Showing papers by "Serge Gauthier published in 2001"
TL;DR: The data suggest that donepezil’s benefits extend into more advanced stages of AD than those previously investigated, with very good tolerability.
Abstract: Objective: To investigate the efficacy and safety of donepezil in patients with moderate to severe AD (standardized Mini-Mental State Examination [sMMSE] scores of 5 to 17; Functional Assessment Staging score ≤6 at baseline). Methods: Two-hundred ninety patients were randomized to treatment in this 24-week, double-blind, placebo-controlled trial. Patients received either donepezil 5 mg/day for the first 28 days and 10 mg/day thereafter as per the clinician’s judgment (n = 144) or placebo (n = 146). The primary outcome measure was the Clinician’s Interview-Based Impression of Change with caregiver input (CIBIC+). Results: Patients’ mean age was 73.6 years (range 48 to 92 years). Baseline demographics were similar between the treatment groups. Least squares (LS) mean ± SE sMMSE scores at baseline were 11.7 ± 0.35 for the donepezil group and 12.0 ± 0.34 for the placebo group. Patients receiving donepezil showed benefits on the CIBIC+, compared with placebo, at all visits up to week 24 ( p p Conclusion: These data suggest that donepezil’s benefits extend into more advanced stages of AD than those previously investigated, with very good tolerability.
615 citations
TL;DR: There is increasing evidence that NO may have a role in the aforementioned AD pathogenetic mechanisms, and putative links between NO and AD are beginning to be recognized.
312 citations
TL;DR: Half of those with vascular CIND developed dementia within 5 years, suggesting a target for preventive interventions, and women were at greater risk of dementia.
Abstract: Little is known about progression, short of dementia, in vascular cognitive impairment. In the Canadian Study of Health and Aging, 149 participants (79.3 +/- 6.7 years; 61% women) were found to have vascular cognitive impairment, no dementia (CIND). After 5 years, 77 participants (52%) had died and 58 (46%) had developed dementia. Women were at greater risk of dementia (OR 2.1, 1.0 to 4.5). Of 32 participants alive without dementia, cognition had deteriorated in seven and improved in four. Half of those with vascular CIND developed dementia within 5 years, suggesting a target for preventive interventions.
233 citations
TL;DR: Using expanded criteria for treatment success and clinically relevant outcome measures, data from currently available studies show that cholinesterase inhibitors produce clinically meaningful long‐term benefits in multiple domains in patients with Alzheimer's disease.
Abstract: The traditional aim of Alzheimer's disease treatment in clinical trials has been to improve cognitive abilities. It has become increasingly clear, however, that other aspects are important in assessing treatment responses. A group of 10 physicians recently gathered to review the current criteria for assessing treatment success in Alzheimer's disease. While cognition has been previously viewed as the primary measure of efficacy, areas such as functional abilities, behaviour, caregiver burden, quality of life and resource utilization all need to be comprehensively assessed to fully evaluate treatment effects in patients with Alzheimer's disease, as well as their impacts on caregivers and society. Postponing or slowing decline in any of these areas may represent an important benefit and should be considered as an outcome measure in clinical trials, clinical practice and decision-making about healthcare budgets. Accepted instruments are available for assessing outcomes in each aspect of Alzheimer's disease, but they need to be selected carefully to provide valid, meaningful data. Some of the most frequently used outcome measures in Alzheimer's disease are reviewed. Using expanded criteria for treatment success and clinically relevant outcome measures, data from currently available studies show that cholinesterase inhibitors produce clinically meaningful long-term benefits in multiple domains in patients with Alzheimer's disease.
124 citations
TL;DR: The rate of decline was consistent across the domains of basic activities of daily living and instrumental ADLs, as well as the scoring of initiation, planning, and organization, which equates to the loss of one item on the DAD scale every 2 months.
Abstract: The Disability Assessment for Dementia (DAD) scale was developed and validated as a measure of functional ability in dementia. DAD results have been reported in Alzheimer disease (AD) randomized, controlled treatment trials of up to 6 months, but results beyond 6 months have yet to be described. SAB INT 12 was a randomized, double-blind, placebo-controlled, parallel-group study in mild to moderate AD that included DAD assessments at baseline, month 6, and month 12. One hundred forty-four patients with AD in the placebo arm of SAB INT 12 were followed up for 12 months. DAD scores were obtained at baseline (mean DAD = 70.1, SD = 22.2), 6 months (mean DAD = 63.7, SD = 25.2), and 12 months (mean DAD = 59.3, SD = 28.9). The rate of decline was consistent across the domains of basic activities of daily living (ADLs) and instrumental ADLs, as well as the scoring of initiation, planning, and organization. The decline in DAD total scores in mild to moderate AD averages about one point per month, which equates to the loss of one item on the DAD scale every 2 months.
