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Aging, Memory and Alzheimer’s Disease

Aging, Memory and Alzheimer’s Disease. Kinga Szigeti, MD, PhD. Aging and Alzheimer’s disease. The biggest challenge in AD: it is superimposed on normal aging Insidious onset No blood test; diagnosis is putting a puzzle together. Major Public Health Problem. Single domain amnestic

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Aging, Memory and Alzheimer’s Disease

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  1. Aging, Memory and Alzheimer’s Disease Kinga Szigeti, MD, PhD

  2. Aging and Alzheimer’s disease • The biggest challenge in AD: it is superimposed on normal aging • Insidious onset • No blood test; diagnosis is putting a puzzle together Major Public Health Problem

  3. Single domain amnestic -Forgetting where we put things -Forgetting appointments -Repeatiing questions or conversations Red-yellow = diff small-diff big Multidomain Z score <-2 Mild AD MMSE 20-26

  4. PET metabolism and amyloid imaging Symptoms late in the disease: cells are damaged We cannot recover nerve cells; goal is to prevent We need biomarkers before the symptoms start

  5. Alzheimer disease as a model of complex genetics Not two patients are exactly alike

  6. APP storyMendelian genetics

  7. Amyloid hypothesis

  8. Linkage Trisomy 21 Partial trisomy 21 not including APP-no AD

  9. Candidate gene: APP • Precursor protein to amyloid in AD brain • Mutations found • Disease and mutation went together within families • Interestingly some of these mutations affect sites where gamma cleavage occurs

  10. Linkage Chr 14 Chr 1

  11. Amyloid hypothesis: genetic confirmation PSEN1 40 and 42 APP PSEN2 D Mutations in APP regulatory sequences

  12. Genetics proves it is heterogeneous

  13. Research at the University at Buffalo Olfactory receptor association with AD age at onset Copy number variation Pieces of chromosomes (genetic material) Missing or in extra copies

  14. Research at the University at Buffalo Deletion upstream from CREB1 association with AD

  15. CHRFAM7A association with AD Raminathan et al,PlosOne Namenda might work better is this group

  16. Alzheimer’s disease model: induced pluripotent stem cells

  17. The goal: prevention • Age 65 well visit/ part of the prevention panel • Primary care physician asks about memory issues • Screening memory test • Blood test for genetic risk factors (gene chip) • Assess family history of dementia Then risk stratification: Low risk Monitor Intermediate risk Consider amyloid imaging then Rx High Risk Amyloid imaging then Rx

  18. The goal: personalized treatment • If memory problem is present: • Clinical workup • Gene chip to determine which drugs work best

  19. Until we have the breakthrough: ADMDC patient care • Diagnose early • Modify risk factors to slow progression • Treat to change slope of decline • Buys us time • Gives years of close to normal life

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