Galantamine for vascular cognitive impairment.

Abstract

Vascular dementia is the second most common form of dementia. Cholinesterase inhibitors modestly improve a broad range of symptoms in some patients with Alzheimer's disease through enhancement of cholinergic neurotransmission. These drugs may also be beneficial in vascular dementia as reductions in acetylcholine and acetyltransferase activity have been reported. To assess the efficacy of galantamine in the treatment of people with vascular cognitive impairment or vascular dementia or "mixed" dementia. Trials were identified from a search of the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group on 19 April 2005 using the terms: galantamine. galanthamine, reminyl. All major health care databases and many ongoing trial databases within the scope of the group are searched regularly to keep this Register up to date. All unconfounded randomised double-blind trials comparing galantamine with placebo were eligible for inclusion. Two RCTs fulfilling the inclusion criteria were included in this review. Two reviewers independently extracted the data from these two inclusion studies. Two trials employing randomized, double-blind, parallel-group methodology were included. GAL-INT-6 reported sub-group data for a pure population of vascular dementia patients showing no significant differences in Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog/11) and Clinician's Interview-based Impression of Change (CIBIC-plus) when galantamine was compared against placebo. When data combining patients with vascular dementia diagnosed according to recognised criteria with a population of patients with Alzheimer's disease and coincidental radiographic findings of cerebrovascular disease was analysed, statistically significant improvements in cognition (ADAS-cog), global functioning (CIBIC-plus), activities of daily living (DAD) and behaviour (NPI) were noted. In the galantamine treated group, significantly higher numbers of patients dropped out and withdrew due to an adverse event. Limited data was available at the time of publication for a second larger trial (GAL-INT-26) involving patients with vascular dementia diagnosed using standard criteria. Statistically significant benefits favouring galantamine over placebo in assessments of cognition (ADAS-cog/11; p < 0.001) and executive function (Executive Interview, EXIT-25, p = 0.041) were recorded. No differences in outcome in measures of behaviour (Neuropsychiatric Inventory, NPI), daily living (Alzheimer's Disease Cooperative Study-Activities of Daily Living inventory, ADCS-ADL) and global functioning (CIBIC-plus) in this trial were seen. Limited data were available when considering the impact of galantamine on vascular dementia or vascular cognitive impairment. The data available at the time of review suggest some advantage over placebo in the areas of cognition and executive functioning in one trial but this was not seen in a second trial which included smaller numbers of relevant patients. In both considered trials galantamine produced higher rates of gastrointestinal side-effects. More studies are needed before firm conclusions can be drawn.