Müller probably because the dementia and AD in particular is heterogeneous, caused by aging in concert with a complex interaction of both genetic and environmental risk factors (Blennow et al 2006). The common mode of action of cholinesterase inhibitors (ChEI) Pathological changes in AD involve cholinergic neuronal pathways that project from the basal forebrain to the cerebral cortex and hippocampus. These pathways are thought to be intricately involved in memory, attention, learning, and other cognitive processes. These are accomplished by decreased concentrations of acetylcholine, which are modulated by the enzyme cholinesterase. This enzyme is of neuronal origin and functions to metabolize acetylcholine at synapses throughout the nervous system. Cholinesterase breaks down acetylcholine, a neurotransmitter which assists in human memory and cognition processes. By inhibiting cholinesterase, more acetylcholine is available to the patient for memory and cognitive functioning. This is effective in treatment of AD, since acetylcholine is at signiﬁcantly lower levels in AD patients than in normally functioning people. These drugs block the enzyme that inactivates the transmitter in the synaptic cleft. It should be noted that ChEI are a symptomatic, not causal, treatment of AD. ChEI increase the concentration of acetylcholine in the brain. As AD progresses and cortical neurons are lost, levels of acetylcholinesterase progressively decline, while levels of butyrylcholinesterase increase. Butyrylcholinesterase can and does take over the function of metabolizing acetylcholine at the synapse, when acetylcholinesterase is lost, a phenomenon that has been demonstrated in an acetylcholinesterase knockout mouse model and which probably occurs in AD (Polinsky 1998). Rivastigmine, but not its competitors, inhibits both acetylcholinesterase and butyrylcholinesterase by covalently binding to active sites on these enzymes, blocking their function. Breaking of these covalent bonds is the ﬁrst and most important step in the degradation of rivastigmine, which is not metabolized in the liver (Greig et al 2002; Darvesh et al 2003; Eskander et al 2005). Symptomatic drug treatment approaches Since the introduction of the first ChEI in 1997, most clinicians and probably most patients would consider the cholinergic drugs donepezil, galantamine, and rivastigmine to be the ﬁrst-line pharmacotherapy for mild to moderate AD. These drugs have slightly different pharmacological properties, but they all work by inhibiting the breakdown of acetylcholine, an important neurotransmitter associated with memory, by blocking the enzyme acetylcholinesterase. The most that these drugs could achieve is to modify the clinical manifestations, in particular the cognitive impairment, of AD. Moreover there is accumulating evidence that they also improve additional affected domains of global functioning, such as activities of daily living or behavior (Cummings 2000; Bonner and Peskind 2002; Clegg et al 2002). Objective Objective is to review the efﬁcacy of rivastigmine in the treatment of AD and to provide an outlook of its effect in the treatment of dementia in Parkinson’s disease (PD). Essential clinical AD trials with rivastigmine The safety and efﬁcacy of rivastigmine were investigated in several placebo-controlled investigations (see Table 1). Participants, all AD patients, were evaluated in terms of their cognitive performance using the Alzheimer’s Disease Assessment Scale (ADAS-cog) and the Clinician’s Interview Based Impression of Change (CIBIC-Plus). The ADAS-cog considers elements of memory, orientation, attention, reasoning, language, and praxis. Improvement in global functioning was measured by the CIBIC-Plus. This instrument of evaluation considers overall patient cognition, behaviour, and functioning. The patient population for these studies tried to reﬂect a real world population, since most of the patients used concomitant medications to treat other conditions during the studies. In a 26-week, US study, patients were divided into three groups, each receiving 1–4 mg/day of rivastigmine, 6–12 mg/day of rivastigmine, or placebo. At the end of the treatment period, both ADAS-cog scores and CIBIC-Plus ratings for those treated in either dose-group of rivastigmine were signiﬁcantly superior to the scores of those who took placebo. Furthermore, the higher-dosage group had better ADAS-cog scores and CIBIC-Plus ratings than the lower-dosage group. Better scores in these assessments indicate greater improvement and less worsening in cognitive function (such as memory, recognition, ability to speak, and other symptoms of dementia) than the average placebo- treated patient. In another 26-week, global study, patients were divided into similar groups. Results of this study also indicated that the 6–12 mg/day group showed signiﬁcantly 212 Neuropsychiatric Disease and Treatment 2007:3(2)