Wang Xinhui, Salminen Lauren E, Petkus Andrew J, Driscoll Ira, Millstein Joshua, Beavers Daniel P, Espeland Mark A, Erus Guray, Braskie Meredith N, Thompson Paul M, Gatz Margaret, Chui Helena C, Resnick Susan M, Kaufman Joel D, Rapp Stephen R, Shumaker Sally, Brown Mark, Younan Diana, Chen Jiu-Chiuan
Department of Neurology, University of Southern California, Los Angeles, California.
Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Los Angeles, California.
medRxiv. 2023 Nov 29:2023.11.28.23298708. doi: 10.1101/2023.11.28.23298708.
Ambient air pollution exposures increase risk for Alzheimer's disease (AD) and related dementias, possibly due to structural changes in the medial temporal lobe (MTL). However, existing MRI studies examining exposure effects on the MTL were cross-sectional and focused on the hippocampus, yielding mixed results.
To determine whether air pollution exposures were associated with MTL atrophy over time, we conducted a longitudinal study including 653 cognitively unimpaired community-dwelling older women from the Women's Health Initiative Memory Study with two MRI brain scans (MRI-1: 2005-6; MRI-2: 2009-10; M at MRI-1=77.3±3.5years). Using regionalized universal kriging models, exposures at residential locations were estimated as 3-year annual averages of fine particulate matter (PM) and nitrogen dioxide (NO) prior to MRI-1. Bilateral gray matter volumes of the hippocampus, amygdala, parahippocampal gyrus (PHG), and entorhinal cortex (ERC) were summed to operationalize the MTL. We used linear regressions to estimate exposure effects on 5-year volume changes in the MTL and its subregions, adjusting for intracranial volume, sociodemographic, lifestyle, and clinical characteristics.
On average, MTL volume decreased by 0.53±1.00cm over 5 years. For each interquartile increase of PM (3.26μg/m) and NO (6.77ppb), adjusted MTL volume had greater shrinkage by 0.32cm (95%CI=[-0.43, -0.21]) and 0.12cm (95%CI=[-0.22, -0.01]), respectively. The exposure effects did not differ by ε4 genotype, sociodemographic, and cardiovascular risk factors, and remained among women with low-level PM exposure. Greater PHG atrophy was associated with higher PM (b=-0.24, 95%CI=[-0.29, -0.19]) and NO exposures (b=-0.09, 95%CI=[-0.14, -0.04]). Higher exposure to PM but not NO was also associated with greater ERC atrophy. Exposures were not associated with amygdala or hippocampal atrophy.
In summary, higher late-life PM and NO exposures were associated with greater MTL atrophy over time in cognitively unimpaired older women. The PHG and ERC - the MTL cortical subregions where AD neuropathologies likely begin, may be preferentially vulnerable to air pollution neurotoxicity.
环境空气污染暴露会增加患阿尔茨海默病(AD)及相关痴呆症的风险,这可能是由于内侧颞叶(MTL)的结构变化所致。然而,现有的关于空气污染对MTL影响的MRI研究均为横断面研究,且主要聚焦于海马体,结果不一。
为了确定空气污染暴露是否与MTL随时间的萎缩有关,我们开展了一项纵向研究,纳入了653名来自女性健康倡议记忆研究的认知功能未受损的社区老年女性,她们接受了两次脑部MRI扫描(MRI - 1:2005 - 2006年;MRI - 2:2009 - 2010年;MRI - 1时的平均年龄M = 77.3±3.5岁)。使用区域化通用克里金模型,将居住地点的暴露估计为MRI - 1之前3年的细颗粒物(PM)和二氧化氮(NO)年均值。将海马体、杏仁核、海马旁回(PHG)和内嗅皮质(ERC)的双侧灰质体积相加,以得出MTL的指标。我们使用线性回归来估计空气污染暴露对MTL及其亚区域5年体积变化的影响,并对颅内体积、社会人口统计学、生活方式和临床特征进行了调整。
平均而言,MTL体积在5年内减少了0.53±1.00cm³。PM(3.26μg/m³)和NO(6.77ppb)每增加一个四分位间距,调整后的MTL体积分别多收缩0.32cm³(95%置信区间=[-0.43, -0.21])和0.12cm³(95%置信区间=[-0.22, -0.01])。暴露的影响在ε4基因型、社会人口统计学和心血管危险因素方面没有差异,并且在低水平PM暴露的女性中仍然存在。更大程度的PHG萎缩与更高的PM(b=-0.24,95%置信区间=[-0.29, -0.19])和NO暴露(b=-0.09,95%置信区间=[-0.14, -0.04])相关。更高的PM暴露(而非NO暴露)也与更大程度的ERC萎缩相关。暴露与杏仁核或海马体萎缩无关。
总之,在认知功能未受损的老年女性中,较高的晚年PM和NO暴露与随时间推移更大程度的MTL萎缩有关。PHG和ERC - AD神经病理学可能起始的MTL皮质亚区域,可能特别容易受到空气污染神经毒性的影响。