Environmental Determinants of Cognitive Function and Decline in Older Adults

描述(由申请人提供)：认知衰退和认知障碍在老年人中很常见，并与显著的发病率和死亡率有关。然而，很少有人发现可以预防或延缓认知衰退的干预措施。广泛存在的环境污染物可能通过神经毒性或对心血管健康的不利影响而与晚年认知能力下降有关，而且可能是可以改变的。如果存在因果关系，对这些风险因素的干预将会带来实质性的好处。这项拟议的工作将探索暴露于两种常见环境污染物--铅和与交通相关的空气污染--是否与认知能力下降有关。将使用护士健康研究(NHS)的参与者子集来评估铅与认知测试成绩随时间的变化之间的关系。NHS是一组居住在社区的老年妇女。广义估计方程将被用来评估较高水平的铅生物标志物是否与随着时间的推移认知测试成绩的变化呈负相关。此外，与更年期相关的骨密度会将以前储存在骨骼中的铅释放到体循环中，并可能增加妇女对过去铅暴露的不利影响的脆弱性。为了评估最近的暴露，包括与绝经相关的铅重新注入，是否与绝经后妇女的认知功能严重下降有关，将在一组妇女中评估血铅水平与认知表现随时间的变化之间的关系，这些妇女的血铅测量反映了在这一关键时期的暴露。对与交通相关的空气污染和认知测试表现之间的关系的评估将在标准老龄化研究(NAS)的参与者中进行，NAS是一组老年男性。混合模型将被用来评估使用经过验证的时空土地使用回归模型估计的较高水平的黑碳暴露是否对该水平或认知表现随时间的变化产生不利影响。了解这些暴露对认知功能的作用可能会提出有益的干预措施，并有助于阐明这种有害条件的潜在生物过程。 公共卫生相关性：识别老年人认知能力下降的可改变危险因素并对其进行干预将会有显著的益处。如果暴露在铅或空气污染中与认知能力下降有关，那么减少暴露的干预措施将是有益的，包括增强骨骼健康或控制污染物。此外，识别认知衰退的危险因素可能为认知衰退的启动和进展以及与痴呆症相关的疾病状态提供有价值的生物学机制。)

DESCRIPTION (provided by applicant): Cognitive decline and cognitive impairment are common in older adults and are associated with significant morbidity and mortality. However, few interventions have been identified to prevent or delay cognitive decline. Widespread environmental pollutants may be related to cognitive decline in later years through neurotoxic effects or adverse effects on cardiovascular health and are potentially modifiable. If a causal relationship exists, intervention on such risk factors would have substantial benefits. The proposed work will explore whether exposures to two common environmental pollutants, lead and traffic-related air pollution, are associated with cognitive decline. Evaluation of the relationship between lead and change in cognitive test performance over time will be conducted using a subset of participants in the Nurses' Health Study (NHS), a cohort of community-dwelling older women. Generalized estimating equations will be used to evaluate whether higher levels of lead biomarkers are adversely associated with change in cognitive test performance over time. In addition, menopause-related bone mineral density releases lead previously stored in bone into the systemic circulation and may increase the vulnerability of women to the adverse effects of past lead exposure. To evaluate the whether recent exposures, including menopause-related reintroduction of lead, is associated with greater declines in cognitive function in postmenopausal women, the relationship between blood lead levels and change in cognitive performance over time will be assessed in a subset of women whose blood lead measurements reflect exposure during this critical period. Evaluation of the relationship between traffic-related air pollution and cognitive test performance will be conducted in subset of participants in the Normative Aging Study (NAS), a cohort of older men. Mixed models will be used to evaluate whether higher levels of exposure to black carbon, estimated using a validated spatiotemporal land-use regression model, have an adverse effect on the level or the change in cognitive performance over time. Understanding the role of these exposures on cognitive function may suggest beneficial interventions and help to elucidate the underlying biologic processes of this detrimental condition. PUBLIC HEALTH RELEVANCE: Identification of and intervention on modifiable risk factors for cognitive decline in older adults would be expected to have significant benefits. If exposure to lead or air pollution is related to cognitive decline, interventions to lessen exposure, including increasing bone health or regulation of pollutants would be beneficial. In addition, identification of risk factors for cognitive decline may provide valuable insight into the underlying biological mechanisms for initiation and progression of cognitive decline and the associated disease state of dementia. )