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Meta-Analysis
. 2006 Jan 25;2006(1):CD004746.
doi: 10.1002/14651858.CD004746.pub2.

Galantamine for vascular cognitive impairment

D Craig  1 , J Birks
Affiliations
Meta-Analysis

Galantamine for vascular cognitive impairment

D Craig et al. Cochrane Database Syst Rev. .

Update in

Abstract

Background: 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.

Objectives: To assess the efficacy of galantamine in the treatment of people with vascular cognitive impairment or vascular dementia or "mixed" dementia.

Search strategy: 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.

Selection criteria: All unconfounded randomised double-blind trials comparing galantamine with placebo were eligible for inclusion.

Data collection and analysis: Two RCTs fulfilling the inclusion criteria were included in this review. Two reviewers independently extracted the data from these two inclusion studies.

Main results: 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.

Authors' conclusions: 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.

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Conflict of interest statement

None known.

Figures

1.1
1.1. Analysis
Comparison 1 Galantamine vs placebo in probable VaD or AD, combined with cerebrovascular disease, Outcome 1 ADAS‐Cog/11 (change from baseline) at 26 weeks ITT.
1.2
1.2. Analysis
Comparison 1 Galantamine vs placebo in probable VaD or AD, combined with cerebrovascular disease, Outcome 2 NPI ‐Behavioural symptoms (change from baseline) at 26 weeks ITT.
1.3
1.3. Analysis
Comparison 1 Galantamine vs placebo in probable VaD or AD, combined with cerebrovascular disease, Outcome 3 DAD ‐ activities of daily living (change from baseline) at 26 weeks ITT.
1.4
1.4. Analysis
Comparison 1 Galantamine vs placebo in probable VaD or AD, combined with cerebrovascular disease, Outcome 4 Total number of deaths at 26 weeks + 30 days after treatment ended.
1.5
1.5. Analysis
Comparison 1 Galantamine vs placebo in probable VaD or AD, combined with cerebrovascular disease, Outcome 5 CIBIC‐plus (improved or no change) at 26 weeks ITT.
1.6
1.6. Analysis
Comparison 1 Galantamine vs placebo in probable VaD or AD, combined with cerebrovascular disease, Outcome 6 Total number of withdrawals before end of treatment at 26 weeks.
1.7
1.7. Analysis
Comparison 1 Galantamine vs placebo in probable VaD or AD, combined with cerebrovascular disease, Outcome 7 Total number of withdrawals due to an adverse event before end of treatment at 26 weeks.
1.8
1.8. Analysis
Comparison 1 Galantamine vs placebo in probable VaD or AD, combined with cerebrovascular disease, Outcome 8 Total number of patients who suffered at least one adverse event before end of treatment at 26 weeks.
1.9
1.9. Analysis
Comparison 1 Galantamine vs placebo in probable VaD or AD, combined with cerebrovascular disease, Outcome 9 Total number of patients who suffered from at least one adverse event of nausea by end of treatment at 26 weeks.
1.10
1.10. Analysis
Comparison 1 Galantamine vs placebo in probable VaD or AD, combined with cerebrovascular disease, Outcome 10 Total number of patients who suffered from at least one adverse event of vomiting before end of treatment at 26 weeks.
1.11
1.11. Analysis
Comparison 1 Galantamine vs placebo in probable VaD or AD, combined with cerebrovascular disease, Outcome 11 Total number of patients who suffered at least one adverse event of injury before end of treatment at 26 weeks.
2.1
2.1. Analysis
Comparison 2 Galantamine vs placebo in probable VaD, Outcome 1 ADAS‐cog/11 (change from baseline) at 26 weeks modified ITT‐LOCF.
2.2
2.2. Analysis
Comparison 2 Galantamine vs placebo in probable VaD, Outcome 2 ADAS‐cog/10 (change from baseline) at 26 weeks modified ITT‐LOCF.
2.3
2.3. Analysis
Comparison 2 Galantamine vs placebo in probable VaD, Outcome 3 ADAS‐cog/13 (change from baseline) at 26 weeks modified ITT‐LOCF.
2.4
2.4. Analysis
Comparison 2 Galantamine vs placebo in probable VaD, Outcome 4 ADAS‐cog/memory (change from baseline) at 26 weeks modified ITT.
2.5
2.5. Analysis
Comparison 2 Galantamine vs placebo in probable VaD, Outcome 5 ADCS‐ADL (change from baseline) at 26 weeks modified ITT‐LOCF.
2.6
2.6. Analysis
Comparison 2 Galantamine vs placebo in probable VaD, Outcome 6 NPI Behavioural symptoms (change from baseline) at 26 weeks modified ITT‐LOCF.
2.7
2.7. Analysis
Comparison 2 Galantamine vs placebo in probable VaD, Outcome 7 CIBIC‐plus (improved or no change) at 26 weeks modified ITT‐LOCF.
2.8
2.8. Analysis
Comparison 2 Galantamine vs placebo in probable VaD, Outcome 8 EXIT‐25 executive function (change from baseline) at 26 weeks modified ITT‐LOCF.
2.9
2.9. Analysis
Comparison 2 Galantamine vs placebo in probable VaD, Outcome 9 Total number of patients who suffered at least one adverse event before end of treatment at 26 weeks.
2.10
2.10. Analysis
Comparison 2 Galantamine vs placebo in probable VaD, Outcome 10 Total number of patients who suffered from at least one adverse event of nausea by end of treatment at 26 weeks.
2.11
2.11. Analysis
Comparison 2 Galantamine vs placebo in probable VaD, Outcome 11 Total number of patients who suffered from at least one adverse event of vomiting before end of treatment at 26 weeks.
2.12
2.12. Analysis
Comparison 2 Galantamine vs placebo in probable VaD, Outcome 12 Total number of patients who suffered at least one adverse event of injury before end of treatment at 26 weeks.
2.13
2.13. Analysis
Comparison 2 Galantamine vs placebo in probable VaD, Outcome 13 Total number of patients who suffered at least one adverse event of diarrhoea before end of treatment at 26 weeks.
2.14
2.14. Analysis
Comparison 2 Galantamine vs placebo in probable VaD, Outcome 14 Total number of patients who suffered at least one adverse event of dizzines before end of treatment at 26 weeks.
2.15
2.15. Analysis
Comparison 2 Galantamine vs placebo in probable VaD, Outcome 15 Total number of patients who suffered at least one adverse event of anorexia before end of treatment at 26 weeks.
2.16
2.16. Analysis
Comparison 2 Galantamine vs placebo in probable VaD, Outcome 16 Total number of patients who suffered at least one adverse event of urinary tract infection before end of treatment at 26 weeks.
2.17
2.17. Analysis
Comparison 2 Galantamine vs placebo in probable VaD, Outcome 17 Total number of patients who suffered at least one adverse event of a fall before end of treatment at 26 weeks.
2.18
2.18. Analysis
Comparison 2 Galantamine vs placebo in probable VaD, Outcome 18 Total number of patients who suffered a possible trial drug related adverse event before end of treatment at 26 weeks.
2.19
2.19. Analysis
Comparison 2 Galantamine vs placebo in probable VaD, Outcome 19 Total number of patients who suffered at least one serious adverse event before end of treatment at 26 weeks.
2.20
2.20. Analysis
Comparison 2 Galantamine vs placebo in probable VaD, Outcome 20 Total number of patients who suffered at least one serious adverse event (cerebrovascular disorder) before end of treatment at 26 weeks.
2.21
2.21. Analysis
Comparison 2 Galantamine vs placebo in probable VaD, Outcome 21 Total number of patients who suffered at least one serious adverse event of urinary tract infection before end of treatment at 26 weeks.
2.22
2.22. Analysis
Comparison 2 Galantamine vs placebo in probable VaD, Outcome 22 Total number of patients who suffered at least one serious adverse event of myocardial infarction before end of treatment at 26 weeks.
2.23
2.23. Analysis
Comparison 2 Galantamine vs placebo in probable VaD, Outcome 23 Total number of patients who suffered at least one serious adverse event of pnemonia before end of treatment at 26 weeks.
2.24
2.24. Analysis
Comparison 2 Galantamine vs placebo in probable VaD, Outcome 24 Total number of withdrawals before end of treatment at 26 weeks.
2.25
2.25. Analysis
Comparison 2 Galantamine vs placebo in probable VaD, Outcome 25 Total number of deaths at 26 weeks + 30 days after treatment ended.
2.26
2.26. Analysis
Comparison 2 Galantamine vs placebo in probable VaD, Outcome 26 Total number of withdrawals due to an adverse event before end of treatment at 26 weeks.
See this image and copyright information in PMC

