The use of cognitive enhancers in behavioral disturbances of Alzheimer's disease.
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.


METHODS
Literature searches were conducted using MEDLINE and EMBASE databases and clinicaltrials.gov.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Miller
Lisa J
LJ
Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas 77030, USA. lisaj.miller@med.va.gov
D000544:Alzheimer Disease / Q000523:psychology*; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use*; D003072:Cognition Disorders / Q000188:drug therapy; D015259:Dopamine Agents / Q000627:therapeutic use*; D006801:Humans; D001523:Mental Disorders / Q000188:drug therapy*; D018697:Nootropic Agents / Q000627:therapeutic use*; D011595:Psychomotor Agitation / Q000188:drug therapy; D011618:Psychotic Disorders / Q000188:drug therapy
D014150:Antipsychotic Agents; D002800:Cholinesterase Inhibitors; D015259:Dopamine Agents; D018697:Nootropic Agents