Table_1_Study Protocol: The Heart and Brain Study.DOCX

BackgroundIt 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 DesignThe 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.
DiscussionThe 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.

研究背景：
已有确凿证据表明，对心脏有益的干预与生活方式同样有益于大脑健康。高血压、糖尿病、高胆固醇血症等血管危险因素，以及载脂蛋白E4等位基因（apolipoprotein E4 allele）等遗传因素，均会增加心血管疾病与痴呆的发病风险。然而，心脏与大脑之间关联的潜在生物学机制仍未明确。近期研究证据显示，血管表型异常与脑血管反应性（cerebrovascular reactivity, CVR）受损可能在认知衰退进程中发挥关键作用。本项心脑研究（Heart and Brain Study）整合了最先进的血管超声、脑血管磁共振成像（magnetic resonance imaging, MRI）与认知测试手段，针对长期随访的怀特霍尔II影像队列（Whitehall II Imaging cohort）的参与者开展联合检测，以全面解析上述关联机制。本文将对该研究的试验方案、数据预处理流程与总体研究目标进行详细阐述。

研究方法与设计：
怀特霍尔II影像队列共纳入775名参与者，他们在2019年时年龄均≥65岁。自1985年起，该队列每5年接受一次临床评估与血管危险因素筛查，并于2012年至2016年间完成了3T颅脑磁共振扫描与神经心理学测试（对应怀特霍尔II MRI波次1，即Whitehall II Wave MRI-1）。该队列中约25%的参与者被纳入本项心脑研究，需前往牛津大学完成单次随访检测（对应MRI波次2，即Wave MRI-2）。在2019年至2023年间，参与者将接受升主动脉与颈总动脉超声扫描、中心与外周血压测量，以及3T磁共振扫描以检测以下指标：吸入5%二氧化碳混合气时的脑血管反应性、血管选择性脑血流量（cerebral blood flow, CBF）与脑血管病变。同时，研究人员还将重复开展MRI-1波次中已进行的结构磁共振与弥散磁共振扫描，以及全套神经心理学测试。依托这套覆盖全生命周期的详实数据，本项心脑研究将解析中年时期（40~70岁）长达30年的血管风险变化轨迹，如何影响老年阶段的血管表型、脑血管健康、纵向脑萎缩与认知衰退进程。

讨论：
本研究将生成目前最全面的数据集之一，用于解析心脏与大脑关联的纵向决定因素。研究将评估全新的生理过程，以明确管理血管风险、延缓认知衰退的最佳干预窗口。最终，本项心脑研究将为制定识别高危个体的策略提供科学依据，从而开展针对性干预以预防或延缓痴呆的发生。