Handbook of Imaging the Alzheimer Brain

825 Pages·2011·18.73 MB·English

by  A. Rosen

HANDBOOK OF IMAGING THE ALZHEIMER BRAIN
Advances in Alzheimer’s Disease

Advances in Alzheimer’s Disease brings together the latest insights in Alzheimer’s disease research in specific
areas in which major advances have been made. This book series assembles and builds on work recently
published in the Journal of Alzheimer’s Disease (JAD) and also includes further contributions to ensure
comprehensive coverage of the topic. The emphasis is on the development of novel approaches to understanding
and treating Alzheimer’s and related diseases.
Series Editors:
George Perry, Ph.D. and Mark A. Smith, Ph.D.†

Volume 2

Previously published in this series

Vol. 1. G. Casadesus (Ed.), Handbook of Animal Models in Alzheimer’s Disease

ISSN 2210-5727 (print)
ISSN 2210-5735 (online)
Handbook of Imaging the Alzheimer Brain

Edited by
J. Wesson Ashford, M.D., Ph.D.
Stanford/VA Palo Alto HCS, USA

Allyson Rosen, Ph.D.
Stanford/VA Palo Alto HCS, USA

Maheen Adamson, Ph.D.
Stanford/VA Palo Alto HCS, USA

Peter Bayley
Stanford/VA Palo Alto HCS, USA

Osama Sabri, M.D.Ph.D.
Leipzig University, Germany

Ansgar Furst, Ph.D.
Stanford/VA Palo Alto HCS, USA

Sandra E. Black M.D. FRCP(C)
Sunnybrook, University of Toronto, Canada

and

Michael Weiner, M.D.
UC San Francisco / VA San Francisco, USA
© 2011 IOS Press and the authors.
All rights reserved. No part of this book may be reproduced, stored in a retrieval system, or transmitted, in any
form or by any means, without prior written permission from the publisher.
ISBN 978-1-60750-792-5 (print)
ISBN 978-1-60750-793-2 (online)

Publisher
IOS Press BV
Nieuwe Hemweg 6B
1013 BG Amsterdam
The Netherlands
fax: [phone]
e-mail: [email protected]
Distributor in the USA and Canada
IOS Press, Inc.
4502 Rachael Manor Drive
Fairfax, VA 22032
USA
fax: [phone]
e-mail: [email protected]

LEGAL NOTICE
The publisher is not responsible for the use which might be made of the following information.
PRINTED IN THE NETHERLANDS
Dedication