117 citations
TL;DR: The incidence and clinical significance of cholinergic adverse events will need to be carefully studied if the drugs are used for indications other than Alzheimer’s disease and the mechanism of syncope and neuromuscular weakness should be resolved through structured pharmacovigilance programmes and clinical studies.
Abstract: Cholinergic adverse effects of acetylcholinesterase inhibitors (AChEIs) are caused by their central and peripheral pharmacological actions on a variety of organ tissues. Gastrointestinal adverse effects predominate and these were relatively common in the phase II and III randomised clinical trials of AChEIs for the treatment of probable Alzheimer's disease. However, in these studies forced and rapid titration of drugs was used, which is not the case in clinical practice. Although there is a risk of pharmacodynamic interactions with other drugs leading to enhanced cholinergic adverse effects, very few of these interactions have proven to be clinically significant. Unresolved issues include the mechanism of syncope and neuromuscular weakness, which should be resolved through structured pharmacovigilance programmes and clinical studies. Loss of bodyweight may prove to be a long term significant complication. As a class, the AChEIs have proven to be well tolerated in the symptomatic treatment of Alzheimer's disease in its mild-to-moderately severe stages. The incidence and clinical significance of cholinergic adverse events will need to be carefully studied if the drugs are used for indications other than Alzheimer's disease.
98 citations
TL;DR: In this paper, consensus statements were developed by a group of experts, guided by a steering committee of eight individuals from the areas of Neurology, Geriatric Medicine, Psychiatry, Family Medicine, Preventive Health Care and Health Care Systems.
Abstract: Objective: i) To develop evidence based consensus statements on which to build clinical practice guidelines for primary care physicians towards the recognition, assessment and management of dementing disorders; ii) to disseminate and evaluate the impact of these statements and guidelines built on these statements. Options: Structured approach to assessment, including recommended laboratory tests, choices for neuroimaging and referral; management of complications (especially behaviour problems and depression) and use of cognitive enhancing agents. Potential outcomes: Consistent and improved clinical care of persons with dementia; cost containment by more selective use of laboratory investigations, neuroimaging and referrals; appropriate use of cognitive enhancing agents. Evidence: Authors of each background paper were entrusted to: perform a literature search, discover additional relevant material including references cited in retrieved articles; consult with other experts in the field and then synthesize information. Standard rules of evidence were applied. Based upon this evidence, consensus statements were developed by a group of experts, guided by a steering committee of eight individuals from the areas of Neurology, Geriatric Medicine, Psychiatry, Family Medicine, Preventive Health Care and Health Care Systems. Values: Recommendations have been developed with particular attention to the context of primary care and are intended to support family physicians in their ongoing assessment and care of patients with dementia. Benefits, harms and costs: Potential for improved clinical care of individuals with dementia. A dissemination and evaluation strategy will attempt to measure the impact of the recommendations. Recommendations: See text. Validation: Four other sets of consensus statements and/or guidelines have been published recently. These recommendations are generally congruent with our own consensus statements. The consensus statements have been endorsed by relevant bodies in Canada. Sponsors: Funding was provided by equal contributions from seven pharmaceutical companies and by a grant from the Consortium of Canadian Centres for Clinical Cognitive Research (C5R). Contributions were received from two Canadian universities (McGill, McMaster). Several societies supported delegates to the conference.
67 citations
TL;DR: The growing list of other diagnostic measures with potential usefulness in diagnosis of Alzheimer’s disease or dementia in general was reviewed, but the evidence was judged as insufficient to support routine use of these tests by physicians.
Abstract: At the Second Canadian Consensus Conference on Dementia (CCCD) (February, 1998), a group of neurologists, geriatricians, and psychiatrists met to consider guidelines for evaluation of dementia in Canada. This review paper formed a background paper for their discussion of dementia diagnosis. These experts from across the country concluded that diagnosis of suspected dementia cases continued to rest on skilled clinical assessment. Mental status exam, preferably in some quantifiable form, has become an essential part of the assessment. Selected laboratory tests are advisable in all cases (CBC, TSH, electrolytes, calcium, and glucose), but the CCCD continued to advise that CT scanning was mandatory only in selected cases where clinical findings pointed to another possibility besides Alzheimer's disease. The growing list of other diagnostic measures with potential usefulness in diagnosis of Alzheimer's disease or dementia in general was reviewed, but the evidence was judged as insufficient to support routine use of these tests by physicians. As new treatments for Alzheimer's disease become available, neurologists face new diagnostic challenges--differentiating Mild Cognitive Impairment, Frontotemporal dementias and Mixed dementias, and Lewy Body Dementia. Guidelines to aid in differential diagnosis are presented.
