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The Use of Cognitive Enhancers in Behavioral Disturbances of Alzheimer's Disease

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Objective: To review the literature for double-blind, placebo-controlled trials that examined the efficacy of cognitive enhancers in the psychopathology of Alzheimer's disease.

Data Sources: Literature searches were conducted using MEDLINE and EMBASE databases and

Study Selection: Overall, 55 articles were reviewed for inclusion. Several open-label studies and case reports were found on this topic, but only those involving both tacrine and use of the Neuropsychiatric Inventory were included. Regarding other drugs, only double-blind, placebo-controlled trials were selected for inclusion.

Data Synthesis: Limited data suggest that the anticholinesterase inhibitors and memantine offer an alternative or adjunct to the antipsychotics for the treatment of moderate-to-severe behaviors. The author reviewed the literature for pharmacological management of behavioral and psychological symptoms of dementia (BPSD) using these cognitive enhancers.

Conclusion: The majority of patients with Alzheimer's disease will experience behavioral disturbances during the course of their disease. Atypical antipsychotics are used routinely in these situations to treat the psychotic features and agitation. However, atypicals now carry a “black box” warning issued by the Food and Drug Administration on the basis of evidence that their use in geriatric patients with dementia-related psychosis may put patients at increased risk of mortality as a result of cardiovascular or infectious events. An alternative to the atypicals may be the acetylcholinesterase inhibitors and memantine, which have been shown to stabilize cognitive as well as behavioral issues in patients, utilizing the “gold standard” for behavior, the Neuropsychiatric Inventory. Efficacy varies among agents, with the greatest positive effects seen with donepezil, which also has the greatest number of studies. Drug benefits were harder to demonstrate for mild-to-moderate BPSD compared with moderate-to-severe symptoms.

Abbreviations: ACh EI = Acetylcholinesterase inhibitor, AD = Alzheimer's disease, BPSD = Behavioral and psychological symptoms of dementia, BuChE = Butyrylcholinesterase, CMAI = Cohen Mansfield Agitation Inventory, LBD = Lewy body dementia, NFT = Neurofibrillary tangles, NMDA = N-methyl-D-aspartate, NPI = Neuropsychiatric Inventory, PANSS = Positive and Negative Symptoms Scale, PD = Parkinson's disease, VD = Vascular dementia.

Consult Pham 2007;22:754-62
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Keywords: Acetylcholinesterase inhibitor; Alzheimer's disease; Behavior; Memantine; Neuropsychiatric; Neuropsychiatric Inventory

Document Type: Research Article

Publication date: September 1, 2007

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  • The Consultant Pharmacist® is the official peer-reviewed journal of the American Society of Consultant Pharmacists. It is dedicated exclusively to the medication needs of the elderly in all settings, including adult day care, ambulatory care, assisted living, community, hospice, and nursing facilities. This award-winning journal is a member benefit of ASCP. Individuals who are not members and wish to receive The Consultant Pharmacist® will want to consider joining ASCP.
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