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 acetylcholin
esterase (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 rivastig mine 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.