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Background: The Alzheimers Disease Assessment Scale – cognitive subscale (ADAS-cog) is the most widely used cognitive outcome measure in AD trials. Although errors in administration and scoring have been suggested as factors masking accurate estimates and potential effects of treatments, there have been few formal examinations of errors with the ADAS-cog. Methods: We provided ADAS-cog administration training using standard methods to raters who were designated as experienced, potential raters by sponsors or contract research organizations for two clinical trials. Training included 1 hour sessions on test administration, scoring, question periods, and required that raters individually view and score a model ADAS-cog administration. Raters scores were compared to the criterion scores established for the model administration. Results: A total of 108 errors were made by 80.6% of the 72 raters; 37.5% made 1 error, 25.0% made 2 errors and 18.0% made 3 or more. Errors were made in all ADAS-cog subsections. The most common were in word finding difficulty (67% of the raters), word recognition (22%), and orientation (22%). For the raters who made 1, 2, or 3 errors the ADAS-cog score was 17.5 (95% CI, 17.3 – 17.8), 17.8 (17.0 – 18.5), and 18.8 (17.6 – 20.0), respectively, and compared to the criterion score, 18.3. ADAS-cog means differed significantly and the variances were more than twice as large between those who made errors on word finding and those who did not, 17.6 (SD=1.4) vs. 18.8 (SD=0.9), respectively (χ2 = 37.2, P < 001). Conclusions: Most experienced raters made at least one error that may affect ADAS-cog scores and clinical trials outcomes. These errors may undermine detection of medication effects by contributing both to a biased point estimate and increased variance of the outcome.

Objective When complex cognitive functions are measured with multi-item scales like the Alzheimer's Disease Assessment Scale – cognitive subscale (ADAS-cog), it seems valuable information can be lost due to combination of the ADAS-cog items results into a total score. We hypothesized, that an analysis of the results of different ADAS-cog item combinations may reveal drug treatment effects in distinct cognitive domains and/or enhance the sensitivity to detect such treatment effects. Here, we present a novel approach called ‘subsetting analysis’ for assessment of drug treatment effects with multi-item scales, like the ADAS-cog. Methods The subsetting approach is a mathematical algorithm designed to select and group scale items in a subset detecting drug treatment effects in a particular study population. The approach was applied in a post-hoc analysis of ADAS-cog results from two randomized, placebo-controlled and double-blind clinical trials with memantine in mild to moderate Alzheimer's disease (AD). The subsetting analysis of the ADAS-cog combined database aimed at selecting the scale items showing no worsening at study end compared to baseline due to memantine treatment in mild AD (Mini-Mental State Examination (MMSE >19)) patients. Results Two ADAS-cog subsets were finally revealed by the analysis: a subset of five ADAS-cog items, identified as most sensitive to memantine effects in mild AD patients, and a subset of six ADAS-cog items shown to detect significant memantine effects in moderate AD patients. Conclusion The subsetting approach of analyzing ADAS-cog data is a powerful alternative for gaining information about drug effects on cognitive performance in mild and moderate AD patients. Copyright © 2011 John Wiley & Sons, Ltd.

The Alzheimer’s Disease Assessment Scale – Cognitive (ADAS-Cog) is the most commonly used primary outcome instrument in clinical trials for treatments of dementia. Variations in forms, administration procedures and scoring rules, along with rater turnover and intra-rater drift may decrease the reliability of the instrument. A survey of possible variations in the ADAS-Cog was administered to 26 volunteer raters at a clinical trials meeting. Results indicate notable protocol variations in the forms used, administration procedures, and scoring rules. Since change over time is used to determine treatment effect in clinical trials, standardizing the instrument’s ambiguities and addressing common problems will greatly increase the instrument’s reliability and thereby enhance its sensitivity to treatment effects.

The Alzheimer's Disease Assessment Scale (ADAS) is designed for screening of cognitive and non-cognitive dysfunctions characteristic of persons with probable Alzheimer's disease (AD). The cognitive part of the scale (ADAS-Cog) is both convenient for screening of probable AD and as a measure of cognitive functioning during drug intervention. The aim of this study was to translate the ADAS-Cognitive sub-test (ADAS-Cog) into Icelandic and to study its application in an elderly Icelandic population. The Mini-Mental State Examination (MMSE) and the ADAS-Cog were administered to 20 AD patients and 20 controls. Each patient was also rated on the Global Deterioration Scale (GDS). The probable AD patients were divided into two groups based on their GDS: 3-4 and 5-6 points. The patients were also divided into two groups based on their MMSE score: very mild to mild (23-30 points) and mild to moderate (15-22 points). Furthermore, the subjects were divided into two age groups: 65-76 and 77-92 years. Results revealed a highly significant difference on MMSE (22.3 +/- 3.4; 26.8 +/- 1.6; P0.05) and ADAS-Cog (18.4 +/- 7.7; 7.3 +/- 3.5; P0.05) scores for patients and controls respectively. AD patients also performed significantly worse than the elderly control group on eight of the 11 sub-tests. Thus, the present findings are mainly in line with those of previous studies. The scale exceeds other screening tests such as the MMSE in that it addresses in more detail the symptoms of AD and is valuable for early detection of the illness and staging. ADAS-Cog plays an important role in the diagnostic makeup of AD along with other detailed investigations, such as neuropsychological assessment.

Background: The Alzheimer’s Disease Assessment Scale Cognitive part is the most widely used cognitive outcome measure in current clinical research of Alzheimer’s Disease. The most commonly used version of this scale contains 11 items 8 of them assessed objectively, while the scoring of the other 3 is subjective in nature. All 3 subjective items Spoken Language Ability, Word-Finding Difficulty in Spontaneous Speech and Comprehension are scored solely on the basis of the rater’s clinical observation. Rater variability between objective and subjective items is compared. Methods: ADAS-Cog rater training was conducted in 18 separate clinical trials that used the 11-item ADAS-Cog. Each of the training programs included the scoring of demonstration ADAS-Cog videos. 3039 raters completed the video scoring a total of 3891 times. (Some raters were tested in more than one protocol.) In assessing each trials’ demonstration video scores, the percent agreement to the scoring mode was calculated for both the objective and subjective items. An aggregate count of modal agreement for objective and subjective items was also calculated. Results: Overall, rater agreement to the mode was 69% for subjective items, and was 85% for objective items. The lowest project rate of modal agreement on subjective items was 35% and the highest was 92%. The lowest project rate of modal agreement on objective items was 72% and the highest was 96%. Conclusions: There is widespread variability regarding the scoring of subjective items on the ADAS-Cog. An effect size of 3.5 points on the 11-item ADAS-Cog has been shown to be statistically significant in previous Alzheimer’s Disease research. Rater standardization, especially in regards to subjective assessments, should be considered for trials that will utilize the ADAS-Cog.