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儿童期铅暴露与成人神经退行性疾病。

Childhood Lead Exposure and Adult Neurodegenerative Disease.

机构信息

Department of Psychology and Neuroscience, Duke University, Durham, NC, USA.

出版信息

J Alzheimers Dis. 2018;64(1):17-42. doi: 10.3233/JAD-180267.

Abstract

Millions of Americans now entering midlife and old age were exposed to high levels of lead, a neurotoxin, as children. Evidence from animal-model and human observational studies suggest that childhood lead exposure may raise the risk of adult neurodegenerative disease, particularly dementia, through a variety of possible mechanisms including epigenetic modification, delayed cardiovascular and kidney disease, direct degenerative CNS injury from lead remobilized from bone, and lowered neural and cognitive reserve. Within the next ten years, the generation of children with the highest historical lead exposures, those born in the 1960s, 1970s, and 1980s, will begin to enter the age at which dementia symptoms tend to emerge. Many will also enter the age in which lead stored in the skeleton may be remobilized at greater rates, particularly for women entering menopause and men and women experiencing osteoporosis. Should childhood lead exposure prove pro-degenerative, the next twenty years will provide the last opportunities for possible early intervention to forestall greater degenerative disease burden across the aging lead-exposed population. More evidence is needed now to characterize the nature and magnitude of the degenerative risks facing adults exposed to lead as children and to identify interventions to limit long-term harm.

摘要

现在,数以百万计的美国中年人甚至老年人在儿童时期都曾接触过高水平的神经毒素——铅。动物模型和人类观察性研究的证据表明,儿童期铅暴露可能通过多种可能的机制增加成人神经退行性疾病的风险,尤其是痴呆症,这些机制包括表观遗传修饰、心血管和肾脏疾病的延迟发生、从骨骼中重新动员的铅对中枢神经系统的直接退行性损伤,以及神经和认知储备的降低。在未来十年内,那些在 20 世纪 60 年代、70 年代和 80 年代出生的,曾受到历史上最高水平铅暴露的一代人,将开始进入痴呆症症状开始出现的年龄。许多人也将进入骨骼中储存的铅可能以更高速度重新动员的年龄,尤其是对于进入更年期的女性以及患有骨质疏松症的男性和女性。如果儿童时期的铅暴露确实会导致退行性病变,那么未来二十年将是可能进行早期干预以防止暴露于铅的老年人群体中退行性疾病负担增加的最后机会。现在需要更多的证据来描述儿童时期接触铅的成年人面临的退行性风险的性质和程度,并确定限制长期危害的干预措施。

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