Environmental Determinants of Cognitive Function and Decline in Older Adults

描述（由申请人提供）：认知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迟认知能力下降。广泛存在的环境污染物可能通过神经毒性效应或对心血管健康的不利影响而与晚年认知能力下降有关，并且可能是可以改变的。如果存在因果关系，对这些风险因素进行干预将带来巨大益处。这项拟议中的工作将探讨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。将使用护士健康研究（NHS）（一个社区居住老年妇女队列）中的一部分参与者对铅与认知测试表现随时间变化之间的关系进行评价。将使用广义估计方程评价较高水平的铅生物标志物是否与认知测试表现随时间的变化存在不良相关性。此外，与绝经期相关的骨矿物质密度会将先前储存在骨骼中的铅释放到体循环中，并可能增加妇女对既往铅暴露不良影响的脆弱性。为了评价近期铅暴露（包括与绝经相关的铅再引入）是否与绝经后女性认知功能的更大下降相关，将在血铅测量反映这一关键时期暴露的女性亚组中评估血铅水平与认知能力随时间变化之间的关系。交通相关的空气污染和认知测试性能之间的关系的评估将在规范老化研究（NAS）的参与者的子集，一个队列的老年男性。将使用混合模型来评估使用经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认知表现的水平或变化产生不利影响。了解这些暴露对认知功能的作用可能会建议有益的干预措施，并有助于阐明这种有害条件的潜在生物学过程。 公共卫生相关性：识别和干预老年人认知能力下降的可改变的风险因素预计将有显着的好处。如果暴露于铅或空气污染与认知能力下降有关，那么减少暴露的干预措施，包括增加骨骼健康或调节污染物将是有益的。此外，认知能力下降的危险因素的识别可能提供有价值的洞察认知能力下降的启动和进展的基础生物学机制和相关的疾病状态的痴呆症。)

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. )