Dementia is the loss of cognitive functioning—thinking, remembering, and reasoning—to such an extent that it interferes with a person’s daily life and activities. To diagnose dementia, doctors first assess whether a person has an underlying, potentially treatable, condition that may relate to cognitive difficulties. A physical exam may be performed to measure blood pressure and other vital signs, as well as laboratory tests to check levels of various chemicals, hormones, and vitamins. Now, researchers at the Okinawa Institute of Science and Technology Graduate University (OIST), report they have discovered 33 metabolic compounds within the blood that are linked to dementia. Their findings may lead to potential new methods in diagnosing and treating dementia.

The new study is published in the journal PNAS in a paper titled, “Whole-blood metabolomics of dementia patients reveal classes of disease-linked metabolites.”

“Metabolites are chemical substances produced by vital chemical reactions that occur within cells and tissues,” explained Takayuki Teruya, PhD, first author of the study who works in the G0 Cell Unit at OIST. “Our body normally keeps these levels in balance, but as we age and if we develop diseases like dementia, these levels can fluctuate and change.”

“Dementia is caused by factors that damage neurons. We quantified small molecular markers in whole blood of dementia patients, using nontargeted liquid chromatography–mass spectroscopy (LC-MS),” the researchers wrote.

The team analyzed samples of blood collected from eight patients with dementia, as well as eight healthy elderly people. They also collected samples from eight healthy young people to use as a reference. Unlike most studies analyzing blood metabolites, this research included compounds found within red blood cells.

“Blood cells are difficult to handle because they undergo metabolic changes if left untreated even for a short period of time,” explained Teruya.

The researchers developed a way to stabilize metabolites in red blood cells to be able to examine the relationship between red blood cell activity and dementia for the first time.

The scientists measured the levels of 124 different metabolites in whole blood and found that 33 metabolites, split into five different sub-groups, correlated with dementia.

A heat-map, where red shows high levels of a compound, and blue shows low levels of a compounds, reveals the link between certain metabolites and dementia. Compounds in sub-group A were typically higher in dementia patients and lower in healthy elderly people. Compounds in sub-group B-E showed the opposite effect. [OIST]
“Identification of these compounds means that we are one step closer to being able to molecularly diagnose dementia,” said senior author of the study, Mitsuhiro Yanagida, PhD, who leads the G0 Cell Unit at OIST.

“It’s still too early to say, but it could suggest a possible mechanistic cause of dementia as these compounds may lead to impairment of the brain,” added Yanagida.

The research team plans to test this idea in the next steps of their research, by seeing if increases in these metabolites can induce dementia in animal models.

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