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

ABSTRACT

For Alzheimer's disease treatment trials that focus on the pre-dementia stage of disease, outcome measures are needed that will enable assessment of disease progression in patients who are clinically normal. The EU/US CTAD Task Force, an international collaboration of investigators from industry, academia, non-profit foundations, and regulatory agencies, met in Philadelphia, Pennsylvania, USA, on November 19, 2014 to discuss existing and novel outcome assessments that may be useful in pre-dementia trials. Composite measures that assess changes in episodic memory, executive function, global cognition, and global function have recently been developed by a number of groups and appear to be sensitive at this stage. Functional measures that involve real-life complex tasks also appear to capture early subtle changes in pre-dementia subjects and have the advantage of representing clinically meaningful change. Patient reported outcomes and novel CSF and imaging biomarkers have also shown promise. More studies are needed to validate all of these tests in the pre-dementia population. Many of them have been incorporated as exploratory measures in ongoing or planned trials.