Absolute and functional iron deficiency were associated with a higher likelihood of dementia diagnosis among adults aged 50 years and older, according to a population-based cohort study published in BMC Medicine.
The analysis included 70,935 individuals in the Swedish Apolipoprotein-Related Mortality Risk cohort who had laboratory markers of iron status measured between 1985 and 1996. Participants were followed for up to 15 years using national registers, with dementia identified primarily through inpatient and specialist outpatient diagnoses, as well as dispensed anti-dementia medications and cause-of-death records.
During a mean follow-up of 12.6 years, 4,994 individuals were diagnosed with dementia. Overall, dementia occurred in 7% of the cohort, including 9.5% of those with absolute iron deficiency and 9.3% of those with functional iron deficiency, compared with 6.9% in the reference group.
Absolute iron deficiency was defined as serum ferritin less than 30 micrograms per liter. Functional iron deficiency was defined as transferrin saturation less than 20% with ferritin at least 30 micrograms per liter. Because ferritin measurements were unavailable in much of the cohort, the reference group—defined by normal hemoglobin, serum iron, and total iron binding capacity—served as a proxy for no iron deficiency.
After adjustment for age, sex, education, history of cardiovascular disease, and Charlson Comorbidity Index score, absolute iron deficiency was associated with a 24% higher likelihood of dementia diagnosis, and functional iron deficiency with a 21% higher likelihood.
Subgroup analyses showed variation by age and comorbidity. Among individuals aged 50 to 74 years, absolute iron deficiency was associated with a 50% higher likelihood of dementia, whereas functional iron deficiency was not statistically significant in this group. Among those aged 75 years and older, functional iron deficiency was associated with a 40% higher likelihood. In individuals with a Charlson Comorbidity Index score of at least one, absolute iron deficiency was associated with a 54% higher likelihood of dementia.
Patterns also differed by sex: men with absolute iron deficiency had higher dementia incidence rates than those with functional iron deficiency, whereas the opposite pattern was observed among women.
When analyses were restricted to individuals without anemia, the association persisted for absolute iron deficiency but was attenuated for functional iron deficiency. Associations were similar for Alzheimer disease but not statistically significant for vascular dementia.
The researchers noted that this is the first longitudinal study to examine iron deficiency—distinct from anemia or isolated iron markers—in relation to dementia risk.
Several limitations were noted. Dementia ascertainment relied primarily on specialist care data, which may miss cases diagnosed solely in primary care. Limited lifestyle data and potential residual confounding may have influenced results, and selection bias related to biomarker testing cannot be fully excluded. However, sensitivity analyses using inverse probability weighting yielded similar results.
“Considering that iron deficiency is a pervasive but often neglected health issue in older adults, resolving iron deficiency may be relevant for dementia prevention,” wrote Mozhu Ding, PhD, of Karolinska Institutet in Stockholm, and colleagues.
The researchers reported no competing interests.
Source: BMC Medicine