Open Access Study protocol

Study protocol: the Whitehall II imaging sub-study

Nicola Filippini12, Enikő Zsoldos1, Rita Haapakoski1, Claire E Sexton1, Abda Mahmood1, Charlotte L Allan1, Anya Topiwala1, Vyara Valkanova1, Eric J Brunner3, Martin J Shipley3, Edward Auerbach4, Steen Moeller4, Kâmil Uğurbil4, Junqian Xu45, Essa Yacoub4, Jesper Andersson2, Janine Bijsterbosch2, Stuart Clare2, Ludovica Griffanti2, Aaron T Hess6, Mark Jenkinson2, Karla L Miller2, Gholamreza Salimi-Khorshidi2, Stamatios N Sotiropoulos2, Natalie L Voets2, Stephen M Smith2, John R Geddes1, Archana Singh-Manoux37, Clare E Mackay1, Mika Kivimäki3 and Klaus P Ebmeier1*

Author Affiliations

1 Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford OX3 7JX, UK

2 Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK

3 Department of Epidemiology & Public Health, University College London, London, UK

4 Center for Magnetic Resonance Research (CMRR), University of Minnesota, Minneapolis, MN, USA

5 Icahn School of Medicine at Mount Sinai, New York, NY, USA

6 Centre for Clinical Magnetic Resonance Research, University of Oxford, Oxford, UK

7 Centre for Research in Epidemiology and Population Health, Hôpital Paul Brousse, INSERM, U1018, 94807 Villejuif, Cedex, France

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BMC Psychiatry 2014, 14:159  doi:10.1186/1471-244X-14-159

Published: 30 May 2014



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.


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.


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.

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