clinician's Interview-Based Impression of Change plus caregiver input (CIBIC+; global function). Secondary end points measured executive function, attention, activities of daily living (ADLs), and behavioral symptoms. Safety and tolerability were assessed. ADAS-cog mean changes from baseline to week 24 (end point) were not significant for donepezil in the intent-to-treat population by the predefined statistical model (difference from placebo: -1.45, P = .050, for 5 mg; -1.45, P = .076, for 10 mg). Alternative ADAS-cog analysis, removing the treatment-by-country interaction term from the model, revealed significant, dose-dependent benefit with donepezil (difference from placebo: -2.08, P = .002, for 5 mg; -3.31, P < .001, for 10 mg). The 10-mg group, but not the 5-mg group, had significantly better CIBIC+ scores compared with placebo (3.7 vs 3.9, P = .113, for 5 mg; 3.6 vs 3.9, P = .040, for 10 mg). Secondary end points-Mini-Mental State Exam; Delis-Kaplan Executive Function System; Brief Test of Attention, representing cognitive functions particularly relevant to PDD-showed significant benefit for both donepezil doses (P ≤ .007). There were no significant differences in ADLs or behavior. Adverse events were more common with donepezil but mostly mild/moderate in severity. Although the study did not achieve its predefined primary end points, it presents evidence suggesting that donepezil can improve cognition, executive function, and global status in PDD. Tolerability was consistent with the known safety profile of donepezil. © 2012 Movement Disorder Society.


Emre M.,Istanbul University | Poewe W.,Innsbruck Medical University | De Deyn P.P.,University of Antwerp | De Deyn P.P.,University of Groningen | And 12 more authors.
Clinical Neuropharmacology | Year: 2014

OBJECTIVE: This study investigated the long-term safety of rivastigmine (12 mg/d capsules, 9.5 mg/24 h patch) and effects on motor symptoms in patients with mild-to-moderately severe Parkinson disease dementia. METHODS: This was a 76-week, prospective, open-label, randomized study in patients aged 50 to 85 years. Primary outcomes included incidence of, and discontinuation due to, predefined adverse events (AEs) potentially arising from worsening of Parkinson disease motor symptoms with capsules. Secondary outcomes included frequency of AEs/serious AEs. Efficacy outcomes included Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL), Neuropsychiatric Inventory (NPI-10), and Mattis Dementia Rating Scale (MDRS). RESULTS: Five hundred eighty-three patients were randomized to rivastigmine capsules (n = 295) or patch (n = 288). Incidence of predefined AEs was 36.1% for capsules, 31.9% for patch; discontinuation due to worsening of motor symptoms was 4.4% and 2.4%, respectively. Most common AEs were nausea (capsules, 40.5%; patch, 8.3%), tremor (24.5%; 9.7%), fall (17.0%; 20.1%), vomiting (15.3%; 2.8%), and application site erythema (0%; 13.9%). Significant efficacy in favor of capsules was observed at weeks 24 to 76 on MDRS; 24 and 76 on NPI-10; weeks 52 and 76 on ADCS-ADL. In patients with Mini-Mental State Examination (MMSE) greater than 21, no differences in efficacy on MDRS and ADCS-ADL were observed at any time point; significant differences in favor of capsules were maintained in patients with MMSE less than or equal to 21. CONCLUSIONS: This study supports the long-term safety of rivastigmine in Parkinson disease dementia. The rate of worsening of motor symptoms was in the range expected due to the natural progression of Parkinson disease, no new or unexpected safety issues emerged in the long-term. [-] [-] [-] [-] [-] [-] [-] [-] [-].


