Clinical Issues in Alzheimer’s Disease

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This activity is jointly provided by Global Education Group and Integritas Communications. This activity is supported by an educational grant from Biogen MA, Inc.

A CME CorporateSponsored Symposium held in conjunction with the Alzheimer’s Association International Conference

Access program front matter, faculty bios, program slides, relevant tools, publications, guidelines, and more! Scan the QR code or log on to ExchangeCME.com/ALZResources22


Alireza Atri, MD, PhD

Dr. Alireza Atri is an internationally renowned cognitive neurologist, and clinical researcher and trialist in Alzheimer’s disease (AD) and Related Dementias (ADRD). He is the Director of the Banner Sun Health Research Institute in Sun City, Arizona; and Co-leader of the Clinical and Biomarker Cores of the National Institute on Aging (NIA)/National Institutes of Health (NIH)-funded Arizona Alzheimer’s Disease Research Center (ADRC). Dr. Atri holds degrees from the University of California, Los Angeles (UCLA; PhD in Biomathematics), University of California, San Francisco (UCSF; MD), and Harvard Medical School–Massachusetts Institute of Technology Division of Health Sciences and Technology (HMS-MIT HST; MMSc). He completed internship (medicine) and residency (neurology) at the Harvard Massachusetts General Hospital (MGH)– Brigham and Women’s Hospital (BWH) programs; postgraduate training and clinical and research fellowships at MGH/HMS (Cognitive Neurology and Dementias), Boston University (Cognitive and Computational Neuroscience), and MIT (Experimental Therapeutics); and served on the MGH faculty from 2001-2015. He continues to serve on the faculty at BWH and HMS in Boston, Massachusetts. He specializes in the care of persons with early-onset cognitive disorders/young-onset AD/ADRD. His research and educational efforts focus on improving detection, prognostication, biomarker validation, experimental therapeutics, and clinical best practices in ADRD. Dr. Atri serves as co-chair of the US Alzheimer’s Association’s national clinical practice guidelines workgroup on the evaluation of suspected cognitive-behavioral impairment and AD/ADRD; as chair of the Alzheimer’s Disease International (ADI) Medical Scientific Advisory Panel; as Project Arm Leader for Dominantly Inherited Alzheimer’s Disease (DIAD) families (DIAN-TU001) gantenerumab open-label extension (OLE) study, and as leader and steering committee member of multiple global AD experimental therapeutics/trials programs and research consortia.

Sharon Cohen, MD, FRCPC

Dr. Sharon Cohen is a behavioral neurologist and the Medical Director of Toronto Memory Program, a community-based medical facility that she established in 1996 for the purpose of enhancing diagnosis and treatment for individuals with Alzheimer’s disease and related disorders. Her memory clinic and dementia research site are among the most active in Canada. Dr. Cohen has over 28 years of experience in clinical research and has been a site Principal Investigator for over 180 pharmacological trials in dementia, including phase 1 trials. She represents Canada on international advisory boards and steering committees and is a consultant to a wide range of stakeholders including government organizations and patient advocacy groups. A frequent lecturer, she contributes to media events including those on medical ethics. She is known for her advocacy for individuals with neurodegenerative diseases. Despite holding academic and hospital appointments, Dr. Cohen chooses to practice in the community, in keeping with her belief that dementia care and clinical research are best offered in the real-world setting.

Director, Banner Sun Health Research Institute Memory and Cognitive Disorders, Neurology Banner Health Sun City, Arizona

Medical Director, Toronto Memory Program Assistant Professor, University of Toronto Consultant Neurologist, North York General Toronto, Ontario, Canada


Marwan N. Sabbagh, MD, FAAN

Professor of Neurology, Alzheimer’s and Memory Disorders Division Barrow Neurological Institute Research Professor University of Arizona College of Medicine-Phoenix Clinical Professor of Neurology, Creighton University Phoenix, Arizona

