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Alzheimer’s Disease Today and Tomorrow

Alzheimer’s Disease Today and Tomorrow. First case reported in 1906 Reported by Alois Alzheimer Patient Augusta D. first treated at 46 years old Paranoia, memory loss, confusion Died in five years Brain stained to show plaques and tangles. Major Pathological Changes in AD.

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Alzheimer’s Disease Today and Tomorrow

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  1. Alzheimer’s Disease Today and Tomorrow • First case reported in 1906 • Reported by Alois Alzheimer • Patient Augusta D. first treated at 46 years old • Paranoia, memory loss, confusion • Died in five years • Brain stained to show plaques and tangles

  2. Major Pathological Changes in AD • Brain shrinkage (atrophy) • Neuritic Plaques • altered metabolism of APP • Deposition of beta amyloid • Neurofibrillary Tangles • Cytoskeletal pathology [girders and trusses] • Altered metabolism of tau protein • Neuronal death in specific brain regions (why some regions and not others?)

  3. Current Status Unclear etiology Progressive course Clinical diagnosis much variability No agreed biomarker Uneven progression Suboptimal Medications

  4. Current Status • 5.5 Million currently • As many as 16 Million by mid century • 10 Million baby boomers • Patient with Alzheimer’s cost three times what a similar patient without Alzheimers would cost

  5. Current Status • $40 million NIH diagnostics alone • Four amyloid imaging reagents in clinical testing • This doesn’t count natural history studies

  6. Current Status • A diagnosis of AD does not equate with the inability to consent

  7. HO S NH11CH3 N 1 H C 6 S C H 3 3 Amyloid Plaques N + C H N 3 C H In vivo Amyloid Imaging withPittsburgh Compound B (PIB) Histology - Thioflavin T PET Imaging - [11C]6-OH-BTA-1 (PIB)

  8. Genes and Risk of Alzheimer’s Disease • Disease Genes • “Deterministic” • rare • monogenic • major effect • little, if any, environmental interaction • Risk Genes • “Susceptibility” • common • polygenic • minimal effect • environment & other genetic factors act as modifiers

  9. Classic AD Trial Designs Symptomatic Agent Disease Modifier PERFORMANCE PERFORMANCE Placebo Placebo Time Time Rx effect increases over time Rx effect is static over time

  10. Alzheimer’s Disease:Course, Prevention, Treatment Strategies Primary Prevention Secondary Prevention Treatment Intervention Normal Pre-symptomatic AD Mild Cognitive Impairment AD Clinical State ??? 10 to 60 Mil 6 to 10 Mil 5 Mil Numbers Brain Pathologic State Early Brain Changes No Symptoms AD Brain Changes Mild Symptoms Mild, Moderate, or Severe Impairment No Disease No Symptoms Strategies Prevent or Delay Emergence Of Symptoms Stimulate Memory; Slow progression Treat cognition Treat behaviors Slow progression Identify at-risk Prevent AD Disease Progression

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