Advancing research diagnostic criteria for Alzheimer's disease: the IWG-2 criteria.
In the past 8 years, both the International Working Group (IWG) and the US National Institute on Aging-Alzheimer's Association have contributed criteria for the diagnosis of Alzheimer's disease (AD) that better define clinical phenotypes and integrate biomarkers into the diagnostic process, covering the full staging of the disease. This Position Paper considers the strengths and limitations of the IWG research diagnostic criteria and proposes advances to improve the diagnostic framework. On the basis of these refinements, the diagnosis of AD can be simplified, requiring the presence of an appropriate clinical AD phenotype (typical or atypical) and a pathophysiological biomarker consistent with the presence of Alzheimer's pathology. We propose that downstream topographical biomarkers of the disease, such as volumetric MRI and fluorodeoxyglucose PET, might better serve in the measurement and monitoring of the course of disease. This paper also elaborates on the specific diagnostic criteria for atypical forms of AD, for mixed AD, and for the preclinical states of AD.
Centre des Maladies Cognitives et Comportementales, Institut du Cerveau et de la Moelle épinière, Paris, France; Université Pierre et Marie Curie-Paris 6, AP-HP, Hôpital de la Salpêtrière, Paris, France. Electronic address: bruno.dubois@psl.aphp.fr.
Bruno
B
Dubois
Division of Neurology, University of British Columbia and Vancouver Coastal Health, Vancouver, BC, Canada.
Howard H
HH
Feldman
UBC Division of Neurology, S152 UBC Hospital, BC, Canada.
Claudia
C
Jacova
Centre des Maladies Cognitives et Comportementales, Institut du Cerveau et de la Moelle épinière, Paris, France; Université Pierre et Marie Curie-Paris 6, AP-HP, Hôpital de la Salpêtrière, Paris, France.
Harald
H
Hampel
Alzheimer's Disease and Other Cognitive Disorders Unit, Neurology Service, IDIBAPS Hospital Clinici Universitari, Barcelona, Spain; BarcelonaBeta Brain Research Centre, Fundació Pasqual Maragall, Barcelona, Spain.
José Luis
JL
Molinuevo
Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospital, Mölndal, Sweden.
Kaj
K
Blennow
Department of Neurology, University of Virginia, Charlottesville, VA, USA.
Steven T
ST
DeKosky
McGill Center for Studies in Aging, Douglas Hospital, Montreal, Quebec, QC, Canada.
Serge
S
Gauthier
Harvard Medical School Center for Neurologic Diseases, Brigham and Women's Hospital, Boston, MA, USA.
Dennis
D
Selkoe
Washington University School of Medicine, St Louis, Missouri, MO, USA.
Randall
R
Bateman
Vita-Salute San Raffaele University, Milan, Italy; Department of Clinical Neurosciences, Cognitive Neurorehabilitation, Milan, Italy.
Stefano
S
Cappa
Dementia Research Centre, Department of Neurodegeneration, Institute of Neurology, University College London, London, UK; Dementia Research Centre, National Hospital, London, UK.
Sebastian
S
Crutch
Department of Neurology and Memory Clinic, Hospital Network Antwerp (ZNA), Middelheim and Hoge Beuken, Antwerp, Belgium; Reference Centre for Biological Markers of Dementia, Institute Born-Bunge, University of Antwerp, Antwerp, Belgium.
Sebastiaan
S
Engelborghs
Hopitaux Universitaires et Université de Genève, Geneva, Switzerland; IRCCS Fatebenefratelli, Brescia, Italy; HUG Belle-Idée, bâtiment les Voirons, Chêne-Bourg, France.
Giovanni B
GB
Frisoni
Dementia Research Centre, Department of Neurodegeneration, Institute of Neurology, University College London, London, UK.
Nick C
NC
Fox
Department of Neurosciences, -University of California, San Diego, CA, USA.
Douglas
D
Galasko
INSERM UMR, Paris, France; AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Service de Médecine Nucléaire, Paris, France.
Marie-Odile
MO
Habert
University of Kentucky Alzheimer's Disease Center, Lexington, KY, USA.
Gregory A
GA
Jicha
Karolinska Institutet, Karolinska University Hospital Huddinge, Alzheimer Neurobiology Center, Stockholm, Sweden.
Agneta
A
Nordberg
Université Lille Nord de France, Lille, France; CHRU, Clinique Neurologique, Hôpital Roger Salengro, Lille, France.
Florence
F
Pasquier
UCSF Memory & Aging Center, Department of Neurology, University of California, San Francisco, CA, USA.
Gil
G
Rabinovici
EA CoBTeK and Memory Center, CHU University of Nice, UNSA, Hôpital de Cimiez 4 av Victoria, Nice, France.
Philippe
P
Robert
FRACP, Department of Nuclear Medicine and Centre for PET, Austin Health, Heidelberg, Melbourne, VIC, Australia.
Christopher
C
Rowe
Neurology and the Memory and Aging Program, Butler Hospital, Department of Neurology and Psychiatry, The Warren Alpert Medical School of Brown University, Providence, RI, USA.
Stephen
S
Salloway
Neurologie de la Mémoire et du Langage, Centre Hospitalier Sainte-Anne, Paris Cedex, France; Université Paris 5, Paris, France.
Marie
M
Sarazin
Centre des Maladies Cognitives et Comportementales, Institut du Cerveau et de la Moelle épinière, Paris, France; Université Pierre et Marie Curie-Paris 6, AP-HP, Hôpital de la Salpêtrière, Paris, France.
Stéphane
S
Epelbaum
Centre des Maladies Cognitives et Comportementales, Institut du Cerveau et de la Moelle épinière, Paris, France; Université Pierre et Marie Curie-Paris 6, AP-HP, Hôpital de la Salpêtrière, Paris, France; Faculty of Medicine, Federal University of Minas Gerais, Belo Horizonte, Brazil.
Leonardo C
LC
de Souza
Gerontopole, Pavillon Junod, University Toulouse 3, Toulouse, France.
Bruno
B
Vellas
Department of Psychiatry and Neuropsychology, Alzheimer Centre Limburg, School of Mental Health and Neuroscience, Maastricht University Medical Centre, Maastricht, Netherlands; Department of Neurology and Alzheimer Center, Amsterdam, Netherlands.
Pieter J
PJ
Visser
Department of Psychiatry, Neurology, and Gerontology, Keck School of Medicine of USC, Los Angeles, CA, USA.
Lon
L
Schneider
Cognitive Neuroscience Division of the Taub Institute, Presbyterian Hospital, New York, NY, USA.
Yaakov
Y
Stern
Alzheimer Centrum Vrije Universiteit Medical Center, VU University, Amsterdam, Netherlands.
Philip
P
Scheltens
Lou Ruvo Center for Brain Health, Cleveland Clinic, Las Vegas, NV, USA.
Jeffrey L
JL
Cummings
D000544:Alzheimer Disease / Q000175:diagnosis* / Q000235:genetics / Q000503:physiopathology; D015415:Biomarkers / Q000032:analysis / Q000737:chemistry; D006801:Humans; D007391:International Cooperation; D010641:Phenotype; D017410:Practice Guidelines as Topic / Q000592:standards; D012955:Societies, Medical / Q000592:standards
D015415:Biomarkers