Abstract
During the past decade, a conceptual shift occurred in the field of Alzheimer's disease (AD) considering the disease as a continuum. Thanks to evolving biomarker research and substantial discoveries, it is now possible to identify the disease even at the preclinical stage before the occurrence of the first clinical symptoms. This preclinical stage of AD has become a major research focus as the field postulates that early intervention may offer the best chance of therapeutic success. To date, very little evidence is established on this "silent" stage of the disease. A clarification is needed about the definitions and lexicon, the limits, the natural history, the markers of progression, and the ethical consequence of detecting the disease at this asymptomatic stage. This article is aimed at addressing all the different issues by providing for each of them an updated review of the literature and evidence, with practical recommendations.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 292-323 |
| Number of pages | 32 |
| Journal | Alzheimer's and Dementia |
| Volume | 12 |
| Issue number | 3 |
| DOIs | |
| State | Published - Mar 1 2016 |
Keywords
- Alzheimer's disease
- Amyloid PET
- Asymptomatic
- Biomarkers
- Blood biomarkers
- CSF biomarkers
- Diagnostic criteria
- Genetics
- MRI
- Pathophysiology
- Preclinical
- Tau PET
ASJC Scopus subject areas
- Epidemiology
- Health Policy
- Developmental Neuroscience
- Clinical Neurology
- Geriatrics and Gerontology
- Psychiatry and Mental health
- Cellular and Molecular Neuroscience
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Preclinical Alzheimer's disease : Definition, natural history, and diagnostic criteria. / Proceedings of the Meeting of the International Working Group (IWG) and the American Alzheimer's Association on "The Preclinical State of AD"; July 23, 2015; Washington DC, USA.
In: Alzheimer's and Dementia, Vol. 12, No. 3, 01.03.2016, p. 292-323.Research output: Contribution to journal › Review article › peer-review
}
TY - JOUR
T1 - Preclinical Alzheimer's disease
T2 - Definition, natural history, and diagnostic criteria
AU - Proceedings of the Meeting of the International Working Group (IWG) and the American Alzheimer's Association on "The Preclinical State of AD"; July 23, 2015; Washington DC, USA
AU - Dubois, Bruno
AU - Hampel, Harald
AU - Feldman, Howard H.
AU - Scheltens, Philip
AU - Aisen, Paul
AU - Andrieu, Sandrine
AU - Bakardjian, Hovagim
AU - Benali, Habib
AU - Bertram, Lars
AU - Blennow, Kaj
AU - Broich, Karl
AU - Cavedo, Enrica
AU - Crutch, Sebastian
AU - Dartigues, Jean François
AU - Duyckaerts, Charles
AU - Epelbaum, Stéphane
AU - Frisoni, Giovanni B.
AU - Gauthier, Serge
AU - Genthon, Remy
AU - Gouw, Alida A.
AU - Habert, Marie Odile
AU - Holtzman, David M.
AU - Kivipelto, Miia
AU - Lista, Simone
AU - Molinuevo, José Luis
AU - O'Bryant, Sid E.
AU - Rabinovici, Gil D.
AU - Rowe, Christopher
AU - Salloway, Stephen
AU - Schneider, Lon S.
AU - Sperling, Reisa
AU - Teichmann, Marc
AU - Carrillo, Maria C.
AU - Cummings, Jeffrey
AU - Jack, Cliff R.
N1 - Funding Information: H.H. is supported by the AXA Research Fund , the Fondation Université Pierre et Marie Curie , and the “Fondation pour la Recherche sur Alzheimer”, Paris, France. The research leading to these results has received funding from the program “Investissements d'avenir” ANR-10-IAIHU-06. S.L. is supported by the European Medical Information Framework (EMIF). R.S. is supported by the National Institute on Aging and Alzheimer's Association . Funding Information: The authors acknowledge the helpful contribution of Zaven Khachaturian as an advisor to the Working Group in charge of the article. The meeting was supported by the French International Foundation for Research in Alzheimer's disease (IFRAD). Funding Information: B.D. serves as member of advisory board for Avid/Lilly, Roche, and Boehringer Ingelheim, and he receives research support from Amivid and Pfizer for his institution. H.H. serves as Senior Associate Editor for the journal Alzheimer's & Dementia; he has been a scientific consultant and/or speaker and/or attended scientific advisory boards of Axovant, Anavex, Eli Lilly and company, GE Healthcare, Cytox, Jung Diagnostics, Roche, Biogen-Idec, Takeda-Zinfandel, and Oryzon and receives research support from the Association for Alzheimer Research (Paris), Pierre and Marie Curie University (Paris), Pfizer & Avid (paid to institution) and has patents as co-inventor but received no royalties. H.F. is a co-investigator on clinical trials sponsored by TauRx, Hoffmann LaRoche, and US National Institutes of Health/Lilly Pharmaceuticals with funding to the UBC Alzheimer Clinic. He receives