Cholinesterase inhibitors for dementia with Lewy bodies

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-blindtrials 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 of rivastigmine compared with placebo on 120 patients.

Neuropsychiatric Inventory
The 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.

Authors' 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.