MRI measure of brain iron linked to higher Alzheimer’s risk years before symptoms
Johns Hopkins researchers report that quantitative susceptibility mapping can detect regional iron increases tied to elevated odds of mild cognitive impairment over 7½ years
Researchers at Johns Hopkins University reported that a specialized MRI technique that measures iron in brain tissue can predict increased risk of mild cognitive impairment (MCI) — a common precursor to Alzheimer’s dementia — years before clinical symptoms appear.
In a study published in Radiology, investigators applied quantitative susceptibility mapping (QSM), an MRI method that quantifies tissue magnetic susceptibility, to scans from 158 cognitively unimpaired adults and followed participants for an average of about 7½ years. They found that higher iron levels in two memory-related regions, the entorhinal cortex and the putamen, were associated with a two- to fourfold greater risk of developing MCI and with faster cognitive decline.
"QSM is an advanced MRI technique developed over the last decade to measure tissue magnetic susceptibility with good precision," said Xu Li, PhD, an associate professor of radiology at Johns Hopkins and the study’s senior author. He said QSM can detect small regional differences in iron that conventional MRI approaches do not measure reliably.
The researchers reported that the risk associated with elevated brain iron was amplified in participants who also had higher levels of amyloid pathology, the abnormal protein deposits that are a hallmark of Alzheimer’s disease. The study suggests that iron accumulation and amyloid may act together to promote neurodegeneration and cognitive decline, although the authors emphasized that their results show association rather than proven cause and effect.
Compared with positron emission tomography (PET) scans, which are commonly used for amyloid and tau imaging but are costly and involve radiotracers, QSM offers a noninvasive and more affordable way to assess a potential biomarker linked to future cognitive decline. "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 said.
The study cohort came from a specialized research population and had several limitations the authors acknowledged. Participants were mainly white, highly educated and had a strong family history of Alzheimer’s disease, which could limit the generalizability of the findings. The cohort size was modest, and the investigators noted that larger, more diverse studies are needed to confirm the associations and to determine how best to apply QSM in clinical practice.
The authors said additional work is required to standardize QSM technology, make acquisitions faster, and validate thresholds that would identify individual patients at elevated risk. They also noted the dual role of iron in the brain: while iron accumulation has been linked to oxidative damage and neurodegeneration, iron is essential for normal neurodevelopment and cognitive function.
Therapies that remove excess iron, known as iron chelation, are being explored in clinical research, but Li cautioned that their benefits for Alzheimer’s remain unclear and require further study. The study was supported by the National Institute of Biomedical Imaging and Bioengineering, the National Institute on Aging and the National Institutes of Health.
If future studies in larger and more diverse populations confirm these findings, QSM could become a part of risk assessment for patients who are cognitively normal but at elevated risk for Alzheimer’s, offering a window for earlier monitoring and potential intervention as disease-modifying therapies advance.