The Aging Brain and Senile Dementia PDF
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THE AGING BRAIN AND SENILE DEMENTIA ADVANCES IN BEHAVIORAL BIOLOGY Editorial Board: Jan Burel Institute of Physiology, Prague, Czechoslovakia Irwin Kopln National Institute of Mental Health, Bethesda, Maryland Bruce McEwen Rockefeller University, New York, New York Jamel McGaugh Universify of California, Irvine, CalifornIa Karl Prlbram Stanford University School of Medicine, Stanford, California Jay ROlenblatt Rutgers University, Newark, New Jersey Lawrence Wellkrantz University of Oxford, Oxford, England Recent Volumes in this Series Volume 12. THE NEUROPSYCHOLOGY OF AGGRESSION Edited by Richard E. Whalen. 1974 Volume 13. ANEURAL ORGANISMS IN NEUROBIOLOGY Edited by Edward M. Eisenstein. 1975 Volume 14. NUTRITION AND MENTAL FUNCTIONS Edited by George Serban • 1975 Volume 15. SENSORY PHYSIOLOGY AND BEHAVIOR Edited by Rachel Galun, Peter Hillman, Itzhak Parnas, and Robert Werman. 1975 Volume 16. NEUROBIOLOGY OF AGING Edited by J. M. Ordy and K. R. Brizzee. 1975 Volume 17. ENVIRONMENTS AS THERAPY FOR BRAIN DYSFUNCTION Edited by Roger N. Walsh and William T. Greenough. 1976 Volume 18. NEURAL CONTROL OF LOCOMOTION Edited by Richard M. Herman, Sten Grillner, Paul S. G. Stein, and Douglas G. Stuart. 1976 Volume 19. THE BIOLOGY OF THE SCHIZOPHRENIC PROCESS Edited by Stewart Wolf and Beatrice Bishop Berle • 1976 Volume 20. THE SEPTAL NUCLEI Edited by Jon F. DeFrance. 1976 Volume 21 • COCAINE AND OTHER STIMULANTS Edited by Everett H. Ellinwood, Jr. and M. Marlyne Kilbey • 1977 Volume 22. DISCRIMINATIVE STIMULUS PROPERTIES OF DRUGS Edited by Harbans Lal • 1977 Volume 23 • THE AGING BRAIN AND SENILE DEMENTIA Edited by Kalidas Nandy and Ira Sherwin. 1977 A Continuation Order Plan la available for this aeries. A continuation order will bring delivery of each new volume immediately upon publication. Volumea are billed only upon actual ahlpment. For further Information pleaae contact the publisher. THE AGING BRAIN AND SENILE DEMENTIA Edited by Kalidas Nandy Geriatric Research, Educational, and Clinical Center Veterans Administration Hospital Bedford, Massachusetts and Boston University School of Medicine Boston, Massachusetts and Ira Sherwin Research and Development Veterans Administration Hospital Bedford, Massachusetts and Harvard Medical School Boston, Massachusetts PLENUM PRESS • NEW YORK AND LONDON Library of Congress Cataloging in Publication Data Symposium on the Aging Brain and Senile Dementia, Boston, 1976. The aging brain and senile dementia. (Advances in behavioral biology; v. 23) Includes index. 1. Senile psychosis-Congresses. 2. Aging-Congresses. 3. Brain-Congresses. I. Nandy, Kalidas. II. Sherwin, Ira. III. United States. Veterans Administration. IV. Title. RC524.S941976 616.8'983 77-8190 ISBN 978-1-4684-3095-0 ISBN 978-1-4684-3093-6 (eBook) 00110.1007/978-1-4684-3093-6 Proceedings of the Symposium on The Aging Brain and Senile Dementia sponsored by the Veterans Administration held in Boston, Massachusetts, June 2-4, 1976 © 1977 Plenum Press, New York Softcover reprint of the hardcover 1s t edition 1977 A Division of Plenum Publishing Corporation 227 West 17th Street, New York, N.Y. 10011 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, electronic, mechanical, photocopying, microfilming, recording, or otherwise, without written permission from the Publisher Preface There are currently about 21 million people over 6S years in the United States and over a million of them suffer from a severe degree of mental impairment. This number will undoubtedly increase as more and more people attain their full lifespan. The Veterans Administration is acutely aware of this problem in the population it serves. Currently, there are about 31 million veterans in the United States. About 13 percent of these veterans are over 6S years of age and the number is expected to increase to 40 percent by the turn of the century. In recognition of the pressing need to address this problem, eight Geriatric Research, Educational and Clinical Centers (GRECC) have been established under the auspices of the Veterans Administration and the guiding spirit of Dr. Paul Haber, Assistant Chief Medical Director for Professional Services, Veterans Administration. The purpose of these centers is to develop a better understanding of the complex biomedical and socio-economic problems of the aged in general and to enhance the quality of life of the older veterans in particular o Gerontologists working towards a better understanding of the aging process and better care of the aged have made major progress in the biomedical field in the last decade. Among the efforts made by the Veterans Administration, the department of Extended