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Study Protocol: The Heart and Brain Study

Suri, Sana; Bulte, Daniel; Chiesa, Scott T.; Ebmeier, Klaus P.; Jezzard, Peter; Rieger, Sebastian W.; Pitt, Jemma E.; Griffanti, Ludovica; Okell, Thomas W.; Craig, Martin; Chappell, Michael A.; Blockley, Nicholas P.; Kivim�ki, Mika; Singh-Manoux, Archana; Khir, Ashraf W.; Hughes, Alun D.; Deanfield, John E.; Jensen, Daria E. A.; Green, Sebastian F.; Sigutova, Veronika; Jansen, Michelle G.; Zsoldos, Enik?; Mackay, Clare E.

Study Protocol: The Heart and Brain Study Thumbnail


Sana Suri

Daniel Bulte

Scott T. Chiesa

Klaus P. Ebmeier

Peter Jezzard

Sebastian W. Rieger

Jemma E. Pitt

Ludovica Griffanti

Thomas W. Okell

Digital Research Developer (Image Processing and Analysis)

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Assistant Professor

Mika Kivim�ki

Archana Singh-Manoux

Ashraf W. Khir

Alun D. Hughes

John E. Deanfield

Daria E. A. Jensen

Sebastian F. Green

Veronika Sigutova

Michelle G. Jansen

Enik? Zsoldos

Clare E. Mackay


Background: It is well-established that what is good for the heart is good for the brain. Vascular factors such as hypertension, diabetes, and high cholesterol, and genetic factors such as the apolipoprotein E4 allele increase the risk of developing both cardiovascular disease and dementia. However, the mechanisms underlying the heart–brain association remain unclear. Recent evidence suggests that impairments in vascular phenotypes and cerebrovascular reactivity (CVR) may play an important role in cognitive decline. The Heart and Brain Study combines state-of-the-art vascular ultrasound, cerebrovascular magnetic resonance imaging (MRI) and cognitive testing in participants of the long-running Whitehall II Imaging cohort to examine these processes together. This paper describes the study protocol, data pre-processing and overarching objectives. Methods and Design: The 775 participants of the Whitehall II Imaging cohort, aged 65 years or older in 2019, have received clinical and vascular risk assessments at 5-year-intervals since 1985, as well as a 3T brain MRI scan and neuropsychological tests between 2012 and 2016 (Whitehall II Wave MRI-1). Approximately 25% of this cohort are selected for the Heart and Brain Study, which involves a single testing session at the University of Oxford (Wave MRI-2). Between 2019 and 2023, participants will undergo ultrasound scans of the ascending aorta and common carotid arteries, measures of central and peripheral blood pressure, and 3T MRI scans to measure CVR in response to 5% carbon dioxide in air, vessel-selective cerebral blood flow (CBF), and cerebrovascular lesions. The structural and diffusion MRI scans and neuropsychological battery conducted at Wave MRI-1 will also be repeated. Using this extensive life-course data, the Heart and Brain Study will examine how 30-year trajectories of vascular risk throughout midlife (40–70 years) affect vascular phenotypes, cerebrovascular health, longitudinal brain atrophy and cognitive decline at older ages. Discussion: The study will generate one of the most comprehensive datasets to examine the longitudinal determinants of the heart–brain association. It will evaluate novel physiological processes in order to describe the optimal window for managing vascular risk in order to delay cognitive decline. Ultimately, the Heart and Brain Study will inform strategies to identify at-risk individuals for targeted interventions to prevent or delay dementia.

Journal Article Type Article
Acceptance Date Mar 3, 2021
Online Publication Date Mar 31, 2021
Publication Date Mar 31, 2021
Deposit Date Apr 14, 2021
Publicly Available Date Apr 16, 2021
Journal Frontiers in Physiology
Electronic ISSN 1664-042X
Publisher Frontiers Media
Peer Reviewed Peer Reviewed
Volume 12
Article Number 643725
Keywords Physiology (medical); Physiology
Public URL
Publisher URL


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