50 citations
TL;DR: The data show that A β1–42 induced NO release in neurons and glial cells, and that Aβ neurotoxicity is, at least in part, mediated by NO.
Abstract: Beta amyloid (Aβ) is implicated in Alzheimer's disease (AD). Aβ1–42 (5, 10, or 20 μM) was able to increase NO release and decrease cellular viability in primary rat cortical mixed cultures.
L-NOARG and SMTC (both at 10 or 100 μM) – type I NOS inhibitors – reduced cellular NO release in the absence of Aβ1–42. At 100 μM, both drugs decreased cell viability.
L-NIL (10 or 100 μM), and 1400W (1 or 5 μM) – type II NOS inhibitors – reduced NO release and improved viability when either drug was administered up to 4 h post Aβ1–42 (10 μM) treatment. L-NOARG and SMTC (both at 10 or 100 μM) were only able to decrease NO release. Carboxy-PTIO or Trolox (both at 10 or 100 μM) – a NO scavenger and an antioxidant, respectively–increased viability when administered up to 1 h post Aβ1–42 treatment. Either L-NIL (50 μM) or 1400W (3 μM) and Trolox (50 μM) showed synergistic actions.
Peroxynitrite (100 or 200 μM) reduced cell viability. Viabilities were improved by L-NIL (100 μM), 1400W (5 μM), carboxy-PTIO (10 or 100 μM), and Trolox (10 or 100 μM).
Hence, the data show that Aβ1–42 induced NO release in neurons and glial cells, and that Aβ neurotoxicity is, at least in part, mediated by NO. NO concentration modulating compounds and antioxidant may have therapeutic importance in neurological disorders where oxidative stress is likely involved such as in AD.
British Journal of Pharmacology (2001) 133, 1114–1124; doi:10.1038/sj.bjp.0704179
47 citations
TL;DR: Clinicians caring for patients with AD have currently available a number of symptomatic drugs, and will have in the future the ability to predict the risk for asymptomatic individuals to develop AD, and provide advice towards prevention.
Abstract: 1. A better understanding of the pathophysiology of AD has been made possible through population-based epidemiological studies, human genetic and post-mortem studies, leading to a number of testable hypothesis towards delaying progression. 2. A number of disease milestones have been identified as therapeutic targets, such as conversion from MCI to diagnosable dementia. 3. Clinicians caring for patients with AD have currently available a number of symptomatic drugs, and will have in the future the ability to predict the risk for asymptomatic individuals to develop AD, and provide advice towards prevention.
29 citations
Journal Article•
TL;DR: Evidence based consensus statements on which to build clinical practice guidelines for primary care physicians toward the recognition, assessment and management of dementing disorders and to disseminate and evaluate the impact of these statements and guidelines built on these statements are developed.
Abstract: Reconnaitre, evaluer et traiter les demences: conclusions de la Conference canadienne de consensus sur la demence. Objectif, i) ) Developper des enonces consensuels bases sur les donnees actuelles de la science sur lesquels on puisse construire des lignes directrices cliniques pour les medecins de premiere ligne pour l'identification, l'evaluation et la prise en charge des patients dements; ii) diffuser et evaluer l'impact de ces enonces et des lignes directrices basees sur ces enonces. Options: Une approche structuree pour l'evaluation, incluant les epreuves de laboratoire recommandees, les choix d'examens de neuroimagerie et de reference en specialite; la prise en charge des complications (specialement des problemes de comportement et de depression) et l'utilisation d'agents qui ameliorent la fonction cognitive. Benefices potentiels: Des soins ameliores et fiables aux personnes dementes; un controle des couts par une utilisation plus judicieuse des examens de laboratoire, de la neuroimagerie et de la reference en specialite; une utilisation appropriee des agents qui ameliorent la fonction cognitive, Evidence: Les auteurs de chaque article de fond ont recu le mandat de faire une recherche de la litterature pour ajouter des informations pertinentes incluant les references citees dans ces articles; consulter d'autres experts dans ce domaine et faire une synthese de l'information. Ces tâches ont ete effectuees conformement aux normes de la preuve. Sur la foi de cette evidence, les enonces consensuels ont ete developpes par un groupe d'experts, guide par un comite de direction de huit individus des domaines de la neurologie, de la geriatrie, de la psychiatrie, de la medecine familiale, de la medecine preventive et des systemes de sante. Valeurs: Des recommandations ont ete developpees en portant une attention particuliere sur le contexte des soins de premiere ligne et sont destinees a supporter les medecins de famille dans l'evaluation et la prise en charge au cours du suivi de leurs patients atteints de demence. Benefices, desavantages et couts: Une amelioration potentielle des soins aux individus atteints de demence. Une diffusion et une strategie d'evaluation tentera de mesurer l'impact des recommandations Recommandations: Voir texte. Validation: Quatre autres ensembles d'enonces consensuels et / ou de lignes directrices ont ete publies recemment. Ces recommandations sont generalement en accord avec notre enonce consensuel. Les enonces consensuels ont ete endosses par les autorites competentes au Canada. Commanditaires: Les fonds proviennent de contributions egales de sept compagnies pharmaceutiques et d'un octroi du Consortium des Centres canadiens pour la recherche clinique cognitive (C5R). Deux universites canadiennes ont contribue (McGill et McMaster). Plusieurs societes ont commandite la participation de delegues a la conference.
