Suchergebnisse

Copyright © 2021 Suri, Bulte, Chiesa, Ebmeier, Jezzard, Rieger, Pitt, Griffanti, Okell, Craig, Chappell, Blockley, Kivimäki, Singh-Manoux, Khir, Hughes, Deanfield, Jensen, Green, Sigutova, Jansen, Zsoldos and 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. ; The Heart and Brain Study is funded by a UK Alzheimer's Society Research Fellowship to SS (Grant Reference: 441). This study was also supported by the Academy of Medical Sciences/the Wellcome Trust/the Government Department of Business, Energy and Industrial Strategy/the British Heart Foundation/Diabetes UK Springboard Award to SS (SBF006\1078). The pilot study was funded by the Oxford Alzheimer's Research UK Thames Valley Network Pilot Project Grant to SS. Work on this study receives institutional support from the UK National Institute of Health Research (NIHR) Oxford Health Biomedical Research Centre (BRC) and the Wellcome Centre for Integrative Neuroimaging (WIN). The WIN was supported by core funding from the Wellcome Trust (203139/Z/16/Z). The Whitehall II study was supported by the British Heart Foundation (RG/16/11/32334), UK Medical Research Council (MR/K013351/1 and MR/R024227/1 to MK), the US National Institute on Aging (RF1AG062553 and R01AG056477 to MK and AS-M), "Adult Determinants of Late Life Depression, Cognitive Decline and Physical Functioning – The Whitehall II Ageing Study" (MR/K013351/1; PI: MK), and "The Whitehall II Study: A Core Resource for Ageing Research" (MR/R024227/1; PI: MK). The Whitehall II Imaging Sub-study was supported by the UK Medical Research Council (MRC) grants "Predicting MRI abnormalities with longitudinal data of the Whitehall II Sub-study" (G1001354; PI KE; ClinicalTrials.gov Identifier: NCT03335696). The authors report the following additional funding: STC: BHF (PG/18/45/33814 and PG/19/31/34343), KE and EZ (HDH Wills 1965 Charitable Trust (1117747), and the European Commission (Horizon 2020 grant "Lifebrain", 732592), MK [UK MRC (MR/K013351/1, MR/R024227/1, and MR/S011676/1), National Institute on Aging (NIH), US (R01AG056477), NordForsk (75021), Academy of Finland (311492), Helsinki Institute of Life Science Fellowship (H970)], LG [Monument Trust Discovery Award from Parkinson's UK (J-1403), the MRC Dementias Platform UK (MR/L023784/2) and the NIHR Oxford Health BRC], AS-M [NIH (R01AG056477 and R01AG062553)], MAC and MC (Engineering and Physical Sciences Research Council UK (EP/P012361/1), MJ [grants from the Disciplinary Honours program of the Radboud University and Alzheimer Nederland (WE.04-2019-64)]. TO was supported by a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (grant number 220204/Z/20/Z). NB was supported by an Early Career Fellowship from the Engineering and Physical Sciences Research Council (grant number EP/K025716/1). PJ was supported by the NIHR Oxford Biomedical Research Centre. AH receives support from the British Heart Foundation, the Economic and Social Research Council (ESRC), the Horizon 2020 Framework Programme of the European Union, the National Institute on Aging, the National Institute for Health Research University College London Hospitals Biomedical Research Centre, the UK Medical Research Council and works in a unit that receives support from the UK Medical Research Council.