Springer-V erlag Italia SrI. s. Govoni. C.L. Bolis • M. Trabucchi (Eds) Dementias Biological Bases and Clinical Approach to Treatment Springer STEFANO GOVONI Institute of Pharmacology Faculty of Pharmacy University of Pavia, Italy CARLA LIANA BOLIS Consultant Office of Research Policy and Strategy Coordination of WHO University of Milan, Italy MARCO TRABUCCHI Department of Neurosciences University of Rome "Tor Vergata", Italy © Springer-Verlag Italia,1 M99i9la no ISBN 978-88-470-0048-3 Library of Congress Cataloging-in-Publication Data: Dementias: biological bases an clinical approach to treatment / S. Govoni, c.L. Bolis, M.Trabucchi (eds.). p. cm. Includes bibliograp- phical references and index. ISBN 978-88-470-0048-3 ISBN 978-88-470-2149-5 (eBook) DOI 10.1007/978-88-470-2149-5 1. Dementia--Physiological aspects.2. Dementia--Treatment I. Govoni, Stefano, 1950-. II. Bolis, C.L. III. Trabucchi, Marco. [DNLM: 1. Dementia. WM 220 D376389 1999] RC521. D4578 1999 616.8'3--dc21 DNLM/DLC for Library of Congress 98-54980 CIP This work is subject to copyright. Ali rights are reserved, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, re-use of illustrations, recitation, broadcasting, reproduction on microfilms or in other ways, and storage in data banks. Duplication of this publication or parts thereof is only permitted under the provisions of the Italian Copyright Law in its current vers ion, and permis sion for use must always be obtained from Springer-Verlag. Violations are liable for prosecution under the Italian Copyright Law. The use of registered names, trademarks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. Product liability: the publisher cannot guarantee the accuracy of any information about dosage and application contained in this book. In every individual case the user must check such informat ion by consult ing the relevant literature. Cover design: Simona Colombo (Milan) Typesetting: Photo Life (Milan) SPIN: 10700076 Preface To a certain extent the dementias have been forgotten diseases until just recen tly when they were brought to the attention of the general public and health authorities as a result of the increasing number of cases in the aging popula tion, especially among famous people, and because of the efforts of private foundations. The goals of the present volume are to present the dementias to health prac titioners, to provide some basic information on their epidemiology and biolo gical basis and to discuss the diagnostic and clinical problems that physicians and institutions face when caring for demented patients. This book explores the various types of dementias and is not limited to Alzheimer's disease although, as expected, more information is available and presented on this pathology. On the other hand, a few fundamental questions on dementia can only be answe red through a comparison of the various forms. Examples of such questions are the following: Is the loss of cerebral tissue sufficient to cause dementia? Are there thresholds or is there a continuous progression toward the irreversible development of dementia? Are there common pathways in the dementing pro cess? Are there common risk factors? Comparative analysis allows the common and distinctive patterns of the various dementias to be defined, ultimately lea ding to more focused therapeutic interventions. This book is not a mere collection of reviews, but is based on the personal experiences of the authors who are all directly involved in dementia research or clinical care of the patient. Each chapter, however, can be read independently. In a few cases information on the epidemiology or biological basis may be redun dant but, as editors, we considered that the perspective of a clinician taking care of a patient is different from that of a basic researcher, and therefore it was important to report both points of view. Finally, we included three "peculiar" chapters devoted to the care of the patient. These chapters illustrate those inter ventions providing care to the patient at home.or in an institution, the econo mic burden of the illness for the family and the healthcare system, and finally, the ethical aspects. Notably, this last chapter is written by a philosopher. We would like to close this preface with a quotation from Mother Theresa reported also in the chapter by Moyra Jones: "The biggest disease today is not leprosy or tuberculosis, but rather the feeling of being unwanted:' The mission of the present book is exactly this: to help us remember through the experien ce of scientists, clinicians and care-givers that science and technology can cope VI Preface with the needs of the demented by working together with all the people willing to recognize, care for and help the person inside the demented patient. Finally, we wish to mention that this book would not have been possible without the financial support of several institutions and Italian divisions of pharmaceutical companies, including Bayer, Bracco, Fondazione Giovanni Lorenzini, Novartis, Pfizer, and the University of Pavia. S.GOVONI c.L. BOLlS M. TRABUCCHI Table of Contents Dementias, the Dimension of the Problem: Epidemiology Notes A. DI CARLO, M. BALDERESCHI, D. INZITARI, and L. AMADUCClt .................. 1 The Biological Basis of Dementias M. RACCHI and S. GOVONI • ...... •••••••• ••••••• ............... •••••• •••••••••••••• 19 Classification and Diagnosis of Dementias F. BOLLER and L. TRAYKOV ......................................................... 51 Alzheimer's Disease A. BIANCHETTI and M. TRABUCCHI 77 Lacunes in - the Knowledge of - Vascular Dementia P. MARTINEZ-LAGE and V. HACHINSKI ............................................. 