Evidence map›Paper›PMID 27012484›Full record

ReviewAlzheimer's & dementia : the journal of the Alzheimer's Association2016

Preclinical Alzheimer's disease: Definition, natural history, and diagnostic criteria.

Bruno Dubois, Harald Hampel, Howard H Feldman, Philip Scheltens, Paul Aisen, Sandrine Andrieu, Hovagim Bakardjian, Habib Benali, Lars Bertram, Kaj Blennow and 26 more

Registry-linked trialAbstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07284316 (Effect of a Multidomain Intervention Plus Turmeric on the Prevention of Cognitive Decline in People Over 55 Years of Age With Insulin Resistance), which is not on this map. Cited by 1,004 papers, 13 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
1,004citing papers in PubMed, 13 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT07284316 phase2 / phase3active not recruitingnot on this mapstarted 2025, after this paper: background citation

Effect of a Multidomain Intervention Plus Turmeric on the Prevention of Cognitive Decline in People Over 55 Years of Age With Insulin Resistance: A Randomized Clinical Trial

TypeinterventionalSponsorInstituto Mexicano del Seguro SocialRan2025 to 2027Enrolled100ConditionsCognitive Decline, Subjective Cognitive Impairment, Insulin ResistanceArmsTurmeric extract, Control: Placebo. 500mg gelatin in capsules 2 times a day
3 · Its place in the literature

Who cites it

1,004 citing papers in PubMed, 13 syntheses or guidelines pooled it.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Pooled it
  6. Tracking electrophysiological signatures of Alzheimer's disease: a systematic review of multimodal studies.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Pooled it
  7. Diagnostic utility of electrophysiological markers for early and differential diagnosis of Alzheimer's, Frontotemporal, and Lewy Body dementias: A systematic review.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2025
    Pooled it
  8. Pooled it
  9. Pooled it
  10. Guideline
  11. Guideline
  12. Pooled it
  13. Pooled it
  14. Plasma P-tau217 for detecting amyloid clearance after donanemab in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Trial
  15. Trial
  16. Trial
  17. Donanemab in preclinical Alzheimer's disease: Screening and baseline data from TRAILBLAZER-ALZ 3.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Trial
  18. Review
  19. Article
  20. Review

944 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

36 authors.

