Table Of ContentAlzheimer’s Disease
C C N
U R R E N T L I N I C A L E U R O L O G Y
Daniel Tarsy, , S E
MD ERIES DITOR
Clinical Handbook of Insomnia, edited by Hrayr P. Attarian, 2004
Critical Care Neurology and Neurosurgery, edited by Jose I. Suarez, 2004
Alzheimer’s Disease:A Physician’s Guide to Practical Management,
edited by Ralph W. Richter and Brigitte Zoeller Richter, 2004
Field of Vision: A Manual and Atlas of Perimetry, edited by Jason J. S. Barton
and Michael Benatar, 2003
Surgical Treatment of Parkinson’s Disease and Other Movement Disorders,
edited by Daniel Tarsy, Jerrold L. Vitek, and Andres M. Lozano, 2003
Myasthenia Gravis and Related Disorders, edited by Henry J. Kaminski, 2003
Seizures:Medical Causes and Management, edited by Norman Delanty, 2002
Clinical Evaluation and Management of Spasticity, edited by David A. Gelber
and Douglas R. Jeffery, 2002
Early Diagnosis of Alzheimer's Disease, edited by Leonard F. M. Scinto
and Kirk R. Daffner, 2000
Sexual and Reproductive Neurorehabilitation, edited by Mindy Aisen, 1997
Alzheimer’s Disease
A Physician’s Guide
to Practical Management
Edited by
Ralph W. Richter,
MD, FACP
Clinical Professor of Neurology and Psychiatry
The University of Oklahoma College of Medicine
Director, Alzheimer’s Disease Research Unit
St. John Medical Center, Tulsa, OK
Brigitte Zoeller Richter,
DiplPharm
Pharmacist, Publicist, Tulsa, OK
SPRINGER SCIENCE+BUSINESS MEDIA, LLC
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ISBN978-1-4757-4485-9
Library of Congress Cataloging-in-Publication Data
Alzheimer’s disease : a physician’s guide to practical management / edited by Ralph W. Richter, Brigitte Zoeller Richter.
p. ; cm. — (Current clinical neurology)
Includes bibliographical references and index.
ISBN 978-1-4757-4485-9 ISBN 978-1-59259-661-4 (eBook)
DOI 10.1007/978-1-59259-661-4
1. Alzheimer’s disease. 2. Alzheimer’s disease—Treatment.
[DNLM: 1. Alzheimer Disease. WT 155 A4756 2004] I. Richter, Ralph W. II. Zoeller Richter, Brigitte. III. Series.
RC523.A3748 2004
616.8’31—dc21
2003006948
Preface
Alzheimer’s disease (AD) is a devastating and dehumanizing illness affecting increasingly large
numbers of elderly and even middle-aged persons in a worldwide epidemic. Alzheimer’s Disease: A
Physician’s Guide to Practical Management was written by selected clinicians and scientists who
represent some of the world’s leading centers of excellence in AD research. The editors are proud and
grateful for their profound contributions.
This book is particularly designed to assist physicians and other health-care professionals in the
evaluation, assessment, and treatment of individuals with AD. At the same time, by illuminating the basic
scientific background, we hope to provide state-of-the art information about the disease and possible
future therapeutic strategies. The recent psychiatric treatment aspects of AD are also clearly presented.
Because the early diagnosis of the dementia process is now considered of increasing importance,
we focus particularly in several chapters on early changes and preclinical conditions, such as mild
cognitive impairment and predementia AD.
The pathway toward reaching the goal of prevention of the disease is arduous and requires patience
and fortitude. Patients and their families are not well served by overenthusiastic releases from
companies or from scientists at a stage of research that can offer only experimental and animal data as
grounds for optimism. Nevertheless, it is necessary to be informed about what might be coming up in
the future. For this reason, comprehensive and timely information about potential future options for
prevention and treatment of AD is included. A number of basic scientists discuss their areas of
research in this volume. As a result, we have provided our readers with broad insight into such new
therapeutic directions as stem cell therapy and other unique strategies.
