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Adding nuances due to risk modifiers to Alzheimer’s Disease models Prashanthi Vemuri, Ph.D.  Assistant Professor of Radiology  Mayo Clinic Rochester, MN, USA
Biomarkers in AD Considered for Clinical Trials and Observational Studies & NIA-AA new criteria ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],PATHOLOGY BIOMARKER  COGNITION
Mechanistic Inferences into the Disease  Jack CR et al. Lancet Neurology 2010
Disease Risk Modifiers ,[object Object],[object Object],[object Object],COGNITIVE FUNCTION  COGNITIVE RESERVE  VARIABLES  E.g. Lifestyle, IQ DISEASE DRIVERS Age, Ds related genes  (APOE)  SURROGATES OF  PATHOLOGY
I. Effect of APOE  ,[object Object],[object Object],[object Object],[object Object],Vemuri et al. 2010 Annals of Neurology
Effect of APOE on biomarkers  ,[object Object],[object Object],Vemuri et al. 2010 Annals of Neurology
Considering the effect of APOE on dynamic models  Main effect of APOE  ε 4 – lowering the age of onset.
Effect of APOE on the functional architecture  Machulda et al. 2011 Archives of Neurology
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
Effect of Cognitive Reserve  ,[object Object],[object Object],Vemuri et al. 2011 Brain
Cognitive Reserve and AD Biomarkers – Independent Determinants of Cognition  Vemuri et al. 2011 Brain
Where are we ? ,[object Object],[object Object]
Future Directions and Considerations  ,[object Object],[object Object],[object Object]
Acknowledgements ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],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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Vemuri alz forum

  • 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.
  • 3. Mechanistic Inferences into the Disease Jack CR et al. Lancet Neurology 2010
  • 4.
  • 5.
  • 6.
  • 7. Considering the effect of APOE on dynamic models Main effect of APOE ε 4 – lowering the age of onset.
  • 8. Effect of APOE on the functional architecture Machulda et al. 2011 Archives of Neurology
  • 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.
  • 11. Cognitive Reserve and AD Biomarkers – Independent Determinants of Cognition Vemuri et al. 2011 Brain
  • 12.
  • 13.
  • 14.