This book is dedicated to Veterans who have returned from combat with traumatic brain injuries (TBI), post-
traumatic stress disorder (PTSD), and other war-related illnesses and injuries that may cause cognitive
dysfunction and increase the risk for developing dementia in the future. TBI and PTSD may contribute to brain
degeneration and AD through attacking common neural substrates. Veterans have made great sacrifices for the
welfare of others, and we are deeply grateful to the Veterans who’ve served their countries and who dedicate
themselves to helping future generations through participating in dementia research.
Considerable support for the organization of this volume was provided by the U.S. Department of Veterans
Affairs, including the War Related Illness and Injury Study Center (WRIISC) at the Veterans Affairs Palo Alto
Health Care System (Drs. Maheen Adamson, J. Wesson Ashford, Peter Bayley, Ansgar Furst, Ahmad Salehi),
based in the VA Office of Public Health and Environmental Hazards, and the Department of Veterans Affairs
Sierra-Pacific Mental Illness Research, Education, and Clinical Center (MIRECC) (Drs. Ruth O’Hara, Allyson
Rosen, Michael Weiner, Jerome Yesavage).
It is hoped that the advances in brain imaging for Alzheimer’s disease described in this book will not only lead to
benefits for people with and predisposed to dementing disorders, but will also help Veterans with TBI and
PTSD, as well as patients with other brain disorders.
A special note is made here to honor the memory of Dr. Mark A. Smith, the late Editor in Chief of the Journal of
Alzheimer’s Disease, who contributed a great deal toward the organization of the systems that led to the creation
of this book.
Commendation is given to Rasjel van der Holst, a publisher at IOS Press, who conceptualized the idea of this
book, participated in the recruitment of the editors, and worked diligently to make this book a reality.
This book was made possible by the efforts and work of Beth Kumar, Managing Editor of the Journal of
Alzheimer’s Disease, and Dr. George Perry, Editor in Chief of the Journal of Alzheimer’s Disease.
Thanks is due to all of the co-editors and section editors who willingly volunteered their time to create this
volume. Further, there are over 400 individual authors from many countries around the world who contributed
their hard work to research and manuscript writing to provide the important content presented here, and their
efforts are also very much appreciated.
A final thank you goes to all research participants, both normal individuals and patients with various serious
conditions, who contributed to the research that made this volume possible. Since there is no true animal model
for Alzheimer’s disease, it is absolutely essential for people, including younger and older individuals without
known problems as well as patients with Alzheimer’s disease, to participate in this kind of research for us to
make progress against the devastating conditions that impair our mental functions in our later years.
J. Wesson Ashford, M.D., Ph.D.
Director, War Related Illness and Injury Study Center, VA Palo Alto Health Care System
Clinical Professor (affiliated), Department of Psychiatry and Behavioral Sciences, Stanford University
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Handbook of Imaging the Alzheimer Brain vii
J.W. Ashford et al. (Eds.)
IOS Press, 2011
© 2011 The authors and IOS Press. All rights reserved.
Preface
Alois Alzheimer first described the syndrome associated with his name in a conference in 1906 and then
published a paper that accurately described this condition, both the clinical presentation and the pathology, in
1907. The patient who he described was 51 years of age when she first presented to him with dementia and
psychosis, at an age close to the average life-expectancy of that region of Germany at that time. He also
described her presentation as a rare, presenile form of dementia, and pathologically she had severe
atherosclerosis as well as a form of changes in the brain that he saw for the first time due to the newly available
silver stains, senile plaques and neurofibrillary changes, which are now the pathological hallmarks of this
disease. Two factors have brought Alzheimer's disease from a rare condition to what is now the leading factor
associated with death in the developed world: 1) the presence of the senile plaques and neurofibrillary changes in
the most common form of dementia in the elderly, and 2) the progressive increase in life-expectancy (about 25
years since Alzheimer's time) leading to a huge growth in the elderly population in the age range which is most
susceptible to this condtion.
The great developments that have led to this handbook are the advances in the technology for imaging the
brain of the living person. In the last 50 years, a wide variety of techniques have emerged, including
measurement of electromagnetic signals, anatomy, functional activity, chemical composition, and
neuropathological changes. These techniques are not yet able to image individually the senile plaques and
neurofibrillary changes that are seen by the pathologists at autopsy, but they are reflecting Alzheimer
pathological changes more and more closely. Now, these techniques allow imaging of brain regions that
estimates the presence of senile plaques that are seen by the pathologists at autopsy, and ligands for
neurofibrillary changes are under active development, so new techniques are able to report more and more
accurate estimations of pathological changes of Alzheimer's disease. Other techniques reviewed in this handbook
are able to convey critical information about the function and connectivity of the brain that is disrupted by
Alzheimer pathology.
This handbook was developed to provide an overview of the state of the art of brain-imaging approaches
that have recently emerged to reveal the critical characteristics of brains of patients with Alzheimer's disease.
The book was initially conceived as an opportunity to present the major findings produced from the Alzheimer's
Disease Neuroimaging Initiative (ADNI), which has been led by Michael Weiner, and has led to the publication
over 200 hundred papers on imaging the brains of individuals along the transition from elderly normal to mild
cognitive impairment to mild dementia. This book provides numerous chapters that examine this critical phase of
Alzheimer's disease, but chapters also discuss diagnosis, early biomarkers, late changes, the role of vascular
disease, and treatment. The book drew from presentations at the International Conference on Alzheimer's
Disease (ICAD), which met in Hawaii in July, 2010, and the associated Alzheimer's Imaging Consortium,
chaired by Sandra Black and Giovanni Frisoni.
This book is organized in 10 sections. Each section addresses a particular neuroimaging modality that has
been found to be useful in understanding or diagnosing Alzheimer's disease. Each section has an introduction to
the particular technique and how it has the potential for informing clinical care or evaluating novel therapies for
Alzheimer's patients. The chapters provide clinicians with specific information as to how the particular
neuroimaging technique is or can be useful in a clinical setting, including the gamut from Radiology to Primary
Care and address specific advances in the various types of neuroimaging. The book includes brief overviews of
imaging of Alzheimer's disease and reviews fundamental principles for neuroimaging pathological changes that
it causes, with an emphasis on practical and future applications.
The basic concept of this compendium is that each section provides an overview of the use of brain imaging
in the specific area of Alzheimer's disease neuroimaging. The chapters in this book provide the field with
perspectives on the value of the various imaging techniques for screening for Alzheimer's disease, determining
the early markers of the disease, making the diagnosis, following the progression of the disease, determining the
variability of the manifestation of Alzheimer's disease, and estimating the utility of these metrics of disease
viii
severity for examining the effects of treatments. However, this work has not addressed all of the numerous
complexities of Alzheimer's disease, including co-occurrence, Parkinson's disease, fronto-temporal dementia,
etc., and only briefly touches on vascular risk factors and subcortical ischemic vasculopathy.
The target audience for this book is the clinical community, including medical students, residents-in-training
with an interest in neuroimaging, as well as clinicians and faculty in fields where neuroimaging of Alzheimer's
disease is and will become even more critical as automatic quatnification methods start coming on-line and
available for practicing clinicians taking care of the affected patients (Family Practitioners, Geriatric Medicine,
Neurologists, Radiologist, Psychiatrists). The overview is relatively brief but highly accessible for students,
clinicians, and other researchers studying Alzheimer's disease, since a need to understand the clinical aspects of
the disease are critical for guiding basic investigations.
Alzheimer's disease is a common problem which is becoming progressively more prevalent and burdensome
to the World. Through better recognition of this disease and more precise diagnosis, led by brain imaging in the
appropriate clinical context, it is our sincere hope that mankind can conquer this terrible disease.

