the clinical spectrum of alzheimer's disease

376 Pages·2011·10.91 MB·English

by  Intech Prepress 2

THE 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
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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