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Alzheimer's Research & Therapy
Published in: Alzheimer's Research & Therapy 1/2015

Open Access 01-12-2015 | Research

New scoring methodology improves the sensitivity of the Alzheimer’s Disease Assessment Scale-Cognitive subscale (ADAS-Cog) in clinical trials

Authors: Nishant Verma, S. Natasha Beretvas, Belen Pascual, Joseph C. Masdeu, Mia K. Markey, The Alzheimer’s Disease Neuroimaging Initiative

Published in: Alzheimer's Research & Therapy | Issue 1/2015

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Abstract

Introduction

As currently used, the Alzheimer’s Disease Assessment Scale-Cognitive subscale (ADAS-Cog) has low sensitivity for measuring Alzheimer’s disease progression in clinical trials. A major reason behind the low sensitivity is its sub-optimal scoring methodology, which can be improved to obtain better sensitivity.

Methods

Using item response theory, we developed a new scoring methodology (ADAS-CogIRT) for the ADAS-Cog, which addresses several major limitations of the current scoring methodology. The sensitivity of the ADAS-CogIRT methodology was evaluated using clinical trial simulations as well as a negative clinical trial, which had shown an evidence of a treatment effect.

Results

The ADAS-Cog was found to measure impairment in three cognitive domains of memory, language, and praxis. The ADAS-CogIRT methodology required significantly fewer patients and shorter trial durations as compared to the current scoring methodology when both were evaluated in simulated clinical trials. When validated on data from a real clinical trial, the ADAS-CogIRT methodology had higher sensitivity than the current scoring methodology in detecting the treatment effect.

Conclusions

The proposed scoring methodology significantly improves the sensitivity of the ADAS-Cog in measuring progression of cognitive impairment in clinical trials focused in the mild-to-moderate Alzheimer’s disease stage. This provides a boost to the efficiency of clinical trials requiring fewer patients and shorter durations for investigating disease-modifying treatments.
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Metadata
Title
New scoring methodology improves the sensitivity of the Alzheimer’s Disease Assessment Scale-Cognitive subscale (ADAS-Cog) in clinical trials
Authors
Nishant Verma
S. Natasha Beretvas
Belen Pascual
Joseph C. Masdeu
Mia K. Markey
The Alzheimer’s Disease Neuroimaging Initiative
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Alzheimer's Research & Therapy / Issue 1/2015
Electronic ISSN: 1758-9193
DOI
https://doi.org/10.1186/s13195-015-0151-0

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