Dr. Marwan Noel Sabbagh is a board-certified neurologist and geriatric neurologist who hopes to work himself out of a job. Dr. Sabbagh has dedicated his career to finding a cure for Alzheimer’s and other age-related neurodegenerative diseases. A leading investigator for many prominent national Alzheimer’s treatment trials, Dr. Sabbagh is on the editorial boards of Journal of Alzheimer’s Disease and Alzheimer’s and Dementia Translational Research and Clinical Interventions. He is editor-in-chief of Neurology and Therapy, and has authored and coauthored hundreds of medical and scientific articles on Alzheimer’s research. A fellow of the American Academy of Neurology since 2004, Dr. Sabbagh has been recognized with numerous awards Dr. Sabbagh is the author of The Alzheimer’s Answer: Reduce Your Risk and Keep Your Brain Healthy, with foreword by Justice Sandra Day O’Connor, and of The Alzheimer’s Prevention Cookbook: 100 Recipes to Boost Brain Health. He has edited Palliative Care for Advanced Alzheimer’s and Dementia: Guidelines and Standards for Evidence-Based Care and Geriatric Neurology, published in 2014 and Fighting for My Life: How to Thrive in the Shadow of Alzheimer’s Disease in 2019. His current book is titled Strong Heart, Sharp Mind. Dr. Sabbagh earned his undergraduate degree from the University of California, Berkeley, and his medical degree from the University of Arizona in Tucson. He received his residency training in neurology at Baylor College of Medicine in Houston, Texas, and completed his fellowship in geriatric neurology and dementia at the University of California, San Diego, School of Medicine, where he served on the faculty as assistant professor. Before joining the faculty of the Barrow Neurological Institute, he was the Camille and Larry Ruvo Endowed Chair for Brain Health and Director of the Cleveland Clinic Lou Ruvo Center for Brain Health in Las Vegas. Prior to that, he was the director of the Banner Sun Health Research Institute in Sun City, Arizona.


TARGET AUDIENCE

PROGRAM AGENDA

This activity is designed to educate a multidisciplinary audience, including neurologists, geriatricians, and other clinicians involved in the management of patients with mild cognitive impairment (MCI) or early-stage Alzheimer’s disease (AD).

12:45 Preactivity Questionnaire and Faculty Introductions 12:50 The Latest on Alzheimer’s Disease Pathophysiology • Alzheimer’s disease pathophysiology, including roles of amyloid-β and tau • Genetic implications of common alleles 1:05 Evaluating Patients With MCI or Early-Stage Alzheimer’s Disease • Patient education on symptoms and risk factors • Cognitive tests • Patient and caregiver interviews • Imaging and biomarkers in Alzheimer’s disease 1:25 New Treatment Strategies for Early-Stage Disease • Clinical trial data for efficacy and safety, regulatory status, and prescribing considerations for targeted therapy • Emerging amyloid-β-, tau-, and neuroinflammation targeted treatments • Selecting patients for targeted therapy • Potential changes to day-to-day practice and health care systems with the introduction of targeted therapies 1:45 Postactivity Questionnaire and Q&A Session

PROGRAM OVERVIEW Alzheimer’s disease is becoming increasingly prevalent as the general population ages and is expected to affect 14 million people by 2050. As research continues to evolve, new understanding of pathophysiological targets has shaped drug development, leading to the recent approval of an anti-amyloid therapy, with hope that additional targeted therapies will follow. Clinicians must incorporate not only traditional means of assessing cognitive decline in practice, but also advances in biomarker techniques and novel therapies. Faculty will discuss and debate topics related to the pathophysiology of Alzheimer’s disease including implications for treatment targets, best practices for assessing patients with MCI or early-stage disease, the latest clinical profiles and trial evidence for newer targeted therapies, and how to best utilize these treatment options in real-world practice.

EDUCATIONAL OBJECTIVES After completing this activity, the participant should be better able to: • Describe clinically relevant aspects of Alzheimer’s disease pathophysiology, including amyloid-β and tau • Evaluate patients with mild cognitive impairment or Alzheimer’s disease using cognitive scales, biomarker imaging, clinical examination, and patient/caregiver interviews • Explain clinical trial data, challenges, and future directions with targeted therapies for early Alzheimer’s disease • Manage patients with early-stage Alzheimer’s disease through ongoing communication, shared decision-making, and appropriate selection for treatment with targeted therapy

FEE INFORMATION & REFUND/ CANCELLATION POLICY There is no fee for this educational activity.

INSTRUCTIONS TO RECEIVE CREDIT In order to receive credit for this activity, the participant must attend the live program and complete the program evaluation.

PHYSICIAN ACCREDITATION STATEMENT This activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint providership of Global Education Group (Global) and Integritas Communications. Global is accredited by the ACCME to provide continuing medical education for physicians.

PHYSICIAN CREDIT DESIGNATION Global Education Group designates this live activity for a maximum of 1.25 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

NURSE PRACTITIONER CONTINUING EDUCATION This activity has been planned and implemented in accordance with the Accreditation Standards of the American Association of Nurse Practitioners (AANP) through the joint providership of Global Education Group and Integritas Communications. Global Education Group is accredited by the American Association of


Nurse Practitioners as an approved provider of nurse practitioner continuing education. Provider number: 110121. This activity is approved for 1.25 contact hour(s) (which includes 0.0 hour(s) of pharmacology).

Marwan N. Sabbagh, MD, FAAN

GLOBAL CONTACT INFORMATION For information about the approval of this program, please contact Global at 303-3951782 or cme@globaleducationgroup.com.

