Unmasking the benefits of donepezil via psychometrically precise identification of mild cognitive impairment: A secondary analysis of the ADCS vitamin E and donepezil in MCI study - PubMed Skip to main page content
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. 2017 Dec 1:4:11-18.
doi: 10.1016/j.trci.2017.11.001. eCollection 2018.

Unmasking the benefits of donepezil via psychometrically precise identification of mild cognitive impairment: A secondary analysis of the ADCS vitamin E and donepezil in MCI study

Emily C Edmonds  1   2 , M Colin Ard  3 , Steven D Edland  3   4 , Douglas R Galasko  1   2   3 , David P Salmon  3 , Mark W Bondi  1   2
Affiliations

Unmasking the benefits of donepezil via psychometrically precise identification of mild cognitive impairment: A secondary analysis of the ADCS vitamin E and donepezil in MCI study

Emily C Edmonds et al. Alzheimers Dement (N Y). .

Abstract

Introduction: Criteria for mild cognitive impairment (MCI) used in many clinical trials are susceptible to "false-positive (FP)" errors that can be avoided by an actuarial psychometric approach.

Methods: Cluster analysis was applied to baseline neuropsychological test data from 756 MCI participants in the Alzheimer's Disease Cooperative Study donepezil trial. Treatment groups were compared after FP MCI cases were removed.

Results: Cluster analyses revealed three groups: "single-domain amnestic MCI" (31%), "multi-domain amnestic MCI" (39%), and "FP MCI" (30%). After removing FP MCI cases, the donepezil treatment group had a lower rate of progression to Alzheimer's disease and better performance on cognitive tests than the placebo/vitamin E group.

Discussion: Removal of FP MCI diagnoses unmasked beneficial effects of donepezil, despite a 30% reduction in sample size. MCI subject selection based on actuarial methods with comprehensive neuropsychological test data can result in more efficient clinical trials and improved ability to detect treatment effects.

Keywords: Alzheimer's disease; Cluster analysis; Dementia; Donepezil; False positive; MCI; Mild cognitive impairment; Misdiagnosis; Neuropsychology; Treatment.

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Figures

Fig. 1
Fig. 1
Neuropsychological performance for the cluster groups. Error bars denote standard error of the mean. Abbreviations: aMCI, amnestic mild cognitive impairment; ADAS-Cog, Alzheimer's Disease Assessment Scale-Cognitive Subscale; BNT, Boston Naming Test; SDMT, Symbol-Digit Modalities Test.
Fig. 2
Fig. 2
Performance of the donepezil and placebo/vitamin E groups in the original MCI sample on the (A) ADAS-Cog Immediate Word Recall and the (B) NYU Paragraph Immediate Recall. Performance of the donepezil and placebo/vitamin E groups in the new MCI sample on the (C) ADAS-Cog Immediate Word Recall and the (D) NYU Paragraph Immediate Recall. *P < .05; **P < .001. Abbreviations: ADAS-Cog, Alzheimer's Disease Assessment Scale-Cognitive Subscale; MCI, mild cognitive impairment; NYU, New York University.
Fig. 3
Fig. 3
Kaplan-Meier survival estimates showing the rate of progression from MCI to AD in the donepezil, vitamin E, and placebo arms in the new MCI sample that remained once the “false-positive” participants were removed. Abbreviations: AD, Alzheimer's disease; MCI, mild cognitive impairment.
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