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Origins of Alzheimer's disease across the life-course

Total Cost €


EC-Contrib. €






Project "ORACLE" data sheet

The following table provides information about the project.


Organization address
postcode: 3015 GD

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Netherlands [NL]
 Total cost 1˙495˙715 €
 EC max contribution 1˙495˙715 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2015-STG
 Funding Scheme ERC-STG
 Starting year 2016
 Duration (year-month-day) from 2016-09-01   to  2021-08-31


Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 


 Project objective

The origins of Alzheimer’s disease (AD) remain elusive. The long pre-clinical phase of AD is universally recognized, but it is not known when predisposition for AD develops nor when the first signs and symptoms become discernable. In this regard, an essential role is played by the ‘reserve’ capacity of the brain, which is built up in early life and acts as buffer against adverse risk factors later in life. However, life-time trajectories of build up and loss of reserve and its determinants remain poorly understood. In ORACLE, I aim to unravel the origins of AD by studying reserve across the entire life-span: from in utero to end of life. The underlying hypothesis is that etiologic factors exert their effect on the risk of AD during the entire life-span, through build-up and loss of reserve. Such life-course approach to study reserve is worldwide unique and constitutes truly ground-breaking research aimed at unraveling the earliest origins of AD. Key objectives are: 1) To study trajectories of reserve across the entire lifespan. 2) To study factors that shape reserve in early life. 3) To study factors that determine onset and early loss of reserve. I will compile a life-course cohort that consists of three population-based samples totalling 40,829 persons that together cover the entire life-span: children in Generation R Study (in utero – 18 yrs); parents in Generation R Study (18–45 yrs); and the Rotterdam Study (45 yrs – death). Reserve will be quantified structurally using imaging techniques that measure volumetry, perfusion and connectivity as well as functionally by measuring cognitive and non-cognitive brain functions. I will study genetic and non-genetic risk factors of AD and their effects on reserve. Results from ORACLE will provide ground-breaking new insights into the earliest origins of AD. In turn, these insights are of major importance to enable the early identification of persons at highest risk of AD and develop targeted prevention for these persons.


