Endpoints for Pre-Dementia AD Trials: A Report from the EU/US/CTAD Task Force

Area of Science:

• Neurology
• Clinical Trials
• Biomarkers

Background:

• Alzheimer's disease (AD) treatment trials targeting the pre-dementia stage require sensitive outcome measures for clinically normal individuals.
• Assessing disease progression in early stages is vital for therapeutic development.

Purpose of the Study:

• To discuss existing and novel outcome assessments for pre-dementia AD trials.
• To identify measures capable of detecting subtle changes in individuals with early-stage Alzheimer's disease.

Main Methods:

• Convened the EU/US CTAD Task Force, an international collaboration.
• Reviewed composite cognitive and functional measures.
• Considered patient-reported outcomes and novel biomarkers (CSF and imaging).

Main Results:

• Composite measures of episodic memory, executive function, global cognition, and function show sensitivity in pre-dementia stages.
• Functional measures involving real-life tasks capture clinically meaningful early changes.
• Patient-reported outcomes and biomarkers show potential for early AD detection.

Conclusions:

• Several novel outcome measures demonstrate promise for assessing Alzheimer's disease progression in pre-dementia trials.
• Further validation studies are needed for these measures in the target population.
• Many promising measures are being incorporated into ongoing and planned clinical trials.