Senile Dementia of the Alzheimer Type: Early Diagnosis, Neuropathology and Animal Models

385 Pages·1985·9.65 MB·English

by  C. Flicker

2
Advances in Applied Neurological Sciences
Editors
R. J. Joynt, Rochester, USA
A. Weindl, Munich, FRG
Senile Dementia
of the Alzheimer Type
Early Diagnosis,
Neuropathology and Animal Models
Edited by
J. Traber and W H. Gispen
With 118 Figures
Springer-Verlag
Berlin Heidelberg New York Tokyo
Dr. J ORG TRABER
Neurobiology Department
Troponwerke GmbH & Co. KG
Neurather Ring 1
D-5000 K6ln 80, FRG
Professor Dr. WILLEM HENDRIK GISPEN
Division of Molecular Neurobiology
Rudolf Magnus Institute for Pharmacology
and Institute of Molecular Biology
State University of Utrecht
Padualaan 8
NL-3508 TB Utrecht, The Netherlands
ISBN-13:978-3-642-70646-2 e-ISBN-13:978-3-642-70644-8
DOl: 10.1007/978-3-642-70644-8
Library of Congress Cataloging-in-Publication Data. Main entry under title: Senile dementia of the
Alzheimer type. (Advances in applied neurological sciences; 2) Contains the proceedings of the
Second International Tropon-Bayer Symposium on Aging of the Brain, held in Cologne in Nov.
1984. Includes index. 1. Alzheimer's disease - Congresses. 2. Brain - Aging - Congresses.
3. Brain - Diseases - Age factors - Congresses. 4. Brain - Diseases - Animal models -Congresses.
I. Traber, Jorg. II. Gispen, Willem Hendrik. III. International Tropon-Bayer Symposium on
Aging of the Brain (2nd: 1984: Cologne, Germany) IV. Series. [DNLM: I. Aging - congresses.
2. Alzheimer's Disease - congresses. 3. Brain - congresses. 4. Disease Models, Animal -
congresses. WI AD436AH v.2fWM 220 S477 1984] RC523.S46 1985 618.97'83 85-17229
ISBN-13:978-3-642-70646-2 (U.S.)
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© by Springer-Verlag Berlin Heidelberg 1985
Softcover reprint of the hardcover 1st edition 1985
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check its accuracy by consulting other pharmaceutical literature.
2125/3130-543210
Foreword
Society is showing increasing concern for disorders related to aging that
lead to a loss of brain function. In view of the enormous proportion of
elderly people in our society today, brain aging is more than ever subject
to challenge to us all, not only politicians and health authorities, but
every individual who is confronted with the difficult situation of
watching the mental powers of apparently healthy elderly friends,
neighbours, or relatives fail, often with alarming rapidity. This challenge
is directed especially toward us scientists. As one of our colleagues
succinctly put it 2 years ago at the close of our First International
Symposium on Brain Aging: "Do something. We are not dealing here
with just another disease; we are concerned with human dignity."
More than any statistics, these words convinced me that Tropon's
decision to leave the field of classic CNS pharmacology and move into
the field of gerontopsychopharmacology was the right one, even though
we knew that success would be uncertain and that, even if it finally comes
it will be many years hence.
At this point, let me add a personal comment: each one of us is judged
by his or her own success. We live in a competitive society where success
counts. This applies not only to the businessman, but also to the scientist,
in particular, to those in industry. Considering this pressure, can we
expect a young generation of scientists to devote themselves to long
term projects such as the investigation of brain aging? My answer is
"yes." In spite of the fact that we can expect to obtain meaningful
results only after years of investigation or, perhaps, not at all, it is my
belief that the rewards of such a large-scale investment will be pro
portional to the input.
The International Tropon-Bayer Symposia on Aging ofthe Brain are
meant to encourage and support neuroscientists in their efforts to
understand the physiologic and pathologic aspects of brain aging.
They are not intended as exclusive gatherings, but are open to all
who can in any way contribute to the subject. They are a vehicle for
the significant, informal exchange of ideas between clinicians and
nonclinicians and between investigators at universities and research
institutes and those in industry.
Various people have asked me why we organized a second workshop
after only 2 years, considering the long-term scale of research I
mentioned above. In response, I would like to point out that, in the
meantime, we have worked hard to check the validity of various models.
