%0 Journal Article %J J Alzheimers Dis %D 2021 %T Hemochromatosis Mutations, Brain Iron Imaging, and Dementia in the UK Biobank Cohort. %A Atkins, Janice L %A Pilling, Luke C %A Heales, Christine J %A Savage, Sharon %A Kuo, Chia-Ling %A Kuchel, George A %A Steffens, David C %A Melzer, David %X

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 estimated 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.

%B J Alzheimers Dis %V 79 %P 1203-1211 %8 2021 Feb 2 %G eng %N 3 %R 10.3233/JAD-201080