AD imposes a tremendously painful burden on caregivers as well as friends. The consequences of
providing this care are associated with deep feelings of isolation, loneliness, and despair. This has led
us to include treatment of these aspects in this volume. We also provide some guidance for caregivers
and medical providers on how to overcome the breakdown of communication that the illness creates.
It was our primary goal as editors to provide established scientific and clinical knowledge in
comprehensible language and to touch upon more recent objects of research. As the reader may notice, we
also cover aspects of the disease that have not yet been discussed in the available textbooks on AD.
We certainly hope that Alzheimer’s Disease: A Physician’s Guide to Practical Management will
serve as a rich source of information that can be utilized by physicians in their daily practice of
diagnosing and treating patients with AD. We must particularly bear in mind that the disease still
appears to be underdiagnosed and undertreated (1).
Supporting physicians in their management of AD is a way of helping patients and families to live
better with the disease and to cope with the problems it poses. As we all know, dealing with an AD
patient can be an extremely sad and frustrating task. Perhaps this book, by providing practical
guidance, can make the task a little easier and help to “keep our hearts open in hell,” as a caregiver
once said (2).
Ralph Walter Richter, MD, FACP
Brigitte Zoeller Richter, DiplPharm
1. Reichman, W.E.: Current pharmacologic options for patients with Alzheimer’s disease. Ann Gen Hosp Psychiatry
2003; 2: 1.
2. Cited from: Thobaben, M.: Helping families understand and communicate with family members who suffer from
dementia. Home Care Provid 1999; 4: 139–139,146.
v
Contents
Preface........................................................................................................................................v
Contributors.............................................................................................................................xi
Part I Scientific Background of Alzheimer’s Disease
1 Genetics of Alzheimer’s Disease and Related Disorders.................................................. 3
John Hardy
2 Neuropathology of Alzheimer’s Disease...........................................................................21
Christian Schultz, Kelly Del Tredici, and Heiko Braak
3 Oxidative Stress in the Development of Alzheimer’s Disease
and Other Dementias........................................................................................................33
Domenico Praticò
4 Metabolism and Alzheimer’s Disease................................................................................39
John P. Blass
Part II Epidemiology
5 Alzheimer’s Disease: Epidemiological and Statistical Data................................................51
Brigitte Zoeller Richter and Ralph W. Richter
6 The Economic Burden of Alzheimer’s Disease and Dementia......................................57
Anders Wimo and Bengt Winblad
7 Potential and Established Risk Factors for Alzheimer’s Disease..................................65
Brigitte Zoeller Richter
Part III Clinical Assessment
8 Medical Diagnosis and Workup of Alzheimer’s Disease...............................................75
Ralph W. Richter
9 Neuroimaging Techniques: CT, MRI, SPECT, PET..........................................................89
Norman L. Foster
10 Biological Markers in Alzheimer’s Disease.....................................................................103
Ramon Diaz-Arrastia and Fred Baskin
11 The Neuropsychology of Alzheimer’s Disease ..............................................................109
Kirsten I. Taylor and Andreas U. Monsch
12 Vascular Cognitive Impairment in Clinical Practice.....................................................121
Kenneth Rockwood and Timo Erkinjuntti
13 Lewy Body Disease..............................................................................................................127
Robert Barber, Jane Newby, and Ian G. McKeith
14 Frontotemporal Lobe Dementia........................................................................................137
Malgorzata Franczak, Diana Kerwin, and Piero Antuono
Part IV The Transitional Stage
15 Mild Forgetfulness: Distinguishing Early AD from Normal Aging................................147
