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. 2003;2003(3):CD003672.
doi: 10.1002/14651858.CD003672.

Cholinesterase inhibitors for dementia with Lewy bodies

R Wild  1 , T Pettit, A Burns
Affiliations

Cholinesterase inhibitors for dementia with Lewy bodies

R Wild et al. Cochrane Database Syst Rev. 2003.

Abstract

Background: Dementia with Lewy bodies (DLB) was first described in 1983, and clinical diagnostic criteria were published in the early to mid 1990s. It has been suggested DLB may account for up to 15-25% of cases of dementia among people aged over 65, although autopsy suggests much lower rates. Characteristic symptoms are dementia, marked fluctuation of cognitive ability, early and persistent visual hallucinations and spontaneous motor features of Parkinsonism. Falls, syncope, transient disturbances of consciousness, neuroleptic sensitivity, and hallucinations in other modalities are also common. This combination of features can be difficult to manage as neuroleptics can make the Parkinsonian and cognitive symptoms worse. There is evidence to suggest that the cholinesterase inhibitors may be beneficial in this disorder; small case series indicate that cholinesterase inhibitors are safe, and will improve both cognitive deficits and neuropsychiatric symptoms in DLB.

Objectives: To assess the use of cholinesterase inhibitors in DLB.

Search strategy: The trials were identified from a search of the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group on 25 February 2002 using the terms 'lewy body', 'Lewy bodies' and 'Lewy'. This register contains records from all major health care databases and trial databases and is updated regularly.

Selection criteria: Randomized, double-blind trials in which treatment with cholinesterase inhibitors was administered and compared with alternative interventions in patients with DLB are included.

Data collection and analysis: Two reviewers (TP, RW) independently assessed quality of trials according to criteria described in the Cochrane Collaboration Handbook. Each drug was to be examined separately, and together as a group. We also analysed data by time to outcome measurement; short-term (up to one month), medium term (one month up to six months) and long term (Six months and longer). The primary outcome measures of interest are in the following areas: neuropsychiatric features. i.e. psychiatric symptoms and behavioural disturbances, cognitive function, activities of daily living, global assessments, quality of life, including maintaining role and social functioning, effect on carers, safety as measured by incidence of adverse events and side effects, acceptability of treatment as measured by withdrawal from trials, and by patient/carer assessment, institutionalization and death.

Main results: There was one included trial (McKeith 2000f) of rivastigmine compared with placebo on 120 patients. Neuropsychiatric InventoryThe 10-item test found no significant difference between the two groups in change of scores from baseline using intention-to-treat (ITT) analysis at 20 weeks and last observation carried forward (LOCF) analysis. The treatment effect was statistically significant in favour of rivastigmine if only observed cases (OC) were analysed (WMD -6.94, 95% CI -11.59 to -2.29, P=0.003). There were similar results for the NPI-4, with only the OC analysis showing a significant superiority of rivastigmine to placebo at 20 weeks (WMD -3.75, 95%CI -6.62 to -0.88, P=0.01).MMSE:Analysis of these results showed no statistically significant difference between the two groups at 20 weeks.CGC-plus:Analysis of the proportion of patients who had no change or became worse found no statistically significant difference between the two groups at 20 weeks for the ITT, LOCK and OC analyses. Adverse Events:The placebo group experienced significantly fewer adverse events than the treatment group (54/59 vs 46/61,OR 3.52, 95%CI 1.19 to 10.43). However, using ITT analysis of 20-week data, there was no significant difference between the two groups when serious adverse events were considered. There were no significant differences in death rates between the two groups at 20 weeks.Drop-out Rates:Analysis of these results showed no difference between the two groups at 20 weeks using ITT analysis.

Reviewer's conclusions: Patients with dementia with Lewy bodies who suffer from behavioural disturbance oS CONCLUSIONS: Patients with dementia with Lewy bodies who suffer from behavioural disturbance or psychiatric problems may benefit from rivastigmine if they tolerate it, but the evidence is weak. Further trials using rivastigmine are needed, as are trials of other cholinesterase inhibitors in dementia with Lewy bodies.

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Conflict of interest statement

Professor Burns has been involved in clinical trials on cholinesterase inhibitors for Alzheimer's Disease, and has received research honoraria and hospitality from Pfizer, Eisai, Novartis, Bristol Myers Squibb, AstraZeneca, Janssen‐Cilag. He holds no shares in any pharmaceutical company.

Figures

1.1
1.1. Analysis
Comparison 1 Rivastigmine versus placebo, Outcome 1 Neuropsychiatric Inventory (10 items). Change from baseline. 20 weeks..
1.2
1.2. Analysis
Comparison 1 Rivastigmine versus placebo, Outcome 2 Neuropsychiatric Inventory (4items). Change from baseline. 20 weeks..
1.3
1.3. Analysis
Comparison 1 Rivastigmine versus placebo, Outcome 3 Proportion with an Adverse Event. ITT analysis. 20 weeks..
1.4
1.4. Analysis
Comparison 1 Rivastigmine versus placebo, Outcome 4 Proportion with a serious Adverse Event. ITT analysis. 20 weeks..
1.5
1.5. Analysis
Comparison 1 Rivastigmine versus placebo, Outcome 5 Drop out Rate. ITT analysis. 20 weeks..
1.6
1.6. Analysis
Comparison 1 Rivastigmine versus placebo, Outcome 6 Death. ITT analysis. 20 weeks..
1.7
1.7. Analysis
Comparison 1 Rivastigmine versus placebo, Outcome 7 Mini‐Mental State Examination. Change from baseline. 20 weeks..
1.8
1.8. Analysis
Comparison 1 Rivastigmine versus placebo, Outcome 8 Clinician Global Change Plus. No change or worse. 20 weeks.
See this image and copyright information in PMC

References

References to studies included in this review

McKeith 2000 {published data only}
    1. Byrne J. Treatment of Lewy body dementia with Exelon. National Research Register 2000. [MEDLINE: ]
    1. Ser T. Efficacy of cholinesterase inhibitors in lewy body dementia. Sixth International Stockholm/Springfield Symposium on Advances in Alzheimer Therapy; April 5‐8, 2000; Stockholm, Sweden 2000:51.
    1. Ser T, McKeith I, Anand R, Cicin‐Sain A, Ferrara R, Spiegel R. Dementia with Lewy bodies: findings from an international multicentre study. Int J Geriatr Psychiatry 2000;15(11):1034‐45. - PubMed
    1. McKeith I, Ser T, Anand R, et al. Rivastigmine provides symptomatic benefit in dementia with lewy bodies: findings from a placebo‐controlled international multicenter study. Neurology 2000e; Vol. 54, issue suppl 3:A450.
    1. McKeith I, Ser T, Spano P, Emre M, Wesnes K, Anand R, Cicin‐Sain A, Ferrara R, Spiegel R. Efficacy of rivastigmine in dementia with Lewy bodies: a randomised, double‐blind, placebo‐controlled international study. Lancet 2000f; Vol. 356, issue 9247:2031‐6. - PubMed

References to studies excluded from this review

Anand 2000 {published data only}
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McKeith 2000a {published data only}
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McKeith 2000b {published data only}
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Samuel 2000 {published data only}
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