Bruno DuboisInstitute of Memory and Alzheimer's Disease (IM2A) and Brain and Spine Institute (ICM) UMR S 1127 Frontlab, Department of Neurology, AP_HP, Pitié-Salpêtrière University Hospital, Sorbonne Universities, Pierre et Marie Curie University, Paris 06, Paris, France. Electronic address: bruno.dubois@aphp.fr.
Harald HampelInstitute of Memory and Alzheimer's Disease (IM2A) and Brain and Spine Institute (ICM) UMR S 1127 Frontlab, Department of Neurology, AP_HP, Pitié-Salpêtrière University Hospital, Sorbonne Universities, Pierre et Marie Curie University, Paris 06, Paris, France; AXA Research Fund & UPMC Chair, Paris, France.
Howard H FeldmanUniversity of British Columbia, Canada.
Philip ScheltensDepartment of Neurology and Alzheimer Center, VU University Medical Center and Neuroscience Campus, Amsterdam, The Netherlands.
Paul AisenUniversity of Southern California San Diego, CA, USA.
Sandrine AndrieuUMR1027, INSERM, Université Toulouse III, Toulouse University Hospital, France.
Hovagim BakardjianIHU-A-ICM-Institut des Neurosciences translationnelles de Paris, Paris, France.
Habib BenaliINSERM U1146-CNRS UMR 7371-UPMC UM CR2, Site Pitié-Salpêtrière, Paris, France.
Lars BertramLübeck Interdisciplinary Platform for Genome Analytics (LIGA), Institutes of Neurogenetics and Integrative and Experimental Genomics, University of Lübeck, Lübeck, Germany; School of Public Health, Faculty of Medicine, Imperial College London, London, UK.
Kaj BlennowClinical Neurochemistry Lab, Department of Neuroscience and Physiology, University of Gothenburg, Mölndal Hospital, Sahlgrenska University Hospital, Mölndal, Sweden.
Karl BroichFederal Institute for Drugs and Medical Devices, Bonn, Germany.
Enrica CavedoAXA Research Fund & UPMC Chair, Paris, France; Laboratory of Alzheimer's Neuroimaging and Epidemiology, IRCCS Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy.
Sebastian CrutchDementia Research Centre, Department of Neurodegenerative Disease, UCL Institute of Neurology, University College London, London, UK.
Jean-François DartiguesINSERM U 1219, Université de Bordeaux, France.
Charles DuyckaertsUniversity Pierre et Marie Curie, Assistance Publique des Hôpitaux de Paris, Alzheimer-Prion Team Institut du Cerveau et de la Moelle (ICM), Paris, France.
Stéphane EpelbaumInstitute of Memory and Alzheimer's Disease (IM2A) and Brain and Spine Institute (ICM) UMR S 1127 Frontlab, Department of Neurology, AP_HP, Pitié-Salpêtrière University Hospital, Sorbonne Universities, Pierre et Marie Curie University, Paris 06, Paris, France.
Giovanni B FrisoniUniversity Hospitals and University of Geneva, Geneva, Switzerland; IRCCS Fatebenefratelli, Brescia, Italy.
Serge GauthierMcGill Center for Studies in Aging, Douglas Mental Health Research Institute, Montreal, Canada.
Remy GenthonFondation pour la Recherche sur Alzheimer, Hôpital Pitié-Salpêtrière, Paris, France.
Alida A GouwUMR1027, INSERM, Université Toulouse III, Toulouse University Hospital, France; Department of Clinical Neurophysiology/MEG Center, VU University Medical Center, Amsterdam.
Marie-Odile HabertSorbonne Universités, UPMC Univ Paris 06, CNRS, INSERM, Laboratoire d'Imagerie Biomédicale, Paris, France; AP-HP, Hôpital Pitié-Salpêtrière, Département de Médecine Nucléaire, Paris, France.
David M HoltzmanDepartment of Neurology, Washington University, Hope Center for Neurological Disorders, St. Louis, MO, USA; Department of Neurology, Washington University, Knight Alzheimer's Disease Research Center, St. Louis, MO, USA.
Miia KivipeltoCenter for Alzheimer Research, Karolinska Institutet, Department of Geriatric Medicine, Karolinska University Hospital, Stockholm, Sweden; Institute of Clinical Medicine/ Neurology, University of Eastern Finland, Kuopio, Finland.
Simone ListaAXA Research Fund & UPMC Chair, Paris, France.
José-Luis MolinuevoAlzheimer's Disease and Other Cognitive Disorders Unit, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Barcelonaβeta Brain Research Center, Pasqual Maragall Foundation, Barcelona, Spain.
Sid E O'BryantCenter for Alzheimer's & Neurodegenerative Disease Research, University of North Texas Health Science Center, TX, USA.
Gil D RabinoviciMemory & Aging Center, Department of Neurology, University of California San Francisco, San Francisco, CA, USA.
Christopher RoweDepartment of Molecular Imaging, Austin Health, University of Melbourne, Australia.
Stephen SallowayMemory and Aging Program, Butler Hospital, Alpert Medical School of Brown University, USA; Department of Neurology, Alpert Medical School of Brown University, USA; Department of Psychiatry, Alpert Medical School of Brown University, USA.
Lon S SchneiderKeck School of Medicine of the University of Southern California, Los Angeles, CA, USA.
Reisa SperlingHarvard Medical School, Memory Disorders Unit, Center for Alzheimer Research and Treatment, Brigham and Women's Hospital, Boston, USA; Harvard Medical School, Memory Disorders Unit, Center for Alzheimer Research and Treatment, Massachusetts General Hospital, Boston, USA.
Marc TeichmannInstitute of Memory and Alzheimer's Disease (IM2A) and Brain and Spine Institute (ICM) UMR S 1127 Frontlab, Department of Neurology, AP_HP, Pitié-Salpêtrière University Hospital, Sorbonne Universities, Pierre et Marie Curie University, Paris 06, Paris, France.
Maria C CarrilloThe Alzheimer's Association Division of Medical & Scientific Relations, Chicago, USA.
Jeffrey CummingsCleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, NV, USA.
Cliff R JackDepartment of Radiology, Mayo Clinic, Rochester MN, USA.
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

Funding

VASCULAR RISK AND COGNITIVE STATUS IN A LATINO POPULATIONP50AG005142 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI BRASKIE, MEREDITH NICOLE · 1985 to 2019
$41.0M
Renewal of Centers of Biomedical Research Excellence (COBRE) (Phase 2) CNTN - ResubmissionP20GM109025 · NIGMS · CLEVELAND CLINIC FOUNDATION · PI JESSICA KIRKLAND CALDWELL · 2015 to 2026
$22.8M
Allopregnanolone Regenerative Therapeutic for MCI/AD: Dose Finding Phase IUF1AG046148 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI BRINTON, ROBERTA EILEEN, SCHNEIDER, LON S · 2013 to 2013
$2.4M
Estrogen Receptor-beta phytoSERMs for Management of Menopause and Memory DeclineR01AG033288 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI SCHNEIDER, LON S · 2010 to 2012
$1.6M
Synthesis of Longer-Term Alzheimer Disease Studies in Order to Model and ImproveR01AG037561 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI SCHNEIDER, LON S · 2011 to 2013
$1.6M
NIA NIH HHS P50 AG005142NIA NIH HHS R01 AG033288NIA NIH HHS R01 AG037561NIA NIH HHS UF1 AG046148NIGMS NIH HHS P20 GM109025
6 · The paper itself

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.

Indexed as

Alzheimer DiseaseAnimalsBrainDisease ProgressionHumansAlzheimer's diseaseAmyloid PETAsymptomaticBiomarkersBlood biomarkersCSF biomarkersDiagnostic criteriaGeneticsMRIPathophysiologyPreclinicalTau PET

Identifiers

PMID27012484
PMCPMC6417794

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.