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: 6.81). 09/2010; 81(12):1363-8. DOI: 10.1136/jnnp.2009.204008
Source: PubMed


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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    • "It should be noted that in RCTs on Alzheimer’s Disease drugs the Evaluation Scale of Behavior-Cognitive Section (ADAS-cog) has been used almost unanimously as a measure of cognitive performance [18,46]. It is a test that provides clinically significant information, which is well considered on a conceptual and neuropsychological basis [47]. The use of the ADAS-cog as a fundamental measure of the cognitive state should be permitted to draw comparisons with the results from other NPT or even with the RCTs, taking all this into account as it has been proposed in recent trials [15,18] and that is why this measure is proposed for our intervention. "
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    ABSTRACT: The aging of the population has led to the increase of chronic diseases, especially dementia and cardiovascular diseases, and it has become necessary for their relatives to dedicate more time in caregiving.The objective in the first phase of this study is to evaluate the effectiveness of a Primary Health Care procedure to increase the physical activity of people with dementia and their relative caregivers. Also the effect on the cognitive state and cardiovascular risk will be assessed. Design: Clinical, multicentric and randomized trial. A simple random sampling to select 134 patients diagnosed with dementia will be carried out. After contacting their relatives, his/her participation in the trial will be requested. A basal assessment will be made and the participants will be asigned to control or intervention group (1:1). Variables: The main measure will be the assessment of physical activity (podometer and 7-PAR) in patients and caregivers. In patients with dementia: ADAS-cog, functional degree and cardiovascular risk. In caregivers: cardiovascular risk, general health and quality of life. Intervention: For 3 months, participants will receive instructions to do physical activity with an adapted program. This program will be designed and applied by Primary Health Care professionals in patients with dementia and their caregivers. The control group will receive regular care. Analysis: An intention-to-treat analysis will be carried out by comparing the observed differences between basal, 6 and 12 months measures. Change in the mean of daily steps assessed with the podometer and 7-PAR will be the main result. If the main hypothesis is confirmed, it could be useful to improve the cognitive state of patients with dementia, as well as the cardiovascular risk of all of them. The results can be good to improve technical features of the devices that register the physical activity in the patients with dementia, and it could facilitate its commercialization.Trial registration: Clinical Identifier: NCT02044887.
    Full-text · Article · Apr 2014 · BMC Neurology
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    • "The ADAS-cog is well established as an outcome measure in mild-to-moderate AD but clearly has several items that are not expected to change in early disease [20]. Including these items in the ADAS-cog can hurt its performance in terms of external responsiveness over time. "
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    Full-text · Article · Jul 2012 · Alzheimer's Research and Therapy
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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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