Jason Hassenstab, Ph.D.Assistant Professor of Neurology and PsychologyKnight Alzheimer’s Disease Research CenterWashington...
Test Selection   DIAN Pharma Consortium Cognitive Endpoint    Working Group    Cognitive Core, incorporate neuropsycholo...
Outcome Variables   Select a measure that optimizes sensitivity to    change in autosomal dominant AD    DIAN participan...
Additional Outcome Variables   Neuropsychological Tests     Episodic Memory      ○ Delayed Recall Tests     Composite C...
Final Thoughts for Discussion Can we develop tests that capture the pathological  course of AD? Detecting treatment vs d...
Final Thoughts for Discussion Can we develop tests that capture the pathological  course of AD? Detecting treatment vs d...
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Hassenstab Alzforum 2 28 2013 Webinar

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Hassenstab Alzforum 2 28 2013 Webinar

  1. 1. Jason Hassenstab, Ph.D.Assistant Professor of Neurology and PsychologyKnight Alzheimer’s Disease Research CenterWashington University in St. Louishassenstabj@wustl.edu
  2. 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. 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. 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. 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. 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

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