February 2019, Volume 25, Issue 1
BROWSE ISSUES

February 2019, Vol.25, No.1

Guest Editor:

Jonathan Graff-Radford, MD

Editor-in-Chief:

STEVEN L. LEWIS, MD, FAAN

ISSN: 1080-2371

Online ISSN: 1538-6899

REVIEW ARTICLES
Late-onset Alzheimer Disease
Rabinovici, Gil D.
CONTINUUM: Lifelong Learning in Neurology
February 2019 - Volume 25 - Issue 1 - p 14-33
doi: 10.1212/CON.0000000000000700
Early-onset Alzheimer Disease and Its Variants
Mendez, Mario F.
CONTINUUM: Lifelong Learning in Neurology
February 2019 - Volume 25 - Issue 1 - p 34-51
doi: 10.1212/CON.0000000000000687
Posterior Cortical Atrophy
Schott, Jonathan M.; Crutch, Sebastian J.
CONTINUUM: Lifelong Learning in Neurology
February 2019 - Volume 25 - Issue 1 - p 52-75
doi: 10.1212/CON.0000000000000696
Behavioral Variant Frontotemporal Dementia
Seeley, William W.
CONTINUUM: Lifelong Learning in Neurology
February 2019 - Volume 25 - Issue 1 - p 76-100
doi: 10.1212/CON.0000000000000698
Primary Progressive Aphasias and Apraxia of Speech
Botha, Hugo; Josephs, Keith A.
CONTINUUM: Lifelong Learning in Neurology
February 2019 - Volume 25 - Issue 1 - p 101-127
doi: 10.1212/CON.0000000000000699
Lewy Body Dementias
Armstrong, Melissa J.
CONTINUUM: Lifelong Learning in Neurology
February 2019 - Volume 25 - Issue 1 - p 128-146
doi: 10.1212/CON.0000000000000685
Vascular Cognitive Impairment
Graff-Radford, Jonathan
CONTINUUM: Lifelong Learning in Neurology
February 2019 - Volume 25 - Issue 1 - p 147-164
doi: 10.1212/CON.0000000000000684
Normal Pressure Hydrocephalus
Graff-Radford, Neill R.; Jones, David T.
CONTINUUM: Lifelong Learning in Neurology
February 2019 - Volume 25 - Issue 1 - p 165-186
doi: 10.1212/CON.0000000000000689
Chronic Traumatic Encephalopathy
Turk, Katherine W.; Budson, Andrew E.
CONTINUUM: Lifelong Learning in Neurology
February 2019 - Volume 25 - Issue 1 - p 187-207
doi: 10.1212/CON.0000000000000686
Hippocampal Sclerosis, Argyrophilic Grain Disease, and Primary Age-Related Tauopathy
Jicha, Gregory A.; Nelson, Peter T.
CONTINUUM: Lifelong Learning in Neurology
February 2019 - Volume 25 - Issue 1 - p 208-233
doi: 10.1212/CON.0000000000000697
Reversible Dementias
Day, Gregory S.
CONTINUUM: Lifelong Learning in Neurology
February 2019 - Volume 25 - Issue 1 - p 234-253
doi: 10.1212/CON.0000000000000688
Editor's Preface
Articles
Key Points
Abbreviations
Appendix
Issue Overview

Issue Overview

CONTINUUM: Lifelong Learning in Neurology February 2019 - Volume 25 - Issue 1 - [no page #] doi: 10.1212/01.CON.0000553461.97084.80

Issue Overview

Dementia, Volume 25, Issue 1, February 2019

Continuum: Lifelong Learning in Neurology® is designed to help practicing neurologists stay abreast of advances in the field while simultaneously developing lifelong self-directed learning skills.