J. Wesson Ashford, Sandra E. Black, Giovanni Frisoni and George Perry
ix
Contents
Preface vii
J. Wesson Ashford, Sandra E. Black, Giovanni Frisoni and George Perry

Section 1: Imaging the Alzheimer Brain: The Pathology and Pathophysiological Bases
of Alzheimer’s Disease: Implications for Advancing Diagnostic Imaging

Introduction: Imaging the Alzheimer Brain: The Pathology and Pathophysiological Bases
of Alzheimer’s Disease: Implications for Advancing Diagnostic Imaging 3
J. Wesson Ashford, Ahmad Salehi, Ansgar J. Furst and Peter J. Bayley

Hippocampal Network Alterations in Alzheimer’s Disease and Down Syndrome: From Structure to Therapy 11
Martha Millan Sanchez, Sarah Moghadam, Priyanka Naik, Kara J. Martin and Ahmad Salehi

Cerebrospinal Fluid Biomarkers of Neurodegenerative and Ventricular Changes in the Elderly 31
Ronald A. Cohen, Assawin Gongvatana, Brian R. Ott and Alzheimer’s Disease Neuroimaging Initiative

Section 2: Structural Imaging

Introduction: Structural Imaging 45
Peter J. Bayley, Giovanni B. Frisoni and Clifford R. Jack Jr

Cognitive Performance and Its Relation to Brain Morphology in MCI and AD 47
Philipp A. Thomann, Vasco Dos Santos, Torsten Wüstenberg, Ulrich Seidl, Marco Essig
and Johannes Schröder

Patterns of Cortical Thickness in Pathologically-Confirmed Typical and Atypical Alzheimer’s Disease 57
Manja Lehmann, Jonathan D. Rohrer, Matthew J. Clarkson, Gerard R. Ridgway, Rachael I. Scahill,
Marc Modat, Jason D. Warren, Sebastien Ourselin, Josephine Barnes, Martin N. Rossor and Nick C. Fox

Volumetry of the Olfactory Bulb and Tract: Relation to Medial Temporal Lobe Atrophy and to Cognitive
Performance in MCI and AD 69
Philipp A. Thomann, Vasco Dos Santos, Torsten Wüstenberg, Ulrich Seidl, Elmar Kaiser, Pablo Toro,
Marco Essig and Johannes Schröder

Presence of ApoE ε4 Allele Associated with Thinner Frontal Cortex in Middle Age 77
Christine Fennema-Notestine, Matthew S. Panizzon, Wesley R. Thompson, Chi-Hua Chen, Lisa T. Eyler,
Bruce Fischl, Carol E. Franz, Michael D. Grant, Amy J. Jak, Terry L. Jernigan, Michael J. Lyons,
Michael C. Neale, Larry J. Seidman, Ming T. Tsuang, Hong Xian, Anders M. Dale and William S. Kremen

Alzheimer’s Disease and Dementia with Lewy Bodies can be Differentiated by High Resolution MR Imaging
of the Hippocampus 89
Michael J. Firbank, Andrew M. Blamire, Andrew Teodorczuk, Dipayan Mitra, Emma Teper
and John T. O’Brien