BACKGROUND: Alzheimer's disease is the commonest cause of dementia affecting 
older people. One of the therapeutic strategies aimed at ameliorating the 
clinical manifestations of Alzheimer's disease is to enhance cholinergic 
neurotransmission in the brain by the use of cholinesterase inhibitors to delay 
the breakdown of acetylcholine released into synaptic clefts. Tacrine, the first 
of the cholinesterase inhibitors to undergo extensive trials for this purpose, 
was associated with significant adverse effects including hepatotoxicity. Other 
cholinesterase inhibitors, including rivastigmine, with superior properties in 
terms of specificity of action and lower risk of adverse effects have since been 
introduced. Rivastigmine has received approval for use in 60 countries including 
all member states of the European Union and the USA.
OBJECTIVES: To determine the clinical efficacy and safety of rivastigmine for 
patients with dementia of Alzheimer's type.
SEARCH METHODS: We searched ALOIS, the Cochrane Dementia and Cognitive 
Improvement Group Specialized Register, on 2 March 2015 using the terms: 
Rivastigmine OR  exelon OR ENA OR "SDZ ENA 713". ALOIS contains records of 
clinical trials identified from monthly searches of a number of major healthcare 
databases (Cochrane Library, MEDLINE, EMBASE, PsycINFO, CINAHL, LILACS), 
numerous trial registries and grey literature sources.
SELECTION CRITERIA: We included all unconfounded, double-blind, randomised, 
controlled trials in which treatment with rivastigmine was administered to 
patients with dementia of the Alzheimer's type for 12 weeks or more and its 
effects compared with those of placebo in a parallel group of patients, or where 
two formulations of rivastigmine were compared.
DATA COLLECTION AND ANALYSIS: One review author (JSB) applied the study 
selection criteria, assessed the quality of studies and extracted data.
MAIN RESULTS: A total of 13 trials met the inclusion criteria of the review. The 
trials had a duration of between 12 and 52 weeks. The older trials tested a 
capsule form with a dose of up to 12 mg/day. Trials reported since 2007 have 
tested continuous dose transdermal patch formulations delivering 4.6, 9.5 and 
17.7 mg/day.Our main analysis compared the safety and efficacy of rivastigmine 6 
to 12 mg/day orally or 9.5 mg/day transdermally with placebo.Seven trials 
contributed data from 3450 patients to this analysis. Data from another two 
studies were not included because of a lack of information and methodological 
concerns. All the included trials were multicentre trials and recruited patients 
with mild to moderate Alzheimer's disease with a mean age of about 75 years. All 
had low risk of bias for randomisation and allocation but the risk of bias due 
to attrition was unclear in four studies, low in one study and high in two 
studies.After 26 weeks of treatment rivastigmine compared to placebo was 
associated with better outcomes for cognitive function measured with the 
Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog) score (mean difference 
(MD) -1.79; 95% confidence interval (CI) -2.21 to -1.37, n = 3232, 6 studies) 
and the Mini-Mental State Examination (MMSE) score (MD 0.74; 95% CI 0.52 to 
0.97, n = 3205, 6 studies), activities of daily living (SMD 0.20; 95% CI 0.13 to 
0.27, n = 3230, 6 studies) and clinician rated global impression of changes, 
with a smaller proportion of patients treated with rivastigmine experiencing no 
change or a deterioration (OR 0.68; 95% CI 0.58 to 0.80, n = 3338, 7 
studies).Three studies reported behavioural change, and there were no 
differences compared to placebo (standardised mean difference (SMD) -0.04; 95% 
CI -0.14 to 0.06, n = 1529, 3 studies). Only one study measured the impact on 
caregivers using the Neuropsychiatric Inventory-Caregiver Distress (NPI-D) scale 
and this found no difference between the groups (MD 0.10; 95% CI -0.91 to 1.11, 
n = 529, 1 study). Overall, participants who received rivastigmine were about 
twice as likely to withdraw from the trials (odds ratio (OR) 2.01, 95% CI 1.71 
to 2.37, n = 3569, 7 studies) or to experience an adverse event during the 
trials (OR 2.16, 95% CI 1.82 to 2.57, n = 3587, 7 studies).
AUTHORS' CONCLUSIONS: Rivastigmine (6 to 12 mg daily orally or 9.5 mg daily 
transdermally) appears to be beneficial for people with mild to moderate 
Alzheimer's disease. In comparisons with placebo, better outcomes were observed 
for rate of decline of cognitive function and activities of daily living, 
although the effects were small and of uncertain clinical importance. There was 
also a benefit from rivastigmine on the outcome of clinician's global 
assessment. There were no differences between the rivastigmine group and placebo 
group in behavioural change or impact on carers. At these doses the transdermal 
patch may have fewer side effects than the capsules but has comparable efficacy. 
The quality of evidence is only moderate for all of the outcomes reviewed 
because of a risk of bias due to dropouts. All the studies with usable data were 
industry funded or sponsored. This review has not examined economic data.