Sex‐specific associations of dietary iron intake with incident dementia: A prospective cohort study

Abstract Background Iron has been associated with age‐related cognitive decline and dementia in middle aged and older adults. Nevertheless, as the major source of iron in the body, whether dietary iron intake is related to incident dementia remains poorly understood. Method A total of 191,694 dementia‐free participants (55.0% female; mean±SD age, 56.2 ± 7.9 years) from the UK Biobank who completed at least one 24h dietary recall at study baseline (2009‐2012) were followed to 2021 (mean = 9.5 years). Dietary iron intake was calculated using the 24h dietary recalls. Incident dementia was identified through hospital admissions and death registries. Cox proportional hazard models were used to assess the overall and sex‐specific associations of dietary iron intake with incident dementia. Participants with iron intake between the 20 th and 80 th percentiles were considered as reference group. Result During a total of 1,813,480 person‐years, a total of 918 (650 women and 268 men) participants developed dementia. When adjusted for sociodemographic, lifestyle, and other dietary factors, participants in the lowest quintile of iron intake were at significantly higher dementia risk (hazard ratios [HR], 1.40, 95% confidence interval [CI], 1.10‐1.78), while the highest quintile was not significantly related to incident dementia (HR, 1.22, 95% CI, 0.97‐1.55). We detected a significant sex difference in the relations of dietary iron intake to dementia (P‐interaction < 0.001). We observed a U‐shaped association between dietary iron intake and incident dementia in male participants (HR low , 1.50, 95% CI, 1.09‐2.07; HR high , 1.40, 95% CI, 1.03‐1.91; P‐nonlinearity<0.001). Nevertheless, no significant correlation was seen in women, regardless of their menopause status. Conclusion Our study findings suggested a U‐curve relationship between dietary iron intake and risk of dementia among males, which may be related to the differences in direct iron metabolism between the sexes. Further research is warranted to confirm the findings and to investigate the underlying mechanisms of the observed gender differences.