Researchers at the University of Kentucky have found that incorporating specific nutrients into a regular diet may reduce iron buildup in the brain — a factor associated with cognitive decline in normal aging.

The study, titled “Exploring the links among brain iron accumulation, cognitive performance, and dietary intake in older adults: A longitudinal MRI study,” was published in Neurobiology of Aging.

The work was supported by multiple grants from the National Institutes of Health’s National Institute on Aging and National Institute of Neurological Disorders and Stroke.

“It’s crucial to understand how diet and other lifestyle factors impact the risk of Alzheimer’s and related dementias as we age,” said Brian Gold, Ph.D., professor in the Department of Neuroscience in the College of Medicine, faculty in the Sanders-Brown Center on Aging and principal investigator of the study.

“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.

In this project, researchers specifically looked at non-heme iron, which is critical for brain health. This type of iron does not bind with storage proteins and, with age and in excess, can contribute to oxidative stress, potentially affecting neuronal integrity and cognition.

Excessive brain iron has been linked to poor cognitive performance, even in normal aging.

“Despite mounting evidence connecting iron overload to negative cognitive outcomes, there are currently no established methods for reducing brain iron accumulation in older adults,” said Valentinos Zachariou, Ph.D., an assistant professor in the Department of Behavioral Science in the College of Medicine and first author of the paper.

This study builds on the research team’s previous work that found that higher intake of antioxidants, vitamins, iron-chelating nutrients and polyunsaturated fatty acids 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 Zachariou.

For a follow-up study, Gold and Zachariou worked with the same research team, including the Department of Neuroscience’s Colleen Papas, Ph.D., Christopher Bauer, Ph.D., and Elayna Seago.

The team reassessed brain iron concentrations approximately three years later in the same cohort of older adults. They measured brain iron levels with a specific MRI technique called quantitative susceptibility mapping.

Researchers also analyzed a month’s worth of dietary information and cognitive performance, which was evaluated using neuropsychological tests of episodic memory (memories of specific events) and executive function.

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

“However, participants who had higher baseline intake of antioxidants, vitamins, iron-chelating nutrients, and polyunsaturated fatty acids showed significantly less iron accumulation over the three-year period,” said Gold.

The research team said the findings offer valuable insights for future clinical trials aimed at evaluating the impact of similar nutritional intake on brain iron accumulation and cognitive function. Further study of iron accumulation and cognition effects of healthy diets rich in the nutrients examined in this study, such as the Mediterranean or DASH diets, would be highly beneficial.

Research reported in this publication was supported by the National Institute on Aging of the National Institutes of Health under Award Numbers R01AG055449, R01AG068055, P30AG072946 and P30AG028383; by the National Institute of Neurological Disorders and Stroke of the National Institutes of Health under Award Number RF1NS122028; and the Office of Research Infrastructure Programs of the National Institutes of Health under Award Number S10OD023573. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.