McDonald J.,Laval University | McDonald J.,Quebec Memory and Motor Skills Disorders Research Center | Corbeil P.,Laval University | Corbeil P.,University of Québec | And 2 more authors.
American Journal Geriatric Pharmacotherapy | Year: 2011

Background: Postural instability is a concern in several neurologic conditions and also among the elderly. Dysfunction in serotonergic, noradrenergic, and dopaminergic pathways may be involved in the etiology of postural imbalance. Objective: The objective of this case report was to quantify, using computerized posturography, substitution with venlafaxine, and later levodopa, in a suspected case of postural instability with paroxetine. Case Summary: Presented is an 86-year-old woman with frequent falls and a Parkinson-like syndrome of the lower limbs secondary to microvascular dementia. Paroxetine was gradually discontinued and exchanged for venlafaxine, 37.5 mg twice daily. Before and after medication changes, static posturography was performed under eyes open and closed conditions. Following 3 months of venlafaxine, the patient showed significant improvement from baseline, however, venlafaxine was then reduced to 37.5 mg at bedtime. Six months later, levodopa was introduced and further improvement was observed. It is possible that venlafaxine, which maintains a more balanced affinity for serotonin and norepinephrine transporters, may have provided postural benefit. Decreased sedation secondary to venlafaxine reduction may have elicited further improvements in addition to the increased lower limb functionality observed with levodopa. Conclusions: For patients on antidepressants, switching medications may be worthwhile in those with balance problems. The prudent addition of medications may also be an option. © 2011 Elsevier HS Journals, Inc. All rights reserved.


Pourcher E.,Quebec Memory and Motor Skills Disorders Research Center | Pourcher E.,University of Paris Descartes | Pourcher E.,Laval University | Remillard S.,Quebec Memory and Motor Skills Disorders Research Center | And 2 more authors.
Journal of the Neurological Sciences | Year: 2010

Since the introduction of levodopa therapy and dopaminergic replacement therapy to abate symptoms of idiopathic Parkinson's disease, repetitive compulsive behaviors have been reported and are now considered to be drug-related response complications. As dopamine (DA) agonists are the licensed treatment in Restless Legs Syndrome (RLS), a survey was conducted to determine the extent to which patients with RLS present compulsive behaviors. The aim of this study was to investigate the relationship between DA agonists and the occurrence of motor or behavioral compulsions, stress, depression, and sleep disturbance in RLS patients. A questionnaire was mailed three times, at four-month intervals over a period of 8 months to all patients of the Quebec Memory and Motor Skills Disorders Clinic diagnosed with RLS. In addition to recording all medication information for RLS treatment, patients were assessed on the International Restless Legs Syndrome Study Group Rating Scale (IRLS), the Beck Depression Inventory-II (BDI-II), the Sleep Scale from the Medical Outcomes Study (MOS) and on a visual analog scale for current level of stress. A section pertaining to hobby, mania, and compulsion was also included. Analyses are based on 97 out of 151 patients (64.2%) with RLS who returned the three questionnaires. Twelve patients (12.4%) on stable DA agonist therapy (average dose 0.52 ± 0.59 mg Pramipexole equivalent) developed a new compulsive behavioral repertoire. Eating (3 women, 1 man), buying food or clothes (2 women, 1 man), trichotillomania (1 woman, 1 man), and gambling (1man) were among the compulsions developed under DA treatment. In addition, two women presented new tic-like phenomena. In contrast to the RLS patients without compulsive behaviors (53 treated with DA agonist; 32 untreated), those with compulsive habits reported experiencing more stress, depression and sleep problems. Patients with RLS with mood and stress states may be at greater risk of developing compulsive behaviors while receiving standard dosage DA agonist treatment. These behaviors are clearly linked to short-term satisfaction and underline the role of dopaminergic mesolimbic stimulation in the reinforcement process of rewarding behavioral sequences. © 2009 Elsevier B.V. All rights reserved.


Pourcher E.,Quebec Memory and Motor Skills Disorders Research Center | Pourcher E.,University of Paris Descartes | Pourcher E.,Laval University | Remillard S.,Quebec Memory and Motor Skills Disorders Research Center | And 2 more authors.
Journal of the Neurological Sciences | Year: 2010

