Recent research has shown that the liver and the brain are closely connected and can affect each other’s functions. So could liver health influence a person’s dementia risk? Here is what experts and the most recent research have to say.

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What does liver health have to do with the brain? Image credit: mikroman6/Getty Images.

Through recent studies, scientists have found that liver-related conditions, such as liver fibrosis and nonalcoholic fatty liver disease (NAFLD), are linked to cognitive decline and changes in the brain’s structure.

Inflammation, which occurs in both the liver and the brain, seems to be a key factor in this connection. Additionally, studies have looked into what researchers now call the gut-liver-brain axis and found that the health of the gut microbiome, the collection of microbes that colonize our intestines, can impact both the liver and the brain.

But does this have any implications for chronic and currently incurable conditions that affect the brain, particularly dementia? And how did scientists zero in on the liver-brain axis, in the first place?

The liver is the biggest organ in our body, and it has many important functions. It helps process and store the three main types of nutrients we get from food: carbohydrates, fats, and proteins.

The liver also helps break down and get rid of alcohol, drugs, and toxic substances in the body, and produces a substance called bile that helps with digestion.

Recently, scientists have discovered that the liver and the brain have a close relationship. They communicate with each other through a special connection called the liver-brain axis.

According to Dr. Blen Tesfu, a general practitioner, the liver-brain axis “refers to the bidirectional communication and interaction between the liver and the brain.”

“The liver plays a crucial role in metabolizing various substances, including toxins and inflammatory mediators. In chronic liver diseases, liver fibrosis can lead to increased inflammation and the release of pro-inflammatory molecules into the bloodstream,” Dr. Tesfu explained.

Recent research suggests a correlation between the liver-brain axis and cognitive decline, with inflammation an underlying cause.

In one study published in the journal Cells in May 2023, scientists looked at the livers of mice that were genetically prone to Alzheimer’s disease and compared them to mice without this genetic predisposition.

Typically, Alzheimer’s research focuses on changes that occur in the brain, but the oxi-inflammation hypothesis suggests that immune system problems and aging also play a role in the disease.

The study found that mice with a genetic predisposition to Alzheimer’s had liver dysfunction, increased oxidative stress, inflammation, and larger livers.

“Inflammatory molecules can cross the blood-brain barrier, potentially affecting the brain and contributing to cognitive impairment,” Dr. Tesfu explained. “Inflammation is known to have detrimental effects on brain health and has been associated with cognitive decline in various conditions.”

Another study, published in the Journal of Hepatology in August 2022, looked at the relationship between NAFLD and cognitive decline.

In this study, mice with NAFLD and obesity showed signs of anxiety and depression-like behavior, reduced brain oxygen levels, and changes in brain cell activity, all of which suggest that liver conditions may affect brain health.

In other research — which appeared in Frontiers in Neuroscience in May 2023 — scientists from Zhejiang University in China, investigated the effects of nutrition in Alzheimer’s disease.

This research found Western diet poses a risk factor for developing Alzheimer’s disease. A Western diet pattern led to brain inflammation and is associated with the accumulation of harmful proteins in the brain.

Metabolic disorders, such as high cholesterol and fatty liver disease, accompanied these brain changes.

In a study of 30,444 human participants using advanced MRI techniques — published in Nature Communications in 2022 — researchers investigated the relationships between the heart, brain, and liver.

They looked at the structure and function of the heart, the size of the brain, abnormalities in the brain’s white matter, and factors related to the liver, such as fat build-up and inflammation.

The analysis showed that there were direct and indirect connections between these organs, highlighting the impact of dysfunction across multiple organs.

In another study — published in Advanced Drug Delivery Reviews — researchers found that people with dementia and cognitive decline have issues with their cellular energy production and how their bodies process insulin and glucose, similar to what we see in type 2 diabetes and aging.

Some dietary changes and medications used for diabetes have shown promise in improving cognition and reducing dementia symptoms.