Care and Academic Affairs have sponsored a number of symposia in the field of Gerontology. Leaders in the field of the Neurobiology of Aging gathered in Boston to present and discuss State-of-the-Art and recent scientific advancements relating to the aging process of the brain and senile dementia. This book covers the proceedings of this symposium in two sections. The first section of the book deals primarily with the neuroanatomical, neurochemical and physio logical changes which occur in the mammalian brain during aging. The second section of the book is devoted to the neuropathological, immunological and clinical aspects of brain aging and senile dementia. An additional chapter correlating the clinical aspects of senile dementia with neuropathological, anatomical, and immunological changes has been added for the benefit of clinicians. Similarly, an introductory chapter has been added to review fundamental concepts of aging in general for the benefit of scientists working in other disciplines. It is our hope that this book will be useful to basic scientists, clinicians, graduate students, and others interested in the field of gerontology. v PREFACE ACKNOWLEDGEMENTS The editors express their appreciation to the publisher for continued cooperation and understanding in dealing with the numerous problems arising during the preparations of the manuscripts. We also express sincere thanks to John D. Chase, M. D., Chief Medical Director, Veterans Administration, for the permission to publish the proceedings of the symposium. We are especially thankful for the encouragement and assistance given to us by Dr. Richard Filer, Acting Assistant Chief Medical Director for Extended Care, and Mr. Phillip Haines, Coordinator of GRECC, V. A. Central Office. We also appreciate the cooperation of the members of the Planning Committee of the symposium, Director, Bedford GRECC, and the Management Staffs of the Bedford V. A. Hospital and the Boston Outpatient Clinic. The editors are also grateful to Mrs. Terry Laffey for her excellent typing and hard work in the preparation of the manuscripts. The help and support of Mead Johnson and Ciba Geigy Pharmaceutical Companies is gratefully acknowledged. Kalidas Nandy, M.D., Ph.D. Ira Sherwin, M.D. Contents Introduction: Biomedical Aspects of Aging Research 1 Paul Haber I. NEUROANATOMICAL, BIOCHEMICAL PHYSIOLOGICAL ASPECTS A.~ 1. Cell Loss with Aging • • • • • • • • 15 Harold Brody and N. Vijayashankar 2. Dendritic Changes in Aging Rat Brain: Pyramidal Cell Dendrite Length and Ultrastructure • • • • 23 Martin L. Feldman 3. Differential Changes with Aging in Old and New Cortices . . . . . . . . . . . . . . 39 Madge E. Scheibel and Arnold B. Scheibel 4. Effects of Age-Related Random and Coordinated Loss of Memory Engrams on Error Rates During Memory Retrieval • • • 59 Bernard L. Streh1er 5. Changes in EEG Amplitude During Sleep with Age 85 Irwin Feinberg, S. Hibi, and V. R. Carlson 6. Biochemical Significance of Age Pigment in Neurones . • . • . • . . . . . . . . . . . 99 A. N. Siakotos, D. Armstrong, N. Koppang, and J. Muller 7. Chromatin in Aging Brain. • • • • • • • • • • • •• 119 F. Marott Sinex 8. Effects of Chronic Dosage with Chlorpromazine and Gerovita1 H3 in the Aging Brain • • • • • 141 T. Samorajski, Albert Sun, and C. Ro1sten vii viii CONTENTS 9. Aging of Neurons in Culture • • • • • • • • • 157 F. Howard Schneider, Suzanne G. Rehnberg, and Mark P. Bear II. NEUROPATHOLOGICAL AND CLINICAL ASPECTS 10. Immune Reactions in Aging Brain and Senile Dementia • • • • 181 Kalidas Nandy 11. Reversible Modification of Blood-Brain Barrier Permeability to Proteins 197 Stanley I. Rapoport 12. Neurofibrillary Pathology: An Update ••• 209 Khalid Iqbal, Henryk M. Wisniewski, Inge Grundke-Iqbal, and Robert D. Terry 13. Aluminum and the Genetic Apparatus in Alzheimer Disease • • • • • • • • • 229 Donald R. Crapper and Umberto De Boni 14. The Fibrous Proteins of Brain: A Primer for Gerontologists • • . • • • • • • • • 247 Dennis J. Selkoe and Michael L. Shelanski 15. Cerebral Circulatory and Electroencephalographic Changes in Aging and Dementia • • • • • • • • . •• 265 Walter Obrist 16. Senile Dementia and Drug Therapy 271 Roland Branconnier and Jonathan O. Cole 17. Senile and Pre-senile Dementia: A Clinical Overview .•..•. 