Pharmacotherapy of mild cognitive impairment

Amnestic mild cognitive impairment (MCI) can be considered as a state with a high risk of developing Alzheimer's disease within 5 years, or as a prodromal stage of this condition. Randomized clinical trials comparing the acetylcholinesterase inhibitor donepezil with placebo have shown some symptomatic benefit on (i) cognition in one short-term (6-month) study; and (ii)conversion to dementia in one long-term (3-year) study, but not for the full duration of the study, except in subjects with the apolipoprotein E4 (APOE-4) mutation, in whoom the benefit was sustained throughout the 3 years. Results from studies on galantamine are still being analyzed; and a rivastigmine study will close in the fall of 2004. It is premature to recommend that acetylcholinesterase inhibitors be used systematically in amnestic MCI. However, important lessons have been learned from studies in this prodromal stage of AD, allowing the testing of hypotheses for disease modification.