Dementias: Handbook of Clinical Neurology Vol 89

887 Pages·2008·32.57 MB·English

by  Charles Duyckaerts

Foreword
It isanimmense pleasureforus tointroducethiseleventhvolumeofthethird series ofthe HandbookofClinical
Neurology,whichisdevotedtothedementias. Untilafewyearsago,itwouldhavebeenunthinkabletohavesuch
avolume.Manypeopledealingwithneuropsychologyandbehaviorbelievedthatsucha“global”deteriorationdid
not warrant their interest. Most clinicians and even neuropathologists considered Alzheimer’s disease to be a rar-
ity,somuchsothatthe1967editionofafamous Americantextbook ofneurology didnoteven have an“Alzhei-
mer’s disease” entry. In previous series of the Handbook of Clinical Neurology, there were very good chapters
dealing with various aspects of dementia, but not a dedicated volume. This new addition to the Handbook series
isjustifiedbytheenormousprogressthathasoccurredregardingvariousaspectsofthedementias,includingtheir
symptomatic treatment, and the development of new perspectives for their prevention. Charles Duyckaerts and
Irene Litvan, editorsofthe present volume, are tobecongratulated forbringing togetherawide rangeofinterna-
tionally acknowledged authorities to summarize these new developments in the area of dementia, from the most
basic aspects to their clinical implications. This ensures that this new volume will be an essential and invaluable
resource for those interested in the fundamental aspects of the diseases that cause dementia, as well as for those
involved in the care of patients with these disorders.
We wish to express our deep gratitude to the numerous authors who contributed their time and expertise to
summarizedevelopmentsintheirfieldandhelpedputtogetherthisoutstandingvolume.Webelievethatitreflects
thehigheststandardsofscholarshipandprovidesacriticalappraisalandsynthesisofcurrentconceptsconcerning
thedementias.Asserieseditors,wereviewedallthechaptersincludedinthisvolumeandweregreatlyimpressed
by their scope and implications. We are proud that this new volume fully exemplifies our concept of the Hand-
bookseries,whichisthatofprovidinggreaterinsighttothebasicmechanismsofdiseaseinordertofurtherabet-
ter appreciation of these disorders by clinicians. As always, we are also grateful to the team at Elsevier in
Edinburgh for their unfailing and expert assistance in the development and production of this volume.
Michael J. Aminoff
Franc¸ois Boller
Dick F. Swaab
Preface
Notsolongago,cognitivedeficitsthatfrequentlyoccurfromagingwerethoughtnormalornearlyso.“Softening
ofthebrain”wasthecommondiagnosis;Alzheimer’sdiseasewasconsideredrareandPick’sdisease,exceptional.
AlthoughPick’sdiseasehasremainedrare,Alzheimer’sdisease,mergingwithseniledementia,hasbecomeoneof
the major foreseen health problems of the near future. Not only has the prevalence of dementias been better per-
ceived,butthediversityofthedisordersthatcausethemhasalsobeenbetterunderstood.Today,weknowthatthe
complexityofthediseasesthataffectthecortexmirrorsthecomplexityofthecortexitselfandnoonedoubtsthat
we are just starting to discover a continent in which only a few spots have been identified.
Our understanding of the biology of the various dementias has recently advanced. In the past few months, the
progranulinmutation—oneofthemostfrequentcausesoffrontotemporaldementia—wasidentified.TDP-43was
recognized as an ubiquitinated molecule in several dementing disorders. These two findings have considerably
changeddiagnosticandresearchperspectives.Wehavebeenaddinginformationtothisvolumeuptothelastmin-
ute, thanks to the patience, kindness and expertise of the multiple contributors. We had to stop updating this
volume, butitwasdifficulttodosoat atimeofconstant change,whenelectronicinformationcrossestheoceans
much more easily than piles of printed papers. If electronic information is so easy to share, what are books for?
What do the readers of this volume expect? What are our expectations?
