The Alzheimer's disease assessment scale: Evaluation of psychometric properties and patterns of cognitive decline in multicenter clinical trials of mild to moderate Alzheimer's disease

Purpose: To evaluate the psychometric properties and patterns of decline on the total score and item scores of the cognitive subscale of the Alzheimer 's Disease Assessment Scale (ADAS-Cog) in patients with Alzheimer Disease ( AD), Methods: We analyzed data from 536 AD outpatients randomized to the pl acebo group in two identical 20-week multicenter drug trials. Results: Mean deterioration at week 26 on the ADAS-Cog total score for subjects with mod erate dementia was 84% greater than that for those with milder severity (p < 0.001). After adjusting for this effect. age (p = 0.015) and educational level (p = 0.01) also predicted cognitive decline. In a model, absolute cha nge for most individual ADAS items was less than 10% of the possible change . and It Was generally smaller than one-third of the standard deviation of the measure. Measurement error variability was greatest for word recognitio n and the "placebo" effect was greatest for word recall. Variability increa sed with trial duration in a model, Conclusions: There is a relationship be tween baseline severity and magnitude of cognitive decline. In 6-month tria ls. measurement error makes a substantial contribution to the variance in A DAS-Cog change scores. Sensitivity to intervention effects ill therefore de pend both on the variability and magnitude of change, Such data must be con sidered when designing future trials to minimize measurement error variabil ity and increase sensitivity for specific populations.