Autonomic Nervous System in Old Age - G. Kuchel, P. Hof (Karger, 2004) WW

148 Pages·2004·3.65 MB·English

Autonomic Nervous System in Old Age

Interdisciplinary Topics in
Gerontology

Vol. 33

Series Editors
Patrick R. Hof, New York, N.Y.
Charles V. Mobbs, New York, N.Y.

Editorial Board
Constantin Bouras, Geneva
Christine K. Cassel, New York, N.Y.
Anthony Cerami, Manhasset, N.Y.
H. Walter Ettinger, Winston-Salem, N.C.
Caleb E. Finch, Los Angeles, Calif.
Kevin Flurkey, Bar Harbor, Me.
Laura Fratiglioni, Stockholm
Terry Fulmer, New York, N.Y.
Jack Guralnik, Bethesda, Md.
Jeffrey H. Kordower, Chicago, Ill.
Bruce S. McEwen, New York, N.Y.
Diane Meier, New York, N.Y.
Jean-Pierre Michel, Geneva
John H. Morrison, New York, N.Y.
Mark Moss, Boston, Mass.
Nancy Nichols, Melbourne
S. Jay Olshansky, Chicago, Ill.
James L. Roberts, San Antonio, Tex.
Jesse Roth, Baltimore, Md.
Albert Siu, New York, N.Y.
John Q. Trojanowski, Philadelphia, Pa.
Bengt Winblad, Huddinge

Autonomic Nervous
System in Old Age

Basel · Freiburg · Paris · London · New York ·
Bangalore · Bangkok · Singapore · Tokyo · Sydney

Volume Editors
George A. Kuchel, Farmington, Conn.
Patrick R. Hof, New York, N.Y.

11 figures and 9 tables, 2004

George A. Kuchel, MD FRCP
UConn Center on Aging
University of Connecticut Health Center
Farmington, Conn., USA

Patrick R. Hof, MD
Associate Professor, Kastor Neurobiology of Aging Laboratories
Dr. Arthur Fishberg Research Centre for Neurobiology
Mount Sinai School of Medicine
New York, N.Y., USA

Bibliographic Indices. This publication is listed in bibliographic services, including Current Contents® and
Index Medicus.

Drug Dosage. The authors and the publisher have exerted every effort to ensure that drug selection and
dosage set forth in this text are in accord with current recommendations and practice at the time of publication.
However, in view of ongoing research, changes in government regulations, and the constant flow of information
relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for
any change in indications and dosage and for added warnings and precautions. This is particularly important
when the recommended agent is a new and/or infrequently employed drug.

All rights reserved. No part of this publication may be translated into other languages, reproduced or
utilized in any form or by any means electronic or mechanical, including photocopying, recording, microcopying,
or by any information storage and retrieval system, without permission in writing from the publisher.

© Copyright 2004 by S. Karger AG, P.O. Box, CH–4009 Basel (Switzerland)
www.karger.com
Printed in Switzerland on acid-free paper by Reinhardt Druck, Basel
ISSN 0074–1132
ISBN 3–8055–7685–4

Library of Congress Cataloging-in-Publication Data

Autonomic nervous system in old age / volume editors, George A. Kuchel, Patrick R. Hof.
p. ; cm. – (Interdisciplinary topics in gerontology, ISSN 0074–1132 ; v. 33)
Includes bibliographical references and index.
ISBN 3–8055–7685–4 (hard cover : alk. paper)
1. Autonomic nervous system–Pathophysiology–Age factors.
2. Autonomic nervous
system–Aging.
I. Kuchel, George A. II. Hof, Patrick R.
III. Series.
[DNLM: 1. Autonomic Nervous System–physiology–Aged.
2. Aging–physiology. WL
600 A939545 2004]
HQ1060.I53 vol. 33
[RC347]
362.6 s–dc22
[612.8�9]
2003064038

Contents

V

VII Preface

1 Age-Related Sympathetic Autonomic Neuropathology.
Human Studies and Experimental Animal Models
Schmidt, R.E. (St. Louis, Mo.)