Theexpertscoveraspecializedfieldandtheyknowwheretofindtheinformationtheyarelookingforbutthey
may have difficulties in exploring areas that they do not master, and especially in synthesizing information that
they could otherwise rapidly collect by Internet. We have planned this book as a handbook, a book close to the
hand,inwhichthereadermayreadilygleaninformationonalargearrayofsubjectsinasyntheticform.Thegen-
eralviewthatthereadermayrapidlyacquiresimplifiestheunderstandingofnewfindingsandgivesabackground
that, for most of the topics, remains stable for years.
The ideal of completeness is clearly out of reach today; we believe that, thanks to the many collaborators of
this book, our coverage has been extensive, with a minimal amount of overlap. The volume deals with neuro-
pathology, physiopathology, biology, clinics, and imaging of all or most dementing disorders that are currently
known. It also includes chapters on the legal and ethical issues to give the health care worker a general view
on diseases that are not only scientific riddles but also the cause of affliction of many patients and families.
We believe that people dealing with dementia, at whatever level of expertise, may find in this book useful and
synthetic information.
We are proud and thankful to have been able to bring together chapters from so many outstanding scholars in
thevariousfields.WewouldalsoliketoacknowledgetheworkofLynnWatt,fromElsevier,whoaccompaniedus
onthislongjourney,andgaveusthesecurehandoftheguideinmanydifficultpasses.TheSeriesEditorsgaveus
much appreciated help by carefully reviewing all the chapters of this book.
Is it useful to end by stating that, even if the scientific questions raised by the dementias may be fascinating
from an intellectual point of view, we must keep in mind that the intellectual curiosity is but a means to reach
the final goal of curing these dreadful diseases. In this sense, this book is obviously dedicated to the patients.
Charles Duyckaerts
Irene Litvan
List of contributors
D. Aarsland S. Baudic
Centre for Clinical Neuroscience Research, INSERM/UPVM,Faculte´deMe´decine,Cre´teil,France
Stavanger University Hospital, Stavanger,
and Institute of Clinical Medicine University of C. Bazille
Bergen, Bergen, Norway Service Central d’Anatomie et de Cytologie
Pathologiques, and Faculte´ de Me´decine de
S. Al-Sarraj l’Universite´, Paris, France
Department of Clinical Neuropathology,
King’s College Hospital, Brain Bank, L.J. Beglinger
Institute of Psychiatry, London, UK University of Iowa, The Roy J. and Lucille A. Carver
College of Medicine, Iowa City, IA, USA
C. Amador-Ortiz
Department of Neuroscience, Mayo Clinic, C. Bergeron
Jacksonville, FL, USA Department of Laboratory Medicine and
Pathobiology and Centre for Research in
M.J. Aminoff Neurodegenerative Diseases, University of Toronto,
Department of Neurology, University of California, Toronto, ON, Canada
San Francisco, CA, USA
J.L. Bernat
K. Andrade Neurology Section, Dartmouth Medical School,
Department of Neurology, and Dementia Research Hanover, NH, USA
Center, INSERM, La Salpeˆtriere Hospital, Paris,
France L. Bertram
Department of Neurology, MassGeneral Institute for
F. Assal Neurodegenerative Diseases (MIND), Massachusetts
Department of Clinical Neurosciences, HUG, Geneva, General Hospital, MA, USA
Switzerland
K. Blennow
S.N. Azher Institute of Clinical Neuroscience, Department of
