Treating Patients With Moderate to Severe Alzheimer’s Disease: Implications of Recent Pharmacologic Studies

Background and Objective: As the prevalence of Alzheimer’s disease (AD) continues to rise, physicians will be challenged to manage increasing numbers of patients with moderate to severe AD. Despite the need for active treatment and management, the growing AD population has been overlooked in the primary care setting. Currently, the approved treatments for AD are the cholinesterase inhibitors donepezil, rivastigmine, and galantamine and the N-methyl-d-aspartate receptor antagonist memantine. The objective of this article is to review recent pharmacologic studies and discuss implications for treatment of moderate to severe AD.

Data Sources and Study Selection: A PubMed search was performed for publications from 1995 to 2004 using the search terms moderate or severe, efficacy, and Alzheimer. The search was limited to randomized, controlled trials published in English. The search was further restricted to prospective studies of pharmacologic agents that included patients with severe dementia (Mini-Mental State Examination score < 10). A total of 96 citations were retrieved. Of these, 5 met the inclusion criteria.

Data Extraction and Synthesis: Randomized, double-blind, placebo-controlled studies in patients with moderate to severe AD have been conducted for donepezil and memantine. Patients treated with donepezil monotherapy showed improved cognition, stabilized function, and improved behavioral symptoms. Patients treated with memantine monotherapy showed less than expected decline in cognition, function, and behavioral symptoms. Patients who received memantine treatment adjunctive to stable, long-term donepezil treatment derived cognitive, functional, and behavioral benefits from add-on therapy.

Conclusion: Overall, published studies of donepezil and memantine report treatment benefits.