Learning Objectives

Upon completion of this Continuum: Lifelong Learning in Neurology Dementia issue, participants will be able to:

  • Describe the epidemiology, genetic and environmental risk factors, clinical diagnosis, biomarkers, and treatment of late-onset Alzheimer disease
  • Discuss the clinical, neuropathologic, and management aspects of early-onset Alzheimer disease that differentiate it from the more common late-onset Alzheimer disease
  • Describe the clinical features, molecular underpinnings, relevant investigation findings, diagnostic criteria, and management of patients with posterior cortical atrophy
  • Define the core clinical features of behavioral variant frontotemporal dementia (bvFTD), distinguish it from other forms of mid- to late-life behavioral change, formulate a pathologic differential diagnosis for individual patients with bvFTD, and identify key aspects of management
  • Discuss the classification and distinguishing clinical and imaging features of primary progressive apraxia and aphasia
  • Describe the diseases included under the Lewy body dementia umbrella and current strategies for evaluating and treating them
  • Describe the diseases included under the vascular cognitive impairment umbrella and current strategies for evaluating and treating them
  • Develop a practical clinical approach to the diagnosis and management of idiopathic normal pressure hydrocephalus and recognize when overlapping diseases are present
  • Describe the current chronic traumatic encephalopathy neuropathologic and research-based diagnostic criteria and the emerging understanding of chronic traumatic encephalopathy risk factors and biomarkers
  • Describe the pathologic entities commonly found in the aging population that can mimic Alzheimer disease and understand the clinical, biomarker-based, and genetic features that may distinguish these entities from the dementia and cognitive decline caused by Alzheimer disease pathology
  • Identify clinical features that distinguish patients with reversible causes of dementia
  • Discuss the reasons medications carry a boxed warning as well as the importance of disclosing (and documenting the discussion of) the risks and benefits of any high-risk medications to patients or patients’ health care proxies

Core Competencies

This Continuum: Lifelong Learning in Neurology Dementia issue covers the following core competencies:

Patient Care

Medical Knowledge

Practice-Based Learning and Improvement

Interpersonal and Communication Skills

Professionalism

Systems-Based Practice

Contributors

Jonathan Graff-Radford, MD, Guest Editor

Assistant Professor of Neurology, Mayo Clinic College of Medicine and Science, Rochester, Minnesota

Relationship Disclosure: Dr Graff-Radford receives research/grant support from the National Institute on Aging/National Institutes of Health (K76AG057015).

Unlabeled Use of Products/Investigational Use Disclosure: Dr Graff-Radford discusses the unlabeled/investigational use of acetylcholinesterase inhibitors and memantine for vascular cognitive impairment.

Melissa J. Armstrong, MD, MSc, FAAN

Assistant Professor of Neurology, University of Florida College of Medicine; Director, University of Florida Mangurian Clinical Research Headquarters for Lewy Body Dementia, Gainesville, Florida

Relationship Disclosure: Dr Armstrong serves on the evidence review board of Neurology journals and as a guideline consultant for the American Academy of Neurology and has received personal compensation for speaking engagements from the American Academy of Neurology and Medscape CME. Dr Armstrong receives research/grant support from the Agency for Healthcare Research and Quality (K08HS24159), 1Florida Alzheimer’s Disease Research Center (AG047266), and the Lewy Body Dementia Association Research Center of Excellence program and receives publishing royalties from Oxford University Press.

Unlabeled Use of Products/Investigational Use Disclosure: Dr Armstrong discusses the unlabeled/investigational use of biomarkers for the diagnosis of dementia with Lewy bodies and the unlabeled/investigational use of donepezil, galantamine, and memantine for cognitive symptoms in Lewy body dementia; clozapine and quetiapine for psychosis in Lewy body dementia; and clonazepam and melatonin for rapid eye movement sleep behavior disorder.

Hugo Botha, MBChB

Assistant Professor of Neurology, Mayo Clinic College of Medicine and Science, Rochester, Minnesota

Relationship Disclosure: Dr Botha receives research/grant support from the National Institutes of Health (R01 DC012519-06).

Unlabeled Use of Products/Investigational Use Disclosure: Dr Botha reports no disclosure.

Andrew E. Budson, MD

Chief, Cognitive and Behavioral Neurology, VA Boston Healthcare System; Professor of Neurology, Boston University School of Medicine, Boston, Massachusetts

Relationship Disclosure: Dr Budson has served as a consultant for Axovant Sciences, Inc, and Eli Lilly and Company and has received personal compensation for speaking engagements from Eli Lilly and Company. Dr Budson receives research/grant support from the US Department of Veterans Affairs (I01CX000736) and publishing royalties from Elsevier and Oxford University Press.

Unlabeled Use of Products/Investigational Use Disclosure: Dr Budson discusses the unlabeled/investigational use of several classes of medications for chronic traumatic encephalopathy, including cholinesterase inhibitors for memory-related issues, selective serotonin reuptake inhibitors for mood and behavioral issues, memantine for attentional issues in those with advanced dementia, and atypical antipsychotics for those who are disinhibited and violent.