Scott A. Small
16 Mild Cognitive Impairment: What the Physician Should Know.....................................153
Brigitte Zoeller Richter
vii
viii Contents
17 Diagnosis of Predementia AD in a Clinical Setting.......................................................157
Pieter Jelle Visser
18 Loss of Olfactory Function in Patients With Alzheimer’s Disease.............................165
Claire Murphy and Paul E. Gilbert
Part V Treatment Options
19 Treatment of Alzheimer’s Disease: Basic Considerations...............................................177
Brigitte Zoeller Richter and Ralph W. Richter
20 Donepezil in Treatment of AD ..........................................................................................179
Ging-Yuek Robin Hsiung and Howard Feldman
21 Rivastigmine for Treatment of AD ...................................................................................187
Martin R. Farlow
22 Galantamine in Treatment of AD......................................................................................193
M. Saleem Ismail and Pierre N. Tariot
23 Memantine in Treatment of AD ........................................................................................203
Hans Jörg Möbius
24 Alternative Treatment Options .........................................................................................211
Brigitte Zoeller Richter
Part VI Late-Stage Therapy
25 Pain and Palliative Care in Late-Stage Dementia Patients...........................................217
Sophie Pautex, Dina Zekry, Gilbert Zulian, Gabriel Gold,
and Jean-Pierre Michel
26 Cardiological Issues in Late-Stage Alzheimer’s Disease:
A Clinician’s Approach .....................................................................................................225
José R. Medina
Part VII Prevention Strategies
27 Neuroprotection and Neurodegenerative Disease........................................................235
Frank John Emery Vajda
28 Neurotrophic Factors for Prevention of Alzheimer’s Disease.....................................245
Mark H. Tuszynski
29 Statins in Prevention and Treatment of Alzheimer’s Disease.....................................253
David A. Drachman
30 Potential Role of Androgens and Androgen Receptors
in Alzheimer’s Disease...................................................................................................259
Jacob Raber
31 Role of Nutrition in Prevention or Delay of Alzheimer’s Disease..............................273
Hannes B. Staehelin
32 Impact of Physical Activity on Prevention of Alzheimer’s Disease...........................281
Danielle Laurin, René Verreault, and Joan Lindsay
Part VIII Future Developments
33 Stem Cell Therapy for Alzheimer’s Disease....................................................................289
Kiminobu Sugaya
34 Secretases as Potential Targets for Treatment of Alzheimer’s Disease......................301
Weiming Xia
Contents ix
35 AMPA Potentiation as a Treatment Option for Alzheimer’s Disease........................309
Amy S. Chappell and Michael M. Witte
36 Glycosaminoglycans as Potential Future Treatment of Alzheimer’s Disease..........315
Umberto Cornelli
37 Implications of Research for Management of AD..........................................................329
Peter J. Whitehouse
Part IX Treatment Outcome Measurement
38 Rating Scales and Outcome Variables Used in Clinical Trials....................................337
Lon S. Schneider
Part X Neuropsychiatric Management
39 Gender Differences in Behavior of AD Patients.............................................................353
Brian R. Ott
40 Management of Emotional and Behavioral Symptoms in AD....................................363
Myron F. Weiner
41 Assessment and Treatment of Neuropsychiatric Symptoms
in Alzheimer’s Disease...................................................................................................371
Andrew R. Gustavson and Jeffrey L. Cummings
42 Neuropsychiatric Symptoms in African American Dementia Patients.....................387
Raymelle Schoos, Carl I. Cohen, and Lorna Walcott-Brown
43 Resource Utilization by African American Dementia Patients...................................395
Beatrice Pollock
44 Apathy in Alzheimer’s Disease: Relationship to Executive Function.............................399
Susan McPherson
45 Are Alzheimer’s Patients Aware of Their Deficits?.......................................................407
