Key lessons learned from short-term treatment trials of cholinesterase inhibitors for amnestic MCI.
OBJECTIVE
This paper reviews the key lessons learned from the first published short-term, placebo-controlled trial of a cholinesterase inhibitor for treatment of mild cognitive impairment (MCI).


METHODS
The study was a 24-week placebo-controlled trial designed to evaluate the efficacy and safety of donepezil HCl (donepezil) in the treatment of cognitive impairment in subjects with MCI. Primary outcome measures were the NYU Paragraphs Test and the ADCS Clinicians Global-Impression of Change in the intent-to-treat last-observation-carried-forward group.


RESULTS
There was no benefit of donepezil treatment on primary outcome measures (NYU Paragraphs and ADCS CGI-C) in the ITT-LOCF group but positive findings were seen on NYU Paragraphs in the fully evaluable group and in certain secondary outcome measures across both groups.


CONCLUSIONS
The results highlight the need for the use of primary cognitive and functional measures that are reliable and sensitive to change in patients with MCI. Measures of episodic memory, psychomotor speed and complex attention were most sensitive in this study. Functional rating scales are needed that measure change in individual subjects' key areas of functional deficit, which typically involve executive aspects of instrumental ADLs. Tolerability can be increased by use of flexible dosing and efficacy is likely to be enhanced by increasing the length of the trial from six to 12 months and by enriching the sample with subjects more likely to decline during the trial.
Salloway
Stephen
S
Department of Clinical Neurosciences Brown Medical School, Rhode Island, USA. SSalloway@butler.org
Correia
Stephen
S
Richardson
Sharon
S
D000368:Aged; D000544:Alzheimer Disease / Q000175:diagnosis / Q000188:drug therapy / Q000523:psychology; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use*; D003072:Cognition Disorders / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D015331:Cohort Studies; D000077265:Donepezil; D049673:History, 20th Century; D006801:Humans; D007189:Indans / Q000627:therapeutic use*; D008569:Memory Disorders / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D009483:Neuropsychological Tests / Q000706:statistics & numerical data; D017063:Outcome Assessment, Health Care / Q000706:statistics & numerical data; D010880:Piperidines / Q000627:therapeutic use*; D010919:Placebos; D011569:Psychiatric Status Rating Scales / Q000706:statistics & numerical data; D011597:Psychomotor Performance; D016032:Randomized Controlled Trials as Topic / Q000266:history / Q000706:statistics & numerical data; D012107:Research Design / Q000592:standards; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014481:United States
D002800:Cholinesterase Inhibitors; D007189:Indans; D010880:Piperidines; D010919:Placebos; D000077265:Donepezil