Health behaviors over the adult lifecourse and cognitive aging

描述（由申请人提供）：越来越多的证据表明健康行为与认知老化之间存在关联。研究发现，吸烟、饮酒、体育锻炼和营养不良都与认知功能低下和痴呆有关。健康行为在多大程度上可以解释认知衰老轨迹具有重大的公共卫生相关性，特别是因为它们可能是痴呆症的“关键”可改变风险因素。本提案的总体目标是检查健康行为在确定中年开始的认知衰老轨迹的成人生命过程中的综合影响。具体目标是：1。研究吸烟、饮酒、体育活动和饮食对认知能力下降的综合影响，以评估中年早期、中期和晚期健康行为的影响是否最重要，以及这种影响是否会随着时间的推移而累积。2. 研究一种行为的改变在多大程度上导致其他行为的改变，以及这些改变在多大程度上影响认知老化。3. 研究健康行为与中年认知衰老之间的双向关系。检查生物变化的程度，如血管危险因素和疾病，解释健康行为和认知衰老之间的联系。我们还将研究健康行为与认知衰老之间关联的两个潜在影响因子：社会经济地位（SES）和载脂蛋白E (APOE) e4等位基因所起的作用。

DESCRIPTION (provided by applicant): There is increasing evidence of an association between health behaviors and cognitive aging. Smoking, alcohol, physical activity and nutrition have all been found to be associated with poor cognitive function and dementia. The extent to which health behaviors can explain cognitive aging trajectories is of substantial public health relevance, particularly as they may be 'the' key modifiable risk factors for dementia. The overarching aim of this proposal is to examine the combined impact of health behaviors over the adult lifecourse in determining cognitive aging trajectories starting from midlife. The specific aims are: 1. To examine the combined impact of smoking, alcohol consumption, physical activity and diet on cognitive decline in order to assess whether the impact of health behaviors in early, mid and late midlife is most important and whether this effect accumulates over time. 2. To examine the extent to which change in one behavior leads to changes in others and the extent to which these changes influence cognitive aging. 3. To examine bidirectional associations between health behaviors and cognitive aging starting in midlife: 4. To examine the extent to which biological changes, such as those in vascular risk factors and diseases, explain the association between health behaviors and cognitive aging. We will also examine the role played by two potential effect modifiers of the association between health behaviors and cognitive aging: socioeconomic status (SES) and the apolipoprotein E (APOE) e4 allele. In addition, our work will focus on issues to do measurement of health behaviors: Detailed attention will be paid to the categorization of the health behaviors in order to understand the shape of the association between each measure of behavior and cognitive aging, whether different measures diet have similar associations with cognitive aging and whether there are discrepancies between the objective and subjective measures of physical activity. We will also examine the impact of health behaviors on specific domains of cognitive aging, with memory and executive function as two major aspects. The Whitehall II test battery was introduced to the full Whitehall II cohort at phase 5 when participants were on average 55 years old and had already been assessed for behaviors over the previous 10 years. A third wave of cognitive data is currently being collected, and will be available late 2009, allowing us look at trajectories of cognitive change. Although the proposal is based primarily on the British Whitehall, the research team is composed of scientists based in France as well as the UK, providing us with the opportunity to validate some of our results in data from the French GAZEL study. PUBLIC HEALTH RELEVANCE: Continuing increases in life expectancy come in tandem with knowledge that the prevalence of dementia rises with age, doubling every 4-5 years after the age of 60. By age 80 over one third of the population is likely to be living with dementia; for industrialized countries an unprecedented challenge in terms of care provision. Although dementia generally occurs late in life, it is increasingly recognized that there is a long preclinical phase, making the evaluation of risk factors prior to and during this phase a crucial next step in the battle to prevent or delay the onset of dementia. Driven by this "long" view of dementia our research focuses on the determinants of heterogeneity in cognitive aging starting from early midlife. Existing research suggests an association between health behaviors and cognitive aging; smoking, alcohol, physical activity and nutrition have all been found to be associated with poor cognitive function and dementia. What remains unknown is the extent to which these behaviors, acting in combination, determine cognitive aging trajectories. In public health terms, why is this knowledge so important? Because these behaviors are likely to be 'the' key risk factors for dementia that are both modifiable and amenable to low-cost intervention at the national level. In research terms, the unique feature of this proposal is three repeat assessments of cognitive function using a comprehensive test battery with a first assessment carried out in early midlife allowing an examination of the inflection point in changes in cognitive functioning.