RESEARCH AND PERSPECTIVES IN ALZHEIMER'S DISEASE Fondation Ipsen Editor Yves Christen, Fondation Ipsen, Paris (France) Editorial Board Yves Agid, H6pital Pitie Salpetriere, Paris (France) Albert Aguayo, McGill University, Montreal (Canada) Brian H. Anderton, Institute of Psychiatry, London (GB) Raymond T. Bartus, Alkermes, Cambridge (USA) Anders Bjorklund, University of Lund (Sweden) Floyd Bloom, Scripps Clinic and Research Foundation, La Jolla (USA) Fran~ois Boller, Inserm U 324, Paris (France) Carl Cotman, University of California, Irvine (USA) Peter Davies, Albert Einstein College of Medicine, New York (USA) Andre Delacourte, Inserm U 422, Lille (France) Steven Ferris, New York University Medical Center, New York (USA) Jean-Fran~ois Foncin, H6pital Pitie Salpetriere, Paris (France) Fran~oise Forette, H6pital Broca, Paris (France) Fred Gage, Salk Institute, La Jolla (USA) Carleton D. Gajdusek, National Institute of Health, Bethesda (USA) Dmitry Goldgaber, State University of New York Stone Brook (USA) John Hardy, Mayo Clinic, Jacksonville (USA) Jean-Jacques Hauw, H6pital Pitie Salpetriere, Paris (France) Claude Kordon, Inserm U 159, Paris (France) Kenneth S. Kosik, Harvard Medical School, Center for Neurological Diseases and Brigham and Women's Hospital, Boston (USA) Jacques Mallet, H6pital Pitie Salpetriere, Paris (France) Colin L. Masters, University of Melbourne, Parkville (Australia) Stanley 1. Rapoport, National Institute on Aging, Bethesda (USA) Andre Rascol, H6pital Purpan, Toulouse (France) Barry Reisberg, New York University Medical Center, New York (USA) Allen Roses, Duke University Medical Center, Durham (USA) Dennis J. Selkoe, Harvard Medical School, Center for Neurological Diseases and Brigham and Women's Hospital, Boston (USA) Michael L. Shelanski, Columbia University, New York (USA) Pierre-Marie Sinet, H6pital Necker, Paris (France) Peter St. George-Hyslop, University of Toronto, Toronto (Canada) Robert Terry, University of California, La Jolla (USA) Henry Wisniewski, Institute for Basic Research in Development Disabilities, Staten Island (USA) Edouard Zarifian, Centre Hospitalier Universitaire, Caen (France) Springer Berlin Heidelberg New York Barcelona Hong Kong London Milan Paris Singapore Tokyo R. Mayeux Y. Christen (Eds.) Epidemiology of Alzheimer's Disease: From Gene to Prevention With 8 Figures and 21 Tables Springer Mayeux, Richard, MD The Gertrude H. Sergievsky Center 630 West 168th Street Columbia University New York, NY 10032 USA Christen, Y., Ph.D. Fondation IPSEN Pour la Recherche Therapeutique 24, rue Erlanger 75781 Paris Cedex 16 France ISSN 0945-6082 ISBN-13:978-3-642-64245-6 e-ISBN-13:978-3-642-60076-0 DOl: 10 .100 7/978-3-642-60076-0 Library of Congress Cataloging-in-Publication Data Epidemiology of Alzheimer's : from gene to prevention 1 R. Mayeux, Y. Christen, eds. p. cm. - (Research and perspectives in Alzheimer's disease, ISSN 0945-6082) Includes bibliographical references and index. ISBN-13:978-3-642-64245-6 (alk. paper) 1. Alzheimer's disease - Epidemiology. I. Mayeux, Richard. II. Christen, Yves. III. Series. [DNLM: 1. Alzheimer Disease - epidemiology. 2. Alzheimer Disease - genetics. 3. Alzheimer Disease'-prevention & control. WT 155 E64 1999) RA645.A49E65 1999614.5'9831 - dc21 DNLM/DLC for Library of Congress This work is subject to copyright. All rights are reserved, whether the whole or part of the mate rial is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recita tion, broadcasting, reproduction on microfilm or in any other way, and storage in data banks. Duplication of this publication or parts thereof is permitted only under the provisions of the German Copyright Law of September 9, 1965, in its current version, and permission for use must always be obtained from Springer-Verlag. Violations are liable for prosecution under the Ger man Copyright Law. © Springer-Verlag Berlin Heidelberg 1999 Softcover reprint of the hardcover 1st edition 1999 The use of general descriptive names, 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 publishers cannot guarantee the accuracy of any information about dos age and application contained in this book. In every individual case the user must check such information by consulting the relevant literature. Production: PRO EDIT GmbH, D-69126 Heidelberg Cover design: Design & Production, D-69121 Heidelberg Typesetting: Mitterweger Werksatz GmbH, Plankstadt SPIN: 10698813 27/3136 - 5 432 1 0 - Printed on acid-free paper Preface This volume contains the proceedings of the 14th Colloque Medecine et Recher che of the Fondation Ipsen pour la Recherche Therapeutique devoted to Alzhei mer's disease. It was held in Paris on May 25, 1998 and dedicated to the epidemi ological study of this dementia, a very important issue because the incidence and prevalence of Alzheimer's disease rise exponentially with age. Epidemiological findings not only confirm dementia as a major challenge for the coming years but also contribute defining risk factors, predicting and may be preventing this disease. All these issues have been tackled at the meeting in Paris and in the present book. Y. C. Contents The World-Wide Impact of Dementia. Projections of Prevalance and Costs R. Katzmann and P.J. Fox ........................................... 