Sebastian J. Crutch, PhD, CPsych

Professor of Neuropsychology, Dementia Research Centre, University College London Institute of Neurology, University College London, London, United Kingdom

Relationship Disclosure: Dr Crutch receives research/grant support from the Alzheimer’s Society (AS-PG-14-022), The Dunhill Medical Trust (R337/0214), the Economic and Social Research Council-National Institute of Health Research (ES/L001810/1), and the Engineering and Physical Sciences Research Council (EP/M006093/1).

Unlabeled Use of Products/Investigational Use Disclosure: Dr Crutch reports no disclosure.

Gregory S. Day, MD, MSc

Assistant Professor of Neurology; Associate Leader, Knight Alzheimer Disease Research Center Clinical Core, Washington University in St. Louis, St. Louis, Missouri

Relationship Disclosure: Dr Day has served as a topic editor on dementia for DynaMed Plus (EBSCO Industries, Inc) and as clinical director for the Anti-NMDA Receptor Encephalitis Foundation. Dr Day receives research/grant support from Avid Radiopharmaceuticals, the Foundation for Barnes Jewish Hospital, and the National Institutes of Health (P01AG03991, R56AG057195) and holds stock in ANI Pharmaceuticals, Inc. Dr Day has provided record review and expert medical testimony on legal cases pertaining to management of Wernicke encephalopathy.

Unlabeled Use of Products/Investigational Use Disclosure: Dr Day reports no disclosure.

Neill R. Graff-Radford, MBBCH, FRCP, FAAN

David Eisenberg Professor, Mayo Clinic College of Medicine and Science, Jacksonville, Florida

Relationship Disclosure: Dr Graff-Radford serves on the editorial board of Alzheimer’s Research & Therapy and receives research/grant support from AbbVie Inc; Axovant Sciences, Inc; Biogen; Eli Lilly and Company; the National Institutes of Health (P50AG16574, 1R01AG045390-01A1, R56AG057195, UF1AG032438, U54NS092089, U01AG24904, U01NS100620); Novartis AG; and the US Department of Defense (WEI1872).

Unlabeled Use of Products/Investigational Use Disclosure: Dr Graff-Radford reports no disclosure.

Gregory A. Jicha, MD, PhD

Professor of Neurology and Behavioral Science, University of Kentucky, Lexington, Kentucky

Relationship Disclosure: Dr Jicha serves as a consultant for the Cure Alzheimer’s Fund and provides contract research for AbbVie Inc; Alltech; Axovant Sciences, Inc; Eli Lilly and Company; Eisai Inc; Janssen Global Services, LLC; Novartis AG; Suven Life Sciences Limited; and VTV Therapeutics. Dr Jicha receives research/grant support from the National Institutes of Health (UH2 NS100606, R01 AG054130, U19 AG010483, U24 AG057437, P30 AG028383, R01 HD064993, R01 AG057187, R01 AG042419, R01 NR014189).

Unlabeled Use of Products/Investigational Use Disclosure: Dr Jicha reports no disclosure.

David T. Jones, MD

Senior Associate Consultant, Department of Neurology, Mayo Clinic; Assistant Professor of Neurology and Radiology, Mayo Clinic College of Medicine and Science, Rochester, Minnesota

Relationship Disclosure: Dr Jones receives research/grant support from the Minnesota Partnership for Biotechnology and Medical Genomics (P006598701) and the National Institutes of Health (U01EB 24450-1, R01DC14942-1, U01AG52943, U01AG45390, U19AG24904).

Unlabeled Use of Products/Investigational Use Disclosure: Dr Jones reports no disclosure.

Keith A. Josephs, MD, MST, MSc

Professor of Neuroscience and Neurology, Mayo Clinic College of Medicine and Science, Rochester, Minnesota

Relationship Disclosure: Dr Josephs receives research/grant support from the National Institutes of Health (R01 AG37491, R01NS89757, R01 DC14942).

Unlabeled Use of Products/Investigational Use Disclosure: Dr Josephs reports no disclosure.

