High cortical iron is associated with the disruption of white matter tracts supporting cognitive function in healthy older adults

Author:

Zachariou Valentinos12ORCID,Bauer Christopher E12,Pappas Colleen12,Gold Brian T1234

Affiliation:

1. University of Kentucky Department of Neuroscience, , Lexington, KY 40536-0298, United States

2. University of Kentucky College of Medicine, , Lexington, KY 40536-0298, United States

3. University of Kentucky Sanders-Brown Center on Aging, , Lexington, KY 40536-0298, United States

4. University of Kentucky Magnetic Resonance Imaging and Spectroscopy Center, , Lexington, KY 40536-0298, United States

Abstract

Abstract Aging is associated with brain iron accumulation, which has been linked to cognitive decline. However, how brain iron affects the structure and function of cognitive brain networks remains unclear. Here, we explored the possibility that iron load in gray matter is associated with disruption of white matter (WM) microstructure within a network supporting cognitive function, in a cohort of 95 cognitively normal older adults (age range: 60–86). Functional magnetic resonance imaging was used to localize a set of brain regions involved in working memory and diffusion tensor imaging based probabilistic tractography was used to identify a network of WM tracts connecting the functionally defined regions. Brain iron concentration within these regions was evaluated using quantitative susceptibility mapping and microstructural properties were assessed within the identified tracts using neurite orientation dispersion and density imaging. Results indicated that high brain iron concentration was associated with low neurite density (ND) within the task-relevant WM network. Further, regional associations were observed such that brain iron in cortical regions was linked with lower ND in neighboring but not distant WM tracts. Our results provide novel evidence suggesting that age-related increases in brain iron concentration are associated with the disruption of WM tracts supporting cognitive function in normal aging.

Funder

NIGMS

NIA

NINDS

National Institutes of Health

Publisher

Oxford University Press (OUP)

Subject

Cellular and Molecular Neuroscience,Cognitive Neuroscience

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