Table Of ContentTHE CLINICAL SPECTRUM
OF ALZHEIMER’S DISEASE –
THE CHARGE TOWARD
COMPREHENSIVE
DIAGNOSTIC AND
THERAPEUTIC STRATEGIES
Edited by Suzanne De La Monte
The Clinical Spectrum of Alzheimer’s Disease –
The Charge Toward Comprehensive Diagnostic and Therapeutic Strategies
Edited by Suzanne De La Monte
Published by InTech
Janeza Trdine 9, 51000 Rijeka, Croatia
Copyright © 2011 InTech
All chapters are Open Access articles distributed under the Creative Commons
Non Commercial Share Alike Attribution 3.0 license, which permits to copy,
distribute, transmit, and adapt the work in any medium, so long as the original
work is properly cited. After this work has been published by InTech, authors
have the right to republish it, in whole or part, in any publication of which they
are the author, and to make other personal use of the work. Any republication,
referencing or personal use of the work must explicitly identify the original source.
Statements and opinions expressed in the chapters are these of the individual contributors
and not necessarily those of the editors or publisher. No responsibility is accepted
for the accuracy of information contained in the published articles. The publisher
assumes no responsibility for any damage or injury to persons or property arising out
of the use of any materials, instructions, methods or ideas contained in the book.
Publishing Process Manager Petra Zobic
Technical Editor Teodora Smiljanic
Cover Designer Jan Hyrat
Image Copyright John Wollwerth, 2010. Used under license from Shutterstock.com
First published August, 2011
Printed in Croatia
A free online edition of this book is available at www.intechopen.com
Additional hard copies can be obtained from [email protected]
The Clinical Spectrum of Alzheimer’s Disease – The Charge Toward Comprehensive
Diagnostic and Therapeutic Strategies, Edited by Suzanne De La Monte
p. cm.
ISBN 978-953-307-993-6
free online editions of InTech
Books and Journals can be found at
www.intechopen.com
Contents
Preface IX
Part 1 Overview: Clinical, Epidemiological, and Genetic Factors 1
Chapter 1 Risk Factors for Disease Progression
in Alzheimer's Disease 3
Schmidt C, Wolff M, Shalash A and Zerr I
Chapter 2 Alzheimer’s Disease Genomics and Clinical Applications 21
Tih-Shih Lee and Mei Sian Chong
Chapter 3 Addressing Risk Factors for Neurocognitive Decline
and Alzheimer’s Disease Among African Americans
in the Era of Health Disparities 43
David L. Mount, Maria Isabel Rego, Alethea Amponsah,
Annette Herron, Darin Johnson, Mario Sims,
DeMarc Hickson and Sylvia A. Flack
Part 2 Non-Standard Features of Alzheimer's 61
Chapter 4 Focal Cortical Presentations
Genetically Proven Alzheimer Disease 63
Naeije G, Van den Berge Delphine, Vokaer M,
Fery P, Vilain C, Abramowicz M, Van den Broeck M,
Van Broeckhoven C and Bier JC
Chapter 5 Spatial Navigation Impairment
in Healthy Aging and Alzheimer’s Disease 75
Kamil Vlček
Chapter 6 Visual Cognition in Alzheimer’s Disease
and Its Functional Implications 101
Philip C. Ko and Brandon A. Ally
Chapter 7 Olfactory Dysfunctions in Alzheimer’s Disease 127
Iuliana Nicola-Antoniu
VI Contents
Part 3 Neuroimaging in the Spotlight 145
Chapter 8 Currently Available Neuroimaging Approaches
in Alzheimer Disease (AD) Early Diagnosis 147
Laura Ortiz-Terán, Juan MR Santos,
María de las Nieves Cabrera Martín and Tomás Ortiz Alonso
Chapter 9 The Clinical Use of SPECT
and PET Molecular Imaging
in Alzheimer’s Disease 181
Varvara Valotassiou, Nikolaos Sifakis, John Papatriantafyllou,
George Angelidis and Panagiotis Georgoulias
Part 4 Biomarkers: Steps Toward Rapid Non-Invasive Tests 205
Chapter 10 Cerebrospinal Fluid Based Diagnosis
in Alzheimer’s Disease 207
Inga Zerr, Lisa Kaerst,
Joanna Gawinecka and Daniela Varges
Chapter 11 Alzheimer’s Diseases:
Towards Biomarkers for an Early Diagnosis 221
Benaïssa Elmoualij, Ingrid Dupiereux,
Jérémie Seguin, Isabelle Quadrio, Willy Zorzi,
Armand Perret-Liaudet and Ernst Heinen
Chapter 12 Phospo-PKCs in Abeta1-42-Specific Human
T Cells from Alzheimer’s Disease Patients 243
Lanuti Paola, Marchisio Marco,
Pierdomenico Laura and Miscia Sebastiano
Chapter 13 The Predictive Role
of Hyposmia in Alzheimer's Disease 259
Alessandra B. Fioretti, Marco Fusetti
and Alberto Eibenstein
Chapter 14 Retinal Nerve Fibre Layer
Thinning in Alzheimer Disease 279
Panitha Jindahra and Gordon T Plant
Part 5 Potential Mechanisms of Neurodegeneration 295
Chapter 15 Modulation of Signal Transduction Pathways
in Senescence-Accelerated Mice P8 Strain:
A Useful Tool for Alzheimer’s Disease Research 297
José Luis Albasanz, Carlos Alberto Castillo,
Marta Barrachina, Isidre Ferrer and Mairena Martín
Contents VII
Chapter 16 Valosin-Containing Protein (VCP) Disease and Familial
Alzheimer’s Disease: Contrasts and Overlaps 331
CD Smith, M Badadani, A Nalbandian, E Dec, J Vesa,
S Donkervoort, B Martin, GD Watts, V Caiozzo and V Kimonis
Chapter 17 Neural Basis of Hyposmia in Alzheimer’s Disease 347
Daniel Saiz-Sánchez, Carlos de la Rosa-Prieto,
Isabel Úbeda-Bañón and Alino Martínez-Marcos
Preface
The Clinical Spectrum of Alzheimer’s Disease: The Charge Toward Comprehensive
Diagnostic and Therapeutic Strategies
Alzheimer’s disease, the most common cause of dementia, is a degenerative
disease associated with progressive destruction of the brain, resulting in
behavioral/psychiatric symptoms, memory and cognitive impairments, and eventually
inability to carry out normal daily activities. For over a century, Alzheimer’s disease,
sometimes mispronounced “old timers’ disease” has been studied by clinicians, basic
scientists, and translational investigators who work to link concepts developed by
each of the other two groups. The term, ‘old timers’ is apt, because aging is by far the
most dominant risk factor for the disease. Alzheimer’s disease is studied all over the
world because as populations age, the prevalence rates of Alzheimer’s increase, and
the personal, social, societal, economic, and emotional hardships endured over its 4 to
20 year span are staggering. Given the almost crusade‐like drive and enormous sums
of money poured into just one field, and the thousands of publications resulting from
decades of dedicated struggle, one cannot help but wonder, “what’s the problem?”