Journal Article•
TL;DR: Assessments of cognitive and global function measures, and assessments of abilities to perform activities of daily living (ADL) must be included as part of the optimal assessment battery in VaD trials, and the best ways of measuring these outcomes are addressed.
Abstract: Vascular dementia (VaD) can be defined as dementia associated with cerebrovascular disease (CVD), and accounts for a large proportion of all dementia cases. There is substantial overlap in the clinical symptomatology, pathophysiology and neurochemical mechanisms in VaD compared with Alzheimer's disease, suggesting that an effective treatment for Alzheimer's disease may also offer benefit as a symptomatic treatment in VaD. However, there are currently no explicit guidelines for conducting clinical pharmacotherapy trials in VaD patients. Two important requirements for assessing therapeutic benefits in such trials are 1) the inclusion of appropriate patients and 2) the use of appropriate outcome measures. Debate on the precise definition of VaD in relation to patient selection criteria continues, but many of the recommendations for outcome measures in Alzheimer's disease are already applicable to VaD. There is consensus that cognitive and global function measures, and assessments of abilities to perform activities of daily living (ADL) must be included as part of the optimal assessment battery in VaD trials. A measure of reduced behavioural symptoms with associated reductions in demands on caregivers would also be desirable. However, care must be taken in extrapolating Alzheimer's disease-specific evaluations to VaD, in that important differences in specific domains affected and characteristics of disease course must be taken into account. Between them, measures such as the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog; perhaps with supplemental tests of attention and other frontal lobe functions), evaluations of clinical global impression of change and a functional assessment addressing instrumental as well as basic ADL, e.g. Disability Assessment in Dementia (DAD) scale, should provide a good overall description of VaD-related deficits and sufficient appraisal of treatment effects. The Neuropsychiatric Inventory has also been shown to have good potential utility for measuring behavioural alterations in VaD. These and other assessments are reviewed to provide a balanced and realistic view of the type of treatment outcomes that can be expected in VaD pharmacotherapy trials, and to address the best ways of measuring these outcomes.
14 Jun 2001
TL;DR: Alzheimer's Disease and Related Disorders Annual 2001 , Alzheimer's disease and related disorders Annual 2001, کتابخانه مرکزی دانشگاه علوم پزδکی اتهران.
Abstract: Alzheimer's Disease and Related Disorders Annual 2001 , Alzheimer's Disease and Related Disorders Annual 2001 , کتابخانه مرکزی دانشگاه علوم پزشکی تهران
01 Jan 2001
TL;DR: Canada is experiencing a renaissance in health research, and the creation of the CIHR in 2000, which replaced the Medical Research Council of Canada, has a noble objective of reversing the downward trend of per capita public funding.
Abstract: Canada is experiencing a renaissance in health research. In 1998, the Federal Government responded to the problem of an ailing health research sector1 by reversing the downward trend of per capita public funding. This was followed in 2000 by the creation of the Canadian Institutes of Health Research (CIHR).2 This new body, which replaced the Medical Research Council of Canada, has a noble objective:
01 Jan 2001
TL;DR: The Canadian Institutes of Health Research (CIHR) as mentioned in this paper was created by the federal government in 2000 to replace the Medical Research Council of Canada (MRC) with an independent body.
Abstract: Canada is experiencing a renaissance in health research. In 1998, the Federal Government responded to the problem of an ailing health research sector1 by reversing the downward trend of per capita public funding. This was followed in 2000 by the creation of the Canadian Institutes of Health Research (CIHR).2 This new body, which replaced the Medical Research Council of Canada, has a noble objective: