Determinants of healthy ageing in the Whitehall II study

Whitehall II 研究中健康老龄化的决定因素

• 批准号: ES/J023299/1
• 负责人: Mika Kivimaki
• 金额: $ 57.16万
• 依托单位: University College London
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2012
• 资助国家: 英国
• 起止时间: 2012 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=ES%2FJ023299%2F1
• 关键词: Determinants; healthy; ageing; Whitehall; II

Utilising 25-year repeat data from the prestigious Whitehall II study (n=10,000) and various replication cohorts (total n=170,000), we will examine the extent to which cognitive reserve, long-term and changing health behaviours and psychosocial factors (physical activity, diet, social engagement) in adulthood predict the risk for age-related functional conditions, such as (1) cognitive impairment, (2) late-onset depression, and (3) disability. Furthermore, we will explore the biological underpinnings of these associations. Besides research on the ability of risk factors to change brain structure and function, there is increasing interest in the brain's ability to resist these changes. The scaffolding theory of ageing and cognition and that of cognitive reserve highlight the role of compensatory activity in response to the challenges posed by declining neural structures and function. Higher cognitive reserve would allow individuals to tolerate age-related changes and disease-related pathology in the brain without developing clinical symptoms. The Whitehall II study with measures of socioeconomic position, education, occupational history and mental engagement is uniquely characterised to assess the role played by cognitive reserve in shaping cognitive ageing trajectories. We hypothesise that higher education as well as social relations and contextual factors, such as socioeconomic circumstances, retirement and bereavement, importantly modify the risk for later-life depression and physical functioning. Plausible biological mediators, also influenced by ageing process, include adulthood low-grade chronic inflammation, vascular and metabolic changes (blood pressure, blood sugar). We will use repeat data to quantify their impact and to determine whether social relations and contextual factors induce change in biology or whether age-related changes in inflammation and cardiometabolic profile are driving ageing outcomes independently of upstream factors.We have previously shown that taking into account change is crucial in understanding contextual behavioural effects. Time varying health behaviours, measured with repeat data, accounted for 45% of the social gradient in cardiovascular mortality compared with 29% with a single baseline measure of these behaviours. The extent to which time varying health behaviours, such as smoking, alcohol intake, diet, and physical activity, over the adult life course account of the variation in old-age depression and disability is unknown, and therefore will be examined in this study.In examining adult-life course determinants of the disabling process, our main outcome is frailty, a syndrome which results from a multi-system reduction in reserve capacity such that a number of physiological systems become close to, or past, the threshold of symptomatic clinical failure. Importantly, primary frailty is not a consequence of comorbidity, such as overt cardiovascular disease (referred to as "secondary" frailty). In order to capture the different stages of disability we will use a range of additional outcomes to characterise functional loss: physical function (balance, upper and lower body strength, gait speed), hospitalisation (including fractures), loss of ability to perform activities of daily living and, finally, loss of autonomy and institutionalization.This programme will provide important insights into determinants of healthy ageing.

