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Key lessons learned from short-term treatment trials of cholinesterase inhibitors for amnestic MCI

Published online by Cambridge University Press:  01 February 2008

Stephen Salloway ,
Stephen Correia  and
Sharon Richardson
Stephen Salloway*
Affiliation:
Department of Clinical Neurosciences, Brown Medical School, Rhode Island, U.S.A. Department of Psychiatry and Human Behavior, Brown Medical School, Rhode Island, U.S.A. Memory and Aging Program, Butler Hospital, Providence, Rhode Island, U.S.A.
Stephen Correia
Affiliation:
Department of Psychiatry and Human Behavior, Brown Medical School, Rhode Island, U.S.A. Memory and Aging Program, Butler Hospital, Providence, Rhode Island, U.S.A.
Sharon Richardson
Affiliation:
Eisai Inc, Teaneck, New Jersey, U.S.A.
*
Correspondence should be addressed to: Stephen Salloway, Department of Neurology, Butler Hospital, 345 Blackstone Blvd., Providence, RI 02906, U.S.A. Phone: +1 401–455-6403. Email: [email protected].
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Abstract

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.

Keywords

mild cognitive impairmentclinical trialstreatmentdonepezilcholinesterase inhibitors
Type
MCI CONFERENCE PAPER
Information
International Psychogeriatrics , Volume 20 , Issue 1 , February 2008 , pp. 40 - 46
Copyright
Copyright © International Psychogeriatric Association 2007

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