Abstract #4215

Mechanistic Links of Insular Cortex Iron to Cardiac Function, Brain Atrophy, Connectivity and Cognition in Women with Microvascular Dysfunction

Arzu C HAS SILEMEK^1,2, Janet Wei ³, Jeffrey C Wertheimer⁴, Yibin Xie², Debiao Li², Mitzi Gonzales¹, Oana Dumitrascu⁵, Michael D Nelson^3,6, Sarah Kremen⁷, Zaldy S Tan^8,9, C Noel Bairey Merz³, Wei Gao², and Pascal Sati¹

¹Department of Neurology, Cedars Sinai Medical Center, Los Angeles, CA, United States, ²Department of Biomedical Sciences and Imaging, Biomedical Imaging Research Institute (BIRI), Cedars Sinai Medical Center, Los Angeles, CA, United States, ³Barbra Streisand Women's Heart Center, Smidt Heart Institute, Cedars Sinai Medical Center, Los Angeles, CA, United States, ⁴Department of Physical Medicine and Rehabilitation, Cedars Sinai Medical Center, Los Angeles, CA, United States, ⁵Department of Neurology, Mayo Clinic College of Medicine and Science, Scottsdale, AZ, United States, ⁶The University of Texas at Arlington, Arlington, TX, United States, ⁷Neurology, Cedars Sinai Medical Center, Los Angeles, CA, United States, ⁸Department of Neurology and Medicine, Cedars Sinai Medical Center, Los Angeles, CA, United States, ⁹David Geffen School of Medicine, UCLA, Los Angeles, CA, United States

Synopsis

Keywords: Aging, Aging, Heart, Brain, Iron, Atrophy, Connectivity, Cognition, Women, CSVD, Cardiovascular, Quantitative susceptibility mapping

Motivation: Excessive brain iron accumulation is a critical issue linked to neurodegeneration and disrupted connectivity, increasing the risk of pathological aging and highlighting the need to understand these mechanisms for improving clinical outcomes.

Goal(s): To examine how cortical and deep-gray-matter iron connects cardiac and cognitive dysfunction with brain atrophy and altered-connectivity in women with suspected coronary-microvascular-dysfunction (CMD).

Approach: Forty-five women underwent clinical, cognitive, cardiac/brain MRI assessments, utilizing sequential mediation analysis to explore pathways from iron to atrophy, connectivity, and cardiac/cognitive outcomes.

Results: Insular cortex iron emerged as a key pathway linking cardiac/cognitive function to atrophy and connectivity, highlighting its role in CMD-related heart-brain interactions.

Impact: This study identifies insular-cortex iron as a potential biomarker linking cardiac and cognitive function in CMD. These findings could guide future interventions targeting brain iron to mitigate cardiovascular and cognitive risks, prompting new research on heart-brain interactions in women’s health.

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