Specific Nutrients May Combat Iron Buildup in the Aging Brain

Could the key to preserving cognitive health as we age lie in the foods we eat?

Researchers from the University of Kentucky have found new insights linking specific nutrients to reduced brain iron accumulation, a factor tied to cognitive decline. Their study, published in Neurobiology of Aging, highlights how diet may help protect the brain from age-related changes, offering a potential strategy to combat dementia.

The role of iron in brain health and aging

As we age, maintaining brain health becomes an increasingly worrying concern, particularly given the rising prevalence of dementia worldwide – rates of which are projected to triple by 2050.

Among the many factors influencing brain health, iron plays a dual role. While essential for neurotransmitter synthesis and energy production in the brain, excessive iron accumulation, particularly non-heme iron, poses a threat. A surplus, often seen in normal aging, contributes to oxidative stress – a harmful process that can damage neurons and other brain structures.

The implications of excess brain iron extend beyond normal aging, linking it to cognitive decline and neurodegenerative diseases such as Alzheimer’s. Studies have consistently shown that elevated brain iron levels are associated with poorer memory and executive function, even in healthy older adults. Despite this, effective strategies to mitigate brain iron accumulation are limited.

“It’s crucial to understand how diet and other lifestyle factors impact the risk of Alzheimer’s and related dementias as we age,” said corresponding author Dr. Brian Gold, a professor in the department of neuroscience at the University of Kentucky.

In a prior cross-sectional study, the team, led by Gold, found that higher dietary intake of antioxidants, vitamins, polyunsaturated fatty acids and iron-chelating nutrients correlated with lower brain iron levels and better working memory performance.

“We still had important questions that remained unanswered in that initial investigation, particularly regarding the long-term effectiveness of these nutrients and their potential to reduce age-related brain iron accumulation,” said lead author Dr. Valentinos Zachariou,  an assistant professor in the department of behavioral science in the college of medicine at the University of Kentucky.

Tracking brain iron accumulation over time

Building on their previous work, the researchers sought to explore whether sustained dietary intake of these nutrients could curb brain iron accumulation over time.

“Despite mounting evidence connecting iron overload to negative cognitive outcomes, there are currently no established methods for reducing brain iron accumulation in older adults,” Zachariou added.

Led by Gold and Zachariou, the team tracked changes in brain iron levels over three years using an imaging technique called quantitative susceptibility mapping (QSM), which allows precise measurement of iron concentration in the brain. The study involved 73 healthy older adults aged between 61 and 86. Participants underwent two MRI scans, one at the start and another at the end of the study, and their dietary habits were assessed through a nutritional questionnaire. Cognitive performance was evaluated using standardized neuropsychological tests, focusing on episodic memory and executive function.

“Our results revealed a broad network of cortical and subcortical brain regions where iron accumulation occurred over the three-year period. These regional increases in iron levels were associated with poorer episodic memory and executive function at the follow-up time-point,” said Zachariou.

Over the three years, brain iron levels increased significantly, particularly in the hippocampus, associated with memory, and the frontal lobe, essential for decision-making and problem-solving. These increases were associated with both structural and functional consequences.

However, dietary habits did appear to play a protective role. Participants with higher baseline intake of antioxidants, vitamins, iron-chelating nutrients and polyunsaturated fatty acids exhibited less brain iron accumulation over the study period.

Implications for diet and brain health

By uncovering the role of diet in moderating brain iron accumulation, the research deepens our knowledge of the aging brain and highlights actionable strategies to potentially preserve cognitive function in later years.

“This study is an example of how we can encourage healthier lifestyle choices to help combat some risk factors that can affect brain health,” said Gold.

The identification of specific nutrients as protective factors against brain iron buildup suggests that diet may be a powerful tool in mitigating age-related cognitive decline. The results also support the case for adopting diets like the Mediterranean or DASH diets, which are naturally rich in the nutrients identified in the study. These diets, already renowned for their cardiovascular benefits, could also have positive effects on brain health. Encouraging dietary changes that support brain health could play a crucial role in reducing the burden of dementia and other age-related cognitive impairments.

While the association between diet and reduced brain iron accumulation is compelling, the study was observational, and causality remains unproven. Randomized clinical trials are needed to confirm the effectiveness of specific dietary interventions and to refine recommendations for optimal nutrient intake.

Reference: Zachariou V, Pappas C, Bauer CE, Seago ER, Gold BT. Exploring the links among brain iron accumulation, cognitive performance, and dietary intake in older adults: A longitudinal MRI study. Neurobiol Aging. 2025;145:1-12. doi: 10.1016/j.neurobiolaging.2024.10.006

This article is a rework of a press release issued by the University of Kentucky. Material has been edited for length and content.