Iron deficiency and dementia risk: evidence from the Swedish population-based cohort study AMORIS

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.