Joseph S. Kass, MD, JD, FAAN

Associate Dean, Office of Student Affairs; Professor of Neurology, Psychiatry, and Medical Ethics; Director, Alzheimer’s Disease and Memory Disorders Center, Baylor College of Medicine; Chief of Neurology, Ben Taub General Hospital, Houston, Texas

Relationship Disclosure: Dr Kass serves as associate editor of ethical and medicolegal issues for Continuum, as an associate editor for Continuum Audio, as a neurology section editor of Ferri’s Clinical Advisor for Elsevier, and as co-editor of Neurology Secrets, Sixth Edition. Dr Kass has received personal compensation for CME lectures from Pri-Med Medical Group and has received personal compensation as a medicolegal consultant in legal cases involving criminal proceedings, malpractice, and personal injury.

Unlabeled Use of Products/Investigational Use Disclosure: Dr Kass reports no disclosure.

Mario F. Mendez, MD, PhD, FAAN

Behavioral Neurology Program Director; Professor of Neurology, Psychiatry, and Biobehavioral Sciences, David Geffen School of Medicine at the University of California, Los Angeles; Director of Neurobehavior, VA Greater Los Angeles Healthcare System, Los Angeles, California

Relationship Disclosure: Dr Mendez serves as a section editor for UpToDate, Inc, and as an associate editor of the Journal of Alzheimer’s Disease. Dr Mendez has received personal compensation for speaking engagements from the Medical Education Speakers Network and receives research/grant support from Biogen and the National Institutes of Health/National Institute on Aging (R01AG050967). Dr Mendez receives publishing royalties from Cambridge University Press.

Unlabeled Use of Products/Investigational Use Disclosure: Dr Mendez reports no disclosure.

Peter T. Nelson, MD, PhD

Professor of Pathology and Laboratory Science, University of Kentucky College of Medicine, Lexington, Kentucky

Relationship Disclosure: Dr Nelson serves on the National Institutes of Health/National Institute on Aging external advisory boards of Mayo Clinic and Rush University and as an associate editor for Acta Neuropathologica and the Journal of Neuropathology & Experimental Neurology.

Unlabeled Use of Products/Investigational Use Disclosure: Dr Nelson reports no disclosure.

Gil D. Rabinovici, MD

Edward Fein and Pearl Landrith Distinguished Professor, Department of Neurology, University of California San Francisco, San Francisco, California

Relationship Disclosure: Dr Rabinovici receives research/grant support from the National Institutes of Health (P01-AG019724, P50-AG23501, R01 AG032289, R01-AG045611, R01-AG048234, R01 AG057204, R56-AG057195) and the National Institute of Neurological Disorders and Stroke (R01-AG038791). Dr Rabinovici receives research support from Avid Radiopharmaceuticals, Eli Lilly and Company, General Electric Healthcare, and Life Molecular Imaging. Dr Rabinovici has served on scientifi c advisory boards for AXON Neuroscience SE; Eisai Co, Ltd; F. Hoffman- La Roche Ltd; Genentech, Inc; and Merck & Co, Inc. Dr Rabinovici serves as an associate editor for JAMA Neurology.

Unlabeled Use of Products/Investigational Use Disclosure: Dr Rabinovici discusses the investigational use of the positron emission tomography (PET) radiotracers [11C]Pittsburgh Compound B and [18F]fl ortaucipir in the diagnosis of Alzheimer disease.

Rachel V. Rose, JD, MBA

Attorney, Rachel V. Rose Attorney at Law PLLC; Affiliated Faculty, Baylor College of Medicine, Houston, Texas

Relationship Disclosure: Ms Rose serves on the editorial board of BC Advantage and receives book royalties from the American Bar Association.

Unlabeled Use of Products/Investigational Use Disclosure: Ms Rose reports no disclosure.

Jonathan M. Schott, BSc, MD, FRCP, FEAN, SFHEA

Professor of Neurology, Honorary Consultant Neurologist, University College London, London, United Kingdom

Relationship Disclosure: Dr Schott serves on advisory boards for Biogen; Eli Lilly and Company; F Hoffman-La Roche Ltd; and Merck & Co, Inc, and on the drug safety monitoring board for AXON Neuroscience SE. Dr Schott has received personal compensation for speaking engagements for Biogen, Eli Lilly and Company, and GE Healthcare Worldwide and receives research/grant support from Alzheimer’s Research UK, Avid Radiopharmaceuticals, Brain Research UK, British Heart Foundation, Engineering and Physical Sciences Research Council (EP/J020990/1), European Commission Horizon 2020, Medical Research Council Dementias Platform UK (MR/L023784/1), Weston Brain Institute, and Wolfson Foundation. Dr Schott receives royalties from Henry Stewart Talks and Oxford University Press.