We have tested, rejected, and started again, and in the process, tried
VI Foreword
completely new approaches. Certainly in the last 2 years, the vast
complexity of the pathology underlying abnormal brain aging as well as
applications of drug research to gerontological health problems have
become increasingly apparent. Hence, it was decided to arrange a
meeting on three important, well-defined topics, including the early
diagnosis of senile dementia of the Alzheimer type, new insights into the
pathology of the aged brain, and animal models in the study of normal
and abnormal brain aging.
It is my hope that the discussion of these topics will be instrumental
in advancing our knowledge of the brain in normal aging and the
malfunctions characterizing the diseased elderly brain.
September, 1985 HARALD HORSTMANN, Cologne
Preface
This volume contains the proceedings of the Second International
Tropon-Bayer Symposium on Aging of the Brain, held in Cologne in
November 1984.
The program focuses on three topics, the first of which concerns the
early diagnosis of senile dementia, especially of the Alzheimer type
(SDAT). We would like to thank Dr. Jellemer Jolles for aiding us in
organizing this part of the program. Contributions to this subject include
the description of clinical phases of senile dementia, the relevance of
neuropsychological tests for early diagnosis, and the application of PET
and NMR scanning in the diagnosis of diseases related to abnormal
brain aging.
The second topic deals with recent developments in the neuro
pathology of the aged and diseased human brain. The presentations in
this area are concerned with both the quantitation of cellular changes
occurring in the brain during normal aging and the role of specific
neurotransmitters, amino acids, and brain structures in the patho
genesis of SDAT.
The last topic covers the selection and assessment of animal models
of "normal" and "abnormal" aging of the human nervous system. These
studies describe novel approaches to the study of brain acetylcholine in
relation to brain function and assess the usefulness of senescent monkeys
and rats in studies of behavioral aspects of brain aging.
A special interest lecture presented by Prof. Stanley Appel of the
University of Houston highlights the relevance of trophic factors and
neural plasticity to the process of brain aging.
The quality of the presentations was superb and provoked lively
discussions on such issues as the cortical as opposed to the subcortical
origin of abnormalities in Alzheimer's disease, patient classification, and
cultural aspects affecting diagnosis.
We are grateful both to the participants of the symposium and to Dr.
Thiekotter of Springer-Verlag for timely publication of the proceedings
of this exciting meeting.
We would like to take this opportunity to give special thanks to
Mrs. A. Bartz for her skillful and efficient help in organizing this meeting.
Furthermore, we are grateful to Mr. H. Demmer and Mr. W. Dreher for
their technical assistance during the symposium. Last but not least, we
acknowledge Prof. F. Hoffmeister (Bayer) and Dr. H. Horstmann
(Tropon) for their valuable comments concerning the program and
format of the meeting and Dr. M. Hebler (Tropon) for making it possible
to organize this symposium.
VIII Preface
We hope that the proceedings will inform the reader about important
issues of current research on brain aging and serve as a basis for the
design of new experimental or theoretical approaches to understanding
the pathogenesis of senile dementia.
September, 1985 JORG TRABER
WILLEM HENDRIK GISPEN
Contents
Early Diagnosis of Senile Dementia of the Alzheimer Type
I. Behavioral and Clinical Aspects
Cognitive Function in Normal Aging and Early Dementia
C. FLICKER, S. H. FERRIS, T. CROOK, R. T. BARTUS, and
B. REISBERG (With 3 Figures) . . . . . . . . . . . . 2
Senile Dementia of the Alzheimer Type: Diagnostic and
Differential Diagnostic Features with Special Reference
to Functional Assessment Staging
B. REISBERG, S. H. FERRIS, and M. J. DE LEON . . . . 18
Assessment of Cognition and Affective Symptoms in Dementia