year authors and title journal last update
List of publications.
2016 Gennady V. Roshchupkin, Boris A. Gutman, Meike W. Vernooij, Neda Jahanshad, Nicholas G. Martin, Albert Hofman, Katie L. McMahon, Sven J. van der Lee, Cornelia M. van Duijn, Greig I. de Zubicaray, André G. Uitterlinden, Margaret J. Wright, Wiro J. Niessen, Paul M. Thompson, M. Arfan Ikram, Hieab H. H. Adams
Heritability of the shape of subcortical brain structures in the general population
published pages: 13738, ISSN: 2041-1723, DOI: 10.1038/ncomms13738
Nature Communications 7 2019-07-08
2016 G. V. Roshchupkin, H. H. H. Adams, M. W. Vernooij, A. Hofman, C. M. Van Duijn, M. A. Ikram, W. J. Niessen
HASE: Framework for efficient high-dimensional association analyses
published pages: , ISSN: 2045-2322, DOI: 10.1038/srep36076
Scientific Reports 6/1 2019-07-08
2016 Hieab H H Adams, Derrek P Hibar, Vincent Chouraki, Jason L Stein, Paul A Nyquist, Miguel E Rentería, Stella Trompet, Alejandro Arias-Vasquez, Sudha Seshadri, Sylvane Desrivières, Ashley H Beecham, Neda Jahanshad, Katharina Wittfeld, Sven J Van der Lee, Lucija Abramovic, Saud Alhusaini, Najaf Amin, Micael Andersson, Konstantinos Arfanakis, Benjamin S Aribisala, Nicola J Armstrong, Lavinia Athanas
Novel genetic loci underlying human intracranial volume identified through genome-wide association
published pages: 1569-1582, ISSN: 1097-6256, DOI: 10.1038/nn.4398
Nature Neuroscience 19/12 2019-07-08
2017 Lori B. Chibnik, Frank J. Wolters, Kristoffer Bäckman, Alexa Beiser, Claudine Berr, Joshua C. Bis, Eric Boerwinkle, Daniel Bos, Carol Brayne, Jean-Francois Dartigues, Sirwan K. L. Darweesh, Stephanie Debette, Kendra L. Davis-Plourde, Carole Dufouil, Myriam Fornage, Leslie Grasset, Vilmundur Gudnason, Christoforos Hadjichrysanthou, Catherine Helmer, M. Arfan Ikram, M. Kamran Ikram, Silke Kern, Lew
Trends in the incidence of dementia: design and methods in the Alzheimer Cohorts Consortium
published pages: 931-938, ISSN: 0393-2990, DOI: 10.1007/s10654-017-0320-5
European Journal of Epidemiology 32/10 2019-07-08
2019 Robert Perneczky, Gerd Kempermann, Amos D. Korczyn, Fiona E. Matthews, M. Arfan Ikram, Nikolaos Scarmeas, Gael Chetelat, Yaakov Stern, Michael Ewers
Translational research on reserve against neurodegenerative disease: consensus report of the International Conference on Cognitive Reserve in the Dementias and the Alzheimer’s Association Reserve, Resilience and Protective Factors Professional Interest Area working groups
published pages: , ISSN: 1741-7015, DOI: 10.1186/s12916-019-1283-z
BMC Medicine 17/1 2019-04-18
2018 Elisabeth J. Vinke, Marius de Groot, Vikram Venkatraghavan, Stefan Klein, Wiro J. Niessen, M. Arfan Ikram, Meike W. Vernooij
Trajectories of imaging markers in brain aging: the Rotterdam Study
published pages: 32-40, ISSN: 0197-4580, DOI: 10.1016/j.neurobiolaging.2018.07.001
Neurobiology of Aging 71 2019-04-18
2018 Dina Vojinovic, Hieab H. Adams, Xueqiu Jian, Qiong Yang, Albert Vernon Smith, Joshua C. Bis, Alexander Teumer, Markus Scholz, Nicola J. Armstrong, Edith Hofer, Yasaman Saba, Michelle Luciano, Manon Bernard, Stella Trompet, Jingyun Yang, Nathan A. Gillespie, Sven J. van der Lee, Alexander Neumann, Shahzad Ahmad, Ole A. Andreassen, David Ames, Najaf Amin, Konstantinos Arfanakis, Mark E. Bastin, Diane M. Becker, Alexa S. Beiser, Frauke Beyer, Henry Brodaty, R. Nick Bryan, Robin Bülow, Anders M. Dale, Philip L. De Jager, Ian J. Deary, Charles DeCarli, Debra A. Fleischman, Rebecca F. Gottesman, Jeroen van der Grond, Vilmundur Gudnason, Tamara B. Harris, Georg Homuth, David S. Knopman, John B. Kwok, Cora E. Lewis, Shuo Li, Markus Loeffler, Oscar L. Lopez, Pauline Maillard, Hanan El Marroun, Karen A. Mather, Thomas H. Mosley, Ryan L. Muetzel, Matthias Nauck, Paul A. Nyquist, Matthew S. Panizzon, Zdenka Pausova, Bruce M. Psaty, Ken Rice, Jerome I. Rotter, Natalie Royle, Claudia L. Satizabal, Reinhold Schmidt, Peter R. Schofield, Pamela J. Schreiner, Stephen Sidney, David J. Stott, Anbupalam Thalamuthu, Andre G. Uitterlinden, Maria C. Valdés Hernández, Meike W. Vernooij, Wei Wen, Tonya White, A. Veronica Witte, Katharina Wittfeld, Margaret J. Wright, Lisa R. Yanek, Henning Tiemeier, William S. Kremen, David A. Bennett, J. Wouter Jukema, Tomas Paus, Joanna M. Wardlaw, Helena Schmidt, Perminder S. Sachdev, Arno Villringer, Hans Jörgen Grabe, W T Longstreth, Cornelia M. van Duijn, Lenore J. Launer, Sudha Seshadri, M Arfan Ikram, Myriam Fornage
Genome-wide association study of 23,500 individuals identifies 7 loci associated with brain ventricular volume
published pages: , ISSN: 2041-1723, DOI: 10.1038/s41467-018-06234-w
Nature Communications 9/1 2019-04-18
2019 Maria J. Knol, Alis Heshmatollah, Lotte G.M. Cremers, M. Kamran Ikram, André G. Uitterlinden, Cornelia M. van Duijn, Wiro J. Niessen, Meike W. Vernooij, M. Arfan Ikram, Hieab H.H. Adams
Genetic variation underlying cognition and its relation with neurological outcomes and brain imaging
published pages: 1440-1456, ISSN: 1945-4589, DOI: 10.18632/aging.101844
Aging 11/5 2019-04-18
2018 Sander Lamballais, Ayesha Sajjad, Maarten J. G. Leening, Romy Gaillard, Oscar H. Franco, Francesco U. S. Mattace‐Raso, Vincent W. V. Jaddoe, Sabine J. Roza, Henning Tiemeier, M. Arfan Ikram
Association of Blood Pressure and Arterial Stiffness With Cognition in 2 Population‐Based Child and Adult Cohorts
published pages: , ISSN: 2047-9980, DOI: 10.1161/jaha.118.009847
Journal of the American Heart Association 7/21 2019-04-18

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