Adult Determinants of Late Life Depression, Cognitive Decline and Physical Functioning - The Whitehall II Ageing Study

患有抑郁症和痴呆症等心理健康问题的老年人数量正在迅速增加。15年后，英国将有超过430万人受到影响。加上身体上的限制，与年龄有关的残疾负担日益加重，将对独立生活能力产生深远影响，并对社会和卫生保健产生重大影响。关于与年龄相关的残疾的大量和信息丰富的研究主要集中在老年时衡量的决定因素上。为了更好地区分因果关系，并在年龄相关残疾发作之前确定新的干预目标，我们建议在白厅II(Wii)队列中研究风险因素和从中年到老年的功能。Wii非常适合这项研究，因为这项研究收集了1985年招聘的10308名伦敦公务员的成年生活过程中的一系列数据。我们拟议的工作计划包括收集新一波临床数据(诊所7)，以涵盖65-85岁的年龄范围，并扩大Wii队列中已有的丰富信息。老年抑郁症的风险因素与认知和身体功能的下降之间存在着惊人的重叠。这可能是由于共同的因果病理和/或共同的生活方式、社会和行为因素造成的。拟议方案在一个单一、连贯的分析框架内审查这些问题。在Wii中发现的资产包括了比其他任何大规模英国队列研究更广泛的成年风险因素的数据。自1985年以来，每隔4-5年定期对这些指标进行重复测量。另一个主要优势是对抑郁和焦虑症状、认知和身体功能的高分辨率测量。该提案要求在2013-2017年期间为基础设施(数据收集的核心资金)和研究相结合提供资源。我们的目标涵盖中年风险的各个领域，以及老年心理健康和功能的保护因素。通过30年的前瞻性跟踪，我们将研究社会经济地位、社会参与度和认知储备作为背景影响(原因的原因)的作用，并量化生活方式因素的重要性，同时关注健康行为变化的作用。我们假设，中年时期炎症、血管和代谢因素的发展轨迹将对晚年抑郁、认知障碍和功能健康产生重大影响。来自Wii的发现将通过其他大规模研究进行复制。然后，我们将利用普通人群中预测的风险因素分布，将任何观察到的影响转化为对功能限制流行率和无残疾预期寿命的影响。该方案将有助于公共卫生政策、卫生和社会护理，并将产生社会影响。随着有效的数据共享政策已经到位，新的数据将有助于更广泛的科学界推进老年学、神经科学、医学、心理学、流行病学和遗传学研究，包括跨部门合作项目。我们与英国和国外的大学和研究机构积极开展研究合作，为该领域未来的研究人员提供能力建设。

The number of older adults with mental health problems, such as depression and dementia, is rapidly increasing. In 15 years time, over 4.3 million people in the UK will be affected. Together with physical limitations, this escalating burden of age-related disability will have a profound impact on the capacity for independent living, as well as major social and health care implications. The voluminous and informative research into age-related disability has largely focused on determinants measured in old age. In order to better separate cause and effect, and to identify novel targets for intervention before the onset of age-related disability, we propose to study risk factors and functioning from mid-life to old-age in the Whitehall II (WII) cohort. WII is perfectly placed for this research as the study has collected an array of data across the adult life course on a cohort of 10,308 London-based civil servants recruited in 1985. Our proposed programme of work includes the collection of a new wave of clinical data (clinic 7) to cover the age range of 65-85 and to extend the wealth of information already available from the WII cohort. There is a striking overlap between the risk factors for late-life depression and the decline in cognitive and physical functioning. This may be due to shared causal pathologies and/or shared lifestyle, social and behavioural factors. The proposed programme examines these issues within a single, cohesive analytic framework. The assets for discovery in WII include data on a wider range of adulthood risk factors than any other large-scale UK cohort study. These have been measured repeatedly at regular 4-5 year intervals since 1985. Another major advantage is the high-resolution measurements of depressive and anxiety symptoms, cognitive and physical functioning. The proposal requests resources for a combination of infrastructure (core funding for data collection) and research over the period 2013-2017. Our objectives cover various domains of midlife risk and protective factors for old-age mental health and functioning. Using 30 years of prospective follow-up, we will examine the role of socioeconomic status, social engagement and cognitive reserve as contextual influences ('the causes of the causes') and quantify the importance of lifestyle factors, with attention to the role of changes in health behaviours. We hypothesise that mid-life trajectories of inflammatory, vascular, and metabolic factors will make a major contribution to later life depression, cognitive impairment, and functional health. Findings from WII will be replicated using other large-scale studies. We will then translate any observed effects into impact on the prevalence of functional limitations and disability-free life expectancy using projected risk factor distributions in the general population. This programme will contribute to public health policy, health and social care, and will have societal impacts. With effective data-sharing policies already in place, the new data will contribute to the wider scientific community advancing gerontological, neuroscientific, medical, psychological, epidemiological and genetic research, including cross-sector collaborative ventures. Our active research collaboration with universities and research institutes in the UK and abroad enable capacity building for future researchers in the field.