Vemuri alz forum

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webinar presented at AlzForum January 5, 2012

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Vemuri alz forum

  1. 1. Adding nuances due to risk modifiers to Alzheimer’s Disease models Prashanthi Vemuri, Ph.D. Assistant Professor of Radiology Mayo Clinic Rochester, MN, USA
  2. 2. Biomarkers in AD Considered for Clinical Trials and Observational Studies & NIA-AA new criteria <ul><li>Brain Amyloid-osis </li></ul><ul><ul><li>Amyloid PET </li></ul></ul><ul><ul><li>CSF Ab1-42 </li></ul></ul><ul><li>Neuronal Dysfunction and Tau mediated Injury </li></ul><ul><ul><li>CSF t-tau </li></ul></ul><ul><ul><li>FDG-PET </li></ul></ul><ul><li>Neurodegeneration </li></ul><ul><ul><li>Structural MRI </li></ul></ul>PATHOLOGY BIOMARKER COGNITION
  3. 3. Mechanistic Inferences into the Disease Jack CR et al. Lancet Neurology 2010
  4. 4. Disease Risk Modifiers <ul><li>Focus on two disease risk modifiers </li></ul><ul><li>I. Apolipoprotein E (APOE) ε4 </li></ul><ul><li>II. Cognitive Reserve </li></ul>COGNITIVE FUNCTION COGNITIVE RESERVE VARIABLES E.g. Lifestyle, IQ DISEASE DRIVERS Age, Ds related genes (APOE) SURROGATES OF PATHOLOGY
  5. 5. I. Effect of APOE <ul><li>ADNI subjects with baseline CSF and MRI </li></ul><ul><li>Amyloid Load (CSF Aβ 1-42 ) </li></ul><ul><li>Neuronal Injury (CSF t-tau) </li></ul><ul><li>Neurodegeneration (MRI – STAND-scores) </li></ul>Vemuri et al. 2010 Annals of Neurology
  6. 6. Effect of APOE on biomarkers <ul><li>MRI – closely related to cognition. </li></ul><ul><li>A β – closely related to APOE ε 4 status. </li></ul>Vemuri et al. 2010 Annals of Neurology
  7. 7. Considering the effect of APOE on dynamic models Main effect of APOE ε 4 – lowering the age of onset.
  8. 8. Effect of APOE on the functional architecture Machulda et al. 2011 Archives of Neurology
  9. 9. II. Cognitive Reserve Why do some subjects with AD pathology remain cognitively normal during life while some others develop dementia? Cognitive Reserve – IQ, Education, Physical activities and Cognitive activities
  10. 10. Effect of Cognitive Reserve <ul><li>No correlations between biomarkers and cognitive reserve variable </li></ul><ul><li>No effect of cognitive reserve variable on the relationship between biomarkers and cognition. </li></ul>Vemuri et al. 2011 Brain
  11. 11. Cognitive Reserve and AD Biomarkers – Independent Determinants of Cognition Vemuri et al. 2011 Brain
  12. 12. Where are we ? <ul><li>Well developed framework - Different biomarkers to measure different aspects of the pathology. </li></ul><ul><li>Since the pathology manifests itself in a temporal sequence — biomarkers have a temporal sequencing that is being currently investigated. </li></ul>
  13. 13. Future Directions and Considerations <ul><li>Longitudinal studies and statistical methods to map the local and global dynamic progression of the disease. </li></ul><ul><li>Account for individual differences in Alzheimer’s disease risk modifiers. </li></ul><ul><li>Efficiently apply these disease models for patient care. </li></ul>
  14. 14. Acknowledgements <ul><li>MAYO CLINIC ROCHESTER: </li></ul><ul><li> Radiology </li></ul><ul><ul><ul><li>Clifford R. Jack Jr., M.D. </li></ul></ul></ul><ul><ul><ul><li>Kejal Kantarci, M.D. </li></ul></ul></ul><ul><ul><li>Health Science Research </li></ul></ul><ul><ul><li> Stephen W. Weigand </li></ul></ul><ul><ul><li> Timothy Lesnick </li></ul></ul><ul><ul><li> Heather D. Wiste </li></ul></ul><ul><ul><li> Scott A. Przybelski </li></ul></ul><ul><ul><li>Neurology </li></ul></ul><ul><ul><li> David S. Knopman, M.D. </li></ul></ul><ul><ul><ul><li>Bradley F. Boeve, M.D. </li></ul></ul></ul><ul><ul><ul><li>Ronald C. Petersen, M.D, Ph.D. </li></ul></ul></ul>GRANT SUPPORT: K99/R00 NIH Pathway to Independence Award NIH grants: P50 AG16574, R01 AG11378. ADNI COLLABORATORS: Les Shaw, Ph.D. John Trojanowski, M.D., Ph.D. Matt Bernstein, Ph.D. Paul Aisen, M.D. Michael Weiner, M.D.

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