Environmental Determinants of Cognitive Function and Decline in Older Adults

描述（由申请人提供）：认知能力下降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相关。然而，很少有干预措施被确定为预防或延缓认知能力下降。广泛存在的环境污染物可能通过神经毒性作用或对心血管健康的不利影响与晚年认知能力下降有关，并且可能是可改变的。如果存在因果关系，对这些风险因素的干预将有实质性的好处。拟议的工作将探索暴露于两种常见的环境污染物——铅和交通相关的空气污染——是否与认知能力下降有关。随着时间的推移，铅与认知测试表现变化之间的关系将通过护士健康研究（NHS）参与者的一个子集进行评估，这是一个社区居住的老年妇女队列。广义估计方程将用于评估是否随着时间的推移，较高水平的铅生物标志物与认知测试表现的变化负相关。此外，与绝经相关的骨密度将先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。为了评估近期接触铅（包括绝经期相关铅的重新引入）是否与绝经后妇女认知功能的更大下降有关，将在一组血铅测量反映这一关键时期接触铅的妇女中评估血铅水平与认知能力变化之间的关系。评估交通相关的空气污染与认知测试表现之间的关系将在规范老龄化研究（NAS）的一部分参与者中进行，这是一组老年男性。混合模型将用于评估高水平的黑碳暴露（使用经过验证的时空土地利用回归模型估算）是否会对认知能力的水平或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状况的潜在生物学过程。

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. )