Midlife Iron Status Is Inversely Associated with Subsequent Cognitive Performance, Particularly in Perimenopausal Women

Abstract

The link between iron status and cognition has been established in infants and children, yet evidence in adults is scant and heterogeneous. We examined sex- and menopause-specific cross-time associations of iron status with cognition in the French Supplémentation en Vitamines et Minéraux Antioxydants Study cohort (1539 men, 1431 pre-/perimenopausal women, 962 postmenopausal women). Serum ferritin and hemoglobin data were obtained in 1995. Cognition was assessed after a mean of 13 y through 6 validated instruments, including the RI-48 cued recall test, phonemic and semantic fluency tasks, forward and backward digit span tasks, and a trail-making test. The standardized individual test scores were summed to form a composite cognitive performance measure. Associations between ferritin and hemoglobin and subsequent cognitive performance were examined through multivariable linear regression. Among men, no significant associations were observed. In postmenopausal women, an inverse association was found between ferritin and phonemic fluency (adjusted β: −0.11; 95% CI: −0.21, −0.01). Significant inverse associations between ferritin and both the composite cognitive measure (adjusted β: −0.09; 95% CI: −0.17, −0.00) and the forward digit span scores (adjusted β: −0.13; 95% CI: −0.22, −0.03) were observed only among premenopausal women aged ≥46 y at baseline. No significant findings with hemoglobin emerged. This study supports an inverse association between midlife iron status and subsequent cognitive performance that is sex- and menopause-dependent. Given the urgent need for prevention research on age-related disorders, future investigations of iron status and cognition are warranted. The study is registered at www.clinicaltrials.gov as NCT00272428.