Parkinson’s Disease Center and Movement Disorders Experimental Neuroscience, Sahlgrenska University
Clinic,BaylorCollege ofMedicine,Houston,TX,and Hospital, Go¨teborg University, Go¨teborg, Sweden
Hudson Valley Neurology, Poughkeepsie, NY, USA
J.A. Bobholz
T.H. Bak Medical College of Wisconsin, Milwaukee, WI, USA
MedicalResearchCouncil—CognitionandBrain
SciencesUnit,Cambridge,andHumanCognitive B.F. Boeve
Neuroscience,UniversityofEdinburgh,Edinburgh,UK Department of Neurology, Mayo Clinic, Rochester,
MN, USA
F. Barkhof
Department of Diagnostic Radiology and Alzheimer J. Bogousslavsky
Center,VrijeUniversiteitMedicalCenter,Amsterdam, Neurology Service, Genolier Swiss Medical Network,
The Netherlands Glion, Switzerland
xii LIST OF CONTRIBUTORS
F. Boller U. De Girolami
Bethesda, Maryland, USA Department of Neuropathology, APHP, La Salpeˆtriere
Hospital, Pierre and Marie Curie University, Paris,
C. Bountra France, and Departments of Pathology
NeurologyandGICEDD,GlaxoSmithKlineR&DLtd, (Neuropathology)BrighamandWomen’sHospitaland
Harlow, UK Children’s Hospital; Harvard Medical School, Boston,
USA
M.G. Bousser
Department of Neurology, Hoˆpital Lariboisie`re, R. de Silva
Universite´ Paris VII, Paris, France Institute of Neurology and Reta Lila Weston Institute
of Neurological Studies, University College London,
London, UK
J.-P. Brion
Laboratory of Histology, Neuroanatomy and
S.T. DeKosky
Neuropathology, Universite´ Libre de Bruxelles,
Departments of Neurology, Psychiatry, and
Brussels, Belgium
Neurobiology and Alzheimer’s Disease Research
Center, University of Pittsburgh School of Medicine,
N.J. Cairns
Pittsburgh PA, USA
Department of Pathology and Immunology,
Washington University School of Medicine, Saint
M. del Pilar Amaya
Louis, MO, USA
New York Brain Bank/Taub Institute, The
Presbyterian Hospital and Columbia University, and
H. Chabriat
the Gertrude H. Sergievsky Center and School of
Department of Neurology, Hoˆpital Lariboisie`re,
Public Health, New York, NY, USA
Universite´ Paris VII, Paris, France
A. Delacourte
L. Crews
INSERM, Lille, France
Department of Neurosciences, University of
California, San Diego, La Jolla, CA, USA
J.-Y. Delattre
Federation de Neurologie Mazarin, La Salpeˆtriere
J.L. Cummings Hospital, Paris, France
Department of Neurology, Psychiatry and
Biobehavioral Sciences, UCLA Alzheimer’s
D.W. Dickson
Disease Center, and Deane F. Johnson Center for
Department of Neuroscience, Mayo Clinic,
Neurotherapeutics, David Geffen School of
Jacksonville, FL, USA
MedicineattheUniversityofCalifornia,LosAngeles,
CA, USA
D.A. Drubach
Department of Neurology, Mayo Clinic, Rochester,
G. Dalla Barba MN, USA
INSERM, La Salpeˆtriere Hospital, Paris, France
F. Dubas
J. Dalmau UPRES EA3143 and Department of Neurology, CHU,
DepartmentofNeurology,UniversityofPennsylvania, Angers, France
Philadelphia, PA, USA
B. Dubois
J.B. Davis Department of Neurology, and Dementia
NeurologyandGICEDD,GlaxoSmithKlineR&DLtd, Research Center, INSERM, La Salpeˆtriere Hospital,
Harlow, UK Paris, France
A. De Calignon K. Duff
Massachusetts General Hospital, Charlestown, MA, University of Iowa, The Roy J. and Lucille A. Carver
USA College of Medicine, Iowa City, IA, USA
LIST OF CONTRIBUTORS xiii
A. Durr D.S. Goodin
INSERM, Pierre and Marie Curie–Paris 6 University, Department of Neurology, University of California,
UMR, Federative Institute for Neuroscience (IFR70), San Francisco, CA, USA
and La Salpeˆtriere Hospital, Paris, France
