Abstract
BackgroundThe 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/designA 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.DiscussionThe 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.
Highlights
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
The primary clinical hypotheses which we will address are: a) The quality of frontal compensatory activity will be affected by vascular risk, hypertension, including absence of protective factors, such as physical fitness, cardio-vascular and cerebrovascular prophylaxis, by mental activity (“use it or lose it”), and by frontal lobe atrophy; b) Time-trajectories derived from the WHII data set, e.g. of cognitive function or depression scores, and vascular risks-factor trajectories, will account for more of the diversity of outcome than singular measurements during any one of the previous follow-phases
The proposed programme of work will lead to the development and validation of methods and measures to integrate biological, physical, psychological, and socioeconomic markers or indicators of health and wellbeing in later life, combining the Whitehall II repeat data from 1985 onwards and the psychiatric assessment in Phase 11 (2012–13), with detailed structural and functional imaging data collected in 2012–2016
Summary
The proposed programme of work will lead to the development and validation of methods and measures to integrate biological, physical, psychological, and socioeconomic markers or indicators of health and wellbeing in later life, combining the Whitehall II repeat data from 1985 onwards and the psychiatric assessment in Phase 11 (2012–13), with detailed structural and functional imaging data collected in 2012–2016. Our focus will be on understanding the development and impact of age-related conditions such as depression and cognitive decline, their implications for employment and work in later life, and the neural mechanisms of compensation for cognitive decline and resilience to age-related stress by identifying the mechanisms of neural scaffolding, and the factors and mechanisms associated with successful ageing in the face of brain changes and risk factors. EZs wrote part of the first draft, planned the imaging, clinical and neuropsychological protocol, as well as the data management, and performed some of the analyses. CES planned the data management, as well as the imaging, clinical and neuropsychological protocol, and critically read the manuscript.
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