Older woman losing parts of head and looking confused as a symbol of dementia.
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Scientists at the National University of Singapore (NUS) and the National University Health System (NUHS) report that they have discovered a new biomarker, ergothioneine (ET), found in blood plasma that may predict an increased risk of cognitive impairment and dementia in adults. The results of their study, published in the journal Antioxidants, point to the potential of leveraging this biomarker for as an early screening method for dementia in the elderly.

According to the research team, led by Prof. Barry Halliwell from the Department of Biochemistry at NUS, ET is a diet-derived compound was first identified more than 100 years ago. Then, in 2005, researchers discovered a transporter for ET that plays a role in the uptake of ET and its accumulation in the body.

Halliwell’s own research previously showed that ET is a potent antioxidant and has the ability to protect human cells from stress and a range of toxins. Its main dietary source in humans is mushrooms and increased consumption of golden, oyster, shiitake and white button mushrooms has been associated with a reduced risk of mild cognitive impairment in elderly Singaporeans.

The NUS and NUHS research team demonstrated that ET is avidly retained in the body following the use of oral supplements containing the compound, and further that preclinical models showed it is transported to virtually all organ, with higher levels found in specific cells and tissues such as the blood cells, eyes, liver, lungs, and the brain. A 2016 study by the Halliwell team showed that participants with mild cognitive impairment displayed lower levels of ET, which was later verified in larger study, published last year in Free Radical Biology and Medicine, of people both with and without dementia who had cognitive impairment.

Based on these findings Halliwell and team launched their most recent work aimed at determining whether this knowledge of low ET levels in blood plasma and its association with cognitive impairment and dementia could be used as a predictive biomarker.

For this work, the researchers recruited 470 elderly patients and followed them for up to five years at the Memory, Aging, and Cognition Centre at NUHS. During this time the investigators measured participant blood plasma ET levels while tracking the patients’ cognitive and functional abilities over time. They then examined the link between low ET levels and the risk of cognitive and functional decline over time looking for a correlation.

The team demonstrated that participants with lower levels of ET displayed poorer cognitive performance at the start of the study and an accelerated rate of decline in cognitive and functional abilities over the follow-up period.

“Before this study, there was little evidence that ET levels in the blood can predict the risk of developing cognitive issues. The current study is significant because it measured the ET levels of elderly participants before developing dementia. Our findings demonstrate that if your ET levels are low, your risk of developing cognitive problems increases,” said Halliwell.

Magnetic resonance imaging (MRI) scans of study participants also showed structural changes in the brain to suggest an association between low levels of ET in the blood and cognitive decline with underlying disease pathology. The structural changes included reduced cortical thickness, lower hippocampus volume, and white matter hyperintensities—all of which are characteristic of neurodegenerative disease.

“This points to the possibility of using a simple blood test to detect ET levels for early screening in the elderly to identify those who may have higher risk of cognitive decline,” said Halliwell. He added that low ET levels are also associated with a number of other age-related diseases such as frailty, cardiovascular disease and macular degeneration, so ET may have a more general role in maintaining health.

Based on their findings, the researchers are launching a double-blinded, placebo-controlled clinical trial to provide further evidence of ET’s therapeutic and diagnostic potential. It is recruiting patients over the age of 60 with mild cognitive impairment to participate in this next round of research.

“If the deficiency in ET is leading to an increased risk of cognitive decline, then we would have the potential to intervene, and that is what we are trying to find out by undertaking this clinical trial,” noted Irwin Cheah, senior research fellow from the NUS Department of Biochemistry.

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