F. Gray
C. Duyckaerts Service Central d’Anatomie et de Cytologie
Escourolle Neuropathology Laboratory, La Salpeˆtriere Pathologiques, and
Hospital, Paris, France Faculte´ de Me´decine de l’Universite´ Paris VII,
Paris, France
J.L. Eriksen
Mayo Clinic, Birdsall, Jacksonville, FL, USA K. Gwinn-Hardy
DepartmentofNeurogenetics,NationalInstituteof
M. Farrer NeurologicalDisordersandStroke,Bethesda,MD,USA
Mayo Clinic College of Medicine, Department of
Neuroscience, Jacksonville, FL, USA J. Hardy
Laboratory of Neurogenetics, National Institute on
I. Ferrer Aging, Bethesda, MD, USA
Institute de Neuropatologia, Servei Anatomia
Patolo`gica, IDIBELL-Hospital Universitari de C. Harper
Belvitge, Facultad de Medicina, Universitat de Department of Neuropathology, University of Sydney,
Barcelona, Spain Sydney, Australia
N.L. Foster J.-J. Hauw
Department of Neurology, Center for Alzheimer’s DepartmentofNeuropathology,LaSalpeˆtriereHospital,
Care, Imaging and Research, University of Utah, Salt PierreandMarieCurieUniversity,Paris,France
Lake City, UT, USA
L.-N. Hazrati
Department of Laboratory Medicine and Pathobiology
A.R. Frank
and Centre for Research in Neurodegenerative
Memory Disorder Clinic, Ottawa, ON, Canada
Diseases,UniversityofToronto,Toronto,ON,Canada
R.L. Frierson
M.W. Head
Department of Neuropsychiatry and Behavioral
National Creutzfeldt-Jakob Disease Surveillance Unit,
Science, University of South Carolina School of
Western General Hospital, and School of Molecular
Medicine, Columbia, SC, USA
and Clinical Medicine, University of Edinburgh,
Edinburgh, UK
D. Galasko
Department of Neurosciences, University of
C.A. Heath
California, San Diego and Veterans Affairs Medical
National CJD Surveillance Unit, Western General
Center, San Diego, CA, USA
Hospital, Edinburgh, UK
S. Gauthier
J.R. Hodges
McGillCenterforStudiesinAging,Montreal,QB,Canada
MedicalResearchCouncil—CognitionandBrain
SciencesUnit,andUniversityofCambridgeNeurology
A. Gleason
Unit,Addenbrooke’sHospital,Cambridge,UK
Medical College of Wisconsin, Milwaukee, WI, USA
S. Humbert
L.I. Golbe
Institut Curie, Orsay, France
DepartmentofNeurology,UniversityofMedicineand
Dentistry of New Jersey—Robert Wood Johnson
M. Hutton
Medical School, New Brunswick, NJ, USA
Department of Neuroscience, Mayo Clinic,
Jacksonville, Jacksonville, FL, USA
T. Gomez-Isla
Massachusetts General Hospital, Charlestown, MA, B.T. Hyman
USA MassachusettsGeneralHospital,Charlestown,MA,USA
xiv LIST OF CONTRIBUTORS
K. Ikeda F. Letournel
Zikei Hospital and Zikei Institute of Psychiatry, Cell Biology Laboratory, CHU, and UPRES EA3143,
Okayama, Japan Angers, France
J.W. Ironside J.B. Leverenz
National Creutzfeldt-Jakob Disease Surveillance Unit, University of Washington, and Mental Illness and
Western General Hospital and School of Molecular Parkinson’s Disease Research, Education and Clinical
and Clinical Medicine, University of Edinburgh, Centers, and VA-PSHCS, Seattle, WA, USA
Edinburgh, UK
R. Levy
K.A. Jacoby
Department of Neurology, and Dementia Research
Department of Neuropsychiatry and Behavioral
Center, INSERM, La Salpeˆtriere Hospital, Paris,
Science, University of South Carolina School of
France
Medicine, Columbia, SC, USA
J. Lewis
J. Jankovic
Mayo Clinic, Birdsall, Jacksonville, FL, USA
Parkinson’s Disease Center and Movement
Disorders Clinic, Baylor College of Medicine,
A.M. Lipton
Houston, TX, USA
Dallas, TX, USA
C. Janvin
I. Litvan
