1. Jason Hassenstab, Ph.D.
Assistant Professor of Neurology and Psychology
Knight Alzheimer’s Disease Research Center
Washington University in St. Louis
hassenstabj@wustl.edu
2. Test Selection
DIAN Pharma Consortium Cognitive Endpoint
Working Group
Cognitive Core, incorporate neuropsychological
measures from DIAN Observational Study
Focus on 6 domains of cognitive functioning
1. Verbal Episodic Memory
2. Spatial Memory
3. Visual Memory
4. Executive Functioning
5. Visuomotor Speed and Immediate Memory
6. Global Measures of Cognitive Functioning
3. Outcome Variables
Select a measure that optimizes sensitivity to
change in autosomal dominant AD
DIAN participants are mostly younger, few
comorbidities, relatively “pure” disease population
Clinical Dementia Rating (CDR) Sum of Boxes score
provided best sensitivity to change in cognitive, clinical,
and ADLs
Ceiling effects? Probably not relevant
○ Sensitive to any noticeable change by the informant or by
the clinician
○ Test performance more sensitive to range of performance
levels, but may be subject to false negatives
Verified by comparing longitudinal DIAN and AIBL
study results with published findings from ADNI and
ADCS
4. Additional Outcome Variables
Neuropsychological Tests
Episodic Memory
○ Delayed Recall Tests
Composite Cognitive Measure
○ Why composite?
Avoid leveraging results on single measures
Better reliability + reduced variance = more statistical power
Other tests
Computerized batteries, ELSMEM, CogState
Other Metrics
Coefficient of Variation (Mean:SD)
Reaction Time Distributional Analysis
Attentional Control Measures
Switching Stroop, others?
Ex-Gaussian function
See work by David Balota, Ph.D.
5. Final Thoughts for Discussion
Can we develop tests that capture the pathological
course of AD?
Detecting treatment vs detecting impairment
Possible Criteria to Evaluate Tasks:
Construct validity
Clarity of link to neural circuits
Clarity of link to cognitive mechanisms
Avoid tasks that involve combinations of cog processes?
Availability of Animal Model
Link to neural systems through neuropsychopharmacology
Amenable for use in human neuroimaging studies
Evidence of impairment specific to AD
Linked to functional outcome in AD
Good psychometric characteristics
6. Final Thoughts for Discussion
Can we develop tests that capture the pathological
course of AD?
Detecting treatment vs detecting impairment
Possible Criteria to Evaluate Tasks:
Construct validity
Clarity of link to neural circuits
Clarity of link to cognitive mechanisms
Avoid tasks that involve combinations of cog processes?
Availability of Animal Model
Link to neural systems through neuropsychopharmacology
Amenable for use in human neuroimaging studies
Evidence of impairment specific to AD
Linked to functional outcome in AD
Good psychometric characteristics