Depression in Idiopathic Parkinson's disease (IPD) is frequent, difficult to recognize, under managed and has a profound impact on quality of life. Current categorization of diagnosis in psychiatry poorly applies to the protean manifestations of mood disorders presented by parkinsonian patients. In this study we have chosen to dissect the state of depressive mood as assessed with the Beck Depression Inventory (BDI) at different points in time of pharmacological interventions using a dimensional approach. The 21 items of the BDI were classified in two new categories or factors: hyperkinetic and hypokinetic. The hyperkinetic factor included all items related to unbalanced intrusions of negative feelings and ideas, as well as to behavioral hyperactivity. The hypokinetic factor included all items related to loss of drive for appetitive behaviors and loss of mental and physical energy. The objectives were to (1) compare different pharmacological treatments on the two-factor approach in PD depression, (2) determine the influence of levodopa therapy on the two-factor approach, and (3) explore the two-factor approach in placebo conditions. Three sets of analyses using the hypo/hyperkinetic dichotomy favour a neurobiological dissociation of these factors in response to pharmacological intervention: symptoms of the hyperkinetic factor are responsive to serotonergic drugs while those of the hypokinetic one are not and may even show deterioration under SSRIs. In contrast, the hypokinetic factor is responsive to dopaminergic drugs and may show deterioration under serotonergic drugs. Furthermore, the two factors seem to transiently dissociate on placebo intervention aiming at correcting either mood or motor status. The dimensional approach to depression symptomatology may thus be of heuristic value in probing aminergic modulation of mood in IPD and establishing new correlations between affective and motor symptoms. © 2009 Elsevier B.V. All rights reserved.


Nadeau A.,Laval University | Nadeau A.,Center Dexcellence Sur Le Vieillissement Of Quebec | Pourcher E.,Quebec Memory and Motor Skills Disorders Research Center | Pourcher E.,Laval University | And 2 more authors.
Medicine and Science in Sports and Exercise | Year: 2014

Purpose: Recent studies suggest that walking on a treadmill improves gait, mobility, and quality of life of patients with Parkinson's disease (PD). Still, there is a need for larger-scale randomized controlled studies that demonstrate the advantages of treadmill training (TT) with control groups that receive similar amounts of attention. Moreover, to date, no study has combined speed and incline as parameters of progression. The aim of the study was to evaluate the effects of 24 wk of TT, with and without the use of incline, on gait, mobility and quality of life in patients with PD. Methods: The sample comprised 34 patients with PD, at the Hoehn and Yahr stage 1.5 or 2. Participants were randomized to speed TT, mixed TT, and control groups. The intervention consisted of 72 one-hour exercise sessions for 24 wk. The main outcome measures are the Movement Disorder Society-Unified Parkinson's Disease Rating Scale, the 39-item Parkinson's Disease Questionnaire, spatiotemporal parameters of gait and 6-min walking distance. The measures were taken at baseline, mid-term and after 6 months. RESULTS: Both TT groups improved in terms of speed, cadence, and stride length during self-selected walking conditions at the study end point. Both groups also showed improvements in distance traveled. Only the Mixed TT group improved their quality of life. The Control group showed no progress. Conclusions: Participants in this study showed significant improvements in walking speed and walking endurance after 6 months of TT. Improvements were observed after 3 months of intensive TT and persisted at 6 months. It appears that individuals with poorer baseline performance may benefit most from TT. © 2014 by the American College of Sports Medicine.


Cohen H.,University of Paris Descartes | Cohen H.,University of Quebec at Montréal | Cohen H.,Quebec Memory and Motor Skills Disorders Research Center | Voss P.,University of Montréal | And 2 more authors.
PLoS ONE | Year: 2010

Blind individuals have been shown on multiple occasions to compensate for their loss of sight by developing exceptional abilities in their remaining senses. While most research has been focused on perceptual abilities per se in the auditory and tactile modalities, recent work has also investigated higher-order processes involving memory and language functions. Here we examined tactile working memory for Braille in two groups of visually challenged individuals (completely blind subjects, CBS; blind with residual vision, BRV). In a first experimental procedure both groups were given a Braille tactile memory span task with and without articulatory suppression, while the BRV and a sighted group performed a visual version of the task. It was shown that the Braille tactile working memory (BrWM) of CBS individuals under articulatory suppression is as efficient as that of sighted individuals' visual working memory in the same condition. Moreover, the results suggest that BrWM may be more robust in the CBS than in the BRV subjects, thus pointing to the potential role of visual experience in shaping tactile working memory. A second experiment designed to assess the nature (spatial vs. verbal) of this working memory was then carried out with two new CBS and BRV groups having to perform the Braille task concurrently with a mental arithmetic task or a mental displacement of blocks task. We show that the disruption of memory was greatest when concurrently carrying out the mental displacement of blocks, indicating that the Braille tactile subsystem of working memory is likely spatial in nature in CBS. The results also point to the multimodal nature of working memory and show how experience can shape the development of its subcomponents. © 2010 Cohen et al.


