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Hendrix Alzforum Feb 28 2013 final
 

Hendrix Alzforum Feb 28 2013 final

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    Hendrix Alzforum Feb 28 2013 final Hendrix Alzforum Feb 28 2013 final Presentation Transcript

    • Improving Measurement of Cognition in Pre-MCI Populations To Support the API Clinical Trials Work supported by Banner Health Data from Rush Religious Orders StudySuzanne B Hendrix, Independent Statistical Consultant Contact email: shendrix@pentaracorp.com
    • API = Alzheimer’s Prevention Initiative PS1 Columbian Cohort Data – Study started in PS1 carriers RUSH Data–Normal progressing to MCI/AD – Support for future APOEe4 study – Additional data sets for validation
    • Problem – Ceiling Effects 14 12Cognitive Performance 10 8 6 Normal Aging 4 Clinical Outcome Alzheimers Disease 2 0 -10 -8 -6 -4 -2 0 Years Relative to Diagnosis
    • Compare Sensitivity toDecline (MSDR or CV) vsNormals 14 MSDR=1, CV=1 12Cognitive Performance 10 8 6 Normal Aging 4 Clinical Outcome Alzheimers Disease 2 0 -10 -8 -6 -4 -2 0 Years Relative to Diagnosis
    • Compare Sensitivity toDecline (MSDR or CV) vsNormals 14 MSDR=0.5, CV=2 12Cognitive Performance 10 8 6 Normal Aging 4 Clinical Outcome Alzheimers Disease 2 0 -10 -8 -6 -4 -2 0 Years Relative to Diagnosis
    • Compare Sensitivity toDecline (MSDR or CV) vsNormals 14 MSDR=0.33, CV=3 12Cognitive Performance 10 8 6 Normal Aging 4 Clinical Outcome Alzheimers Disease 2 0 -10 -8 -6 -4 -2 0 Years Relative to Diagnosis
    • Compare Sensitivity toDecline (MSDR or CV) vsNormals 14 MSDR=0.25, CV=4 12Cognitive Performance 10 8 6 Normal Aging 4 Clinical Outcome Alzheimers Disease 2 0 -10 -8 -6 -4 -2 0 Years Relative to Diagnosis
    • Best Individual Items – 5 yrs(converters vs. non-converters) Logical Memory IIa (Delayed) Category fluency – Fruits Logical Memory Ia (Immediate) Mini-Mental Status Examination Word list memory (Delayed recall) Word list recall (Immediate)All CVs 7.5 to 10 per year and are adjusted for normal aging.n per group for 1 year study >4000 for detecting a 50% effect size with 80% power (even with a population of 100% converters at 5 years)
    • More Items Helps, Then Hurts (Composite is sum of weighted items) Exhaustive Search Modeling Best Mean to Standard Deviation MSDR – Ordinary Least Squares 0.45 Ratio for ADAS-cog Items Regression – OLS 0.4 – Partial Least Squares 0.35 Regression – PLS 0.3 Unique items that 0.25 decline help 0.2 Multiple correlated 0.15 sensitive items help 0.1 0.05 Several combinations 0 give similar sensitivity 1 3 5 7 9 Number of Items 11 13
    • Potential Items for a Composite(converters vs. non-converters) Good combinations (5 yrs~0.17/yr, n=2160*) – East Boston Immediate, Delayed Recall (Logical Memory IIa), MMSE, Fruit, Progressive Matrices – Ideational Praxis, Delayed Recall, Animals, Fruits, Progressive Matrices Good combination (2 yrs~0.45/yr, n=315*) – Delayed Recall (or LM 1a), Word list memory (delayed), Line Orientation, Progressive Matrices, Orientation to time * Sample size for detecting a 50% effect in a 1 year study with 80% power, alpha 0.05 Numbers shown for MSDR are “best case” assuming a pure population.
    • Conclusions Composite scores add power over individual items – even in pre-MCI population Composites need validation for phase 3 Data based decision making is critical – can compare MSDR across studies for same populations Multiple data sets are also critical for not overfitting the data, and for generalizable results.
    • Thanks! Banner  Pentara – Jessica Langbaum – Stephanie Stanworth – Napatakamon Ayutyanont – Leah Garriott – Adam Fleisher – Brian Wells – Pierre Tariot – Eric Reiman RUSH – David A. Bennett – Study Personnel – Patients & families