Ben Seltzer
Part XI Family and Care Issues
46 Diagnostic Family Conference in AD:
Issues and Recommendations............................................................................................415
Paul Michael Ramirez, David Castro-Blanco, and Michelle Kehn
47 Care, Caregiver Issues, and Communication With the Demented Patient...............421
Ralph W. Richter and Brigitte Zoeller Richter
48 Dental Care of AD Patients................................................................................................427
Christina A. Gitto, Michael J. Moroni, Geza T. Terezhalmy,
and Satinderpal K. Sandu
49 Long-Term Medical Care Issues........................................................................................441
Vonda K. Gravely and Jacobo Mintzer
50 Loneliness and Depression in Caregivers .......................................................................449
Rose A. Beeson
51 Frequently Asked Questions About Alzheimer’s Disease...........................................455
Brigitte Zoeller Richter
Appendix:Resources.............................................................................................................461
Index.......................................................................................................................................465
Contributors
PIERO ANTUONO,MD• Professor of Neurology and Pharmacology, The Medical College
of Wisconsin, Milwaukee, WI
ROBERT BARBER, MD,MRCPsych• Centre for Health of the Elderly, Newcastle General Hospital,
Newcastle upon Tyne, United Kingdom
FRED BASKIN,PhD• Associate Professor, Department of Neurology, University of Texas
Southwestern Medical Center, Dallas, TX
ROSE A. BEESON,DNSc, RN• Assistant Professor, William F. Connell School of Nursing, Boston
College, Cushing Hall, Chestnut Hill, MA
JOHN P. BLASS,MD,PhD• Director, Dementia Research Service, Burke Medical Research Institute;
Professor of Neurology and Medicine, Weill Medical College of Cornell University, White
Plains, NY
HEIKO BRAAK,MD• Professor, Institute for Clinical Neuroanatomy, Johann-Wolfgang-Goethe-
University, Frankfurt/Main, Germany
DAVID CASTRO-BLANCO,PhD• Associate Professor, Doctoral Program in Clinical Psychology,
Department of Psychology, Long Island University, Brooklyn Campus, New York, NY
AMY S. CHAPPELL,MD• Lilly Corporate Center, Indianapolis, IN
CARL I. COHEN,MD• Professor and Director, Division of Geriatric Psychiatry, Department of
Psychiatry, SUNY Downstate Medical Center, Brooklyn, NY
UMBERTO CORNELLI,MD,PhD,DrScHc• Adjunct Professor of Pharmacology, Loyola University
Stritch School of Medicine Chicago, Milan, Italy
JEFFREY L. CUMMINGS,MD• Professor of Neurology and Psychiatry, Reed Neurological Research
Center, Department of Neurology, UCLA School of Medicine, Los Angeles
KELLY DEL TREDICI,PhD• Institute for Clinical Neuroanatomy, Johann-Wolfgang-Goethe-
University, Frankfurt/Main, Germany
RAMON DIAZ-ARRASTIA• Associate Professor, Department of Neurology, University of Texas
Southwestern Medical School, Dallas, TX
DAVID A. DRACHMAN,MD• Professor of Neurology, Department of Neurology, University
of Massachusetts Medical School, Worcester, MA
TIMO ERKINJUNTTI,MD,PhD•Department of Neurology, University of Helsinki, Helsinki, Finland
MARTIN R. FARLOW,MD• Professor and Vice Chairman for Research in Neurology, Department
of Neurology, Indiana University School of Medicine, IUPUI; Director, Clinical Care of
Alzheimer Disease Care Center; Co-Director Alzheimer's Disease Clinic; Affiliated Scientist,
Indiana University Center for Aging Research, Indianapolis, IN
HOWARD FELDMAN,MD,FRCP(C)• Professor and Head, Division of Neurology, University of British
Columbia Hospital, Vancouver, BC, Canada
NORMAN L. FOSTER,MD• Professor, Department of Neurology, Senior Research Scientist, Institute
of Gerontology, University of Michigan, Ann Arbor, MI
MALGORZATA FRANCZAK,MD• Assistant Professor of Neurology, The Medical College of Wisconsin,
Milwaukee, Wisconsin
PAUL E. GILBERT,PhD• Department of Head and Neck Surgery, University of California San Diego,
School of Medicine; Lifespan Human Senses Laboratory, San Diego, CA
CHRISTINA A. GITTO,DDS• Department of Dentistry and Maxillofacial Prosthetics, The Cleveland
Clinic Foundation, Cleveland, OH
GABRIEL GOLD,MD• Hôpital de Gériatrie, Thônex-Genève, Switzerland
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