PET in the Evaluation of Alzheimer’s Disease and Related Disorders

292 Pages·2009·51.1 MB·English

by  Dan Silverman

Daniel H.S. Silverman (ed.), PET in the Evaluation of Alzheimer's Disease and Related Disorders,
DOI: 10.1007/978-0-387-76420-7, © Springer-Verlag New York 2009
Editor Daniel H.S. Silverman
PET in the Evaluation of Alzheimer's Disease and Related Disorders
Editor
Daniel H.S. Silverman
David Geffen School of Medicine, University of California, Los Angeles, CA,
USA
ISBN 978-0-387-76419-1 e-ISBN 978-0-387-76420-7
Library of Congress Control Number: 2008940848
© Springer-Verlag New York 2009
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Preface
Among all the clinical indications for which radiologists, nuclear medicine
physicians, neurologists, neurosurgeons, psychiatrists (and others examining
disorders of the brain) order and read brain PET scans, demand is greatest for
those pertaining to dementia and related disorders. This demand is driven by the
sheer prevalence of those conditions, coupled with the fact that the differential
diagnosis for causes of cognitive impairment is wide and often difficult to
distinguish clinically.
The conceptual framework by which evaluation and management of
dementia is guided has evolved considerably during the last decade. Although
we still are far from having ideal tests or dramatic cures for any of the
established causes of dementia, our options have expanded with respect to both
the diagnostic and therapeutic tools now available. In the first chapter of this
book, the contribution and limitations of different elements of the clinical
examination for diagnosis of cognitive symptoms are described, and the roles of
structural and functional neuroimaging in the clinical workup are given context.
The clinical utility of brain positron emission tomography (PET), as with
other imaging modalities, depends in part on how accurately and fully the
information inherently represented in the scans is appreciated and relayed in the
interpretation of the images. Even highly trained imaging specialists are
challenged by this since, for example, neuroradiologists are generally far more
familiar with computed tomography (CT) and magnetic resonance (MR) studies
of the brain than with PET studies, and specialists in PET and PET/CT facilities
tend to be much more experienced with oncology studies than with dedicated
brain studies performed for the evaluation of neurologic disorders. To help meet
this challenge, the second chapter offers practical instruction on adopting a
systematic method for visual analysis of scans, describes how quantification
with clinically available and friendly software tools can be employed to assist
with analysis, and then illustrates a straightforward approach for integrating the
qualitative and quantitative findings in meaningful interpretations. An Atlas in
the final section of this book complements Chapter 2 by providing interpretive
practice for many real (and clinically realistic) cases, to which the tools outlined
in the second chapter can be directly applied.
The most frequent causes of dementia are neurodegenerative disorders, with
Alzheimer’s disease being the most common. By the time patients are
symptomatic with these disorders, they have undergone significant distinct
symptomatic with these disorders, they have undergone significant distinct
alterations in brain metabolism. The increasing use of brain PET stems from the
high sensitivity of this imaging tool in identifying those alterations. The third
chapter looks at the full spectrum of changes in glucose metabolism detectable
with PET in monitoring the course of cognitive decline, beginning before the
emergence of the first neurologic symptoms, in people who are predisposed to
developing problems, in some cases many years into the future. Progressive
changes observed with PET in the brains of patients who experience very mild
symptoms, to those who meet criteria for having mild cognitive impairment, to
those suffering from full-blown dementia, are described, as is the role of PET in
the differential diagnosis of the underlying cause for the dysfunction.
Neurodegenerative diseases often impact not only on cognitive function, but
also on motor function. The two neurologic domains can be affected in isolation,
but frequently a mixed presentation of symptoms occurs. For example,
approximately one third of Alzheimer’s patients eventually experience
parkinsonian symptoms and, conversely, a similar proportion of patients with
Parkinson’s disease develop significant cognitive impairment. Other conditions,
such as dementia with Lewy bodies, may be characterized at an early stage by
both motor and cognitive problems. Chapter 4 examines neuronuclear imaging
studies explicitly aimed at illuminating changes in the brain associated with
movement disorders. Their potential utility with respect to drug development, as
well as in direct clinical application, is explained.
Although the most commonly performed clinical PET studies by far are
carried out with [18F]fluorodeoxyglucose (FDG) as the imaged radiotracer,
substantial advances have occurred in the development of other radiotracers with
which to probe brain processes associated with neurodegenerative disease.
Chapter 5 describes work that is making it possible to observe and measure the
molecular participants of such processes as they accumulate, or are lost from,
living brain tissue. In the setting of Alzheimer-related changes, one molecular
participant in particular, the β-amyloid of extracellular plaques constituting one
of the histopathologic hallmarks of Alzheimer’s disease, has attracted substantial
attention in both industry and academic scientific settings. Following the
introduction of this area of investigation in the fifth chapter, Chapter 6 is devoted
to expanding on the scientific implications and clinical potential of radiotracers
