Department of Psychology and Neuroscience, Duke University, Durham, NC, USA; Department of Psychiatry & Behavioral Medicine, Medical University of South Carolina, Charleston, SC, USA.
Department of Psychology and Neuroscience, Duke University, Durham, NC, USA.
Ecotoxicol Environ Saf. 2024 Aug;281:116658. doi: 10.1016/j.ecoenv.2024.116658. Epub 2024 Jun 28.
Millions of adults and children are exposed to high levels of lead, a neurotoxicant, each year. Recent evidence suggests that lead exposure may precipitate neurodegeneration, particularly if the exposure occurs early or late in life, with unique alterations to the structure or function of specific subfields of the hippocampus, a region involved in memory and Alzheimer's disease. It has been proposed that specific hippocampal subfields may thus be useful biomarkers for lead-associated neurological disease. We turned to a population-representative New Zealand birth cohort where the extent of lead exposure was not confounded by social class (the Dunedin Study; born 1972-1973 and followed to age 45) to test the hypothesis that early life lead exposure (blood-lead level at age 11 years) is associated with smaller MRI-assessed gray matter volumes of specific subfields of the hippocampus at age 45 years. Among the 508 Dunedin Study members with childhood lead data and adult MRI data passing quality control (93.9 % of those with lead data who attended the age-45 assessment wave, 240[47.2 %] female), childhood blood-lead levels ranged from 4 to 31 µg/dL (M[SD]=10.9[4.6]). Total hippocampal volumes were lower among adults with higher childhood blood-lead levels (b=-102.6 mm per 5 ug/dL-unit greater blood-lead level, 95 %CI: -175.4 to -29.7, p=.006, β=-.11), as were all volumes of the 24 hemisphere-specific subfields of the hippocampus. Of these 24 subfields, 20 demonstrated negative lead-associations greater than β=-.05 in size, 14 were statistically significant after adjustment for multiple comparisons (p<.05), and 9 remained significant after adjustment for potential confounders and multiple comparisons. Children exposed to lead demonstrate smaller volumes across all subfields of the hippocampus in midlife. The hypothesis that lead selectively impairs specific subfields of the hippocampus, or that specific subfields may be markers for lead-associated neurological disease, requires further evaluation.
每年都有数百万人接触到高水平的铅，这是一种神经毒素。最近的证据表明，铅暴露可能会引发神经退行性变，特别是如果暴露发生在生命早期或晚期，并且海马体的特定亚区的结构或功能发生了独特的改变，海马体是一个与记忆和阿尔茨海默病有关的区域。有人提出，特定的海马体亚区可能是铅相关神经疾病的有用生物标志物。我们转向一个具有代表性的新西兰出生队列，其中铅暴露的程度不受社会阶层的影响（达尼丁研究；1972-1973 年出生，随访至 45 岁），以检验假设，即生命早期的铅暴露（11 岁时的血铅水平）与 45 岁时特定海马体亚区的 MRI 评估灰质体积较小有关。在有儿童铅数据和成人 MRI 数据通过质量控制的 508 名达尼丁研究成员中（参加 45 岁评估波的有铅数据者的 93.9%，240[47.2%]为女性），儿童血铅水平范围为 4 至 31µg/dL（M[SD]=10.9[4.6]）。在儿童血铅水平较高的成年人中，总海马体体积较低（每增加 5µg/dL 血铅水平，b=-102.6mm，95%CI：-175.4 至-29.7，p=.006，β=-.11），24 个半球特异性海马体亚区的所有体积也较低。在这 24 个亚区中，有 20 个亚区的铅关联呈负相关，大小大于β=-.05，14 个在进行多次比较调整后具有统计学意义（p<.05），9 个在进行潜在混杂因素和多次比较调整后仍然具有统计学意义。暴露于铅的儿童在中年时表现出所有海马体亚区的体积较小。铅选择性损害海马体特定亚区的假设，或特定亚区可能是铅相关神经疾病的标志物，需要进一步评估。
