Exploring the role of donepezil in dementia with Lewy bodies

Dementia with Lewy bodies (DLB) is considered the second most common form of dementia in the elderly. The cognitive fluctuations, hallucinations and extrapyramidal symptoms and signs suggest simultaneous neurodegeneration in multiple neuronal pathways including both dopaminergic and cholinergic transmission. In the past few years, several small studies have demonstrated the benefit of acetylcholinesterase inhibitors (AChEIs) on the cognitive and behavioral symptoms of DLB. These drugs, by reversibly blocking the hydrolytic activity of AChE, increase the availability of synaptic acetylcholine. Neuropathological and neuroimaging studies demonstrated that cholinergic neurotransmission is more defective in DLB than in Alzheimer's disease (AD). Despite the relevance of AChEIs to DLB, there are no FDA-approved drugs for its management. The aim of this review is to summarize the literature on the application of donepezil in DLB. Although the results are inconclusive, when one compares and contrasts them to the results of the AD-donepezil trials, the effect size appears larger. Placebo-controlled, randomized, well-powered studies of adequate length are needed to avoid underutilization of a potentially efficacious drug.