Effect of rivastigmine in the treatment of behavioral disturbances associated with dementia: review of neuropsychiatric impairment in Alzheimer's disease

Cognitive decline is conventionally regarded as the defining clinical symptom of Alzheimer's disease (AD), but behavioral and neuropsychiatric symptoms are also present throughout the course of the disease. In fact, behavioral symptoms may appear before cognitive decline is diagnosed. The presence of these symptoms may predict an increasing need for community-based services or even nursing home placement. The characteristic behavioral and neuropsychiatric symptoms associated with AD may be related to the same pathophysiology that underlies the cognitive abnormalities. AD is characterized by a loss of cholinergic neurons as well as by the presence of neurofibrillary tangles (NFTs) and senile plaques in brain regions with cholinergic deficits, resulting in a deficiency in acetylcholine (ACh) in areas of the brain that modulate cognition, behavior, and emotion. Cholinesterase inhibitors are thought to augment or maximize the concentration of ACh in the synaptic cleft. Rivastigmine is a dual inhibitor of both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), enzymes involved in hydrolysis of ACh. Literature searches using MEDLINE and EMBASE databases were performed to identify studies of rivastigmine (through August 2005) that assessed neuropsychiatric aspects of AD. Rivastigmine has been demonstrated to be safe and effective in stabilizing or improving the cognitive symptoms of AD in 3 large, well-controlled, randomized clinical trials, which also demonstrated that rivastigmine improves overall global functioning. Smaller studies and meta-analyses of pooled data from the 3 large trials have suggested that rivastigmine may improve the behavioral and neuropsychiatric symptoms associated with AD.