peer reviewed funding from the Canadian Institutes of Health Research, National Institute on Aging and Brain Canada MIRI. He has received personal fees for consulting for the Bluefield Foundation to Cure Frontotemporal dementia advisory board (2012), for Danone Nutricia (2012), for the Innovative Medicines Initiative 2014 and for being a member of the Scientific Advisory Board of the Tau Consortium 2015–2016. He has provided consultations through UBC service agreements for the following: Hakko Kyowa Kirin Pharmaceuticals, Lilly Pharmaceutical, General Electric, Biogen-Idec, Eisai Pharmaceuticals, Banner Institute and Genentech Pharmaceuticals, Merck Pharmaceuticals, Arena Pharmaceuticals, ISIS Pharmaceuticals, and Eisai DSMB. No personal compensation was received; all funds received by UBC. He has a patent issued for Detecting and Treating Dementia Serial #12/3-2691 US Patent no. PCT US2007/07008 Washington DC. No funds received. He receives royalties from the book Atlas of Alzheimer's Disease (2007) Informa Health London. P.S. has received research support from Merck, GE Healthcare, and Piramal (paid to institution) and has consulting agreements with Takeda, Lilly, Nutricia, Probiodrug, and EIP Pharma (paid to institution). He reports no conflicts with the present work. P.A. has served as a consultant to the following companies: NeuroPhage, Eisai, Bristol-Myers Squibb, Eli Lilly, Merck, Roche, Genentech, Abbott, Pfizer, Novartis, AstraZeneca, Janssen, Ichor, Lundbeck, Biogen, iPerian, Probiodrug, Anavex, Abbvie, Janssen, Cohbar, aTyr, Axovant, and CogRx. P.A. receives research support from Eli Lilly, Janssen, the Alzheimer's Association, and the NIH. S.A. reported support from Beaufour Ipsen Pharma, Pierre Fabre, Lilly, Nestle, Servier, and Sanofi outside the submitted work. H.Ba., H.Be., and L.B. declare no conflicts of interest. K.Bl. has served as a consultant for Alzheon, Eli Lilly, Novartis, Roche Diagnostics, and Sanofi-Aventis, at Advisory Boards for Amgen and IBL International, and given lectures for Fujirebio Europe and Lundbeck. K.Bl.'s research team has received grants for collaborative research projects from Eli Lilly and Roche Diagnostics. K.Br. declares no conflict of interests in relation with the article. Personal views are presented, which cannot be regarded as official opinion of the BfArM or EMA. E.C. has received funding from the grant Conv. n.130/GR-2011-02350494 funded by the Italian Ministry of Health (Bando Giovani Ricercatori 2011–2012). S.C. is supported by an Alzheimer's Research UK Senior Research Fellowship and ESRC/NIHR (ES/L001810/1) and EPSRC (EP/M006093/1) grants. J.-F.D. has received research grants from IPSEN and Roche. C.D. is the administrator of the Brain Bank GIE NeuroCEB funded by the patients' associations Fondation ARSEP, France Alzheimer, France Parkinson, Comprendre les syndromes cérébelleux. He has received financial supports from grants of the Agence Nationale de la Recherche (ANR) and from the foundation Plan Alzheimer. S.E. has no conflict of interest. G.F. has served in advisory boards for Lilly, BMS, Bayer, Lundbeck, Elan, Astra Zeneca, Pfizer, TauRx, Wyeth, GE, Baxter and received unrestricted grants from Wyeth Int.l, Lilly Int.l, Lundbeck Italia, GE Int.l, Avid/Lilly, Roche, Piramal, and the Alzheimer's Association. S.G. is a member of scientific advisory board of TauRx, Roche, Boeringer, Takeda, and he has done paid lectures for EverPharma, Schwabe. R.G. declares no conflict of interest on the current work. He is a former employee of sanofi, holding stocks of sanofi. A.A.G. receives research support from Probiodrug AG and Boehringer Ingelheim via the VUmc Alzheimer center. She reports no conflicts with the present work. M.-O.H. received honoraria from MIRAMAL and ROCHE as a speaker and from GE Healthcare as a consultant. D.H. is a co-founder, has equity interests, and is on the scientific advisory board of C2N Diagnostics, LLC. He consults for Genentech, AbbVie, Eli Lilly, Denali, Novartis, and Neurophage. M.K. declares grant support from Academy of Finland, Swedish Research Council, Center of Innovative Medicine (CIMED), EU Joint Programme—Neurodegenerative Disease Research (JPND), Innovative Medicine Initatives (IMI), AXA Research Fund, Alzheimer foundation. M.K. has served as a consultant for Pfizer, Merz, Alzheon, Nutricia, Nestle, and Neurotrack. She reports no conflicts with the present work. S.L. has received lecture honoraria from Roche. J.L.M. has no conflict of interests. S.E.O. has no conflicts of interest in relation with the article. G.D.R. receives research support from Avid Radiopharmaceuticals and has received speaking honoraria from GE Healthcare, Piramal Imaging, and