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儿童时期铅暴露与中年脑结构完整性MRI测量值的相关性
作者:小柯机器人 发布时间:2020/11/19 11:17:21

美国杜克大学Terrie E. Moffitt团队研究了儿童时期铅暴露与中年脑结构完整性MRI测量值的相关性。2020年11月17日,《美国医学会杂志》发表了该研究。

儿童时期接触铅与大脑发育受阻有关,但对大脑结构完整性的长期影响尚不清楚。

为了检验儿童时期接触铅与中年时磁共振成像(MRI)检测大脑结构完整性较低相关的假设,研究组追踪了新西兰的一个具有人口代表性的1972-1973年出生队列,共564人,随访至45岁。主要结局为通过MRI来评估参与者45岁时结构性大脑的完整性:灰质、白质、脑年龄差距估算。通过Wechsler成人智力量表IV客观评估参与者45岁时的认知功能。

在1037位初始参与者中,997位在45岁时仍存活,其中564位(57%)在11岁时接受了血铅检测(54%为男性),中位随访时间为34年。11岁时的平均血铅水平为10.99 μg/dL。校正协变量后,儿童血铅水平每升高5 μg/dL,在45岁时大脑皮层表面积减小1.19 cm2,海马体积缩小0.10 cm3,整体分数各向异性降低,脑龄指数衰老0.77岁。血铅水平和经对数转换的白质高血容量或平均皮层厚度之间无统计学关联。儿童血铅水平每升高5 μg/dL,45岁时的智商得分就降低2.07点,但知情者评估的认知问题得分提高0.12点。儿童血铅水平与自我报告的认知问题之间无统计学关联。

研究结果表明,较高的儿童血铅水平与脑结构的某些MRI测量值的差异相关,即中年时脑结构完整性较低。

附:英文原文

Title: Association of Childhood Lead Exposure With MRI Measurements of Structural Brain Integrity in Midlife

Author: Aaron Reuben, Maxwell L. Elliott, Wickliffe C. Abraham, Jonathan Broadbent, Renate M. Houts, David Ireland, Annchen R. Knodt, Richie Poulton, Sandhya Ramrakha, Ahmad R. Hariri, Avshalom Caspi, Terrie E. Moffitt

Issue&Volume: 2020/11/17

Abstract:

Importance  Childhood lead exposure has been linked to disrupted brain development, but long-term consequences for structural brain integrity are unknown.

Objective  To test the hypothesis that childhood lead exposure is associated with magnetic resonance imaging (MRI) measurements of lower structural integrity of the brain in midlife.

Design, Setting, and Participants  The Dunedin Study followed a population-representative 1972-1973 birth cohort in New Zealand (N=564 analytic sample) to age 45 years (until April 2019).

Exposures  Childhood blood lead levels measured at age 11 years.

Main Outcomes and Measures  Structural brain integrity at age 45 years assessed via MRI (primary outcomes): gray matter (cortical thickness, surface area, hippocampal volume), white matter (white matter hyperintensities, fractional anisotropy [theoretical range, 0 {diffusion is perfectly isotropic} to 100 {diffusion is perfectly anisotropic}]), and the Brain Age Gap Estimation (BrainAGE), a composite index of the gap between chronological age and a machine learning algorithm–estimated brain age (0 indicates a brain age equivalent to chronological age; positive and negative values represent an older and younger brain age, respectively). Cognitive function at age 45 years was assessed objectively via the Wechsler Adult Intelligence Scale IV (IQ range, 40-160, standardized to a mean of 100 [SD, 15]) and subjectively via informant and self-reports (z-score units; scale mean, 0 [SD, 1]).

Results  Of 1037 original participants, 997 were alive at age 45 years, of whom 564 (57%) had received lead testing at age 11 years (302 [54%] male) (median follow-up, 34 [interquartile range, 33.7-34.7] years). Mean blood lead level at age 11 years was 10.99 (SD, 4.63) μg/dL. After adjusting for covariates, each 5-μg/dL higher childhood blood lead level was significantly associated with 1.19-cm2 smaller cortical surface area (95% CI, 2.35 to 0.02 cm2; P=.05), 0.10-cm3 smaller hippocampal volume (95% CI, 0.17 to 0.03 cm3; P=.006), lower global fractional anisotropy (b=0.12; 95% CI, 0.24 to 0.01; P=.04), and a BrainAGE index 0.77 years older (95% CI, 0.02-1.51 years; P=.05) at age 45 years. There were no statistically significant associations between blood lead level and log-transformed white matter hyperintensity volume (b=0.05 log mm3; 95% CI, 0.02 to 0.13 log mm3; P=.17) or mean cortical thickness (b=0.004 mm; 95% CI, 0.012 to 0.004 mm; P=.39). Each 5-μg/dL higher childhood blood lead level was significantly associated with a 2.07-point lower IQ score at age 45 years (95% CI, 3.39 to 0.74; P=.002) and a 0.12-point higher score on informant-rated cognitive problems (95% CI, 0.01-0.23; P=.03). There was no statistically significant association between childhood blood lead levels and self-reported cognitive problems (b=0.02 points; 95% CI, 0.10 to 0.07; P=.68).

Conclusions and Relevance  In this longitudinal cohort study with a median 34-year follow-up, higher childhood blood lead level was associated with differences in some MRI measures of brain structure that suggested lower structural brain integrity in midlife. Because of the large number of statistical comparisons, some findings may represent type I error.

DOI: 10.1001/jama.2020.19998

Source: https://jamanetwork.com/journals/jama/article-abstract/2772961

期刊信息

JAMA-Journal of The American Medical Association:《美国医学会杂志》,创刊于1883年。隶属于美国医学协会,最新IF:51.273
官方网址:https://jamanetwork.com/
投稿链接:http://manuscripts.jama.com/cgi-bin/main.plex