Study protocol: The Whitehall II imaging sub-study

Nicola Filippini, Eniko Zsoldos, Rita Haapakoski, Claire E. Sexton, Abda Mahmood, Charlotte L. Allan, Anya Topiwala, Vyara Valkanova, Eric J. Brunner, Martin J. Shipley, Edward Auerbach, Steen Moeller, Kâmil Uǧurbil, Junqian Xu, Essa Yacoub, Jesper Andersson, Janine Bijsterbosch, Stuart Clare, Ludovica Griffanti, Aaron T. HessMark Jenkinson, Karla L. Miller, Gholamreza Salimi-Khorshidi, Stamatios N. Sotiropoulos, Natalie L. Voets, Stephen M. Smith, John R. Geddes, Archana Singh-Manoux, Clare E. Mackay, Mika Kivimäki, Klaus P. Ebmeier

Research output: Contribution to journalArticlepeer-review

56 Scopus citations


Background: The Whitehall II (WHII) study of British civil servants provides a unique source of longitudinal data to investigate key factors hypothesized to affect brain health and cognitive ageing. This paper introduces the multi-modal magnetic resonance imaging (MRI) protocol and cognitive assessment designed to investigate brain health in a random sample of 800 members of the WHII study.Methods/design: A total of 6035 civil servants participated in the WHII Phase 11 clinical examination in 2012-2013. A random sample of these participants was included in a sub-study comprising an MRI brain scan, a detailed clinical and cognitive assessment, and collection of blood and buccal mucosal samples for the characterisation of immune function and associated measures. Data collection for this sub-study started in 2012 and will be completed by 2016. The participants, for whom social and health records have been collected since 1985, were between 60-85 years of age at the time the MRI study started. Here, we describe the pre-specified clinical and cognitive assessment protocols, the state-of-the-art MRI sequences and latest pipelines for analyses of this sub-study.Discussion: The integration of cutting-edge MRI techniques, clinical and cognitive tests in combination with retrospective data on social, behavioural and biological variables during the preceding 25 years from a well-established longitudinal epidemiological study (WHII cohort) will provide a unique opportunity to examine brain structure and function in relation to age-related diseases and the modifiable and non-modifiable factors affecting resilience against and vulnerability to adverse brain changes.

Original languageEnglish (US)
Article number159
JournalBMC Psychiatry
Issue number1
StatePublished - May 30 2014

Bibliographical note

Funding Information:
The sub-study is funded by the Lifelong Health and Well-being Phase-3 programme grant “Predicting MRI abnormalities with longitudinal data of the Whitehall II sub-study” (MRC-G1001354; Ebmeier KP (PI), Geddes JR, Kivimäki M, Mackay CE, Singh-Manoux A, Smith SM), as well as the HDH Wills 1965 (English Charity Register: 1117747; Ebmeier KP (PI)), and the Gordon Edward Small Charitable (Scottish Charity Register: SC008962; Ebmeier KP (PI)) Trusts. Collection of blood and buccal mucosal samples for a characterisation of immune function and associated measures is funded by the UK Medical Research Council programme grant K013351 (“Adult determinants of late life depression, cognitive decline and physical functioning - The Whitehall II Ageing Study”, Kivimäki M (PI), Singh-Manoux A, Brunner E, Batty GD, Kumari M, Ebmeier KP, Hingorani A) and the ESRC professional fellowship scheme to Kivimäki.

Funding Information:
Thank you to all participants and to the Whitehall staff at UCL, who so helpfully collaborated with us. We are grateful to all FMRIB staff, in particular radiographers Jon Campbell, Michael Sanders, Caroline Young and David Parker, IT staff David Flitney, Christopher Gallagher, Duncan Mortimer and Matthew Webster, FMRIB administrative staff Sue Field and Marilyn Goulding, and last but not least my PA Amanda Pipkin, for help with coordinating the appointments. We would like to thank Martin Turner and his colleagues for advising on incidental findings and taking over clinical responsibility for such participants. We are grateful for provision of the multiband pulse sequence and reconstruction algorithms to the Center for Magnetic Resonance Research, University of Minnesota, USA. We are grateful to Siemens Healthcare for the provision of the DTI and MEMPR sequences. The DTI sequence was a Works-in-Progress package for advanced EPI diffusion imaging, developed by Thorsten Feiweier, Siemens AG, Healthcare Sector, Erlangen, Germany. The Multi-Echo MPRAGE sequence is a Works-in-Progress package, developed by Siemens in collaboration with the Athinoula A. Martinos, Center for Biomedical Imaging, Massachusetts General Hospital. Work on this study was mainly funded by the “Lifelong Health and Wellbeing” Programme Grant: “Predicting MRI abnormalities with longitudinal data of the Whitehall II Substudy” (UK Medical Research Council: G1001354). Collection of blood and buccal mucosal samples for a characterisation of immune function and associated measures is supported by the UK Medical Research Council grant K013351 and the ESRC professional fellowship scheme to Kivimäki. NF and AM are funded by the HDH Wills 1965 Charitable Trust (Nr: 1117747). CLA and AT are supported by Oxford University Clinical Academic Graduate School. NLV is funded by the Medical Research Council, RH by the Economic and Social Research Council (ES/J023299/1). KU receives funding from NIH (NIH U54MH091657, NIH P41 EB015894). LG was funded by Ricerca Corrente 2012–2013 (Italian Ministry of Health). KLM is funded by the Wellcome Trust. SNS is funded by the WU-Minn Human Connectome Project (1U54MH091657-01) from the 16 NIH Institutes and Centers that support the NIH Blueprint for Neuroscience Research; ASM receives research support from the US National Institutes of Health (R01AG013196, R01AG034454). Some researchers (CEM, NLV) are supported by the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre based at Oxford University Hospitals NHS Trust and University of Oxford (The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health).


  • Affective disorders
  • Connectome
  • Dementia
  • Diffusion tensor imaging
  • Epidemiology
  • Functional MRI
  • Magnetic resonance imaging
  • Neuropsychology
  • Resting state brain networks
  • White matter


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