24 Clinical and Therapeutic Implications of Aging Changes in
Autonomic Function
Ford, G.A. (Newcastle upon Tyne)

32 Normal and Pathological Changes in Cardiovascular
Autonomic Function with Age
Attavar, P.; Silverman, D.I. (Farmington, Conn.)

45 The Autonomic Nervous System and Blood Pressure
Regulation in the Elderly
Bourke, E. (Brooklyn, N.Y.); Sowers, J.R. (Columbia, Mo.)

53 Aging, Carbohydrate Metabolism and the Autonomic
Nervous System
Madden, K.M.; Meneilly, G.S. (Vancouver)

67 Aging and the Gastrointestinal Tract
Pilotto, A. (San Giovanni Rotondo); Franceschi, M. (Schio);
Orsitto, G.; Cascavilla, L. (San Giovanni Rotondo)

78 Structure and Function of the Aged Bladder
Tannenbaum, C. (Montréal); Zhu, Q.; Ritchie, J.; Kuchel, G.A. (Farmington, Conn.)

94 Impact of Aging on Reproduction and Sexual Function
Beshay, E.; Rehman, K.-u.; Carrier, S. (Montreal)

107 Aging of the Autonomic Nervous System. Pain Perception
Lussier, D. (Montreal); Cruciani, R.A. (New York, N.Y.)

120 Aging and Thermoregulation
McDonald, R.B.; Gabaldón, A.M.; Horwitz, B.A. (Davis, Calif.)

134 Author Index

135 Subject Index

Contents
VI

Preface

In recent years, all western industrialized countries, and to a growing extent
even many developed and developing Asian nations, have witnessed a remarkable
growth in numbers of older people [1]. Future projections anticipate continued
increases, particularly in numbers of individuals who are 85 years and older [1].
Although US statistics have indicated recent declines in disability trends [2], over-
all numbers of older individuals living with disability and functional dependence
are likely to increase given projected increases in life expectancy [3]. For example,
average life expectancy for women born today in the United States is nearly 80; for
men, it is nearly 75 [1]. With these considerations in mind, many investigators have
begun to pay increasing attention to identifying factors which may predict the
transition from health and independence to disability and dependence in older
individuals, eventually providing useful targets for interventions [3, 4].
Neurodegenerative disorders such as Alzheimer’s and Parkinson’s diseases
are both common and important causes of cognitive and motor deficits in later
life. Moreover, the presence of cognitive and motor deficits resulting from these
disorders represents a major risk for the development of disability, dependence
and need for institutionalization among older individuals [1]. Thus, it is not at all
surprising that the central nervous system has received far more research atten-
tion than has the peripheral nervous system. Nevertheless, age-related changes
and diseases involving the peripheral nervous system, particularly its autonomic
elements, do frequently play determining roles in late life health and functional
independence.
Homeostasis, the need for the body to maintain a constant internal milieu,
was first defined by Claude Bernard in the mid 19th century [5]. In a 1932 book,

