Updates on the Diagnosis and Management of Alzheimer's Disease

Dear Participant,

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Welcome to the Interactive ShowCASE™, a self-guided, multimedia educational program that engages clinicians with a dynamic mix of live faculty presentations and iPod touch-enhanced posters and case studies.

The Interactive ShowCASE™ comprises 3 distinct yet interrelated modules that progress as follows:

MULTIMEDIA POSTER GALLERY After you complete the pre-activity questionnaire, Dennis Selkoe, MD, will explore scientific insights into Alzheimer’s disease pathophysiology, including implications for early diagnosis and emerging treatment strategies. Copies of the poster figures are included in this workbook.

LIVE PRESENTATION Following the poster presentation, please make your way into the live presentation area where Adam Fleisher, MD, MAS, and Michael S. Rafii, MD, PhD, will examine best practices in the differential diagnosis and management of various stages of Alzheimer’s disease, including time-sensitive approaches to cognitive assessment and biomarker testing. The presentation is included in this workbook.

INTERACTIVE CASE STUDY Finally, before completing the post-activity questionnaire and program evaluation form, you will use the iPod touch to engage in a case study. Eric Tangalos, MD, FACP, AGSF, CMD, will present a case study representing an early presentation of Alzheimer’s disease, and you will have the opportunity to weigh in at key clinical decision points during the case.

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FACULTY Adam S. Fleisher, MD, MAS Associate Professor, Department of Neurosciences University of California, San Diego School of Medicine San Diego, California Director of Brain Imaging Banner Alzheimer's Institute Phoenix, Arizona

Michael S. Rafii, MD, PhD Director, Memory Disorders Clinic Clinical Director, Down Syndrome Research and Treatment Center Associate Medical Director, Alzheimer’s Disease Cooperative Study Program Director, Neurology Residency Program Assistant Professor of Neurosciences University of California, San Diego Health System San Diego, California

Dennis J. Selkoe, MD (Prerecorded) Vincent and Stella Coates Professor of Neurologic Diseases Harvard Medical School Co-Director, Center for Neurologic Diseases Department of Neurology Brigham and Women’s Hospital Boston, Massachusetts

Eric G. Tangalos, MD, FACP, AGSF, CMD (Prerecorded) Professor of Medicine Mayo Clinic Rochester, Minnesota

Jessica L. Zwerling, MD, MS CME Reviewer Assistant Professor, Saul R. Korey Department of Neurology Assistant Professor, Department of Pediatrics (Neurology) Albert Einstein College of Medicine Bronx, New York

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INTENDED AUDIENCE PREAMBLE

This activity is intended for primary care providers and other health care professionals involved in the early recognition, diagnosis, and long-term management of Alzheimer’s disease.

LEARNING OBJECTIVES At the conclusion of this educational activity, participants should be better prepared to: 1. Describe the pathophysiologic underpinnings of Alzheimer’s disease, including the role of amyloid β 2. Identify patients with risk factors and clinical symptoms that suggest a more formal evaluation for Alzheimer’s disease is warranted 3. Employ new diagnostic criteria for mild cognitive impairment and dementia due to Alzheimer’s disease from the National Institute on Aging – Alzheimer’s Association 4. Discuss options for biomarker testing and brain imaging in patients who are being evaluated for Alzheimer’s disease 5. Evaluate emerging therapeutic approaches that target aberrant amyloid production and deposition in patients with Alzheimer’s disease 6. Coordinate Alzheimer’s disease care through open communication with patients, family members, specialists, and other members of the health care team

NEEDS ASSESSMENT AND LEARNER’S GAP Alzheimer’s disease is the most common form of dementia, affecting approximately 6% to 7% of the population over 65 years of age.1,2 The multifactorial etiology of Alzheimer’s disease involves complex interplay among genetic, biochemical, and physiologic factors, which manifest clinically as a range of progressive cognitive, affective, and behavioral symptoms.3-5 Despite its prevalence and significant associated medical, psychosocial, and economic burden, Alzheimer’s disease often remains undiagnosed and untreated.6 In particular, studies have shown that rates of diagnosis in primary care are well