being developed to localize and measure β-amyloid deposits occurring in the
brain. In the latter chapter, particular attention is given to characterizing β-
amyloid deposition in older people who would not be considered cognitively
impaired by standard clinical criteria.
PET scans, particularly with FDG, have demonstrated diagnostic and
prognostic utility in evaluating patients with cognitive impairment and in
prognostic utility in evaluating patients with cognitive impairment and in
distinguishing among primary neurodegenerative disorders and other etiologies
for cognitive decline. Since the diagnostic capabilities of this medical
technology have outpaced therapeutic advances, a look into the future of PET
requires concomitant consideration of the future of therapeutic strategies for
addressing the underlying conditions. As preventive and specific disease-
modifying treatments are developed, early detection of accurately diagnosed
neuropathologic processes, facilitated by appropriate use of PET and other
neuroimaging technologies, can be expected to increasingly impact on the
enormous human toll currently exacted by these disorders.
Daniel H.S. Silverman
Acknowledgements
There are many to whom much is owed for their roles in the creation of the
present work, moving it from the realm of abstract ideas into its present reality. I
would like to thank Rob Albano who, representing the publisher (at a time when
Springer was still Springer-Verlag), was present from its inception and first
invited me to consider a project along these lines. I felt fairly sure at the time
that taking on this project was a bad move, but he managed not to let me talk
him (or myself) out of it prematurely. I also wish to thank developmental editor
Margaret Burns who, working with me from almost the earliest days of the
project, managed to stay perfectly poised on the fine line between helpful
prodding to keep the project moving forward and patient understanding when
that forward motion may have seemed imperceptible to an external observer
(particularly as obstacles to our originally anticipated timeline arose and had to
be creatively overcome). Thanks are also due to Springer’s book production
manager Frank Ganz, and associate editor Katherine Cacace, for ably guiding
this project through the final stretch and across the finish line. I am indebted to
all of my colleagues who contributed as authors and coauthors to the final work:
my friends and colleagues at UCLA, Linda Ercoli, Gary Small, Vladimir Kepe,
Henry Huang, Saty Satyamurthy, and Jorge Barrio, with whom I have been
fortunate to collaborate over the past decade on a wide range of imaging-related
projects; Lisa Mosconi, who has shared her considerable experience on changes
in brain metabolism associated with the earliest stages of Alzheimer’s disease;
John Seibyl, a friend of many years who has always sportingly accepted my
invitations to participate in any number of forums of symposia and writing
projects and has once again offered his insights into the movement side of the
neurodegenerative coin, much to the benefit of this text; Bill Klunk, for readily
agreeing at the outset to take responsibility, along with Chet Mathis and
colleagues Julie Price, Steve DeKosky, Brian Lopresti, Nicholas Tsopelas,
Judith Saxton, and Robert Nebes, for their excellent contribution on amyloid
imaging; my colleague Karl Herholz, for his insights in attempting the
impossible task of forecasting the future; and Vicky Lau, Cheri Geist, and Erin
Siu, who applied their trained eyes, creative talents, and organizational skills to
successfully bringing to life reams of clinical data and images into cogent
clinical cases. Finally, I wish to express my appreciation to those who have
played roles less directly related to this actual text, but no less important to its
realization: Johannes Czernin, with whom I literally worked alongside since my
realization: Johannes Czernin, with whom I literally worked alongside since my
first day on the Nuclear Medicine Service at UCLA, and Mike Phelps, whose
pioneering work with PET served as a major source of my inspiration to enter
the nuclear medicine field to begin with, for the nearly one and a half decades of
friendship and support they have offered personally and, in addition,
professionally in their roles heading the Ahmanson Biological Imaging Division,
and Department of Molecular and Medical Pharmacology, respectively; and my
family—my wife Wei, our kids, our parents Donna and Robert and Pei and
Robert, and my sibs Anne, Beth, and Mikhael, whose contributions of
friendship, love, understanding of my professional commitments (and over-
commitment), as well as the many more specific roles played in day-to-day life
throughout the time that this text has been in preparation (and long before),
would require another book to fully enumerate.
Contents
Part I Imaging Applications in Current Clinical Practice
1 Clinical Evaluation of Dementia and When to Perform PET
Linda M. Ercoli and Gary W. Small
2 Clinical Interpretation of Brain PET Scans: Performing Visual
Assessments, Providing Quantifying Data, and Generating Integrated
Reports
Daniel H.S. Silverman
3 FDG PET in the Evaluation of Mild Cognitive Impairment and Early
Dementia
Lisa Mosconi and Daniel H.S. Silverman
4 PET and SPECT in the Evaluation of Patients with Central Motor
Disorders
John P. Seibyl
Part II Emerging Approaches Using PET
5 Microstructural Imaging of Neurodegenerative Changes
Vladimir Kepe, Sung-Cheng Huang, Gary W. Small,
Nagichettiar Satyamurthy and Jorge R. Barrio
6 Amyloid Imaging with PET in Alzheimer’s Disease, Mild Cognitive
Impairment, and Clinically Unimpaired Subjects
William E. Klunk, Chester A. Mathis, Julie C. Price, Steven T. DeKosky,
Brian J. Lopresti, Nicholas D. Tsopelas, Judith A. Saxton and Robert
D. Nebes
Part III Atlas
7 Interpretive Practice Atlas
Daniel H.S. Silverman, Victoria Lau, Cheri Geist and Erin Siu
Index