Air pollution and noise exposures in relation to dementia: from brain imaging markers to clinical disease

项目摘要 越来越多的证据表明，暴露于空气污染可能会导致认知功能受损， 阿尔茨海默病和相关痴呆症（ADRD）的风险增加。较新、较稀疏的证据 暗示这些结果也可能受到环境噪声的影响。如果这些环境暴露 恶化老年人的认知能力，它们将是少数几个普遍存在的认知能力丧失的危险因素之一， 大规模改造，造福全体人民。尽管对公共卫生有重大影响， 我们对空气污染和噪音如何影响神经认知老化的认识存在严重局限性。大多数研究 这些与ADRD相关的暴露依赖于医疗或卫生管理记录， 关于痴呆状态的数据非常不可靠。这两种暴露都会增加心血管风险。如果医疗保健使用 因为这些条件使痴呆症患者更有可能被诊断出来，然后使用医疗记录， 估计空气污染和噪声与ADRD风险的关系可能会高估这些关联。一 第二个限制是，这些暴露促进认知退化的机制是 虽然脑血管通路已被提出，但尚不清楚。最后，空气污染和环境噪音往往 同时发生，但很少有研究能够确定这些暴露是否会放大彼此的影响。到 为了克服这些局限性和知识空白，我们建议调查空气污染的影响， 噪声暴露对认知能力下降和ADRD的影响，并使用脑MRI测量来评估这些影响。 暴露对脑血管损伤和神经元死亡的影响。我们利用两大种族， 不同人群为基础的老年人队列研究，芝加哥健康和老龄化项目（CDC）和 亲子弹性和认知健康（PORCH）研究。我们将整合来自队列的数据 认知能力下降、ADRD和脑部MRI的参与者，以及对他们长期暴露于噪声的估计 与梅萨Air和配套项目的持续合作产生的交通和空气污染。我们 将重点关注与交通有关的空气污染（TRAP），因为交通仍然是最普遍的污染源之一。 空气污染暴露。这项工作通过以下方式扩展了我们正在进行的研究： 脑血管损伤;评估TRAP的其他成分，包括制动释放的金属， 轮胎磨损;并评估陷阱和噪音的组合影响。我们的首要假设是 TRAP和噪声暴露加速认知能力下降，增加ADRD风险，并促进脑血管疾病 缺血和脑萎缩。我们进一步假设，陷阱和噪音暴露共同影响这些 结果，超出了他们与这些结果的个别联系所预期的。 环境污染物的减少已经有益于人民的健康。从这个数据 项目可能提供动力-减少ADRD人口负担的前景-进一步减少 并确定空气污染和噪音作为ADRD预防的人群水平策略的目标。

PROJECT ABSTRACT Burgeoning evidence suggests that exposure to air pollution may result in impaired cognitive function, cognitive decline, and increased risk of Alzheimer's disease and related dementias (ADRD). Newer, sparser evidence hints that these outcomes could also be influenced by ambient noise. If these environmental exposures do worsen cognition in older adults, they would be among the few pervasive risk factors for cognitive loss that can be modified on broad scale to benefit entire populations. Despite major implications for public health, there are critical limitations in our knowledge of how air pollution and noise affect neurocognitive aging. Most studies of these exposures in relation to ADRD have relied on medical or health administrative records, which provide strikingly unreliable data on dementia status. Both exposures increase cardiovascular risk. If health care use for these conditions makes it more likely that a person with dementia is diagnosed, then using medical records to estimate of the relation of air pollution and noise to ADRD risk could overestimate these associations. A second limitation is that the mechanisms by which these exposures promote cognitive deterioration are unclear, although cerebrovascular pathways have been proposed. Finally, air pollution and ambient noise often co-occur, yet few studies have been able to determine if these exposures amplify each other's effects. To overcome these limitations and knowledge gaps, we propose to investigate the effects of air pollution and noise exposure on cognitive decline and ADRD and, using brain MRI measurements, to evaluate these exposures' influence on cerebrovascular injury and neuronal death. We take advantage of 2 large, racially diverse population-based cohort studies of older adults, the Chicago Health and Aging Project (CHAP) and the Parent Offspring Resilience and Cognitive Health (PORCH) study. We will integrate data from cohort participants on cognitive decline, ADRD, and brain MRI with estimates of their long-term exposures to noise and air pollution from traffic, generated in ongoing collaboration with the MESA Air and ancillary projects. We will focus on traffic-related air pollution (TRAP), because traffic remains one of the most pervasive sources of air pollution exposure. This work extends our ongoing research by: investigating brain MRI measures of cerebrovascular injury; evaluating other constituents of TRAP, including the metals released from brake and tire wear; and evaluating the effects of TRAP and noise in combination. Our overarching hypothesis is that TRAP and noise exposures hasten cognitive decline, increase ADRD risk, and promote cerebrovascular ischemia and brain atrophy. We further hypothesize that TRAP and noise exposure together influence these outcomes, above and beyond what would be expected from their individual associations with these outcomes. Reductions in environmental pollutants have already benefited the population's health. The data from this project may provide impetus—the prospect of reducing the population burden of ADRD—for further reductions and identify both air pollution and noise as targets for population-level strategies for ADRD prevention.