Evidence map›Paper›PMID 41547517›Full record

ArticleNeuroImage2026

Excess iron in deep gray matter is associated with cognitive and functional decline: The mediating role of white matter myelin.

Jonghyun Bae, Angelique De Rouen, Zhaoyuan Gong, Nathan Zhang, Noam Y Fox, Murat Bilgel, Christopher M Bergeron, Luigi Ferrucci, Mustapha Bouhrara

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In one paragraph

Article in NeuroImage, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

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5 · Who and what money

Authors and funding

9 authors.

Jonghyun BaeLaboratory of Clinical Investigation, National Institute on Aging, National Institutes of Health, Baltimore, MD, 21224, USA. Electronic address: jonghyun.bae@nih.gov.
Angelique De RouenLaboratory of Clinical Investigation, National Institute on Aging, National Institutes of Health, Baltimore, MD, 21224, USA.
Zhaoyuan GongLaboratory of Clinical Investigation, National Institute on Aging, National Institutes of Health, Baltimore, MD, 21224, USA.
Nathan ZhangLaboratory of Clinical Investigation, National Institute on Aging, National Institutes of Health, Baltimore, MD, 21224, USA.
Noam Y FoxLaboratory of Clinical Investigation, National Institute on Aging, National Institutes of Health, Baltimore, MD, 21224, USA.
Murat BilgelLaboratory of Behavioral Neuroscience, National Institute on Aging, National Institutes of Health, Baltimore, MD, 21224, USA.
Christopher M BergeronLaboratory of Clinical Investigation, National Institute on Aging, National Institutes of Health, Baltimore, MD, 21224, USA.
Luigi FerrucciTranslational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, MD, 21224, USA.
Mustapha BouhraraLaboratory of Clinical Investigation, National Institute on Aging, National Institutes of Health, Baltimore, MD, 21224, USA.

Funding

Intramural NIH HHS Z99 AG999999
6 · The paper itself

Abstract

backgroundCerebral iron accumulation is a hallmark of aging and age-related neurodegenerative conditions. This study explored whether higher iron levels in deep gray matter (DGM) structures contribute to motor and cognitive decline and whether this association is mediated by demyelination in white matter (WM) tracts connecting the DGM to the cortex.

methodWe used quantitative susceptibility mapping (QSM) to quantify brain iron and multi-component relaxometry to estimate myelin content in 86 cognitively unimpaired adults (ages 22-94) who underwent longitudinal assessments of cognitive and motor function. We analyzed age-related differences in DGM iron levels, examined their association with cognitive and functional decline, and conducted mediation analyses to evaluate the role of WM myelination.

resultsHigher iron levels in the putamen and caudate nucleus were significantly correlated with older age. Higher putamen iron level was negatively associated with usual and rapid gait speed. In longitudinal analyses, higher iron levels in DGM were associated with a steeper decline in verbal fluency, processing speed, and motor function. Myelin content revealed a significant indirect mediated effect on the relationship between high iron content and motor function in the superior corona radiata, a WM tract connecting the putamen to the cortex.

conclusionThese findings suggest that excessive iron is linked to cognitive and functional decline in aging, with motor deterioration specifically mediated by demyelination of white matter pathways connecting the deep gray matter to the cortex. Together, iron and myelin metrics may serve as early biomarkers of age-related clinical decline and represent promising therapeutic targets for preserving motor function in older adults.

Indexed as

AgingCognitive DysfunctionGray MatterIronMyelin SheathWhite MatterAdultAgedAged, 80 and overFemaleHumansLongitudinal StudiesMagnetic Resonance ImagingMaleMiddle AgedPutamenIronDemyelinationIron accumulationMyelin water fractionQuantitative susceptibility mapping

Identifiers

PMID41547517
PMCPMC12990093

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.