Evidence suggests exposure to particulate matter with aerodynamic diameter <2.5 μm (PM2.5) may increase the risk for Alzheimer's disease and related dementias. Whether PM2.5 alters brain structure and accelerates the preclinical neuropsychological processes remains unknown. Early decline of episodic memory is detectable in preclinical Alzheimer's disease. Therefore, we conducted a longitudinal study to examine whether PM2.5 affects the episodic memory decline, and also explored the potential mediating role of increased neuroanatomic risk of Alzheimer's disease associated with exposure. Participants included older females (n = 998; aged 73-87) enrolled in both the Women's Health Initiative Study of Cognitive Aging and the Women's Health Initiative Memory Study of Magnetic Resonance Imaging, with annual (1999-2010) episodic memory assessment by the California Verbal Learning Test, including measures of immediate free recall/new learning (List A Trials 1-3; List B) and delayed free recall (short- and long-delay), and up to two brain scans (MRI-1: 2005-06; MRI-2: 2009-10). Subjects were assigned Alzheimer's disease pattern similarity scores (a brain-MRI measured neuroanatomical risk for Alzheimer's disease), developed by supervised machine learning and validated with data from the Alzheimer's Disease Neuroimaging Initiative. Based on residential histories and environmental data on air monitoring and simulated atmospheric chemistry, we used a spatiotemporal model to estimate 3-year average PM2.5 exposure preceding MRI-1. In multilevel structural equation models, PM2.5 was associated with greater declines in immediate recall and new learning, but no association was found with decline in delayed-recall or composite scores. For each interquartile increment (2.81 μg/m3) of PM2.5, the annual decline rate was significantly accelerated by 19.3% [95% confidence interval (CI) = 1.9% to 36.2%] for Trials 1-3 and 14.8% (4.4% to 24.9%) for List B performance, adjusting for multiple potential confounders. Long-term PM2.5 exposure was associated with increased Alzheimer's disease pattern similarity scores, which accounted for 22.6% (95% CI: 1% to 68.9%) and 10.7% (95% CI: 1.0% to 30.3%) of the total adverse PM2.5 effects on Trials 1-3 and List B, respectively. The observed associations remained after excluding incident cases of dementia and stroke during the follow-up, or further adjusting for small-vessel ischaemic disease volumes. Our findings illustrate the continuum of PM2.5 neurotoxicity that contributes to early decline of immediate free recall/new learning at the preclinical stage, which is mediated by progressive atrophy of grey matter indicative of increased Alzheimer's disease risk, independent of cerebrovascular damage.

中文翻译：

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阿尔茨海默病的早期神经解剖生物标志物介导的颗粒物质和情景记忆衰退。


有证据表明，接触空气动力学直径为 <2.5 μm (PM2.5) 的颗粒物可能会增加患阿尔茨海默病和相关痴呆症的风险。 PM2.5 是否会改变大脑结构并加速临床前神经心理过程仍不清楚。在临床前阿尔茨海默病中可以检测到情景记忆的早期衰退。因此，我们进行了一项纵向研究来检验PM2.5是否影响情景记忆衰退，并探讨了与暴露相关的阿尔茨海默病神经解剖学风险增加的潜在中介作用。参与者包括参加妇女健康倡议认知老化研究和妇女健康倡议磁共振成像记忆研究的老年女性（n = 998；73-87 岁），并由加州每年（1999-2010 年）进行情景记忆评估言语学习测试，包括立即自由回忆/新学习的测量（列表 A 试验 1-3；列表 B）和延迟自由回忆（短延迟和长延迟），以及最多两次脑部扫描（MRI-1：2005- 06；MRI-2：2009-10）。受试者被分配阿尔茨海默病模式相似性评分（脑部核磁共振成像测量阿尔茨海默病的神经解剖学风险），该评分由监督机器学习开发，并使用阿尔茨海默病神经影像计划的数据进行验证。根据居住历史、空气监测和模拟大气化学的环境数据，我们使用时空模型来估计 MRI-1 之前的 3 年平均 PM2.5 暴露量。在多级结构方程模型中，PM2.5 与即时回忆和新学习的较大下降相关，但未发现与延迟回忆或综合分数的下降存在关联。对于 PM2.5 的每个四分位增量 (2.81 µg/m3)。如图 5 所示，试验 1-3 的年下降率显着加快了 19.3% [95% 置信区间 (CI) = 1.9% 至 36.2%]，列表 B 的年下降率显着加快了 14.8%（4.4% 至 24.9%），调整了倍数潜在的混杂因素。长期接触 PM2.5 与阿尔茨海默病模式相似性评分增加相关，占总数的 22.6%（95% CI：1% 至 68.9%）和 10.7%（95% CI：1.0% 至 30.3%） PM2.5 分别对试验 1-3 和列表 B 产生不利影响。在排除随访期间发生的痴呆和中风病例或进一步调整小血管缺血性疾病体积后，观察到的关联仍然存在。我们的研究结果说明了 PM2.5 神经毒性的连续性，导致临床前阶段立即自由回忆/新学习的早期下降，这是由灰质进行性萎缩介导的，表明阿尔茨海默病风险增加，与脑血管损伤无关。