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The Meaning of Alzheimer’s Disease Across Time and Place: From the Bedside to the Desktop Jason Karlawish University of Pennsylvania

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Presentation on theme: "The Meaning of Alzheimer’s Disease Across Time and Place: From the Bedside to the Desktop Jason Karlawish University of Pennsylvania"— Presentation transcript:

1 The Meaning of Alzheimer’s Disease Across Time and Place: From the Bedside to the Desktop Jason Karlawish University of Pennsylvania Disclosures: Site PI for Pfizer/NIA sponsored clinical trial in persons with AD Professional advisory board for Senior Bridge Inc.

2 Support Robert Wood Johnson Foundation Investigator Award in Health Policy Research National Institute on Aging P30-AG10124 The Marian S. Ware Alzheimer Program Very special thanks to Kristin Harkins and Sarah Maceda-Maciel for their assistance with research and slide preparation.

3 The meaning of Alzheimer’s disease Alzheimer’s disease is a disease The disease is caused by pathology in the brain that leads to… –Disability –Lost productivity –Mortality Physicians diagnose Alzheimer’s disease using a careful history and physical

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6 “Soon she developed a rapid loss of memory...” “…only a tangle of fibrils indicates the place where a neuron was previously located.”

7 “Both Alzheimer disease and senile dementia are progressive dementias … that are indistinguishable by careful clinical analyses.” “The pathological findings are identical.” Archives of Neurology. 33; 1976:

8 Neurofibrillary tangles, neuritic plaques, and dystrophic neurites in CA1 subfield PHF1

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10 Petersen RC et al. Current concepts in Mild Cognitive Impairment. Arch Neurol 2001;58: Survival curve of persons characterized as having a mild cognitive impairment for 6 years

11 The Fourth Age of Alzheimer's Disease The meaning of Alzheimer's disease has changed. In this century it is changing again: from pathology in a person that is the cause of disability to the risk of disability that a person faces. What are the clinical and policy implications of this new meaning of Alzheimer's disease?

12 MEDLINE citations for "biomarker," per 100,000 articles

13 MEDLINE citations for [biomarker AND Alzheimer’s], per 100,000 articles

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15 Probable AD: A plus one or more supportive features B, C, D, or E Core diagnostic criteria A. Presence of an early and significant episodic memory impairment: 1. Gradual and progressive change in memory function reported by patients or informants over more than 6 months 2. Objective evidence of significantly impaired episodic memory on testing 3. The episodic memory impairment can be isolated or associated with other cognitive changes at the onset of AD or as AD advances Supportive features B. Presence of medial temporal lobe atrophy C. Abnormal cerebrospinal fluid biomarker D. Specific pattern on functional neuroimaging with PET E. Proven AD autosomal dominant mutation within the immediate family Lancet Neurology. 6;2007:

16 Desktop diseases DiseaseDiagnostic tool (DT) Discrete clinical event (DCE) Intervention to validate link between DT and DCE Dyslipemia or high cholesterol NCEPIII 10- year risk calculator stroke, MIstatin drug

17 National Cholesterol Education Program (NCEP) Third Report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) Risk Assessment Tool for Estimating Your 10-year Risk of Having a Heart Attack. The National Heart, Lung, and Blood Institute (NHLBI). (Accessed June 8, 2010, at

18 Desktop diseases DiseaseDiagnostic tool (DT) Discrete clinical event (DCE) Intervention to validate link between DT and DCE dyslipemiaNCEPIII 10- year risk calculator stroke, MIStatin drug hypertensionBlood pressure reading stroke, MI, CHF Thiazide, beta-blocker osteoporosisFRAXbone fractureBisphosphonate

19 From:

20 World Health Organization. FRAX: WHO fracture risk assessment tool. World Health Organization Collaborating Centre for Metabolic Bone Diseases, University of Sheffield, UK, (Accessed January 19, 2010, at

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23 Feeling risk: getting the gist “‘I know what you told me, but this is what I think:’ Perceived risk of Alzheimer disease among individuals who accurately recall their genetics-based risk estimate.” Among 158 participants who accurately recalled their AD risk assessment 6 weeks after risk disclosure… –75 (47.5%) said AD risk was more than 5% points different from their calculated AD risk estimate. Linnenbringer et al. Genetics in Medicine. in press.

24 National Cholesterol Education Program (NCEP) Third Report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) Risk Assessment Tool for Estimating Your 10-year Risk of Having a Heart Attack. The National Heart, Lung, and Blood Institute (NHLBI). (Accessed June 8, 2010, at

25 Country Old Age Dependency Ratio (2020) (medium variant) Japan47.7 Finland36.5 Italy36.1 Germany35.5 Sweden34.0 France33.9 Belgium32.3 Denmark31.8 Greece31.6 Bulgaria31.6 The old-age dependency ratio is the ratio of the population aged 65 years or over to the working age population (ages 15-64), presented as number of elderly per 100 persons of working age. Red = national dementia plan Nations with highest old age dependency ratios Blue = some nation-wide efforts or initiatives

26 Desktop diseases DiseaseDiagnostic tool (DT) Discrete clinical event (DCE) Intervention to validate link between DT and DCE DyslipemiaNCEPIIIstroke, MIstatin drug HTNBPstroke, MIthiazide, beta-blocker OsteoporosisFRAXbone facture bisphosphonate DiabetesHgA1CDx of DMinsulin, thiaglitazone Alzheimer's Disease ???

27 The Fourth Age of Alzheimer's Disease Drugs & multivariate models will define the disease –What will be the discrete clinical event? –How can we break the logjam that proprietary control and asymmetric information create? –Who will control the drugs and models?

28 The Fourth Age of Alzheimer's Disease Drugs & multivariate models will define the disease Risk information will be on-line and with wide access –How will we foster better risk perception and communication? –How will we foster appropriate and sustained risk reduction behaviors (e.g. retention in a RCT and adherence to an Rx)?

29 The Fourth Age of Alzheimer's Disease Drugs & multivariate models will define the disease Risk information will be on-line and with wide access Risk is a continuum -- treatment recommended beyond upfront clinical trial results –How will we develop guidelines that are fair and unbiased and use all the data?

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31 The Meaning of Alzheimer's Disease Across Time and Place: From the Bedside to the Desktop Jason Karlawish University of Pennsylvania

32 The Fourth Age of Alzheimer's Disease Drugs & multivariate models will define the disease Alzheimer's disease may not work as our organizing term Risk information will be on-line and with wide access –How will we foster better risk perception and communication? –How will we foster sustained risk reduction (AKA retention in a RCT and to an Rx)?

33 The Fourth Age of Alzheimer's Disease Drugs & multivariate models will define the disease Alzheimer's disease may not work as our organizing term Risk information will be on-line and with wide access Risk is a continuum -- treatment recommended beyond upfront clinical trial results –How will we develop guidelines that are fair and unbiased using all the data?


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