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below epidemiologic estimates.7 Primary care providers (PCPs) may incorrectly believe that diagnosing dementia early is not important, and instead may feel that it can be harmful to patients and their families.7 Yet PCPs are increasingly called on to provide care for cognitively impaired individuals, playing critical roles in detecting early symptoms of dementia, communicating with patients and caregivers about the disease, coordinating with specialists on multimodal therapeutic plans, and following up to tailor treatment, minimize complications, and head off medical crises.8 Appropriately trained PCPs are also best positioned to assess cognition and function over time, identify behavioral symptoms, and manage common comorbidities.8 This Interactive ShowCASE™ is designed to improve patient care by arming PCP attendees with the latest insights into the pathophysiology of Alzheimer’s disease; new staging and diagnostic criteria from national and international study groups; brain imaging modalities and biomarkers to support a differential diagnosis of cognitive impairment; and current and emerging treatment strategies for various stages of disease.9,10

REFERENCES 1. Alzheimer's Association. 2012 Alzheimer’s Disease Facts and Figures. Available at: http:// www.alz.org/downloads/facts_figures_2012.pdf. Accessed November 7, 2012.

2. Leifer BP. Early diagnosis of Alzheimer's disease: clinical and economic benefits. J Am Geriatr Soc. 2003;51(suppl 5 Dementia):S281-S288.

3. Petersen RC. Mild cognitive impairment as a diagnostic entity. J Intern Med. 2004;256:183-194.

4. Citron M. Alzheimer's disease: strategies for disease modification. Nat Rev Drug Discov.

2010;9:387-398.

5. Funke SA, Willbold D. Peptides for therapy and diagnosis of Alzheimer's disease. Curr Pharm Des. 2012;18:755-767.

6. Bradford A, Kunik ME, Schulz P, Williams SP, Singh H. Missed and delayed diagnosis of dementia in primary care: prevalence and contributing factors. Alzheimer Dis Assoc Disord. 2009;23:306-314.

7. Hansen EC, Hughes C, Routley G, Robinson AL. General practitioners' experiences and understandings of diagnosing dementia: factors impacting on early diagnosis. Soc Sci Med. 2008;67:1776-1783.

8. Villars H, Oustric S, Andrieu S, et al. The primary care physician and Alzheimer's disease: an international position paper. J Nutr Health Aging. 2010;14:110-120.

9. Dubois B, Feldman HH, Jacova C, et al. Revising the definition of Alzheimer's disease: a new lexicon. Lancet Neurol. 2010;9:1118-1127.

10. Nordberg A. Molecular imaging in Alzheimer's disease: new perspectives on biomarkers for early diagnosis and drug development. Alzheimers Res Ther. 2011;3:34.

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ACCREDITATION STATEMENT PREAMBLE

This activity has been planned and implemented in accordance with the Essential Areas and Policies of the Accreditation Council for Continuing Medical Education (ACCME) through joint sponsorship of Albert Einstein College of Medicine of Yeshiva University, Montefiore Medical Center and Integritas Communications. Albert Einstein College of Medicine of Yeshiva University is accredited by the ACCME to provide continuing medical education for physicians.

CREDIT DESIGNATION Albert Einstein College of Medicine of Yeshiva University designates this live activity for a maximum of 1.5 AMA PRA Category 1 Credit(s)TM .

Physicians should claim only the credit commensurate with the extent of their participation in the activity.

CONFLICT OF INTEREST The Conflict of Interest Disclosure Policy of Albert Einstein College of Medicine of Yeshiva University requires that faculty participating in any CME activity disclose to the audience any relationship(s) with a pharmaceutical, product, or device company. Any presenter whose disclosed relationships prove to create a conflict of interest with regard to their contribution to the activity will not be permitted to present.

