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

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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Available from: Stephen Wayne Hurt, Sep 25, 2015
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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.
    BMC Neurology 04/2014; 14(1):63. DOI:10.1186/1471-2377-14-63 · 2.04 Impact Factor
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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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    ABSTRACT: Recent biomarker research has improved the identification of individuals with very early stages of Alzheimer's disease (AD) and has demonstrated that biomarkers are sensitive for measuring progression in the pre-dementia or mild cognitive impairment (MCI) stage and even pre-symptomatic or pre-MCI stage of AD. Because there are no validated biomarkers in AD, it is important to seek out clinical outcomes that are also sensitive for measuring progression in these very early stages of disease. Clinical outcomes are more subjective and more affected by measurement error than biomarkers but represent the core aspects of the disease and are critical for validation of biomarkers and for evaluation of clinical relevance. Identification of individuals with pre-MCI stages of AD will need to continue to rely on biomarkers, but the identification of individuals with MCI who will progress to AD can be achieved with biomarkers or clinical criteria. Although standard clinical outcomes have been shown to be less sensitive to progression than biomarker outcomes in MCI and pre-MCI populations, non-standard scoring has improved the performance of the Alzheimer's Disease Assessment Scale cognitive subscale, making it more sensitive to progression. Neuropsychological cognitive testing items are optimal for measuring progression in pre-MCI populations, and current research is exploring the best ways to combine these items into a composite cognitive score with maximum responsiveness. In an MCI stage, cognitive, functional, and global items all change, and the best single composite score for measuring progression may involve all of these aspects of the disease. The best chance of success in demonstrating treatment effects in clinical trials will be achieved in a well-defined pre-MCI or MCI population and with an outcome that tracks well with clinical progression over time and with time. A partial least squares model can be used to identify these optimal weighted combinations.
    Alzheimer's Research and Therapy 07/2012; 4(4):24. DOI:10.1186/alzrt127 · 3.98 Impact Factor
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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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    ABSTRACT: Better tools for assessing cognitive impairment in the early stages of Alzheimer's disease (AD) are required to enable diagnosis of the disease before substantial neurodegeneration has taken place and to allow detection of subtle changes in the early stages of progression of the disease. The National Institute on Aging and the Alzheimer's Association convened a meeting to discuss state of the art methods for cognitive assessment, including computerized batteries, as well as new approaches in the pipeline. Speakers described research using novel tests of object recognition, spatial navigation, attentional control, semantic memory, semantic interference, prospective memory, false memory and executive function as among the tools that could provide earlier identification of individuals with AD. In addition to early detection, there is a need for assessments that reflect real-world situations in order to better assess functional disability. It is especially important to develop assessment tools that are useful in ethnically, culturally and linguistically diverse populations as well as in individuals with neurodegenerative disease other than AD.
    Alzheimer's & dementia: the journal of the Alzheimer's Association 05/2011; 7(3):e60-e76. DOI:10.1016/j.jalz.2011.05.001 · 12.41 Impact Factor
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