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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由阿尔茨海默病的早期神经解剖生物标志物介导的颗粒物和情景记忆衰退。

有证据表明，接触空气动力学直径小于 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然未知。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，以检查 PM2.5 是否影响情景记忆力下降，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。参与者包括年龄较大的女性（n = 998；年龄在 73-87 岁之间），他们参加了认知老化的女性健康倡议研究和磁共振成像的女性健康倡议记忆研究，加州语言学习测试每年（1999-2010）情景记忆评估，包括立即自由回忆/新学习（清单 A 试验 1-3；清单 B）和延迟自由回忆（短期和长期延迟）的措施，以及最多两次脑部扫描（MRI-1：2005-06；MRI-2：2009-10）。受试者被分配了阿尔茨海默氏病模式相似性分数（大脑 MRI 测量阿尔茨海默氏病的神经解剖学风险），该分数由监督机器学习开发并使用阿尔茨海默氏病神经影像学倡议的数据进行验证。基于空气监测和模拟大气化学的居住历史和环境数据，我们使用时空模型来估计 MRI-1 之前的 3 年平均 PM2.5 暴露。在多级结构方程模型中，PM2. 5 与即时回忆和新学习的更大下降有关，但与延迟回忆或综合分数的下降没有关联。对于 PM2.5 的每个四分位数增量 (2.81 μg/m3)，试验 1-3 和 14.8% (4.4 % 至 24.9%）的 List B 性能，针对多个潜在混杂因素进行调整。长期 PM2.5 暴露与阿尔茨海默病模式相似性评分增加相关，分别占总数的 22.6%（95% CI：1% 至 68.9%）和 10.7%（95% CI：1.0% 至 30.3%）分别对试验 1-3 和清单 B 产生不利的 PM2.5 影响。在排除随访期间发生的痴呆症和中风病例后，观察到的关联仍然存在，或进一步调整小血管缺血性疾病体积。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。