Laura Brennan1,2,3, Alexander Pantelyat4, John E Duda1,5, James F Morley1,5, Daniel Weintraub1,2,5, Jayne R Wilkinson1,5, Paul J Moberg1,2,5. 1. Parkinson's Disease Research, Education and Clinical Center (PADRECC) Philadelphia Veteran's Affairs Hospital Philadelphia Pennsylvania USA. 2. Department of Psychiatry University of Pennsylvania Perelman School of Medicine Philadelphia Pennsylvania USA. 3. Drexel Neurosciences Institute Philadelphia PA USA. 4. Department of Neurology Johns Hopkins University School of Medicine Baltimore Maryland USA. 5. Department of Neurology University of Pennsylvania Perelman School of Medicine Philadelphia Pennsylvania USA.
Abstract
BACKGROUND: The aim of this work was to utilize meta-analysis in examining the effects of memantine on neuropsychological functioning in patients with Parkinson's disease dementia (PDD) and dementia with Lewy bodies (DLB). METHODS: Included studies fulfilled these criteria: included objective cognitive measures, a comparison group of participants not taking memantine, and provided sufficient data for calculation of effect size. We examined effect sizes across global cognition and five specific neuropsychological domains. Moderator variables examined included neuropsychological domain, diagnostic cohort (PDD, DLB, or mixed PDD-DLB cohort), study design (open label or placebo-controlled), and trial length. RESULTS: Six publications met inclusion criteria totaling 57 effects. Homogeneity analysis across cognitive domains revealed a small overall effect size (d = 0.25) that was significantly heterogeneous (P < 0.001). Specific neuropsychological domains did not moderate effect size, though. Moderator analysis studies using a mix of DLB and PDD subjects showed larger effects than those that included DLB or PDD patients only. Additionally, open-label trials had significantly (P < 0.001) larger effect sizes (d = 1.32) than placebo-controlled trials (d = 0.12). CONCLUSIONS: The present study indicates that effect-size heterogeneity across studies of memantine in DLB and PDD patients is moderated by diagnostic makeup of the cohort and study design. The small overall effect size noted in placebo-controlled trials versus open-label trials indicates that memantine has minimal effects on cognition in PDD and DLB and is unlikely to demonstrate clinically significant improvements in cognition.
BACKGROUND: The aim of this work was to utilize meta-analysis in examining the effects of memantine on neuropsychological functioning in patients with Parkinson's disease dementia (PDD) and dementia with Lewy bodies (DLB). METHODS: Included studies fulfilled these criteria: included objective cognitive measures, a comparison group of participants not taking memantine, and provided sufficient data for calculation of effect size. We examined effect sizes across global cognition and five specific neuropsychological domains. Moderator variables examined included neuropsychological domain, diagnostic cohort (PDD, DLB, or mixed PDD-DLB cohort), study design (open label or placebo-controlled), and trial length. RESULTS: Six publications met inclusion criteria totaling 57 effects. Homogeneity analysis across cognitive domains revealed a small overall effect size (d = 0.25) that was significantly heterogeneous (P < 0.001). Specific neuropsychological domains did not moderate effect size, though. Moderator analysis studies using a mix of DLB and PDD subjects showed larger effects than those that included DLB or PDD patients only. Additionally, open-label trials had significantly (P < 0.001) larger effect sizes (d = 1.32) than placebo-controlled trials (d = 0.12). CONCLUSIONS: The present study indicates that effect-size heterogeneity across studies of memantine in DLB and PDD patients is moderated by diagnostic makeup of the cohort and study design. The small overall effect size noted in placebo-controlled trials versus open-label trials indicates that memantine has minimal effects on cognition in PDD and DLB and is unlikely to demonstrate clinically significant improvements in cognition.
Authors: Bruno Dubois; David Burn; Christopher Goetz; Dag Aarsland; Richard G Brown; Gerald A Broe; Dennis Dickson; Charles Duyckaerts; Jefferey Cummings; Serge Gauthier; Amos Korczyn; Andrew Lees; Richard Levy; Irene Litvan; Yoshikuni Mizuno; Ian G McKeith; C Warren Olanow; Werner Poewe; Cristina Sampaio; Eduardo Tolosa; Murat Emre Journal: Mov Disord Date: 2007-12 Impact factor: 10.338
Authors: Kajsa Stubendorff; Victoria Larsson; Clive Ballard; Lennart Minthon; Dag Aarsland; Elisabet Londos Journal: BMJ Open Date: 2014-07-03 Impact factor: 2.692