Brain Iron Levels Linked to Cognitive Decline, MRI Study Suggests

Researchers have uncovered new evidence connecting brain iron levels to cognitive decline, offering potential pathways for earlier detection and targeted therapy in neurodegenerative disease. The findings, published in Radiology, center on an advanced MRI technique known as quantitative susceptibility mapping (QSM), which can detect subtle differences in tissue susceptibility and quantify iron levels across different brain regions.

Excess iron in the brain has been under scrutiny in recent years. When present in high concentrations, it can trigger oxidative stress, worsening amyloid toxicity and contributing to neuronal cell death. Together, these processes are thought to accelerate cognitive decline and raise the risk of conditions such as Alzheimer’s disease. While elevated brain iron has been proposed as a biomarker for neurodegeneration, its predictive value for the onset of mild cognitive impairment (MCI) and longer-term changes in cognition has remained uncertain.

“Elevated brain iron is a potential marker for neurodegeneration, but its role in predicting onset of mild cognitive impairment and prospective cognitive trajectories remains unclear,” said Xu Li, PhD, associate professor of radiology at Johns Hopkins University and lead author of the study.

To investigate, Li and colleagues analyzed QSM MRI scans from 158 cognitively unimpaired individuals, including a subgroup of 110 participants who also underwent PET imaging. Follow-up data spanning more than seven years allowed the team to assess whether baseline tissue susceptibility could be linked to later outcomes such as MCI onset and declines in cognitive performance.

Their analysis revealed that higher magnetic susceptibility in the entorhinal cortex and putamen—regions associated with memory and cognitive processing—was linked to an increased risk of developing MCI. These findings held true across both the MRI-only and PET subgroups. Importantly, in the PET subgroup, the same pattern was associated with greater global cognitive decline, particularly among individuals who already showed amyloid abnormalities on imaging.

The study highlights a possible interaction between iron accumulation and amyloid pathology in driving cognitive deterioration. By combining iron-sensitive MRI data with amyloid imaging, clinicians may gain a clearer picture of patients at greatest risk for decline.

If validated in larger, prospective trials, the findings could open the door to iron-targeted interventions. Potential therapies might aim to reduce iron buildup in the brain or protect neurons from iron-induced oxidative stress.

“We can use this kind of tool to help identify patients at higher risk of developing Alzheimer’s disease and potentially guide early interventions as new treatments become available,” Li explained. “Also, besides serving as a biomarker, brain iron may become a future therapeutic target.”

For now, QSM remains primarily a research tool, but its ability to noninvasively track brain iron offers a promising avenue for both diagnosis and treatment planning. By capturing changes years before symptoms arise, the approach could support proactive strategies to slow or prevent cognitive decline in aging populations.