The Albert Einstein College of Medicine of Yeshiva University also requires that faculty participating in any CME activity disclose to the audience when discussing any unlabeled or investigational use of any commercial product or device not yet approved for use in the United States. Albert Einstein College of Medicine of Yeshiva University, CCME staff, has no conflicts of interest with commercial interests related directly or indirectly to this educational activity.

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FACULTY AND PLANNING COMMITTEE DISCLOSURES Adam S. Fleisher, MD Consultant to Avid Radiopharmaceuticals, Eli Lilly and Company, Merck & Co. Inc., Pfizer Inc., and Quintiles Inc. Eric G. Tangalos, MD

Has nothing to disclose.

Michael S. Rafii, MD, PhD Grant Research support from Janssen Pharmaceuticals, Genentech, Hoffman-La Roche and Elan Corporation, plc. Consultant to Nestle Health Science and a member of the speakers bureau for Novartis AG. Dennis J. Selkoe, MD Consultant to and a stockholder of Elan Corporation, plc.

Jim Kappler, PhD Integritas Communications has nothing to disclose.

Steven J. Feld Albert Einstein College of Medicine, or a member of his household, owns securities in Bioheart, Inc., Chelsea Therapeutics, Depomed, Inc., and Pharmacopeia, Inc. Jessica L. Zwerling, MD, MS Albert Einstein College of Medicine has nothing to disclose.

DISCLAIMER The opinions expressed herein are those of the faculty and do not necessarily represent the views of the Albert Einstein College of Medicine, Montefiore Medical Center, Eli Lilly and Company, or Integritas Communications. Please review complete prescribing information of specific drugs or combination of drugs, including indications, contraindications, warnings, and adverse effects before administering pharmacologic therapy to patients.

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BIBLIOGRAPHY »»The diagnosis of mild cognitive impairment due to Alzheimer’s disease: Recommendations from the National Institute on AgingAlzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease Albert MS, et al. Alzheimers Dement. 2011;7:270-279.

»»Therapeutic application of melatonin in mild cognitive impairment Cardinali DP, et al. Am J Neurodegener Dis. 2012;1:280-291.

»»Alzheimer’s disease: strategies for disease modification Citron M. Nat Rev Drug Discov. 2010;9:387-398.

»»International Work Group criteria for the diagnosis of Alzheimer disease Cummings JL, et al. Med Clin N Am. 2013;97:363-368.

»»Amyloid-beta assessed by florbetapir F-18 PET and 18-month cognitive decline: A multicenter study Doraiswamy PM, et al. Neurology. 2012;79:1636-1644.

»»Cerebrospinal fluid tau/beta amyloid 42 ratio as a prediction of cognitive decline in nondemented older adults Fagan AM, et al. Arch Neurol. 2007;64:343-349.

BIBLIOGRAPHY

»»The diagnosis of dementia due to Alzheimer’s disease: recommendations from the National Institute on Aging and the Alzheimer’s Association workgroup McKhann GM, et al. Alzheimers Dement. 2011;7:263-269.

»»Practical guidelines for the recognition and diagnosis of dementia Galvin JE, Sadowsky CH. J Am Board Fam Med. 2012;25:367-382.

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»»Multi-modal techniques for diagnosis and prognosis of Alzheimer’s disease Perrin RJ, et al. Nature. 2009;461:916-922.

»»Snapshot:pathology of Alzheimer’s disease Selkoe DJ. Cell. 2013;154:468-468.e1.

»»Toward defining the preclinical stages of Alzheimer’s disease: recommendations from the National Institute on Aging and the Alzheimer’s Association workgroup Sperling RA, et al. Alzheimers Dement. 2011;7:280-292.

»»Comparison of International Working Group criteria and National Institute on Aging-Alzheimer’s Association criteria for Alzheimer’s disease

BIBLIOGRAPHY

Visser PJ, et al. Alzheimers Dement. 2012;8:560-563.

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