Treatment strategies for the behavioral symptoms of Alzheimer's disease: focus on early pharmacologic intervention

Abstract

The impact of behavioral symptoms associated with Alzheimer's disease is substantial. These symptoms contribute to diminished quality of life for patients and caregivers and increase the cost of care in nursing homes. Early recognition of behavioral symptoms and appropriate treatment are important for successful management. Nonpharmacologic strategies remain the cornerstone of the management of Alzheimer's disease-related behavioral symptoms. However, nonpharmacologic strategies may not be effective for problem behaviors, and pharmacologic intervention may be necessary. Relevant articles were identified through various MEDLINE searches with no date restrictions, with an emphasis on recent studies that used cholinesterase inhibitors and memantine. Additional reports of interest were identified from the reference lists of these articles. To facilitate cross-study analyses in the review of cholinesterase inhibitors and memantine, the database search was limited to randomized, placebo-controlled trials that used the Neuropsychiatric Inventory to assess behavioral symptoms of Alzheimer's disease. Overall, evidence from trials of cholinesterase inhibitors and memantine suggests that when these agents are optimized for the various stages of Alzheimer's disease, they can also prevent the emergence of neuropsychiatric symptoms. Although results from the literature are not uniformly positive, cholinesterase inhibitors have been shown to produce significant improvements in behavioral symptoms in patients with both mild- to-moderate and moderate-to-severe Alzheimer's disease. Evidence also indicates that memantine might be of benefit as an adjunct to long-term cholinesterase inhibitor treatment in patients with moderate-to-severe Alzheimer's disease and that memantine monotherapy may have some beneficial effects on behavior in patients with mild-to-moderate disease. Of importance, although no direct comparisons have been performed, these agents seem to have an improved safety and tolerability profile compared with the frequently used antipsychotic drugs. When nonpharmacologic strategies are deemed insufficient to ease problem behaviors in patients with Alzheimer's disease, treatment with cholinesterase inhibitors, alone or in combination with memantine as appropriate for the stage of disease, may be considered as a first-line option in the early pharmacologic management of Alzheimer's disease-related behavioral symptoms.