MRI-Based Brain Iron Mapping May Predict Early Cognitive Decline, Study Finds

A recent study published in Radiology, a journal of the Radiological Society of North America (RSNA), highlights a breakthrough in predicting cognitive decline. Researchers found that a specialized MRI technique known as quantitative susceptibility mapping (QSM) can detect elevated iron levels in specific brain regions, potentially forecasting the onset of mild cognitive impairment (MCI) in older adults who currently show no signs of cognitive issues. This discovery may pave the way for earlier interventions in Alzheimer’s disease.

Alzheimer’s remains the leading cause of dementia globally, presenting an urgent public health challenge. The disease is primarily marked by the build-up of amyloid beta and tau proteins in the brain, often detectable years before symptoms appear through PET scans. However, treatments aimed at these proteins have shown only limited success, prompting researchers to explore additional contributing factors.

Among these factors, abnormal iron accumulation in the brain has gained increasing attention. Excess iron is known to trigger oxidative stress—a harmful imbalance between free radicals and antioxidants—thereby intensifying amyloid toxicity, disrupting tau function, and promoting the death of neurons.

QSM offers a non-invasive way to assess iron distribution in the brain by measuring tissue magnetic susceptibility with high precision. “QSM is an advanced MRI technique developed over the last decade to measure tissue magnetic susceptibility with good precision,” said Dr. Xu Li, Ph.D., the study’s senior author and associate professor of radiology at Johns Hopkins University. “QSM can detect small differences in iron levels across different brain regions, providing a reliable and non-invasive way to map and quantify iron in patients, which is not possible with conventional MR approaches.”

Dr. Li and his team utilized QSM in a cohort of 158 cognitively healthy participants enrolled in the Johns Hopkins BIOCARD Study, which focuses on early detection of Alzheimer’s disease. PET scan data was also available for 110 of these individuals. Researchers collected baseline QSM imaging and followed participants for up to 7.5 years.

Their findings showed that higher magnetic susceptibility—indicating greater iron levels—in two key brain regions, the entorhinal cortex and the putamen, was strongly linked to an increased risk of developing MCI. These regions are crucial for memory and other cognitive abilities. “Using QSM, we found higher brain iron in some memory-related regions that are linked to a higher risk of developing cognitive impairment and faster cognitive decline,” Dr. Li explained. “This risk is even higher when the participants have higher levels of amyloid pathologies.”

The study also revealed a compounding effect: although amyloid burden and iron levels in these brain regions were independently associated with cognitive decline, their combination accelerated the deterioration more rapidly.

If validated in larger and more diverse populations, QSM could become a valuable tool for identifying individuals at elevated risk of Alzheimer's. “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,” said Dr. Li. Moreover, brain iron itself could emerge as a future therapeutic target.

Looking ahead, the researchers aim to refine QSM for broader clinical use and explore iron-focused treatments in clinical trials. “At the same time, we hope to make the QSM technology more standardized, faster and more widely accessible in clinical practice,” Dr. Li added.