利用著名的白厅II研究(n=10,000)和各种重复队列(总计n=170,000)的25年重复数据，我们将检查认知储备、长期和不断变化的健康行为以及成年后的心理社会因素(体育活动、饮食、社交)在多大程度上预测与年龄相关的功能疾病的风险，例如(1)认知障碍、(2)迟发性抑郁症和(3)残疾。此外，我们还将探讨这些关联的生物学基础。除了研究危险因素改变大脑结构和功能的能力外，人们对大脑抵抗这些变化的能力也越来越感兴趣。老化和认知的支架理论以及认知储备理论强调了补偿活动在应对神经结构和功能衰退带来的挑战方面的作用。较高的认知储备将使个人能够容忍大脑中与年龄相关的变化和与疾病相关的病理，而不会出现临床症状。怀特霍尔二世的这项研究以社会经济地位、教育、职业史和精神投入为衡量指标，其独特之处在于评估认知储备在塑造认知老化轨迹中所起的作用。我们假设，高等教育以及社会关系和背景因素，如社会经济状况、退休和丧亲，对晚年抑郁和身体功能的风险有重要影响。看似合理的生物介体也受到老龄化过程的影响，包括成年后轻度慢性炎症、血管和代谢变化(血压、血糖)。我们将使用重复数据来量化它们的影响，并确定社会关系和背景因素是否会导致生物学上的变化，或者与年龄相关的炎症和心脏代谢状况的变化是否独立于上游因素而推动衰老结果。我们之前已经表明，考虑变化对于理解背景行为影响至关重要。用重复数据测量的时变健康行为占心血管死亡率的社会梯度的45%，而用这些行为的单一基线测量的这一比例为29%。在成年人的一生中，吸烟、饮酒、饮食和体力活动等时变的健康行为在多大程度上解释了老年抑郁症和残疾的变化，这是未知的，因此将在这项研究中进行检验。在检查致残过程的成人一生过程的决定因素时，我们的主要结果是虚弱，这是一种综合征，由多种系统储备能力的减少引起，使得许多生理系统变得接近或超过症状性临床衰竭的阈值。重要的是，原发虚弱不是共病的结果，例如明显的心血管疾病(称为“继发性”虚弱)。为了捕捉残疾的不同阶段，我们将使用一系列其他结果来描述功能丧失：身体功能(平衡、上下半身力量、步态速度)、住院(包括骨折)、日常生活能力丧失，最后是自主性和制度化的丧失。该计划将为健康老龄化的决定因素提供重要的见解。

项目成果

Assessing cortisol from hair samples in a large observational cohort: The Whitehall II study.

• DOI: 10.1016/j.psyneuen.2016.07.214
• 发表时间: 2016-11
• 期刊: PSYCHONEUROENDOCRINOLOGY
• 影响因子: 3.7
• 作者: Abell, Jessica G.;Stalder, Tobias;Ferrie, Jane E.;Shipley, Martin J.;Kirschbaum, Clemens;Kivimaki, Mika;Kumari, Meena
• 通讯作者: Kumari, Meena

Physical Activity, Sedentary Behavior, and Long-Term Changes in Aortic Stiffness: The Whitehall II Study.

• DOI: 10.1161/jaha.117.005974
• 发表时间: 2017-08-07
• 期刊: Journal of the American Heart Association
• 影响因子: 5.4
• 作者: Ahmadi-Abhari S;Sabia S;Shipley MJ;Kivimäki M;Singh-Manoux A;Tabak A;McEniery C;Wilkinson IB;Brunner EJ
• 通讯作者: Brunner EJ

Temporal trend in dementia incidence since 2002 and projections for prevalence in England and Wales to 2040: modelling study.

• DOI: 10.1136/bmj.j2856
• 发表时间: 2017-07-05
• 期刊: BMJ (Clinical research ed.)
• 作者: Ahmadi-Abhari S;Guzman-Castillo M;Bandosz P;Shipley MJ;Muniz-Terrera G;Singh-Manoux A;Kivimäki M;Steptoe A;Capewell S;O'Flaherty M;Brunner EJ
• 通讯作者: Brunner EJ

Development and validation of a risk prediction model for work disability: multicohort study.

• DOI: 10.1038/s41598-017-13892-1
• 发表时间: 2017-10-19
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Airaksinen J;Jokela M;Virtanen M;Oksanen T;Pentti J;Vahtera J;Koskenvuo M;Kawachi I;Batty GD;Kivimäki M
• 通讯作者: Kivimäki M

Association of circulating metabolites with healthy diet and risk of cardiovascular disease: analysis of two cohort studies.

• DOI: 10.1038/s41598-018-26441-1
• 发表时间: 2018-06-05
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Akbaraly T;Würtz P;Singh-Manoux A;Shipley MJ;Haapakoski R;Lehto M;Desrumaux C;Kähönen M;Lehtimäki T;Mikkilä V;Hingorani A;Humphries SE;Kangas AJ;Soininen P;Raitakari O;Ala-Korpela M;Kivimäki M
• 通讯作者: Kivimäki M