title: Galantamine for vascular cognitive impairment.
abstract: BACKGROUND
  Vascular dementia represents the second most common type of dementia after that caused by Alzheimer's disease. Particularly in older patients, the combination of vascular dementia and Alzheimer's disease is common and is referred to as mixed dementia. The classification of vascular dementia broadly follows three clinico-pathological processes: multi-infarct dementia, single strategic infarct dementia and subcortical dementia. Not all patients fulfil strict criteria for dementia and may be significantly cognitively impaired without memory loss and the term vascular cognitive impairment is more useful. Currently, no established standard treatment for vascular cognitive impairment exists. Reductions in acetylcholine and acetyltransferase activity are common to both Alzheimer's disease and vascular cognitive impairment raising the possibility that cholinesterase inhibitors such as galantamine may be beneficial for the latter.
  
  
  OBJECTIVE
  To assess the efficacy of galantamine in the treatment of people with vascular cognitive impairment or vascular dementia or mixed dementia.
  
  
  METHODS
  The trials were identified from a search of ALOIS: the Cochrane Dementia and Cognitive Improvement Group's Specialized Register on 12 January 2013. The register contains information on trials identified from frequent searches of a number of major healthcare and medical databases (MEDLINE, EMBASE, PsycINFO, CINAHL and LILACS) as well as from a number of international and national trial registries and grey literature sources. The terms used were: galantamine, galanthamine, Reminyl, Razadyne, Nival in.
  
  
  METHODS
  All unconfounded randomised double-blind trials comparing galantamine with placebo were eligible for inclusion.
  
  
  METHODS
  Two review authors independently extracted the data from included studies.
  
  
  RESULTS
  Two trials, 1378 participants, employing randomised, double-blind, parallel-group methodology were included. Both trials were of six months duration and were testing a galantamine dose of 16-24 mg/day in two divided doses. Both trials had an overall low risk of bias.The GAL-INT-6 trial included 592 patients with vascular dementia diagnosed according to recognised criteria and patients with Alzheimer's disease and coincidental radiographic findings of cerebrovascular disease. Limited outcome data were reported for the subgroup data with vascular dementia. In the whole trial population, statistically significant treatment effects in favour of galantamine compared with placebo in cognition (ADAS-cog,mean difference (MD) -2.29, 95%confidence interval (CI) -3.46 to -1.12, P = 0.0001), activities of daily living (DAD, MD 4.10, 95% CI 1.25 to 6.95, P = 0.005) and behaviour (NPI, MD -2.06, 95% CI -4.09 to -0.03,P = 0.05 ) were noted. Significantly higher numbers of patients dropped out, (102/396 galantamine, 33/196 placebo odds ratio (OR)1.71, 95% CL 1.11 to 2.65, P = 0.02) and withdrew due to an adverse event from the group treated with galantamine compared with the placebo group (79/396 galantamine, 16/196 placebo, OR 2.80, 95% CI 1.59 to 4.95, P =0.0004).Data were also included from a second larger trial (GAL-INT-26) involving 788 patients with vascular dementia diagnosed using standard criteria. Statistically significant benefits favouring galantamine over placebo in assessments of cognition (ADAS-cog, MD -1.50, 95% CI -2.39 to -0.61, P = 0.0009), and favouring placebo compared with galantamine for behaviour (NPI, MD 1.80, 95% CI0.29 to 3.31, P = 0.02) are recorded. Significantly higher numbers of patients dropped out from the group treated with galantamine compared with the placebo group (50/396 galantamine, 25/390 placebo OR 2.11, 95% CL 1.28 to 3.49, P = 0.004).
  
  
  CONCLUSIONS
  Limited data were available when considering the impact of galantamine on vascular dementia or vascular cognitive impairment. The data available suggest some advantage over placebo in the areas of cognition and global clinical state. In both included trials galantamine produced higher rates of gastrointestinal side-effects. More studies are needed before firm conclusions can be drawn.
authors.affiliation: Centre for Statistics inMedicine, University of Oxford, Oxford, UK. jacqueline.birks@csm.ox.ac.uk.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Birks
authors.forename: David
authors.initials: D
authors.lastname: Craig
mesh_terms: D000544:Alzheimer Disease / Q000150:complications / Q000188:drug therapy*; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use*; D003072:Cognition Disorders / Q000188:drug therapy / Q000209:etiology; D015140:Dementia, Vascular / Q000188:drug therapy*; D005702:Galantamine / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D018697:Nootropic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic
chemical_list: D002800:Cholinesterase Inhibitors; D018697:Nootropic Agents; D005702:Galantamine