Hemochromatosis Mutations, Brain Iron Imaging, and Dementia in the UK Biobank Cohort.

Journal Article (Journal Article)

BACKGROUND: 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. OBJECTIVE: To estimate p.C282Y associations with brain MRI features plus incident dementia diagnoses during follow-up in a large community cohort. METHODS: 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). RESULTS: 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. CONCLUSION: Studies are needed of whether early iron reduction prevents or slows related brain pathologies in male HFE p.C282Y homozygotes.

Full Text

Duke Authors

Cited Authors

  • Atkins, JL; Pilling, LC; Heales, CJ; Savage, S; Kuo, C-L; Kuchel, GA; Steffens, DC; Melzer, D

Published Date

  • 2021

Published In

Volume / Issue

  • 79 / 3

Start / End Page

  • 1203 - 1211

PubMed ID

  • 33427739

Pubmed Central ID

  • PMC7990419

Electronic International Standard Serial Number (EISSN)

  • 1875-8908

Digital Object Identifier (DOI)

  • 10.3233/JAD-201080


  • eng

Conference Location

  • Netherlands