Psychiatric Clinic, Stavanger University Hospital,
Movement Disorders Program, University of
Stavanger, Norway
Louisville, Louisville, KY, USA
K.A. Josephs
O.L. Lo´pez
Department of Neurology, Divisions of Behavioral
Departments of Neurology, Psychiatry, Neurobiology
NeurologyandMovementDisorders,MayoClinicand
and Psychology and Alzheimer’s Disease Research
Mayo Foundation, Rochester, MN, USA
Center, University of Pittsburgh School of Medicine,
Pittsburgh, PA, USA
G. Karas
Department of Diagnostic Radiology and Alzheimer
J. Lowe
Center,VrijeUniversiteitMedicalCenter,Amsterdam,
School of Molecular Medical Sciences, Medical
The Netherlands
School, Queens Medical Centre, Nottingham, UK
C. Keller
G.A. Marshall
New York Brain Bank/Taub Institute, The
Department of Neurology and Memory Disorders
Presbyterian Hospital and Columbia University, and
Unit, Brigham and Women’s Hospital, Harvard
the Gertrude H. Sergievsky Centre and School of
Medical School, Boston, MA, USA
Public Health, New York, NY, USA
J.K. Krauss E. Masliah
Department of Neurosurgery, Medical University Department of Neurosciences, University of
Hannover, Hannover, Germany California, San Diego, La Jolla, CA, USA
A. Kutzelnigg I. Matsumoto
Division of Neuroimmunology, Center for Brain Department of Pathology, University of Sydney,
Research, Medical University of Vienna, Austria Sydney, Australia
H. Lassmann R. Mayeux
Division of Neuroimmunology, Center for Brain The Taub Institute on Alzheimer’s Disease and the
Research, Medical University of Vienna, Austria Aging Brain, The Gertrude H. Sergievsky Center and
School of Public Health, New York, NY, USA
A.J. Lees
Institute of Neurology and Reta Lila Weston Institute I. McKeith
of Neurological Studies, University College London, Institute for Ageing and Health, Newcastle General
London, UK Hospital, Newcastle upon Tyne, UK
LIST OF CONTRIBUTORS xv
M. Mesulam A. Pittman
CognitiveNeurologyandAlzheimer’sDisease Center, Institute of Neurology and Reta Lila Weston Institute
NorthwesternUniversityFeinbergSchoolofMedicine, of Neurological Studies, University College London,
Chicago, IL, USA London, UK
J. Miklossy A. Probst
University of British Columbia, Kinsmen Laboratory Department of Neuropathology, University Hospital
of Neurological Research, Vancouver, BC, Canada Basel, Basel, Switzerland
G.D. Rabinovici
B.L. Miller
Memory and Aging Center, University of California, Memory and Aging Center, University of California,
San Francisco, CA, USA San Francisco, CA, USA
K. Rascovsky
S. Miller
Memory and Aging Center, University of California,
Medical College of Wisconsin, Milwaukee, WI, USA
San Francisco, CA, USA
L. Morrow
A. Richardson
Department of Psychiatry, University of Pittsburgh,
Clinical Neuroscience Group, Salford Royal Hospital,
PA, USA
Salford, UK
D.G. Munoz
J.C. Richardson
StMichael’sHospital,UniversityofToronto,Toronto,
NeurologyandGICEDD,GlaxoSmithKlineR&DLtd,
ON, Canada
Harlow, UK
D. Neary
K. Ritchie
Clinical Neuroscience Group, Salford Royal Hospital,
INSERM, Hoˆpital La Colombie`re, Montpellier,
Salford, UK
France
R. Nitrini
E. Rockenstein
University of Sa˜o Paulo School of Medicine, Sa˜o
Department of Neurosciences, University of
Paulo, Brazil
California, San Diego, La Jolla, CA, USA
A.M.P. Omuro G.C. Roma´n
Federation de Neurologie Mazarin, La Salpeˆtriere
University of Texas Health Science Center at San
Hospital, Paris, France
Antonio and Veteran Administration, Audie L.
