Rivastigmine is a slowly reversible AChE inhibitor and BuChE inhibitor approved for use in mild-to-moderate AD Rivastigmine is metabolized at the synapse rather than by hepatic cytochrome enzymes; hence, thereare no drug-drug interactions.The role ofBuChE inhibition in glial cells in AD remains unclear.

After treatment of AD with rivastigmine for 12 months,CSF andplasma AChE activity decreased by 46% and BuChE by 65%from baseline.There was a sig-nificant correlation between plasma ChE inhibition andcognition，particularly in relation to attention. Rivastigmine was used in small open-label studies ofpatients with subcortical VaD followed for 12 months and 22 months; rivastigmine resulted in the stabilization of cognition and ADLs, with slight improvement of executive function and planning,less caregiver stress and improved behaviour. 

More recently，Moretti et al. observed significantimprovement in behavioural symptoms in two forms ofVaD, MID and subcortical VaD, except delusions, suggest-ing that rivastigmine helps reduce concomitant neurolepticand benzodiazepine use. Rivastigmine effects in VaD were studied in the aDtrial studying Exelon (VantagE), a Phase III, double-blind,placebo-controlled RCT. This 24-week,multicentre study randomized 710 VaD patients aged 50-85years to rivastigmine capsules (3-12 mg/day) or placebo.

Efficacy assessments included globaland cognitive performances，ADLs and neuropsychiatricsymptoms. Rivastigmine was superior to placebo on threemeasures of cognitive performance (but no other out-comes). Cognitive improvement occurred in older patients,probably likely to have concomitant AD as evidenced bymedial temporal atrophy. The problems associated with gastrointestinal side effectsrequiring slow oral titration of rivastigmine were solvedto a large extent with the use of a dermal patch. The patch is associated with threetimes fewer reports of nausea and vomiting.The rivastigmine patch has not been evalu-ated in VaD.