Hemochromatosis Mutations, Brain Iron Imaging, and Dementia in the UK Biobank Cohort.
Hemochromatosis Mutations, Brain Iron Imaging, and Dementia in the UK Biobank Cohort.
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DOI：
10.3233/jad-201080
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Melzer D
中科院分区：
文献类型：
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作者：
Atkins JL;Pilling LC;Heales CJ;Savage S;Kuo CL;Kuchel GA;Steffens DC;Melzer D
脑铁沉积发生在痴呆症。在欧洲血统人群中，HFE p.C282Y变异体可导致铁过载和血色素沉着症，主要发生在纯合子男性中。 在一个大型社区队列中，评估p.C282Y与脑MRI特征以及随访期间发生的痴呆诊断的相关性。 有随访住院记录（平均10.5年）的英国生物样本库参与者。206例p.C282Y纯合子与23，349例无变异体的MRI，包括T2* 测量（较低的值表明更多的铁）。 欧洲血统的参与者包括2,890个p.C282Y纯合子。男性p.C282Y纯合子有较低的T2* 措施，包括壳核，丘脑和海马，相比没有HFE突变。痴呆事件在p.C282Y纯合子男性中更常见（风险比HR = 1.83; 95% CI 1.23至2.72，p = 0.003），谵妄也是如此。 在纯合子女性和杂合子女性中没有相关性。 需要研究早期铁减少是否预防或减缓男性HFE p.C282Y纯合子的相关脑病理。
Brain iron deposition occurs in dementia. In European ancestry populations, the HFE p.C282Y variant can cause iron overload and hemochromatosis, mostly in homozygous males. To estimate p.C282Y associations with brain MRI features plus incident dementia diagnoses during follow-up in a large community cohort. UK Biobank participants with follow-up hospitalization records (mean 10.5 years). MRI in 206 p.C282Y homozygotes versus 23,349 without variants, including T2* measures (lower values indicating more iron). European ancestry participants included 2,890 p.C282Y homozygotes. Male p.C282Y homozygotes had lower T2* measures in areas including the putamen, thalamus, and hippocampus, compared to no HFE mutations. Incident dementia was more common in p.C282Y homozygous men (Hazard Ratio HR = 1.83; 95% CI 1.23 to 2.72, p = 0.003), as was delirium. There were no associations in homozygote women or in heterozygotes. Studies are needed of whether early iron reduction prevents or slows related brain pathologies in male HFE p.C282Y homozygotes.