A meta-analysis of the efficacy of donepezil, rivastigmine, galantamine, and memantine in relation to severity of Alzheimer's disease.

BACKGROUND

Randomized clinical trials have evaluated the efficacy of acetylcholinesterase inhibitors (AChE-Is) and memantine across a wide range of Alzheimer's disease (AD) severity. However, these drugs are prescribed and reimbursed according to precise upper and lower cut off scores of cognitive tests.

OBJECTIVES

To verify whether the efficacy of pharmacological treatment had any dependence on the severity of dementia in AD patients.

METHODS

Published English-language randomized, placebo-controlled trials evaluating the efficacy of AChE-Is or memantine at any dose, over any length of time, in patients with any severity of dementia due to AD were included. Cognitive, behavioral, and functional outcomes were extracted from each study and multiple outcomes from the same trial were pooled to obtain a unique indicator of efficacy for cognition, functional impairment, and behavioral and psychological disturbances. The existence of a relationship between size of the treatment effect and severity of dementia, measured with the Mini-Mental State Examination, was determined using parametric and non-parametric correlation analyses.

RESULTS

Both AChE-Is and memantine had significant effects on cognition. Functional and psycho-behavioral outcomes were reported less frequently but also showed significant efficacy of treatment. High heterogeneity among studies was found within and between the different drugs. The efficacy of all drugs except memantine was independent from dementia severity in all domains. Memantine effect on functional impairment was better in more severe patients.

CONCLUSIONS

The modest beneficial effects of anti-dementia drugs on cognition are independent from dementia severity. Memantine is more effective on functional incompetence only in severe patients.