The ADAS-cog in Alzheimer's Disease clinical trials: Psychometric evaluation of the sum and its parts

Clinical Neurology Research Group, Peninsula College of Medicine and Dentistry, Plymouth, UK.
Journal of neurology, neurosurgery, and psychiatry (Impact Factor: 5.58). 09/2010; 81(12):1363-8. DOI: 10.1136/jnnp.2009.204008
Source: PubMed

ABSTRACT The Alzheimer's Disease Assessment Scale Cognitive Behavior Section (ADAS-cog), a measure of cognitive performance, has been used widely in Alzheimer's disease trials. Its key role in clinical trials should be supported by evidence that it is both clinically meaningful and scientifically sound. Its conceptual and neuropsychological underpinnings are well-considered, but its performance as an instrument of measurement has received less attention. Objective To examine the traditional psychometric properties of the ADAS-cog in a large sample of people with Alzheimer's disease.
Data from three clinical trials of donepezil (Aricept) in mild-to-moderate Alzheimer's disease (n=1421; MMSE 10-26) were analysed at both the scale and component level. Five psychometric properties were examined using traditional psychometric methods. These methods of examination underpin upcoming Food and Drug Administration recommendations for patient rating scale evaluation.
At the scale-level, criteria tested for data completeness, scaling assumptions (eg, component total correlations: 0.39-0.67), targeting (no floor or ceiling effects), reliability (eg, Cronbach's α: = 0.84; test-retest intraclass correlations: 0.93) and validity (correlation with MMSE: -0.63) were satisfied. At the component level, 7 of 11 ADAS-cog components had substantial ceiling effects (range 40-64%).
Performance was satisfactory at the scale level, but most ADAS-cog components were too easy for many patients in this sample and did not reflect the expected depth and range of cognitive performance. The clinical implication of this finding is that the ADAS-cog's estimate of cognitive ability, and its potential ability to detect differences in cognitive performance under treatment, could be improved. However, because of the limitations of traditional psychometric methods, further evaluations would be desirable using additional rating scale analysis techniques to pinpoint specific improvements.

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    • "However, in recent trials in participants with MCI and mild AD, no cognitive decline has been seen in the placebo arm, indicating that changes in early stages are subtler and harder to detect with the ADAS-cog. Thus, although it has been used successfully and has proven neuropsychological underpinnings, the ADAS-cog exhibits a ceiling effect in MCI and mild AD [15], which contributes to an inability to assess cognitive decline in mildly affected individuals. For clinical trials of drugs intended to halt the early stages of dementia, the ADAS-cog would be improved by incorporating more difficult cognitive measures in a neuropsychologically sound manner using modern psychometric techniques, for example, Rasch analysis. "
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    • "Thus, it seems that careful experimental design is needed and it should consider patient selection aspects, stimulation parameters, and clinical, cognitive and behavioral assessment tools. For example, it would be valuable for all future studies examining therapeutic efficacy of TMS or tDCS in AD to employ (in addition to any other desired outcome measures) the neuropsychological battery of the UDS or outcome scales commonly used in trials of pharmacological agents for AD, such as the Cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-Cog) (Rosen et al., 1984), despite its several limitations (Cano et al., 2010). This will enable comparison across studies. "
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