103 Dementia with Lewy Bodies C. BALLARD, C. MORRIS, and M. PIGGOTT .......................................... 137 Frontotemporal Dementia L. GUSTAFSON and A. BRUN ......................................................... 151 Pseudodementia D. DE LEO and W. PADOANI ......................................................... 173 Neuropsychiatric Symptoms in Dementia Patients S.T. CHEN and J.L. CUMMINGS ...................................................... 195 Non-Cognitive Symptoms and Alterations in Demented Patients W.C. MCCORMICK •••• ............ ........ ••••••• ................................ ••• 223 Pharmacotherapeutic Approach to the Treatment of Alzheimer Disease E. GIACOBINI ••••••• •••••••••••••••••• ••••••••• •••••••• ••••••••••••• ••••••••• •••••••• 233 Non-Pharmacological Treatment of Alzheimer's Disease and Related Disorders O. ZANETTI and M. TRABUCCHI • •••••••• .............................. •••••••••••• 253 VIII Table of Contents GENTLECARE: the Prosthetic Life Care Approach to Providing Dementia Care at Home or in Institutions M.J.D. JONES •••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••• 273 Economics of Dementia c. GEROLDI, A. BIANCHETTI, and M. TRABUCCHI ••••••••••••••••••••••••••••••••• 287 Ethical Problems in Caring for Demented Patients G.J. AGICH ••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••• 297 List of Contributors GEORGE J. AGICH F. J. O'Neill Chair in Clinical Bioethics, Department of Bioethics, Cleveland Clinic Foundation, Cleveland, Ohio 44122, USA LUIGI AMADUCCIt Italian National Research Council, Targeted Project on Aging, Via Leone Pancaldo 21, 50127 Florence, Italy MARZIA BALDERESCHI Italian National Research Council, Targeted Project on Aging, Via Leone Pancaldo 21, 50127 Florence, Italy CLIVE BALLARD MRC Neurochemical Pathology Unit, Newcastle General Hospital, Westgate Road, Newcastle upon Tyne NE4 6BE, UK ANGELO BlANCHETT! Geriatric Research Group, Via Romanino 1,25122 Brescia, Italy Department of Medicine, ''Ancelle della Carita" Hospital, Cremona, Italy FRANGms BOLLER INSERM U 324, 2ter rue d'Alesia, 75014 Paris, France ARNE BRUN Department of Pathology and Cytology, Lund University Hospital, 22185 Lund, Sweden STEPHEN T. CHEN Department of Psychiatry and Biobehavioral Sciences, Neuropsychiatric Institute and Hospital, University of California, Los Angeles, 760 Westwood Plaza C8-849, Los Angeles, CA 90024, USA JEFFREY L. CUMMINGS Departments of Psychiatry and Biobehavioral Sciences and Neurology, Alzheimer's Disease Center, Reed Neurological Research Center, University of California, Los Angeles, 710 Westwood Plaza, Los Angeles, CA 90095-1769, USA DIEGO DE LEO Psychogeriatric Service, Department of Neurology and Psychiatry, University of Padova, Via Vendramini 7, 35137 Padova, Italy Australian Institute for Suicide Research and Prevention, Griffith University, Nathan, Queensland 4111, Australia IRCCS "S. Giovanni di Dio", "S. Cuore-Fatebenefratelli" Institute,Via Pilastroni 4, 25125 Brescia, Italy x List of Contributors ANTONIO DI CARLO Italian National Research Council, Targeted Project on Aging, Via Leone Pancaldo 21, 50127 Florence, Italy CRISTINA GEROLDI Geriatric Research Group, Via Romanino 1,25122 Brescia, Italy EZIO GIACOBINI Institutions Universitaires de Geriatrie de Geneve, Route de Mon-Idee, 1226 Thonex- Geneva, Switzerland STEFANO GOVONI Institute of Pharmacology, University of Pavia, Viale Taramelli 14,27100 Pavia, Italy IRCCS "S. Giovanni di Dio", "S. Cuore-Fatebenefratelli" Institute, Via Pilastroni 4, 25125 Brescia, Italy LARS GUSTAFSON Department of Psychogeriatrics, Lund University Hospital, 221 85 Lund, Sweden VLADIMIR HACHINSKI Department of Clinical Neurological Sciences, London Health Sciences Centre, University of Western Ontario, London, Ontario, Canada DOMENICO INZITARI Italian National Research Council, Targeted Project on Aging, Via Leone Pancaldo 21, 50127 Florence, Italy MOYRA J.D. JONES Moyra Jones Resources Ltd., 8264 Burnlake Dive, Burnaby, BC, Canada, V5A 3K9 PABLO MARTINEZ-LAGE Department of Clinical Neurological Sciences, London Health Sciences Centre, University of Western Ontario, London, Ontario, Canada Centro Terapeutico Alzheimer, Centro Psicogerhitrico Landazabal, Burlada, Navarra, Spain WAYNE C. MCCORMICK Department of Medicine, Division of Geriatrics, Box 359755, University of Washington, Seattle, WA 98195, USA CRISTOPHER MORRIS MRC Neurochemical Pathology Unit, Newcastle General Hospital, Westgate Road, Newcastle upon Tyne NE4 6BE, UK WALTER PADOANI Psychogeriatric Service, Department of Neurology and Psychiatry, University of Padova, Via Vendramini 7,35137 Padova, Italy MARGARET PIGGOTT MRC Neurochemical Pathology Unit, Newcastle General Hospital, Westgate Road, Newcastle upon Tyne NE4 6BE, UK MARCO RACCHI Institute of Pharmacology, University of Pavia, Viale Taramelli 14,27100 Pavia, Italy List of Contributors XI MARCO TRABUCCHI Geriatric Research Group,Via Romanino 1,25122 Brescia, Italy Department of Neurosciences, University of Rome "Tor Vergata", Rome, Italy Alzheimer's Unit, IRCCS "S. Giovanni di Dio", "S. Cuore-Fatebenefratelli" Institute, Via Pilastroni 4,25125 Brescia, Italy LATCHEZAR TRAYKOV INSERM U 324, 2ter rue d'Alesia,75014 Paris, France State University Hospital of Neurology and Psychiatry, Medical University, blvd. Tzarigradsko chosse IV km, 1113 Sofia, Bulgaria ORAZIO ZANETTI Alzheimer's Unit, IRCCS "S. Giovanni di Dio", "S. Cuore-Fatebenefratelli" Institute, Via Pilastroni 4, 25125 Brescia, Italy