Abstract
Background. A short yet reliable cognitive measure is needed that separates treatment and placebo for treatment trials for Alzheimer’s disease. Hence, we aimed to shorten the Alzheimer’s Disease Assessment Scale Cognitive Subscale (ADAS-Cog) and test its use as an efficacy measure. Methods. Secondary data analysis of participant-level data from five pivotal clinical trials of donepezil compared with placebo for Alzheimer’s disease (N = 2,198). Across all five trials, cognition was appraised using the original 11-item ADAS-Cog. Statistical analysis consisted of sample characterization, item response theory (IRT) to identify an ADAS-Cog short version, and mixed models for repeated-measures analysis to examine the effect sizes of ADAS-Cog change on the original and short versions in the placebo versus donepezil groups. Results. Based on IRT, a short ADAS-Cog was developed with seven items and two response options. The original and short ADAS-Cog correlated at baseline and at weeks 12 and 24 at 0.7. Effect sizes based on mixed modeling showed that the short and original ADAS-Cog separated placebo and donepezil comparably (ADAS-Cog original ES = 0.33, 95% CI = 0.29, 0.40, ADAS-Cog short ES = 0.25, 95% CI =0.23, 0.34). Conclusions. IRT identified a short ADAS-cog version that separated donepezil and placebo, suggesting its clinical potential for assessment and treatment monitoring.
| Original language | English |
|---|---|
| Article number | e19 |
| Journal | European Psychiatry |
| Volume | 67 |
| Issue number | 1 |
| DOIs | |
| State | Published - 23 Feb 2024 |
| Externally published | Yes |
Bibliographical note
Publisher Copyright:© The Author(s), 2024. Published by Cambridge University Press on behalf of European Psychiatric Association.
Funding
Authors Levine and Goldberg contributed equally to this study and are joint first authors. The authors acknowledge Eisai Co. Ltd for providing us with the study data. Eisai Co. Ltd did not provide study design, critical input, or manuscript review for the study. The authors also acknowledge http://www.clinicalstudydatarequest.com for hosting the study data. Data are available based on a request to http://www.clinicalstudydatarequest.com. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Cipriani is supported by the National Institute for Health Research (NIHR) Oxford Cognitive Health Clinical Research Facility, by an NIHR Research Professorship (grant RP-2017-08-ST2-006), by the NIHR Oxford and Thames Valley Applied Research Collaboration and by the NIHR Oxford Health Biomedical Research Centre (grant BRC-1215-20005). The views expressed are those of the authors and not necessarily those of the UK National Health Service, the NIHR, or the UK Department of Health.
| Funders | Funder number |
|---|---|
| Eisai Canada | |
| National Institute for Health and Care Research Applied Research Collaboration Oxford and Thames Valley | |
| National Health Service | |
| National Institute for Health and Care Research | RP-2017-08-ST2-006 |
| NIHR Oxford Biomedical Research Centre | BRC-1215-20005 |
Keywords
- Alzheimer’s disease
- assessment
- clinical trials
- cognition
- item response theory
- psychometric