VII

Walter B. Cannon clearly recognized that as the body ages its ability to maintain
normal homeostasis in response to common challenges is altered [6]. In fact,
many of the physiologic parameters discussed by Cannon – temperature, blood
sugar and blood pressure – are all closely regulated by autonomic function and
are discussed in some detail in this book. However, our understanding of auto-
nomic system aging and its role in human health and disability has increased a
great deal since the time of Bernard and Cannon.
Above all, modern clinical investigators typically study autonomic aging in
healthy older individuals and are thus able to dissect the contribution being made
by aging from that caused by disease. Such studies clearly indicate that while
basal sympathetic activity increases with normative aging, there is evidence of
considerable dysregulation in terms of the ability of the aging sympathetic
nervous system to respond to a variety of challenges. Moreover, markers of
elevated sympathetic activity appear to predict increased mortality among ill
[7, 8], as well as community dwelling independent older individuals [9, 10].
Although many questions remain unanswered, recent conceptual and tech-
nological advances have provided both the clinician and investigator with much
new information drawn from clinical, as well as basic research. In the follow-
ing pages, investigators from several different disciplines discuss aging of the
autonomic nervous system from a variety of perspectives. Given the fact that
aging of the parasympathetic elements of the autonomic nervous system is not
nearly as well understood as that of its sympathetic portions, greater emphasis
has been placed on the latter. Some authors are basic scientists, while others are
clinical investigators, yet efforts have been made by all to begin bridging the
barriers between the two perspectives in a fashion that is meaningful to both.
In the first chapter, Dr. Schmidt discusses the major neuropathological and
cellular changes that have been described during autonomic aging in both
animal and human studies. Dr. Ford addresses the impact of physiologic
changes involving the autonomic nervous system, but does so from the point of
view of a clinical pharmacologist and clinician in describing the impact of age-
related changes in autonomic function on responses to common medications. In
Chapter 3, Drs. Attavar and Silverman discuss the impact of autonomic aging
on cardiac performance and the management of common cardiac conditions.
Drs. Bourke and Sowers focus their discussion on autonomic mechanisms
involved in the regulation of blood pressure and the impact of age-related
changes on the management of both hypertension and hypotension in older
individuals. Aging is associated with specific deficits in the body’s capacity to
handle glucose and the role of autonomic aging in these changes is addressed
by Drs. Madden and Meneilly. Many aspects of gastrointestinal function,
particularly motility, are closely influenced by autonomic function. Drs. Pilotto,
Franceschi, Orsitto and Cascavilla discuss the role of autonomic changes on

Preface
VIII

gastrointestinal performance in late life. Urinary incontinence is a major cause
of morbidity and disability in older individuals. Drs. Tannenbaum, Zhu, Ritchie
and Kuchel provide an overview of age-related changes in the autonomic
elements that closely regulate bladder performance and discuss their potential
roles in maintaining continence in older women and men. As discussed by
Drs. Beshay, Rehman and Carrier, both reproductive function and sexual
performance decline in advanced age, with autonomic changes providing a
contribution to both. The management of pain is a crucial element in improv-
ing the quality of life older patients and, as discussed by Drs. Lussier and
Cruciani, autonomic changes are among the many important considerations
needed to be brought into the assessment of an older individual in pain. Finally,
the inability of many older individuals to appropriately regulate their body tem-
peratures in response to both high and low extremes of environmental temper-
ature is a major risk factor for death. Drs. McDonald, Gabaldón and Horwitz
provide an excellent overview addressing a number of clinically important
questions by highlighting key clinical and basic research studies.
Clearly, the years since Claude Bernard’s first presentation of the concept
of homeostasis and Cannon’s comments regarding the influence of aging on
these mechanisms have witnessed a tremendous growth in our knowledge. At
the same time, the coming decade should lead to an even better understanding
of this area. This will take place as more ambitious and well-defined clinical
studies are undertaken and as the power of basic research is harnessed, partic-
ularly in terms of using genetically modified animals, with real efforts made to
move or translate knowledge between the two fields.

George A. Kuchel, Farmington, Conn.
Patrick R. Hof, New York, N.Y

References

1
Guralnik JM, Ferrucci L: Demography and epidemiology; in Hazzard WR, Blass JP, Halter JB,
Ouslander JG, Tinetti ME (eds): Principles of Geriatric Medicine and Gerontology. New York,
McGraw-Hill, 2003, pp 53–76.
2
Fries JF: Measuring and monitoring success in compressing morbidity. Ann Intern Med 2003;139:
455–459.
3
Guralnik JM, Fried LP, Salive ME: Disability as a public health outcome in the aging population.
Annu Rev Public Health 1996;17:25–46.
4
Fried LP, Tangen CM, Walston J, Newman AB, Hirsch C, Gottdiener J, et al: Frailty in older adults:
Evidence for a phenotype. J Gerontol A Biol Sci Med Sci 2001;56:M146–M156.
5
Grande F, Visscher MB: Claude Bernard and Experimental Medicine. Cambridge, Mass.,
Schenkman, 1967.
6
Cannon WB: The aging of homeostatic mechanisms; in Cannon WB (ed): The Wisdom of the
Body. New York, Norton, 1932, pp 202–215.

Preface
IX