Unlabeled Use of Products/Investigational Use Disclosure: Dr Schott reports no disclosure.

William W. Seeley, MD

Professor of Neurology and Pathology, University of California San Francisco, San Francisco, California

Relationship Disclosure: Dr Seeley serves on the editorial boards of Acta Neuropathologica, Annals of Neurology, and NeuroImage: Clinical and as a consultant for Biogen; Merck & Co, Inc; and Third Rock Ventures, LLC. Dr Seeley receives research/grant support from the Bluefield Project to Cure FTD, the National Institutes of Health/National Institute on Aging (AG023501, AG019724), and the National Institutes of Health/National Institute of Neurological Disorders and Stroke (NS1104437, NS092474). Dr Seeley has provided expert medical testimony on legal cases related to violence in patients with neuropsychiatric illness.

Unlabeled Use of Products/Investigational Use Disclosure: Dr Seeley discusses the unlabeled/investigational use of medications for the treatment of behavioral variant frontotemporal dementia, none of which are approved by the US Food and Drug Administration.

Katherine W. Turk, MD

Cognitive and Behavioral Neurologist, VA Boston Healthcare System; Assistant Professor of Neurology, Boston University School of Medicine, Boston, Massachusetts

Relationship Disclosure: Dr Turk receives research/grant support from the Alzheimer’s Association.

Unlabeled Use of Products/Investigational Use Disclosure: Dr Turk discusses the unlabeled/investigational use of several classes of medications for chronic traumatic encephalopathy, including cholinesterase inhibitors for memory-related issues, selective serotonin reuptake inhibitors for mood and behavioral issues, memantine for attentional issues in those with advanced dementia, and atypical antipsychotics for those who are disinhibited and violent.

Self-Assessment and CME Test Writers

D. Joanne Lynn, MD, FAAN

Associate Dean for Student

Life, Clinical Professor

of Neurology, The Ohio

State University College of

Medicine, Columbus, Ohio

Relationship Disclosure: Dr Lynn receives book royalties from Lippincott Williams & Wilkins and holds stock in Abbott Laboratories; AbbVie Inc; Amgen Inc; Bristol-Myers Squibb Company; CVS Health Corporation; Express Scripts Holding Company; General Electric; Merck & Co, Inc; and Zimmer Biomet.

Unlabeled Use of Products/Investigational Use Disclosure: Dr Lynn reports no disclosure.

Allyson R. Zazulia, MD

Professor of Neurology and Radiology, Associate Dean for Continuing Medical Education, Washington University, St. Louis, Missouri

Relationship Disclosure: Dr Zazulia reports no disclosure.

Unlabeled Use of Products/Investigational Use Disclosure: Dr Zazulia reports no disclosure.

Methods of Participation and Instructions for Use

Continuum: Lifelong Learning in Neurology® is designed to help practicing neurologists stay abreast of advances in the field while simultaneously developing lifelong self-directed learning skills. In Continuum, the process of absorbing, integrating, and applying the material presented is as important as, if not more important than, the material itself.

The goals of Continuum include disseminating up-to-date information to the practicing neurologist in a lively, interactive format; fostering self-assessment and lifelong study skills; encouraging critical thinking; and, in the final analysis, strengthening and improving patient care.

Each Continuum issue is prepared by distinguished authors who are acknowledged leaders in their respective fields. Six issues are published annually and are composed of review articles, case-based discussions on ethical and practice issues related to the issue topic, coding information, and comprehensive continuing medical education (CME) and self-assessment offerings. For detailed instructions regarding Continuum CME and self-assessment activities, visit continpub.com/CME.

The review articles emphasize clinical issues emerging in the field in recent years. Case reports and vignettes are used liberally, as are tables and illustrations. Audio interviews with the authors of Continuum articles are published alongside each article, and video material relating to the issue topic accompanies issues when applicable.

The text can be reviewed and digested most effectively by establishing a regular schedule of study in the office or at home, either alone or in an interactive group. If subscribers use such regular and perhaps new study habits, Continuum’s goal of establishing lifelong learning patterns can be met.

© 2019 American Academy of Neurology