Why are we still so deficient in our understanding of this disease? How much more
time and effort are needed to finally have ways to make early, rapid, and accurate
diagnoses? When will we finally have the cure, or at least some kind of treatment that
can slow down the process and provide a bit more time to enjoy life in a compos mentis
state?
The Overview chapters in, “The Clinical Spectrum of Alzheimer’s Disease: The Charge
Toward Comprehensive Diagnostic and Therapeutic Strategies”, summarize the basics
and provide up‐to‐date summaries of the salient clinical, epidemiological, and genetic
features of Alzheimer’s. The Chapter by Dr. Lee Tih‐Shih, in addition to reviewing
genetic factors mediating Alzheimer’s, covers the use of genomics and chip arrays,
approaches that will certainly be utilized in the future to identify individuals at
increased risk for developing Alzheimer’s, so that preventative measures, once
determined, could be implemented. The final chapter in the Overview section is
unique because it highlights the shifting demographics of Alzheimer’s. Previously,
Alzheimer’s was not prevalent among African American, but now is. The author links
the increased rates of Alzheimer’s among African Americans to the increased rates of
diabetes mellitus. Type 2 diabetes mellitus is now a very well recognized risk factor for
X Preface
sporadic AD, and its precursor, mild cognitive impairment. The author suggests
practical measures to combat this emerging epidemic; the concepts expressed may
have broader implications for the management and possibly prevention of sporadic
Alzheimer’s, which accounts for at least 90 percent of all cases.
The next section covers the non‐standard features of Alzheimer’s. All too often,
physicians and caretakers look for only the classical features of Alzheimer’s. The four
chapters included in this section discuss problems related to focal cortical degenerative
effects and disorders of spatial navigation and spatial memory. Such deficits quite
likely account for the increased propensity of individuals with early Alzheimer’s to get
lost and become confused in new environments. The chapter by Dr. Ally Brandon
discusses impairments in visual memory and cognition, which dovetails with the
chapter on visual‐spatial memory impairments in Alzheimer’s. The last chapter
summarizes olfactory sensory deficits in Alzheimer’s. These concepts are important
because, in addition to problems with perception and memory, the primary sensory
organs, eyes and nose, can and often do undergo degenerative changes, some due to
aging, and others possibly as components of Alzheimer’s. The bottom line is that
“non‐standard” does not mean exceptional; instead it refers to the broader spectrum of
abnormalities that exist in Alzheimer’s, and that could be tapped to better understand
the disease as well as improve diagnosis using non‐invasive methods.
The ability to detect and monitor the progression and regional distributions of brain
atrophy through neuro‐imaging approaches provides excellent tools for supporting a
clinical diagnosis of Alzheimer’s, and can help distinguish the different causes of
dementia. In addition, there is a growing realization that neuro‐imaging, when
combined with function, such as in vivo measures of blood flow, biochemistry, and
metabolism, can be powerful for improving the accuracy of early diagnosis, and
potentially monitoring responses to treatment. The section, ‘Neuroimaging in the
Spotlight” decodes the different approaches to neuro‐imaging currently used to
evaluate people with mild cognitive impairment, Alzheimer’s disease, and other
dementias. It is worthwhile knowing that as neuro‐imaging approaches become more
sophisticated and refined, functional assays will become incorporated more routinely.
The limitations mainly pertain to the ability to identify pathological, biochemical, and
molecular markers of neurodegeneration that correlate with structural and functional
neuroimaging abnormalities, and the severity of dementia. This segment of the book is
particularly useful for non‐specialists and early‐stage career specialists.
As mentioned, the growth and sophistication of neuroimaging are partly dependent
upon understanding which molecular, biochemical, and structural abnormalities are
significantly correlated with progressive neurodegeneration, and specifically,
Alzheimer’s. Research in the field of Alzheimer biomarkers is robust, and the
combined effects of shifting targets, paradigms, and approaches, together with the
difficulties in achieving high levels of inter‐study concordance rates, make this area of
investigation difficult to follow. The field is at the stage where clinicians, educators,
and researchers must be knowledgeable about the state‐of‐the‐art approaches to
