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Alzheimer’s Disease Landscape

Alzheimer’s Disease Landscape. James R. Burke, MD, PhD Professor of Medicine (Neurology) Duke University Medical Center 9 th June 2012. Alzheimer’s Disease. Most common cause of dementia Clinical Insidious onset of cognitive decline- prominent memory problems. Pathology Brain atrophy

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Alzheimer’s Disease Landscape

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  1. Alzheimer’s Disease Landscape James R. Burke, MD, PhD Professor of Medicine (Neurology) Duke University Medical Center 9th June 2012

  2. Alzheimer’s Disease Most common cause of dementia Clinical Insidious onset of cognitive decline- prominent memory problems. Pathology Brain atrophy Amyloid plaques Neurofibrillary tangles

  3. Etiology Kawas C et al. Neurology 2000;54:2072-2077 • Age • Genetics • Autosomal Dominant - rare, early-onset forms- All are related to mutations in amyloid pathway. • Late-onset AD- Apolipoprotein E- susceptibility gene. Individuals who inherit APOE 4 form are at increased risk of AD AD Roses Sci Am Sci Med 1995, 2:16-25

  4. Epidemiology 1950 1980 2000 2020 >65 yrs <65 years • Risk Factors for AD • Age • Genetics • Education • Head trauma • Medical conditions: • Hypertension, Diabetes mellitus, Hypercholesterolemia, Obesity, Smoking Source: U.S. Census Bureau

  5. World-wide incidence of AD Ziegler Graham et al., 2008 Alz & Dementia 316-323    CCMS • AD incidence higher in US, Canada, and Europe • What accounts for differences in disease rates? Obesity, diabetes, smoking, hypertension? Lifestyle? Genetics? Systematic review (1998-2005) AD incidence studies (n=27)

  6. Pathology/Pathophysiology:Biomarkers and pathology precede symptoms http://adni.loni.ucla.edu/about/biomarkers/ Braak and Braak

  7. Diagnosis • History of insidious onset memory problems • Impairments on cognitive testing- especially delayed memory • No focal deficits on neurologic examination • Neuroimaging- atrophy and absence of significant cerebrovascular disease

  8. Clinical features of AD • MCI due to AD- Forgetful, repetitive questions. No impairment in ADLs (2-5 years) • Mild AD- Disoriented for date/time, word-finding difficulty, trouble organizing tasks at home and work. May be lost away from home. Depression common (2-4 years) • Moderate AD- Decline in personal hygiene and dress, unable to perform routine tasks around the house. May wander from home. Agitation and sleep problems common. Cannot be left alone (2-10 years) • Severe AD- Requires assistance in all ADL (bathing, dressing, feeding and toileting) Falls, infection, malnutrition common. Total care (1-3 years)

  9. Biomarkers in AD

  10. Disease burden Cost Dementia vs National Economies World Alzheimer’s Report 2010 • AD is the 6th cause of death in the US. • Average survival after diagnosis is 4 to 8 years • Impact on family and caregivers Alzheimer’s Association $ Billions

  11. Treatment options No Disease Modifying Therapies • Cholinesterase inhibitors • Donepezil • Galantamine • Rivastigmine • Tacrine • NMDA receptor antagonist • Memantine • Caprylidene

  12. Disease modification Figure quoted from: Hampel H et al. (2010)

  13. Perspectives: Drugs in Development Amyloid Neurofibrillary tangles (NFTs) Inflammation Energy Folding and removal Roberson and Mucke Science 314: 781 (2006)

  14. Competitive landscape

  15. Unmet medical needs • Disease modifying therapies • Prevention of symptom development • Therapies for behavioral problems • Effective management of sleep Plassman et al. Ann Int Med, 2008 148:427-34

  16. Conclusions Alzheimer’s disease is the most common cause of dementia with major costs for individuals, families and society. No current therapies prevent development of symptoms or modify disease progression. The aging of the population will lead to a dramatic increase in the number of individuals with Alzheimer’s disease.

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