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Abstract
Objective To establish the minimal clinically relevant change (MCRC) on the Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog) for patients with mild Alzheimer's disease (AD).
Design Cohort study.
Setting 59 recruiting sites for the Alzheimer's Disease Neuroimaging Initiative.
Patients Outpatients with AD in the Alzheimer's Disease Neuroimaging Initiative.
Main outcome measures The authors applied anchor-based MCRC methodology comparing ADAS-Cog change against clinicians' judgement of clinically relevant worsening between baseline and 6 months in four domains: memory and non-memory cognitive performance; Clinical Dementia Rating Scale; and Functional Assessment Questionnaire. The analysis was repeated for the 6–12-month interval. To support these findings, the authors calculated distribution-based measures including half-baseline SD (1/2 SD) and SEM.
Results 181 patients (baseline ADAS-Cog score 18.5±6.4) had ADAS-Cog data at 0 and 6 months. Those undergoing clinically significant worsening on any of the four anchor questions (n=41–47) had an average ADAS-Cog change of 3.1–3.8 points. Similar results were found for the 177 patients with 6–12-month data. The average 1/2 SD for the baseline ADAS-Cog score was 3.2, and the SEM was 3.7.
Conclusions 3 points decline on the ADAS-Cog may be an appropriate MCRC for clinical trials of patients with early AD. However, further studies assessing the MCRC for improvement on the ADAS-Cog, using patient-based judgement as an anchor, and determining the minimal clinically relevant difference between change on two treatments are required.
Clinical trial registration number http://clinicalTrials.gov Identifier: NCT00106899.
- Alzheimer's disease
- outcome measure
- scale
- minimal clinically relevant change
- ADAS-Cog
- parkinson s disease
- MRI
- dementia
- clinical neurology
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Footnotes
Funding This work was undertaken at UCLH/UCL, which received a proportion of funding from the Department of Health's NIHR Biomedical Research Centres funding scheme. JMS receives research funding from Alzheimer's Research UK. Data collection and sharing for this project were funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904). ADNI is funded by the National Institute on Ageing, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: Abbott, AstraZeneca AB, Bayer Schering Pharma AG, Bristol-Myers Squibb, Eisai Global Clinical Development, Elan Corporation, Genentech, GE Healthcare, GlaxoSmithKline, Innogenetics, Johnson & Johnson, Eli Lilly and Co, Medpace, Merck and Co, Novartis AG, Pfizer, F. Hoffman-La Roche, Schering-Plough, Synarc, as well as non-profit partners the Alzheimer's Association and Alzheimer's Drug Discovery Foundation, with participation from the US Food and Drug Administration. Private-sector contributions to ADNI are facilitated by the Foundation for the National Institutes of Health (http://www.fnih.org). The grantee organisation is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of California, Los Angeles. This research was also supported by NIH grants P30 AG010129, K01 AG030514, and the Dana Foundation.
Competing interests None.
Ethics approval Provided by Local Review Boards of the ADNI participating centres.
Provenance and peer review Not commissioned; externally peer reviewed.