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[Preprint]. 2025 Jan 29:2025.01.28.25321122. [Version 1] doi: 10.1101/2025.01.28.25321122

Cognitive Performance in Relation to Systemic and Brain Iron at Perimenopause

Amy L Barnett, Michael J Wenger, Pamela Miles, Dee Wu, Zitha Redempta Isingizwe, Doris M Benbrook, Han Yuan
PMCID: PMC11838962  PMID: 39974002

Abstract

Background

The literature on the relationships among blood iron levels, cognitive performance, and brain iron levels specific to women at the menopausal transition is ambiguous at best. The need to better to understand these potential relationships in women for whom monthly blood loss (and thus iron loss) is ceasing is highlighted by the fact that iron accumulates in brain tissue over time and that accumulation is thought to be a factor in the development of neurodegenerative disease.

Methods

Non-anemic women who were either low in iron or had normal iron levels for their age and race/ethnicity provided blood samples, underwent MRI scans to estimate brain iron levels, and performed a set of cognitive tasks with concurrent EEG. Results: Cognitive performance as well as brain dynamics were positively related to iron levels, including measures associated with oxygen transport. There were no relationships between any of the blood measures of iron and brain iron.

Conclusions

Higher iron status was associated with better cognitive performance in a sample of women who were neither iron deficient nor anemic, without there being any indication that higher levels of systemic iron were related to higher levels of brain. Consequently, addressing low iron levels at the menopausal transition may be a candidate approach for alleviating the “brain fog” commonly experienced at menopause.

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