Medscape. C.R. is a member of Advisory Board for Janssen and Grant recipient—GE Healthcare, Avid Radiopharmaceuticals, Piramal Imaging, Navidea Biopharmaceuticals, Astra Zeneca. S.S. received research support and consulting fees from Biogen, Merck, Genentech, Roche, and Lilly and research support from Avid, Novartis, and Functional Neuromodulation. He holds no patents and receives no royalties, and he reports no direct conflicts with this work. L.S.S. (within the past 3 years) has received grant or research support for industry-sponsored studies from Pfizer, Baxter, Eli Lilly, Forum, Lundbeck, Merck, Novartis (Alzheimer Prevention Initiative and NIH), Roche/Genentech, TauRx; for NIH sponsored research, USC ADRC, ADCS (UCSD), ADNI (NCIRE), Banner Alzheimer Prevention Initiative, P50 AG05142, R01 AG033288, R01 AG037561, UF1 AG046148; from the State of California, the California Alzheimer Disease Center (CADC), and California Institute for Regenerative Medicine (CIRM). L.S.S. within the past 3 years, has consulted or served on committees for AC Immune, Accera, Avraham, Axovant, Baxter, Boehringer Ingelheim, Bracket, Cerespir, Cognition, Forum, Insys, Medavante, Merck, Neurim, Novartis, Roche, Stemedica, Takeda, TauRx, Transition, vTv Therapeutics, Toyama/FujiFilm, Zinfandel. R.S. has research support from Eli Lilly and Co. and Janssen Pharmaceuticals. She has served as a consultant for Biogen, Bracket, Genentech, Lundbeck, Roche, and Sanofi. M.T. and M.C. declares no conflicts of interest. J.C. has provided consultation to Abbvie, Acadia, Actinogen, ADAMAS, Alzheon, Anavex, Avanir, Biogen-Idec, Biotie, Boehinger-Ingelheim, Chase, Eisai, Forum, Genentech, Grifols, Intracellular Therapies, Lilly, Lundbeck, Merck, Neurotrope, Novartis, Nutricia, Otsuka, QR Pharma, Resverlogix, Roche, Servier, Suven, Takeda, and Toyoma companies and to GE Healthcare and MedAvante. J.C. owns stock in ADAMAS, Prana, Sonexa, MedAvante, Neurotrax, and Neurokos and the copyright of the Neuropsychiatric Inventory. Cliff Jack provided consultation to Eli Lily. Publisher Copyright: © 2016 The Alzheimer's Association. Copyright: Copyright 2019 Elsevier B.V., All rights reserved.
PY - 2016/3/1
Y1 - 2016/3/1
N2 - During the past decade, a conceptual shift occurred in the field of Alzheimer's disease (AD) considering the disease as a continuum. Thanks to evolving biomarker research and substantial discoveries, it is now possible to identify the disease even at the preclinical stage before the occurrence of the first clinical symptoms. This preclinical stage of AD has become a major research focus as the field postulates that early intervention may offer the best chance of therapeutic success. To date, very little evidence is established on this "silent" stage of the disease. A clarification is needed about the definitions and lexicon, the limits, the natural history, the markers of progression, and the ethical consequence of detecting the disease at this asymptomatic stage. This article is aimed at addressing all the different issues by providing for each of them an updated review of the literature and evidence, with practical recommendations.
AB - During the past decade, a conceptual shift occurred in the field of Alzheimer's disease (AD) considering the disease as a continuum. Thanks to evolving biomarker research and substantial discoveries, it is now possible to identify the disease even at the preclinical stage before the occurrence of the first clinical symptoms. This preclinical stage of AD has become a major research focus as the field postulates that early intervention may offer the best chance of therapeutic success. To date, very little evidence is established on this "silent" stage of the disease. A clarification is needed about the definitions and lexicon, the limits, the natural history, the markers of progression, and the ethical consequence of detecting the disease at this asymptomatic stage. This article is aimed at addressing all the different issues by providing for each of them an updated review of the literature and evidence, with practical recommendations.
KW - Alzheimer's disease
KW - Amyloid PET
KW - Asymptomatic
KW - Biomarkers
KW - Blood biomarkers
KW - CSF biomarkers
KW - Diagnostic criteria
KW - Genetics
KW - MRI
KW - Pathophysiology
KW - Preclinical
KW - Tau PET
UR - http://www.scopus.com/inward/record.url?scp=84962325429&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84962325429&partnerID=8YFLogxK
U2 - 10.1016/j.jalz.2016.02.002
DO - 10.1016/j.jalz.2016.02.002
M3 - Review article
C2 - 27012484
AN - SCOPUS:84962325429
VL - 12
SP - 292
EP - 323
JO - Alzheimer's and Dementia
JF - Alzheimer's and Dementia
SN - 1552-5260
IS - 3
ER -