Sex-Specific Associations of Dietary Iron Intake with Brain Iron Deposition on Imaging and Incident Dementia: A Prospective Cohort Study.

Abstract

The study aimed to evaluate the association of dietary iron intake with incident dementia and brain iron deposition. We included dementia-free participants from the UK Biobank who completed at least one 24-hour dietary recall at study baseline (2009-2012) and were followed up to 2021. Incident dementia was determined through linkage to medical records and death registries. Brain MRI was conducted in a subgroup of participants since 2014, with T2* measurements being used as indicators of brain iron deposition. Cox proportional hazard models were used to assess the associations of high (top quintile) and low (bottom quintile) versus medium (quintile 2 to 4) level of dietary iron intake with incident dementia, respectively. Linear regression was applied to assess the relations between dietary iron intake and brain T2* measurements. During follow-up (mean = 9.5 years), a total of 1,454 participants (650 women and 804 men) developed dementia among 191,694 participants (55.0% female; mean age, 56.2 years). When adjusted for sociodemographic, lifestyle, and other dietary factors, participants with low dietary iron intake (< 10.05 mg/day) had a significantly higher dementia risk (hazard ratio [HR], 1.50, 95% confidence interval [CI], 1.19-1.89), while the relation for high intake (> 16.92 mg/day) was non-significant (HR, 1.16, 95% CI, 0.92-1.46). A significant gender difference (P-interaction < 0.001) was observed, with a U-shaped association in male participants (HR for low vs. medium, 1.56, 95% CI, 1.14-2.13; HR for high vs. medium, 1.39, 95% CI, 1.03 - 1.88; P-nonlinearity < 0.001) and no significant association in females, regardless of their menopause status. In general, dietary iron intake was not related to T2* measurements of iron deposition in most brain regions. Our findings suggested a U-shape relationship between dietary iron intake and risk of dementia among males, but not females.