兒童時期鉛暴露與中年腦結構完整性MRI測量值的相關性
作者：
小柯機器人發布時間：2020/11/19 11:17:21
美國杜克大學Terrie E. Moffitt團隊研究了兒童時期鉛暴露與中年腦結構完整性MRI測量值的相關性。2020年11月17日，《美國醫學會雜誌》發表了該研究。
兒童時期接觸鉛與大腦發育受阻有關，但對大腦結構完整性的長期影響尚不清楚。
為了檢驗兒童時期接觸鉛與中年時磁共振成像（MRI）檢測大腦結構完整性較低相關的假設，研究組追蹤了紐西蘭的一個具有人口代表性的1972-1973年出生隊列，共564人，隨訪至45歲。主要結局為通過MRI來評估參與者45歲時結構性大腦的完整性：灰質、白質、腦年齡差距估算。通過Wechsler成人智力量表IV客觀評估參與者45歲時的認知功能。
在1037位初始參與者中，997位在45歲時仍存活，其中564位（57％）在11歲時接受了血鉛檢測（54％為男性），中位隨訪時間為34年。11歲時的平均血鉛水平為10.99 μg/dL。校正協變量後，兒童血鉛水平每升高5 μg/dL，在45歲時大腦皮層表面積減小1.19 cm2，海馬體積縮小0.10 cm3，整體分數各向異性降低，腦齡指數衰老0.77歲。血鉛水平和經對數轉換的白質高血容量或平均皮層厚度之間無統計學關聯。兒童血鉛水平每升高5 μg/dL，45歲時的智商得分就降低2.07點，但知情者評估的認知問題得分提高0.12點。兒童血鉛水平與自我報告的認知問題之間無統計學關聯。
研究結果表明，較高的兒童血鉛水平與腦結構的某些MRI測量值的差異相關，即中年時腦結構完整性較低。
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