References

References to studies included in this review

GAL‐INT‐26 {published and unpublished data}
    1. Anon. GAL‐INT‐26. Johnson and Johnson Pharmceutical Research and Development 26 February 2004.
    1. Auchus AP, Brashear HR, Salloway S, Korczyn AD, Deyn PP, Gassmann‐Mayer C, GAL‐INT‐26 Study Group. Galantamine treatment of vascular dementia: a randomized trial. Neurology 2007;69(5):448‐58. - PubMed
    1. Gassmann‐Mayer C. Email author. E‐mail correspondence from Dr Cristina Gassmann‐Mayer. Email to: R Malouf. Email recipient 24 October 2008.
GAL‐INT‐6 {published data only}
    1. Bullock R, Erkinjuntti T, Lilienfeld S, GAL INT 6 Study Group. Management of patients with Alzheimer's disease plus cerebrovascular disease: 12‐month treatment with galantamine. Dementia and Geriatric Cognitive Disorders 2004;17(1‐2):29‐34. - PubMed
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    1. Burke W, Lilienfeld S. Galantamine improves behaviour and relieves caregiver distress in Alzheimer's disease (AD), vascular dementia and AD with cerebrovascular disease. Proceedings of the 8th International Conference on Alzheimer's Disease and Related Disorders; 2002 July 20‐25, Stockholm, Sweden 2002:Abstract No 428. 2002.
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    1. Erkinjuntti T, Gauthier S, Bullock R, Kurz A, Hammond G, Schwalen S, et al. Galantamine treatment in Alzheimer's disease with cerebrovascular disease: Responder analyses from a randomized, controlled trial (GAL‐INT‐6). Journal of Psychopharmacology 2008;22(7):761‐8. - PubMed

References to studies excluded from this review

Senanarong 2004 {published data only}
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References to other published versions of this review

Craig 2006
    1. Craig D, Birks J. Galantamine for vascular cognitive impairment. Cochrane Database of Systematic Reviews 2006, Issue 1. [DOI: 10.1002/14651858.CD004746.pub2] - DOI - PMC - PubMed

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