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

  • Stephen Salloway (a1) (a2) (a3), Stephen Correia (a2) (a3) and Sharon Richardson (a4)


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.


Corresponding author

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:


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Folstein, M., Folstein, E. and McHugh, P. 1975. “Mini-mental state”: a practical method for grading the cognitive state of patients for the clinician. Journal of Psychiatric Research, 12, 189198.
Grundman, M. et al. 2004. Mild Cognitive Impairment can be distinguished from Alzheimer's disease and normal aging for clinical trials. Archives of Neurology, 61, 5966.
Kluger, A., Ferris, S. H., Golomb, J., Mittelman, M. S. and Reisberg, B. 1999. Neuropsychological prediction of decline to dementia in nondemented elderly. Journal of Geriatric Psychiatry and Neurology, 12, 168179.
Mohs, R. C. and Cohen, L. 1988. Alzheimer's. Disease Assessment Scale (ADAS). Psychopharmacology Bulletin, 24, 627628.
Mohs, R. C. et al. 1997. Development of cognitive instruments for use in clinical trials of antidementia drugs: additions to the Alzheimer's Disease Assessment Scale that broaden its scope. Alzheimer Disease and Associated Disorders, 11 (Suppl 2), S13S21.
Morris, J. C. 1993. The Clinical Dementia Rating (CDR): current version and scoring rules. Neurology, 43, 24122414.
Petersen, R., Grundman, M., Thomas, R. and Thal, L. 2004. Donepezil and vitamin E as treatments for mild cognitive impairment. Neurobiology of Aging, 25, S20.
Petersen, R. C., Smith, G. E., Waring, S. C., Ivnik, R. J., Tangalos, E. G. and Kokmen, E. 1999. Mild cognitive impairment: clinical characterization and outcome. Archives of Neurology, 56, 303308.
Salloway, S. et al. 2004. Efficacy of donepezil in mild cognitive impairment: a randomized. placebo-controlled trial. Neurology, 63, 651657.
Schneider, L. S. et al. 1997. Validity and reliability of the Alzheimer Disease Cooperative Study-Clinical Global Impression of Change. Alzheimer Disease and Associated Disorders, 11 (Suppl. 2), S22S32.
Smith, A. 1982. Symbol Digit Modalities Test. Los Angeles: Western Psychological Service.
Wechsler, D. 1987. Wechsler Memory Scale – Revised. San Antonio: Psychological Corporation.



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