Morphy Hospital, San Antonio, TX, USA
J.S. Paulsen
University of Iowa, The Roy J. and Lucille A. Carver S.M. Rosso
College of Medicine, Iowa City, IA, USA Department of Neurology, Erasmus Medical Centre,
Rotterdam, The Netherlands
M.-T. Pelle
Service Central d’Anatomie et de Cytologie N. Sacktor
Pathologiques, and Faculte´ de Me´decine de Department of Neurology, Johns Hopkins University
l’Universite´ Paris VII, Paris, France School of Medicine, Baltimore, MD, USA
R.C. Petersen S.A. Sami
Memory Disorder Clinic, Ottawa, ON, Canada University Memory and Aging Center, University
Hospitals of Cleveland, Cleveland, OH, USA
S. Pickering-Brown
Clinical Neurosciences, University of Manchester, F. Saudou
Manchester, UK Institut Curie, Orsay, France
xvi LIST OF CONTRIBUTORS
J. Saxton S.F. von Stuckrad-Barre
Department of Neurology, University of Pittsburgh, Department of Neurology, Goethe-Universita¨t
PA, USA Frankfurt, Frankfurt, Germany
P. Scheltens S. Weintraub
Department of Diagnostic Radiology and Alzheimer CognitiveNeurologyandAlzheimer’sDiseaseCenter,
Center,VrijeUniversiteitMedicalCenter,Amsterdam, NorthwesternUniversityFeinbergSchoolofMedicine,
The Netherlands Chicago, IL, USA
D.J. Selkoe P.J. Whitehouse
Department of Neurology, Center for Neurologic University Memory and Aging Center, University
Diseases, Brigham and Women’s Hospital and Hospitals of Cleveland, Cleveland, OH, USA
Harvard Medical School, Boston, MA, USA
R.G. Will
T. Spires National CJD Surveillance Unit, Western General
MassachusettsGeneralHospital,Charlestown,MA,USA
Hospital, Edinburgh, UK
M. Tolnay
A. Wimo
Department of Neuropathology, University Hospital
Neurotec, Karolinska Institutet, Stockholm, Sweden
Basel, Basel, Switzerland
B. Winblad
L. Traykov
Neurotec, Karolinska Institutet, Stockholm, Sweden
University Hospital Alexandrovska, Department of
Neurology, Medical University, Sofia, Bulgaria, and
N.W. Wood
CHU, Henri Mondor Department of Neurology,
Department of Molecular Neuroscience, Institute of
University Paris XII, Creteil, France
Neurology, University College London, London, UK
K. Tsuchiya
S.H. Zarit
DepartmentofLaboratoryMedicineandPathology,
Department of Human Development and Family
TokyoMetropolitan,MatsuzauraHospital,Tokyo,Japan
Studies, Pennsylvania State University, PA, USA
T. Uchihara
C. Zehr
Department of Neurology, Tokyo Metropolitan
Mayo Clinic, Birdsall, Jacksonville, FL, USA
Institute for Neuroscience, Fuchu, Tokyo, Japan
D. Zekry
I. van Balken
Department of Neuropathology, La Salpeˆtriere
Movement Disorders Program, University of
Hospital, Pierre and Marie Curie
Louisville, Louisville, KY, USA
University, Paris, France, and Department of
Rehabilitation and Geriatrics, Thoˆnex, Switzerland
J.C. van Swieten
Department of Neurology, Erasmus Medical Centre,
I. Zerr
Rotterdam, The Netherlands
DementiaResearchCenter,NationalReference Center
for TSE, Department of Neurology, Georg-August
A. Venkataramana
University, Go¨ttingen, Germany
Department of Neurology, Johns Hopkins University
School of Medicine, Baltimore, MD, USA
H. Zetterberg
D. Villebrun Institute of Clinical Neuroscience, Department
INSERM,HoˆpitalLaColombie`re,Montpellier,France of Experimental Neuroscience, Sahlgrenska
University Hospital, Go¨teborg University,
J.P.G. Vonsattel Go¨teborg, Sweden
New York Brain Bank/Taub Institute,
The Presbyterian Hospital and Columbia University,
NewYork,andtheGertrudeH.SergievskyCentreand
School of Public Health, NY, USA
HandbookofClinicalNeurology,Vol.89(3rdseries)
Dementias
C.Duyckaerts,I.Litvan,Editors
#2008ElsevierB.V.Allrightsreserved
Chapter 1
History of dementia
FRANC¸ OIS BOLLER *
Bethesda,Maryland,USA
1.1. Introduction 44BC) that, on the contrary, aging is not necessarily
accompanied by significant mental changes.
