Improving Measurement of Cognition in           Pre-MCI Populations     To Support the API Clinical Trials         Work su...
API = Alzheimer’s Prevention Initiative   PS1 Columbian Cohort Data    – Study started in PS1 carriers   RUSH Data–Norma...
Problem – Ceiling Effects                        14                        12Cognitive Performance                        ...
Compare Sensitivity toDecline (MSDR or CV) vsNormals                        14                                            ...
Compare Sensitivity toDecline (MSDR or CV) vsNormals                        14                                            ...
Compare Sensitivity toDecline (MSDR or CV) vsNormals                        14                                            ...
Compare Sensitivity toDecline (MSDR or CV) vsNormals                        14                                            ...
Best Individual Items – 5 yrs(converters vs. non-converters)   Logical Memory IIa (Delayed)   Category fluency – Fruits...
More Items Helps, Then               Hurts    (Composite is sum of weighted items)   Exhaustive Search   Modeling       ...
Potential Items for a Composite(converters vs. non-converters)   Good combinations (5 yrs~0.17/yr, n=2160*)    – East Bos...
Conclusions   Composite scores add power over individual    items – even in pre-MCI population   Composites need validat...
Thanks!   Banner                          Pentara    –   Jessica Langbaum             – Stephanie Stanworth    –   Napat...
Upcoming SlideShare
Loading in...5
×

Hendrix Alzforum Feb 28 2013 final

5,340

Published on

1 Comment
0 Likes
Statistics
Notes
  • Be the first to like this

No Downloads
Views
Total Views
5,340
On Slideshare
0
From Embeds
0
Number of Embeds
8
Actions
Shares
0
Downloads
0
Comments
1
Likes
0
Embeds 0
No embeds

No notes for slide

Transcript of "Hendrix Alzforum Feb 28 2013 final"

  1. 1. 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
  2. 2. 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
  3. 3. 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
  4. 4. 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
  5. 5. 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
  6. 6. 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
  7. 7. 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
  8. 8. 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)
  9. 9. 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
  10. 10. 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.
  11. 11. 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.
  12. 12. 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

×