Since the liver plays a vital role in processing nutrients, it becomes a crucial target for interventions.

“Understanding the interconnectedness of physical and mental health is vital for comprehensive healthcare. It highlights the need for a holistic approach that considers the impact of various organs and systems on mental well-being and cognitive function. Further research in this field can help unravel the underlying mechanisms of the liver-brain axis and potentially lead to new therapeutic strategies for both liver diseases and cognitive impairment.”

– Dr. Blen Tesfu

A group of studies presented at the Alzheimer’s Association International Conference (AAIC) 2018 explored the connection between the gut, liver, and brain in relation to Alzheimer’s disease. Further results are expected in 2023.

The gut microbiome, diet, and lipid metabolism were identified as key factors. Changes in gut bacteria composition and dietary choices can influence brain health, particularly in Alzheimer’s disease.

Modifying gut bacteria through dietary interventions has shown promising results in improving memory and reducing inflammation in animal models.

Disruptions in lipid metabolism, specifically lower levels of plasmalogens in the liver, may contribute to cognitive impairment and neurodegeneration in Alzheimer’s disease.

Ongoing research aims to understand the complex gut-brain relationship and its implications for the prevention and treatment of Alzheimer’s disease.

More recently, scientists discovered a notable association between liver fibrosis, the formation of scar tissue in the liver due to chronic liver diseases, and a decline in cognitive function.

These findings — published in eBiomedicine in July 2023 — provide support for the existence of a liver-brain axis, emphasizing the interrelationship between the liver and the brain.

The research suggests that specific regions of the brain may experience reduced volume in association with liver fibrosis.

The study revealed that individuals with liver fibrosis displayed lower cognitive abilities and reduced grey matter volume in multiple brain regions, including the hippocampus, thalamus, striatum, brain stem, and cerebellum when compared to healthy participants.

The study underscores the importance of early monitoring and surveillance of liver disease to identify potential cognitive impairments.

Dr. Rongtao Jiang, the lead author of the study, and a postdoctoral associate at Yale, spoke to Medical News Today, noting “that people with advanced liver fibrosis had worse cognitive functioning and grey matter atrophy, and serum [C-reactive protein] mediated the liver-brain associations.”

“Our findings argue for increased attention to those individuals with liver fibrosis, which is associated with both cognitive impairment and brain volume loss. Since early-stage liver fibrosis is reversible, early surveillance and prevention of liver diseases may reduce cognitive decline and brain volume loss.”

– Dr. Rongtao Jiang

Although the study could not establish a cause-and-effect relationship, only correlations, the researchers investigated potential mediators of the connection between liver disease and brain health.

Inflammation, which is associated with numerous liver and brain diseases, was examined as a potential factor.

Using a marker of systemic inflammation called C-reactive protein, the researchers found higher levels of this protein in participants with liver fibrosis compared to those without.

They also discovered a modest yet significant mediating effect of C-reactive protein on the association between liver fibrosis, cognitive function, and brain volume.

These findings suggest that inflammation may partially contribute to the link between the liver and the brain.

Dr. Jiang pointed out that although their study results provided support for a relationship between liver health and cognition function, they could not draw the conclusion that interventions on liver health can help lower the risk of dementia, without further clinical investigation.

Dr. Saurabh Sethi, a gastroenterologist and hepatologist, agreed, telling MNT that “further research is needed to fully understand the complex liver-brain axis and how specific interventions, including diet, exercise, and other lifestyle factors, may impact both liver and brain health.”

“Nevertheless, this study highlights the importance of considering liver health as a potential factor in brain-related conditions and encourages further exploration into the potential benefits of safeguarding liver health for overall brain health.”

However, “maintaining a healthy liver through diet and lifestyle choices is generally recommended for overall well-being,” Dr. Sethi said.

“While it is too early to make definitive claims about preventing dementia solely through liver health, adopting a liver-friendly diet may have broader benefits for brain health and reduce the risk of other diseases.”

– Dr. Saurabh Sethi