R. C. MORs, B. S. GREENWALD, D. D. DUNN, and K. L. DAVIS. 38
The AGP System: Assessment of Symptoms in Psychogeriatric
Patients
S. KANOWSKI, H. KRUGER, and K.-P. KDHL (With 6 Figures). 44
Cognitive Deficits in Parkinson's Disease
A. J. LEES .................. . 60
Differential Diagnosis: Depression Versus Dementia
J. R. M. COPELAND and M. E. DEWEY. . . . . . . 72
Early Diagnosis of Dementia: Possible Contributions
of Neuropsychology
J. JOLLES (With 2 Figures) . . . . . . . . . . . 84
Early Diagnosis of Senile Dementia of the Alzheimer Type
II. Brain Tissue Parameters
EEG and Evoked Potentials in the Diagnosis of Dementias
S. L. VISSER (With 3 Figures) . . . . . . . . . . . . . 102
Nuclear Magnetic Resonance and Early Diagnosis
of Brain Pathology
W. L. CURATI and R. E. STEINER (With 6 Figures) 117
Positron Tomography and the Differential Diagnosis and
Pathophysiology of Alzheimer's Disease
R. P. FRIEDLAND, T. F. BUDINGER, W. J. JAGUST,
E. Koss, S. DERENZO, R. H. HUESMAN, and
Y. YANO (With 4 Figures). . . . . . . . . . . . . . . . . 124
x Contents
Investigation of Regional Cerebral Blood Flow and Metabolism
in Dementia
W.-D. HEISS, G. PAWLIK, K. HERHOLZ, B. SZELIES, C. BElL, and
K. WIENHARD (With 8 Figures) . . . . . . . . . . . .. 134
Novel Developments in the Neuropathology of Senile Dementia
of the Alzheimer Type
Are Neurons of the Human Cerebral Cortex Really Lost
During Aging? A Morphometric Examination
H. HAUG (With 7 Figures) . . . . . . . . . . . . . 150
Senile Dementia of the Alzheimer Type: Morphological and
Immunocytochemical Studies
J. P. BRION, P. VAN DEN BOSCH DE AGUILAR, and
J. FLAMENT-DURAND (With 5 Figures) . . . . . . . . .. 164
Neurotransmitter Receptor Alterations in Alzheimer's Disease
P. J. WHITEHOUSE and K.-S. Au . . . . . . . . . . . .. 175
Co-Localization of Aluminium and Silicon in Senile Plaques:
Implications for the Neurochemical Pathology of
Alzheimer's Disease
J. M. CANDY, J. A. EDWARDSON, J. KLINOWSKI, A. E. OAKLEY,
E. K. PERRY, and R. H. PERRY (With 7 Figures) . . . . . 183
Biochemical Changes in Alzheimer's Disease: A Comment
A. N. DAVISON (With 1 Figure) . . . . . . . . . . . . 198
The Nature of Neurofibrillary Tangles
B. H. ANDERTON, M. C. HAUGH, J. KAHN, C. MILLER, A. PROBST,
and J. ULRICH (With 6 Figures) . . . . . . . . . . . . . . 205
Brain Plasticity and Trophic Factors
Trophic Factors in Brain Aging and Disease
S. H. ApPEL, K. OJIKA, Y. TOMOZAWA, and R. BOSTWICK 218
Melanocortin Peptides and Neural Plasticity
P. M. EDWARDS and W. H. GISPEN (With 4 Figures) 231
Brain Plasticity and Aging
S. HOYER and L. FROLICH (With 4 Figures) . . . . 241
Animal Models
Parallels and Contrasts Between Scrapie and Dementia of the
Alzheimer Type and Ageing: Strategies and Problems for
Experiments Involving Life Span Studies
H. FRASER and P. A. McBRIDE (With 16 Figures).. ... 250
Animal Models of Geriatric Cognitive Dysfunction:
Evidence for an Important Cholinergic Involvement
R. L. DEAN and R. T. BARTUS (With 4 Figures) . . . . . . . 269
Contents XI
Animal Models of Jacksonian Dissolution of Memory in the Aged
B. A. CAMPBELL, C. B. SANANES, and J. R. GADDY
(With 3 Figures). . . . . . . . . . . . . . . . . . .. 283
Mechanisms Underlying Pharmacologic Modifications of the
Hippocampal Lesion Syndrome
R. L. ISAACSON and J. P. RYAN (With 6 Figures) . . . . .. 292
Lesions of the Nucleus Basalis in the Rat: Functional Changes
G. PEPEU, F. CASAMENT!, L. BRACCO, H. LADINSKY, and
S. CONSOLO (With 2 Figures) . . . . . . . . . . . . . . . 305
AF64A Cholinotoxicity: Functional Aspects
S. M. LEVENTER and I. HANIN ...... . 316
Novel Approaches in the Study of Brain Acetylcholine Function:
Neuropharmacology, Neuroanatomy, and Behavior
D. G. SPENCER, JR., E. HORVATH, P. LUITEN, T. SCHUURMAN,
and J. TRABER (With 6 Figures) . . . . . . . . . . . 325
Immunologic Factors Related to Cognitive/Behavioral
Dysfunctions in Aging
H. LAL, M. J. FORSTER, and K. NANDY (With 3 Figures) 343
Morphological Studies on Brain Structures of the NZB Mouse:
An Animal Model for the Aging Human Brain?
K. ZILLES (With 12 Figures). . . . . . . . . . . . . . . . 355
Subject Index . . . . . . . 367