C Rosano, V Wheeler , EM Novelli , J Tukakira , L LittleIhrig , Y Yien, S Fein , I Miljkovic

O-33 Iron deficiency is associated with risk of Alzheimer’s Dementia in Tobagonian women of African ancestry

Author(s): C Rosano, V Wheeler , EM Novelli , J Tukakira , L LittleIhrig , Y Yien, S Fein , I Miljkovic
Type Of Study:
  • Quantitative
Country(ies) Of Focus:
  • Trinidad and Tobago
Year of Presentation: 2025

Abstract

Objective: To test whether iron deficiency is associated with risk of Alzheimer’s Disease (AD) in African Caribbean women. Iron deficiency disproportionately affects women, particularly those of African ancestry. In women from the Tobago Health Study cohort of African Caribbeans aged ≥60, lower levels of amyloid beta (Aβ)42/40 ratio and higher phosphorylated tau (p-tau181) levels—both indicators of elevated AD risk—were previously observed when compared to men. These sex differences persisted after adjusting for age, cardiometabolic diseases, and lifestyle. Considering the role of iron in amyloid clearance, we hypothesized a link between iron deficiency and AD biomarkers in women.

Methods: We analyzed fasting serum iron biomarkers, including functional iron deficiency (iron saturation ≤20% with ferritin >100 ng/mL), ferritin, hepcidin, and soluble transferrin receptor (sTfR), in a random sample of 109 postmenopausal women aged 65+ years from the Tobago Health Study. Associations between iron parameters, AD biomarkers (Aβ42/40 ratio, p-tau181), and cognitive function (Digit Symbol Substitution Test, DSST) were explored.

Results: Women had high prevalence of hypertension (80%), diabetes (25%), obesity (average BMI 31.5), and sedentary behavior (16 min/week physical activity) in this postmenopausal cohort. Lower ferritin was associated with a lower Aβ42/40 ratio, indicating greater AD risk. Among women with functional iron deficiency (51%), higher sTfR levels correlated with worse DSST scores (r=-0.35, p=0.0154), independent of age, linking poor iron status with reduced cognitive function.

Conclusion: Caribbean women and its potential role as an early AD risk factor. While inflammation from cardiometabolic factors likely elevated ferritin levels, true iron deficiency was uncommon. Findings suggest a J-shaped relationship between serum and brain iron levels in AD pathology. Measuring iron status in populations at high risk for AD and iron deficiency could inform early interventions and risk assessment.

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