DISCLOSURES OF CONFLICTS OF INTEREST Global Education Group (Global) adheres to the policies and guidelines, including the Standards for Integrity and Independence in Accredited CE, set forth to providers by the Accreditation Council for Continuing Medical Education (ACCME) and all other professional organizations, as applicable, stating those activities where continuing education credits are awarded must be balanced, independent, objective, and scientifically rigorous. All persons in a position to control the content of an accredited continuing education program provided by Global are required to disclose all financial relationships with any ineligible company within the past 24 months to Global. All financial relationships reported are identified as relevant and mitigated by Global in accordance with the Standards for Integrity and Independence in Accredited CE in advance of delivery of the activity to learners. The content of this activity was vetted by Global to assure objectivity and that the activity is free of commercial bias. All relevant financial relationships have been mitigated. The faculty have the following relevant financial relationships with ineligible companies: Alireza Atri, MD, PhD Consulting: Acadia Pharmaceuticals Inc., AZTherapies, Inc., Biogen Inc., Eisai Co., Ltd., JOMDD (Japanese Organization for Medical Device Development), F. Hoffmann-La Roche/Genentech, Inc., H. Lundbeck A/S, Novo Nordisk A/S, Qynapse; Grants/Research: Alzheon, Inc., Athira Pharma, Biohaven Pharmaceutical Holding Company Ltd. (with Alzheimer’s Disease Cooperative Study [ADCS]), Eisai Co., Ltd. (with Alzheimer’s Clinical Trials Consortium), Eli Lilly and Company (with NIH), Vivoryon Therapeutics NV (with ADCS) VIVA-MIND Clinical Trial Sharon Cohen, MD, FRCPC

Nothing to disclose

Consulting: Alzheon, Inc., Biogen Inc,, Eisai Co., Ltd., F. Hoffmann-La Roche-Genentech, Inc., KeifeRx, Eli Lilly and Company, NeuroTherapia, Inc., Novo Nordisk A/S, Signant Health, Synaptogenix, Inc., T3D Therapeutics, Inc.; Stock Option Holder: Athira Pharma, Cognoptix Inc, Cortexyme, Inc., NeuroReserve, NeuroTau, Inc., Optimal Cognitive Health Company LLC, Seq Biomarque LLC, TransDermix, uMETHOD Health, Versanum Inc.

The planners and managers have the following relevant financial relationships with ineligible companies: Kristin Delisi, NP Nothing to disclose Lindsay Borvansky Nothing to disclose Andrea Funk Nothing to disclose Liddy Knight Nothing to disclose Ashley Cann Nothing to disclose Gena Dolson, MS Nothing to disclose

DISCLOSURE OF UNLABELED USE This educational activity may contain discussion of published and/or investigational uses of agents that are not indicated by the US Food and Drug Administration. Global Education Group (Global) and Integritas do not recommend the use of any agent outside of the labeled indications. The opinions expressed in the educational activity are those of the faculty and do not necessarily represent the views of any organization associated with this activity. Please refer to the official prescribing information for each product for discussion of approved indications, contraindications, and warnings.

DISCLAIMER Participants have an implied responsibility to use the newly acquired information to enhance patient outcomes and their own professional development. The information presented in this activity is not meant to serve as a guideline for patient management. Any procedures, medications, or other courses of diagnosis or treatment discussed in this activity should not be used by clinicians without evaluation of patient conditions and possible contraindications or dangers in use, review of any applicable manufacturer’s product information, and comparison with recommendations of other authorities.

















CLINICAL PRACTICE GUIDELINES

SUGGESTED READINGS

The diagnosis of mild cognitive impairment due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease.

2022 Alzheimer’s disease facts and figures.

Albert MS, DeKosky ST, Dickson D, et al. Alzheimers Dement. 2011;7(3):270-279. https://alz-journals.onlinelibrary.wiley.com/doi/abs/10.1016/j.jalz.2011.03.008

The diagnosis of dementia due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease.

Alzheimer’s Association. https://www.alz.org/media/Documents/alzheimers-facts-and-figures.pdf

The Alzheimer’s disease clinical spectrum: diagnosis and management. Atri A. Med Clin North Am. 2019;103(2):263-293. https://www.sciencedirect.com/science/article/pii/S0025712518301317

Neuropathological stageing of Alzheimer-related changes.

McKhann GM, Knopman DS, Chertkow H, et al. Alzheimers Dement. 2011;7(3):263-269.

Braak H, Braak E. Acta Neuropathol. 1991;82(4):239-259.

https://alz-journals.onlinelibrary.wiley.com/doi/abs/10.1016/j.jalz.2011.03.005

https://pubmed.ncbi.nlm.nih.gov/1759558/

PATIENT AND CAREGIVER RESOURCES

Two randomized phase 3 studies of aducanumab in early Alzheimer’s disease.