1 Predicting Who Will Develop Alzheimer's Disease R. Mayeux ........................................................ 19 Genetic Factors in Early- and Late-Onset Alzheimer's Disease J. Tol, A.J.e. Slooter, and e.M. Van Duijn .............................. 33 Heterogeneity in Alzheimer's Disease: Implications for Epidemiology T.S. Radebaugh, M. Ganguli, and Z.S. Khachaturian ......... . ... . ....... 41 The Epidemiology of Alzheimer's Disease: The Role of Estrogen in Reducing Risk v.w. Henderson............ . . . .... .... ..... . . .... . .... . ... . ........ 49 Inflammation, Anti-Inflammatory Drugs and Alzheimer's Disease C.H. Kawas ....................................................... 65 Socio-Demographic Risk Factors for Dementia and Alzheimer's Disease in the Paquid Study e. J.P. Dartigues, Helmer, and L. Letenneur ............................ 73 Vascular Disease and Vascular Risk Factors and Dementia M.M.B. Breteler, M.e. Bots, A. Ott, and A. Hofman...................... 79 Alzheimer's Disease: A Review of Cross-Cultural Studies H.C. Hendrie...................................................... 87 The Implications of Epidemiological Findings for the Prevention of Alzheimer's Disease e. e. Brayne, Dufouil, and M. McGee ................................. 103 VIII Contents The Primary Prevention of Alzheimer's Disease: Should We Develop Large-Scale Trials? D.A. Evans . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. III Possibilities for Secondary Prevention of Alzheimer's Disease 1. Skoog .......................................................... 121 Subject Index ..................................................... 135 List of Contributors Bots, M.L. Department of Epidemiology & and Biostatistics, Erasmus University Medical School, PO Box 1738, 3000 DR Rotterdam, The Netherlands and Julius Center for Patient Oriented Research, University Medical Center, Heidel berglaan 100,3584 CX Utrecht, The Netherlands Brayne, C. Department of Community Medicine-Institute of Public Health, Forvie Site Robinson Way, Cambridge CB2 2SR, United Kingdom Breteler, M. M. B. Department of Epidemiology & and Biostatistics, Erasmus University Medical School, PO Box 1738, 3000 DR Rotterdam, The Netherlands Dartigues, 1.P. INSERM U 330, Universite de Bordeaux II, 146 rue Leo Saignat, 33076 Bordeaux Cedex, France Dufouil, C. INSERM Unit 360, Hopital La Salpetriere, 75651 Paris Cedex 13, France Evans, D.A. Rush University and Rush Institute for Healthy Aging, 1645 W. Jackson Blvd., Chicago, IL 6061, USA Fox, P.I. Institute for Health and Aging, University of California, San Francisco, San Fran cisco, CA 94143-0612, USA Ganguli, M. University of Pittsburgh, Pittsburgh, PA 15213-3593, USA Helmer, C. INSERM U 330, Universite de Bordeaux II, 146 rue Leo Saignat, 33076 Bordeaux Cedex, France X List of Contributors v.w Henderson, Department of Neurology, University of Southern California School of Medicine, 1420 San Pablo Street, Suite PMB-B105, Los Angeles, CA 90033, USA Hendrie, H.C. Department of Psychiatriy, Indiana University School of Medicine, 541 Clinical Drive, Room 298, Indianapolis, IN 46202-5111, USA Hofman, A. Department of Epidemiology & and Biostatistics, Erasmus University Medical School, PO Box 1738, 3000 DR Rotterdam, The Netherlands Katzman, R. Alzheimer's Disease Research Center, Department of Neurosciences, University of California, San Diego, La Jolla, CA 92093-0949, USA Kawas, C.H. Johns Hopkins University School of Medicine, 5501 Hopkins Bayview Circle, Room 1B.82, Baltimore, MD, 21224, USA Khachaturian, Z.S. Alzheimer's Association, Ronald & Nancy Reagan Research Institute, Chicago, IL 60611, USA Letenneur, L. INSERM U 330, Universite de Bordeaux II, 146 rue Leo Saignat, 33076 Bordeaux Cedex, France Mayeux, R. The Gertrude H. Sergievsky Center, 630 West 168th Street, Columbia University, New York, NY 10032, USA McGee, M. MRC Biostatistics Unit-Institute of Public Health, Forvie Site-Robinson Way, Cambridge CB2 2SR, United Kingdom Ott, A. Department of Epidemiology & and Biostatistics, Erasmus University Medical School, PO Box 1738, 3000 DR Rotterdam, The Netherlands and Department of Medical Microbiology, University Hospital Rotterdam, Dr. Mole waterplein 40,3015 GD Rotterdam, The Netherlands Radebaugh, T.S. Alzheimer's Association, Ronald & Nancy Reagan Research Institute, Chicago, IL 60611, USA List of Contributors XI Skoog, 1. Institute of Clinical Neuroscience, Department of Psychiatry, Sahlgrenska Uni versity Hospital, 413 45 G6teborg, Sweden Slooter, A.J.C. Department of Epidemiology & Biostatistics, Erasmus University Medical School, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands Tol, J. Department of Epidemiology & Biostatistics, Erasmus University Medical School, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands van Duijn, C.M. Department of Epidemiology & Biostatistics, Erasmus University Medical School, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands