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Alzheimers Res Ther. 2015 Nov 12;7(1):64. doi: 10.1186/s13195-015-0151-0.

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

Author information

1
Department of Biomedical Engineering, The University of Texas at Austin, 107 W. Dean Keeton Street Stop C0800, Austin, TX, 78712, USA. nishant3115@gmail.com.
2
NeuroTexas Institute Research Foundation, St. David's HealthCare, 1015 E. 32nd Street Suite 404, Austin, TX, 78705, USA. nishant3115@gmail.com.
3
Department of Educational Psychology, The University of Texas at Austin, 1 University Station D5800, Austin, TX, 78712, USA. tberetvas@austin.utexas.edu.
4
Nantz National Alzheimer Center, Houston Methodist Neurological Institute, 6560 Fannin Street, Houston, TX, 77030, USA. bpascual@houstonmethodist.org.
5
Nantz National Alzheimer Center, Houston Methodist Neurological Institute, 6560 Fannin Street, Houston, TX, 77030, USA. jcmasdeu@houstonmethodist.org.
6
Department of Biomedical Engineering, The University of Texas at Austin, 107 W. Dean Keeton Street Stop C0800, Austin, TX, 78712, USA. mia.markey@utexas.edu.
7
Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, 1400 Pressler Street FCT14.50000, Houston, TX, 77030, USA. mia.markey@utexas.edu.

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.

PMID:
26560146
PMCID:
PMC4642693
DOI:
10.1186/s13195-015-0151-0
[Indexed for MEDLINE]
Free PMC Article

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