Alzheimer's disease; EFNS/ENS Guidelines; Grading of Recommendations Assessment, Development and Evaluation; cholinesterase inhibitors; dementia; memantine; meta-analysis; treatment; Cholinesterase Inhibitors; Excitatory Amino Acid Antagonists; Memantine; Alzheimer Disease/drug therapy; Cholinesterase Inhibitors/therapeutic use; Excitatory Amino Acid Antagonists/therapeutic use; Humans; Memantine/therapeutic use; Drug Therapy, Combination; Practice Guidelines as Topic; Neurology; Neurology (clinical); EFNS; ENS Guidelines; Grading of Recommendations Assessment; Development and Evaluation
Résumé :
[en] [en] BACKGROUND AND PURPOSE: Previous studies have indicated clinical benefits of a combination of cholinesterase inhibitors (ChEI) and memantine over ChEI monotherapy in Alzheimer's disease (AD). Our objective was the development of guidelines on the question of whether combined ChEI/memantine treatment rather than ChEI alone should be used in patients with moderate to severe AD to improve global clinical impression (GCI), cognition, behaviour and activities of daily living (ADL).
METHODS: A systematic review and meta-analysis of randomized controlled trials based on a literature search in ALOIS, the register of the Cochrane Dementia and Cognitive Improvement Group, was carried out with subsequent guideline development according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system.
RESULTS: Pooled data from four trials including 1549 AD patients in the moderate to severe disease stage demonstrated significant beneficial effects of combination therapy compared to ChEI monotherapy for GCI [standardized mean difference (SMD) -0.20; 95% confidence interval (CI) -0.31; -0.09], cognitive functioning (SMD -0.27, 95% CI -0.37; -0.17) and behaviour (SMD -0.19; 95% CI -0.31; -0.07). The quality of evidence was high for behaviour, moderate for cognitive function and GCI and low for ADL. Agreement of panellists was reached after the second round of the consensus finding procedure. The desirable effects of combined ChEI and memantine treatment were considered to outweigh undesirable effects. The evidence was weak for cognition, GCI and ADL so that the general recommendation for using combination therapy was weak.
CONCLUSIONS: We suggest the use of a combination of ChEI plus memantine rather than ChEI alone in patients with moderate to severe AD. The strength of this recommendation is weak.
Disciplines :
Neurologie
Auteur, co-auteur :
Schmidt, R; Department of Neurology, Medical University of Graz, Graz, Austria
Hofer, E; Department of Neurology, Medical University of Graz, Graz, Austria ; Institute for Medical Informatics, Statistics and Documentation, Medical University of Graz, Graz, Austria
Bouwman, F H; Alzheimer Centre, VU University Medical Centre, Amsterdam, Netherlands
Buerger, K; Institute for Stroke and Dementia Research (ISD), Klinikum der Universität München, Munich, Germany
Cordonnier, C; Department of Neurology, Univ Lille Nord de France, UDSL, CHU Lille, Lille, France
Fladby, T; Department of Neurology, Akershus University Hospital, Ahus, Norway
Galimberti, D; Neurology Unit, Department of Pathophysiology and Transplantation, University of Milan, IRCCS Ospedale Maggiore Policlinico, Fondazione Cà Granda, Milan, Italy
Georges, J; Alzheimer Europe, Luxembourg City, Luxembourg
HENEKA, Michael ; Clinic and Polyclinic for Neurology, Clinical Neuroscience Unit, German Centre for Neurodegenerative Diseases (DZNE), Bonn, Germany
Hort, J; Second Faculty of Medicine, Department of Neurology, Charles University in Prague and Motol University Hospital, Prague 5, Czech Republic ; International Clinical Research Centre, St Anne's University Hospital, Brno, Czech Republic
Laczó, J; Second Faculty of Medicine, Department of Neurology, Charles University in Prague and Motol University Hospital, Prague 5, Czech Republic ; International Clinical Research Centre, St Anne's University Hospital, Brno, Czech Republic
Molinuevo, J L; Alzheimer's Disease and other Cognitive Disorders Unit, Department of Neurology, Hospital Clínic, IDIBAPS, Barcelona, Spain
O'Brien, J T; Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom
Religa, D; Karolinska Institutet Alzheimer Disease Research Centre, Karolinska University Hospital, Stockholm, Sweden ; Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland
Scheltens, P; Alzheimer Centre, VU University Medical Centre, Amsterdam, Netherlands
Schott, J M; Dementia Research Centre, Institute of Neurology, UCL Queen Square, London, United Kingdom
Sorbi, S; Department of Neuroscience, Psychology, Drug Research and Child Health (NEUROFARBA), University of Florence, Florence, Italy
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