Rmillard S.,University of Quebec at Montréal | Pourcher E.,Quebec Memory and Motor Skills Disorders Research Center | Pourcher E.,University of Paris Descartes | Cohen H.,University of Quebec at Montréal | And 2 more authors.
Journal of the International Neuropsychological Society | Year: 2010

Previous studies had revealed no specific effect under haloperidol (typical) and risperidone (atypical) neuroleptic (NLP) treatments for schizophrenia (SZ) on a variety of neurocognitive functions relying on the dopaminergic meso-cortico-limbic system (Rmillard et al., 2005, 2008). Considering the different affinities of D2 dopamine receptors for typical and atypical NLPs, these drugs may differentially affect the functions of the striatum, a determinant brain structure involved in procedural learning. The influence of risperidone (26 mg) and haloperidol (240 mg) on a nonmotor procedural task involving semantically related pairs of words with inverted letters was investigated in this double-blind study. The performance of 26 patients with SZ, randomly assigned to risperidone or haloperidol, was compared to that of 18 healthy controls at baseline, 3, 6, and 12 months. Results revealed that all patients with SZ exhibited slower reading speed of the word pairs than healthy controls at all assessment periods. In addition, procedural learning characterized as a significant decrease in the time taken to read aloud the target word pairs was more impaired in the haloperidol- than in the risperidone-treated group at all assessment periods. Healthy controls showed steady improvement in reading speed over the 12 months of the study, in contrast to SZ patients, who reached a plateau in their capacity to improve mirror-reading skill over time. However, all SZ participants in the study showed near normal learning profiles from exposure to semantic associations embedded in the procedural memory task, providing evidence for the preservation of associative connections in the semantic network of these patients. The observed impairment in procedural learning in SZ may thus reflect, at least in part, the influence of neuroleptic medication on striatal functions. (JINS, 2010, 16, 148156.) © The International Neuropsychological Society 2009.


PubMed | Quebec Memory and Motor Skills Disorders Research Center
Type: Journal Article | Journal: Journal of the neurological sciences | Year: 2010

Since the introduction of levodopa therapy and dopaminergic replacement therapy to abate symptoms of idiopathic Parkinsons disease, repetitive compulsive behaviors have been reported and are now considered to be drug-related response complications. As dopamine (DA) agonists are the licensed treatment in Restless Legs Syndrome (RLS), a survey was conducted to determine the extent to which patients with RLS present compulsive behaviors. The aim of this study was to investigate the relationship between DA agonists and the occurrence of motor or behavioral compulsions, stress, depression, and sleep disturbance in RLS patients. A questionnaire was mailed three times, at four-month intervals over a period of 8 months to all patients of the Quebec Memory and Motor Skills Disorders Clinic diagnosed with RLS. In addition to recording all medication information for RLS treatment, patients were assessed on the International Restless Legs Syndrome Study Group Rating Scale (IRLS), the Beck Depression Inventory-II (BDI-II), the Sleep Scale from the Medical Outcomes Study (MOS) and on a visual analog scale for current level of stress. A section pertaining to hobby, mania, and compulsion was also included. Analyses are based on 97 out of 151 patients (64.2%) with RLS who returned the three questionnaires. Twelve patients (12.4%) on stable DA agonist therapy (average dose 0.52+/-0.59 mg Pramipexole equivalent) developed a new compulsive behavioral repertoire. Eating (3 women, 1 man), buying food or clothes (2 women, 1 man), trichotillomania (1 woman, 1 man), and gambling (1man) were among the compulsions developed under DA treatment. In addition, two women presented new tic-like phenomena. In contrast to the RLS patients without compulsive behaviors (53 treated with DA agonist; 32 untreated), those with compulsive habits reported experiencing more stress, depression and sleep problems. Patients with RLS with mood and stress states may be at greater risk of developing compulsive behaviors while receiving standard dosage DA agonist treatment. These behaviors are clearly linked to short-term satisfaction and underline the role of dopaminergic mesolimbic stimulation in the reinforcement process of rewarding behavioral sequences.

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