285 Ira Sherwin and Benjamin Seltzer Contributors 299 Index • • • • 303 BIOMEDICAL ASPECTS OF AGING RESEARCH Paul A. L. Haber Asst. Chief Medical Director for Professional Services, Department of Medicine and Surgery, Veterans Administration, Washington, D. C. and Asst. Clinical Professor of Medicine, George Washington University School of Medicine Few subjects available to intellectual scrutiny at the present time offer the author of an introductory chapter as much challenge and breadth of scope as does this - THE BIOMEDICAL ASPECTS OF AGING RESEARCH which opens this text of AGING BRAIN AND SENILE DEMENTIA. The array of subject material is vast; the evidence leading to any one set of conclusions is confusing and contradictory; the interest is intense. Theories of aging develop rapidly only to fall into discard within a few short years or even months and lines of investigation that seemed to hold promise a short while ago are found to be "blind alleys". To those of us who have worked in the field of aging for most of our professional lives it is difficult to understand the rapidly crescendoing interest in aging and aging research which has been taking place in the past half decade since the second White House Conference on Aging; difficult because no new factors have entered the basic equation. That there are growing numbers of aging Americans (and indeed growing number of humans worldwide who are reaching old age) comes as no surprise. Demographers have been telling us for years that there would be more older people around. But the fact that interest in Aging is on the increase is undeniable. To attest to such public interest one need only be reminded of the recent creation of the new National Institute of Aging in the National Institutes of Health, of the enlargement of the Administration on Aging, of the proliferation of various consumer groups representing the aging population, of the passage of a flood of legislation affecting the elderly such as the Older American Acts and the resurgence of attention paid by a large number of governmental agencies such as the Department of Health, Education, and Welfare, 2 P.HABER the Department of Housing and Urban Development, the Department of Transportations and The Veterans Administration to the problems of the aged and aging. The phenomenon that may help explain the interest in aging is the recent juxtaposition of two previously extant factors: one is the admitted increase in the physical presence of augmented numbers of older Americans - now totalling some 10.5% of the 220 million and there are expected to be almost 24 million by 1980; the other factor is the growing concern of Americans about health care in general (Source Book of Health Insurance Data, 1975-76). A great deal of popular attention is manifest in public forums, in the press, in the news media centers about health care these days and since older people are greater consumers of health services than the general population (accounting for more hospital admissions, days of hospital and long-term care, and visitsto physicians' offices) it follows that more attention is paid to the aging segment of the population than any other. As one example, the number of visits to physicians' offices in 1974 by populations of all ages was 4.9 visits per year, while the number of visits for both sexes over the age of 65 was 6.8 visits per year. In sum, the reasoning goes something like this: health care is rapidly growing more expensive amounting to 104.2 billion dollars in 1974 (representing 7.7% of the GNP) and the elderly are the most significant group of health care consumers in proportion to their numbers, and the numbers of elderly are daily increasing; therefore, anything that can reduce the morbidity and mortality of the elderly becomes exceedingly important. Not only does the general population feel that way but the elderly themselves, increasingly aware of their growing political and economic strength and importance,are beginning to have a larger voice in the decision making processes that determine the national policy. It has been broughtto our attention by Hayflick and many others that although the phenomenon of aging is not new, it has not until recent times been of any particular significance. The parsimony of biology dictates that the individual has little value for the survival of the race once the child bearing function has been con summated. Since the vigorous young animal in the post pubertal state is designed for optimal function in producing progeny and in raising offspring, his survival past young middle age is a biological luxury. It remained for the species Homo Sapiens in the latter half of the twentieth century to accumulate the material wealth and the sagacity to be able to indulge that luxury. Never before in the history of living things have so many individuals survived beyond the period during which they were needed for the continuation of the race. But while the relative and absolute numbers of aging and aged individuals has reached an all time high, the life span of older individuals seems to have remained relatively constant. For awhile
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