Abstract
BACKGROUND: Iron deficiency (ID) is proposed to be involved in cognitive aging and dementia; however, empirical data is lacking to support this hypothesis. We examined the association between absolute and functional ID and incident dementia diagnosis. METHODS: Data from 70,935 individuals aged ≥ 50 years from the Swedish AMORIS cohort, who had blood measurements indicative of iron status between 1985-1996, were used. Participants were followed for incident dementia diagnosis recorded in National Patient Register (inpatient and specialist outpatient) and Prescribed Drug Register (dispensed anti-dementia drugs) for up to 15 years. Two exposure groups were defined: absolute iron deficiency (serum ferritin < 30 ug/L) and functional iron deficiency (transferrin saturation < 20% and serum ferritin ≥ 30 ug/L). The reference group included individuals with measurements in the normal range of hemoglobin, serum iron, and total iron binding capacity. RESULTS: A total of 4,994 individuals received a dementia diagnosis over a mean of 12.6 years. Compared with the reference group, absolute and functional ID was associated with increased dementia diagnosis (adjusted hazard ratio (HR) = 1.24, 95% confidence interval (CI): 1.18-1.42; HR = 1.21, 95% CI: 1.05-1.39, respectively), after adjusting for age, sex, education, and comorbidities. The associations were essentially consistent across subgroups, and when further adjusting for kidney function, body mass index, and smoking in subsamples. CONCLUSIONS: Even though absolute and functional iron deficiency has different underlying mechanisms, we found that both conditions are associated with an increased risk of dementia. Considering that iron deficiency is a pervasive but often neglected health issue in older adults, resolving iron deficiency may be relevant for dementia prevention.