AD8 dementia screening interview https://www.alz.org/media/Documents/ad8-dementia-screening.pdf

Alzheimer’s Association

Budd Haeberlein S, Aisen PS, Barkhof F, et al. J Prev Alzheimers Dis. 2022;9(2):197-210. https://link.springer.com/article/10.14283/jpad.2022.30

https://www.alz.org/

Costly new Alzheimer disease medications on the horizon—financing alternatives for Medicare.

The Alzheimer’s Questionnaire

Fleming WK, Brown CR, Shrank WH. JAMA Health Forum. 2020;1(9):e201148.

https://www2.gov.bc.ca/assets/gov/health/practitioner-pro/bc-guidelines/cogimp-alzheimerquestionnaire.pdf

General Practitioner Assessment of Cognition (GPCOG) http://gpcog.com.au/

Mini-Mental State Exam (MMSE) Alzheimer’s / dementia test: administration, accuracy and scoring https://www.dementiacarecentral.com/mini-mental-state-exam/

Montreal Cognitive Assessment Test (MoCA) for dementia & Alzheimer’s https://www.dementiacarecentral.com/montreal-cognitive-assessment-test/

Standardized Mini-Cog© Instrument https://mini-cog.com/mini-cog-instrument/standardized-mini-cog-instrument/

https://jamanetwork.com/channels/health-forum/fullarticle/2771217

Assessment of a plasma amyloid probability score to estimate amyloid positron emission tomography findings among adults with cognitive impairment. Hu Y, Kirmess KM, Meyer MR, et al. JAMA Netw Open. 2022;5(4):e228392. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9024390/

Pharmacotherapy of Alzheimer’s disease: seeking clarity in a time of uncertainty. Husna Ibrahim N, Yahaya MF, Mohamed W, et al. Front Pharmacol. 2020;11:261. https://www.frontiersin.org/articles/10.3389/fphar.2020.00261/full


A/T/N: an unbiased descriptive classification scheme for Alzheimer disease biomarkers. Jack CR Jr, Bennett DA, Blennow K, et al. Neurology. 2016;87(5):539-547. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4970664/

Molecular biomarkers of Alzheimer’s disease: progress and prospects. Lashley T, Schott JM, Weston P, et al. Dis Model Mech. 2018;11(5):dmm031781. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5992610/

Neuroinflammation and microglial activation in Alzheimer disease: where do we go from here? Leng F, Edison P. Nat Rev Neurol. 2021;17(3):157-172.

Cognitive assessment of Alzheimer’s disease and dementias in clinical practice: pragmatics of brief instruments and neuropsychological evaluation. Shaughnessy L, Sheard S, Goldfarb D, Atri A. J Clin Psychiatry. 2019;80(4):MS18002BR2C. https://www.psychiatrist.com/jcp/neurologic/neurology/cognitive-assessment-for-alzheimersdisease/

A randomized, double-blind, phase 2b proof-of-concept clinical trial in early Alzheimer’s disease with lecanemab, an anti-Aβ protofibril antibody. Swanson CJ, Zhang Y, Dhadda S, et al. Alzheimers Res Ther. 2021;13(1):80.

https://www.nature.com/articles/s41582-020-00435-y

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8053280/

Donanemab in early Alzheimer’s disease.

What are the difficulties of implementing innovative pharmacy practice models in the care of patients with dementia?

Mintun MA, Lo AC, Duggan Evans C, et al. N Engl J Med. 2021;384(18):1691-1704. https://www.nejm.org/doi/full/10.1056/NEJMoa2100708

Wimo A. Expert Rev Pharmacoecon Outcomes Res. 2021;21(1):1-4.

Prediction of future Alzheimer’s disease dementia using plasma phospho-tau combined with other accessible measures.

Economic burden of Alzheimer disease and managed care considerations.

Palmqvist S, Tideman P, Cullen N, et al. Nat Med. 2021;27(6):1034-1042. https://www.nature.com/articles/s41591-021-01348-z

Increasing precision of clinical diagnosis of Alzheimer’s disease using a combined algorithm incorporating clinical and novel biomarker data. Sabbagh MN, Lue LF, Fayard D, Shi J. Neurol Ther. 2017;6(suppl 1):83-95. https://link.springer.com/article/10.1007%2Fs40120-017-0069-5

Amyloid-related imaging abnormalities in 2 phase 3 studies evaluating aducanumab in patients with early Alzheimer disease. Salloway S, Chalkias S, Barkhof F, et al. JAMA Neurol. 2022;79(1):13-21. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8609465/

https://www.tandfonline.com/doi/full/10.1080/14737167.2021.1848551

Wong W. Am J Manag Care. 2020;26(suppl 8):S177-S183. https://www.ajmc.com/view/economic-burden-of-alzheimer-disease-and-managed-careconsiderations


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