Study protocol: the Whitehall II imaging sub-study

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.

Moderate alcohol consumption as risk factor for adverse brain outcomes and cognitive decline: longitudinal cohort study

“…We used T1-weighted and diffusion tensor (DTI) 3T MRI sequences for these analyses. 30 Full technical details are in the appendix. In brief, we initially examined associations between alcohol use and grey matter using voxel based morphometry, an objective method to compare grey matter density between individuals in each voxel (smallest distinguishable image volume) of the structural image.…”

Peripheral DNA Methylation, Cognitive Decline and Brain Aging: Pilot Findings from The Whitehall II Imaging Study

“…Forty-eight participants were selected from subjects recruited to the Whitehall II imaging sub-study between May 2012 and December 2014 [19]. All participants were members of the Whitehall II study, a prospective occupation cohort study established in 1985 [20].…”

“…Ethical approval was obtained from the University of Oxford Central University Research Ethics Committee, and the University College London Medical School Committee on the Ethics of Human Research. Informed written consent was obtained from all participants [19].…”

“…The detailed study protocol has been previously published elsewhere [19]. We assessed cognitive impairment using the Montreal Cognitive Assessment (MoCA) [21], and studied 24 cognitively impaired participants (MoCA <26), who would qualify for a clinical diagnosis of mild cognitive impairment (MCI), alongside 24 age and gender matched cognitively normal participants (MoCA >26), who were free from other comorbidities such as depression (Supplementary Table 1).…”

“…As such, brain imaging changes are useful surrogate markers of brain health and aging. Here, we investigated the potential utility of DNAm profiling as a peripheral marker for cognitive decline and brain health in the Whitehall II imaging sub-study [19], which provides a valuable source of longitudinal data to explore factors hypothesized to affect brain health and cognitive aging.…”