Thehistoryofdementiaobviouslydidnotstartwiththe Aretaeus of Cappadocia (end of the second century
contributions of Alzheimer and his colleagues. How- AD)wroteaboutorganicmentaldisordersandwasprob-
ever,theyearsaroundthebeginningofthe20thcentury ably the first to distinguish between acute and chronic
saw a series of neurological and neuropathological neurologicalandpsychiatricdisorders.Acute disorders,
breakthroughs in the field of dementia which certainly which he described as reversible, were called delirium,
did not happen by chance. This chapter will mention whereaschronicdisorders(dementia)werecharacterized
some of the early central characters in the fieldaswell byirreversibleimpairmentofhighercognitivefunctions.
astheevolutionoftheconceptofdementiabeforeAlz- GalenandbeforehimHippocratesthoughtthatthesedis-
heimer.Itwilldiscussimportanttechnicaladvancesthat orderswereduetoacerebralimpairmentwhichcouldbe
ledtotheearly20th-centurycontributions.Finallyitwill eitherprimaryorsecondarytoadiseaseprocesslocated
conclude with a brief presentation of the work of more inotherorgansofthebody.Galen,AretaeusandHippo-
recent protagonists in the field of Alzheimer’s disease. crates wrote in Greek and unfortunately their writings
Thehistoryofotherdegenerativedementiascanbefound were not translated into Latin and therefore not easily
intheappropriatechaptersofthisvolume. availabletoWesternscholarsuntilmuchlater.Actually
Galen was active in Rome for more than twenty years
1.2. Ancient notions and contributions inhiscapacityaspersonalphysiciantoseveralemperors,
before Alzheimer including Marcus Aurelius. Nevertheless his most
important writings were translated into Arabic before
The diseases that can produce dementia are as old as Latin.Meanwhile,becausethesecontributionswerenot
mankind. The major risk factor for degenerative recognized, and on the basis of Aristotle’s theories, the
dementias was and remains age. Around the year brain continued to be seen as an organ not necessarily
2000 BC, ancient Egyptians, even though they held related to the control of motor or cognitive functions.
that the heart and diaphragm were the seats of mental Inmedicalthinking,thecenterofthe“mind”wandered
life, were aware that age could be accompanied by a fromthelivertothelungsandotherorgans.
major memory disorder (Signoret and Hauw, 1991). In the Middle Ages, dementia does not seem to
Greco-Roman authors also frequently pointed it out haveinspiredmuchinterestorconcern,perhapsinpart
and many, including Plato and later Horatius, seem because of the prominence of deadlier epidemics such
to have thought that old age per se was often synon- astheplague.TheZeitgeistalsoundoubtedlyplayeda
ymouswith dementia. Solon (activein the 6thcentury role. At a time when society explained the mysterious
BC), whom some consider the father of modern legal forces of nature through mysticism, the philosopher
thinking, wrote that judgment can be impaired by Roger Bacon (1214–1294) could “reasonably” express
“physical pain, violence, drugs, old age or the persua- theviewthat“senilityisaconsequenceoftheoriginal
sionofawoman”(Freeman,1926).Thismayhaveled sin” (Albert and Mildworf, 1989). Not many more
Cicero (Fig. 1.1) to point out in De Senectute (Cicero, advances occurred at the time of the Renaissance,
*Correspondence to: Francois Boller MD, PhD, 4301 Military Road, NW. Washington DC 20015. E-mail: bollermeister@gmail.
com.