University of Southern California, 2001 N Soto St, Los Angeles, CA, USA.
University of California at Riverside, 900 University Ave, Riverside, CA, USA.
Brain. 2020 Jan 1;143(1):289-302. doi: 10.1093/brain/awz348.
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.
有证据表明，暴露于空气动力学直径<2.5μm 的颗粒物（PM2.5）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学过程尚不清楚。在临床前阿尔茨海默病中，可以检测到情景记忆的早期下降。因此，我们进行了一项纵向研究，以检验 PM2.5 是否会影响情景记忆的下降，并探讨了与暴露相关的阿尔茨海默病相关神经解剖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；年龄 73-87 岁），每年（1999-2010 年）通过加利福尼亚词语学习测试评估情景记忆，包括即时自由回忆/新学习（List A 试验 1-3；List B）和延迟自由回忆（短延迟和长延迟）的测量，以及最多两次脑部扫描（MRI-1：2005-06 年；MRI-2：2009-10 年）。根据居住史和有关空气质量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 前 3 年的 PM2.5 平均暴露量。在多层次结构方程模型中，PM2.5 与即时回忆和新学习的下降幅度更大相关，但与延迟回忆或综合分数的下降无关。对于每增加一个四分位距（2.81μg/m3）的 PM2.5，调整多个潜在混杂因素后，每年的下降速度显著加快了 19.3%（95%置信区间[CI]：1.9%至 36.2%），List B 成绩的下降速度加快了 14.8%（4.4%至 24.9%）。长期 PM2.5 暴露与阿尔茨海默病模式相似性评分的增加有关，这占试验 1-3 和 List B 中 PM2.5 总不利影响的 22.6%（95%CI：1%至 68.9%）和 10.7%（95%CI：1.0%至 30.3%）。在随访期间排除痴呆症和中风的发病病例后，或进一步调整小血管缺血性疾病体积后，观察到的相关性仍然存在。我们的研究结果说明了 PM2.5 神经毒性的连续性，它导致了临床前阶段即时自由回忆/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，而与脑血管损伤无关。
