Japanese researchers have identified metabolic chemicals in the blood that have been linked to dementia.

The study, published this week in PNAS, discovered that the levels of 33 metabolites varied significantly between dementia sufferers and healthy elderly adults.

“Metabolites are chemical substances produced by vital chemical reactions that occur within cells and tissues,” said first author Dr Takayuki Teruya.

“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 not a single disease, but a collection of symptoms that include a gradual but typically irreversible decline in the ability to remember, think, make decisions, or execute daily activities. Dementia is one of the most significant aging-related disorders, affecting not just patients and their families but also society as a whole, with an estimated 55 million individuals suffering from the disease globally.

While scientists are aware that dementia is caused by nerve damage, the actual origin of this damage, as well as strategies for diagnosing and treating it, have remained elusive.

The study examined blood samples taken from eight patients with dementia and eight healthy elderly persons. Additionally, they gathered samples from eight healthy young adults to serve as a control. In contrast to the majority of studies examining blood metabolites, this study examined chemicals contained 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 Dr Teruya.

However, the research team has established a method for stabilizing metabolites in red blood cells, allowing them to examine the association between red blood cell activity and dementia for the first time.

The researchers measured the concentrations of 124 different metabolites in whole blood and revealed that 33 metabolites, classified into five distinct subgroups, were associated with dementia. Seven of these chemicals showed an increase in levels in dementia patients, whereas 26 indicated a drop in levels. Twenty-one of these chemicals, including nine that were plentiful in red blood cells, have not before been related to dementia.

“Identification of these compounds means that we are one step closer to being able to molecularly diagnose dementia,” said the senior author of the study, Professor Mitsuhiro Yanagida.

The seven metabolites with elevated levels in dementia patients were identified in blood plasma and were classified as subgroup A metabolites. Notably, it is considered that several of these chemicals are harmful to the central nervous system.

“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,” said Prof. Yanagida.

The research team intends to explore this hypothesis further by examining if increased levels of these metabolites can develop dementia in animal models such as mice.

The remaining 26 molecules that dropped in dementia patients relative to healthy elderly people were members of four additional metabolite subgroups, B-E.

Six metabolites were sorted into subgroup B due to their comparable structure and lower levels in dementia patients. These metabolic products operate as antioxidants, preventing damage to cells and tissues caused by free radicals — unstable molecules formed during chemical processes in cells. The researchers discovered that these food-derived antioxidants were plentiful in the red blood cells of healthy elderly persons.

“It could be that red blood cells deliver not only oxygen but also crucial metabolites that protect the nervous system from damage,” said Dr Teruya.

The remaining subgroups contain substances believed to aid in the provision of nutrients, the maintenance of energy reserves, and the protection of neurons from harm.

“In the future, we hope to start some intervention studies, either by supplementing dementia patients with metabolic compounds in sub-groups B-E, or by inhibiting the neurotoxins from sub-group A, to see if that can slow, prevent, or even reverse symptoms of dementia,” said Prof. Yanagida.

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