Research led by Yale scientists has uncovered a relationship between liver fibrosis – the scarring of liver tissue caused by many chronic liver diseases – and diminished cognitive abilities, potentially mediated in part by inflammation.
The study, published in the journal eBioMedicine on June 23, supports the concept of a liver-brain axis and underscores the need for early monitoring and intervention for liver diseases.
Interconnected Health: The Mind and Body
There is growing scientific evidence that the health of the brain is interconnected with the overall health of the body.
This has led to a changing perspective on the separation between disorders affecting the brain and other types of physical health.
As Dustin Scheinost, Associate Professor at Yale School of Medicine and senior author of the study, explains, “We’re starting to understand that liver disease, heart disease, and other diseases will have impacts on the brain, and brain disorders have impacts on the body.”
The UK Biobank Study and Findings
In this study, Scheinost and his team utilized data from the UK Biobank, a large health information database containing data from over half a million adults.
The extensive dataset enabled the researchers to investigate the potential liver-brain connection across a subset of the general population, and uncover impacts that may be difficult to detect in smaller datasets.
The team evaluated data on liver fibrosis, cognitive function – such as working memory, problem-solving skills, and processing speed – and gray matter volume in different brain regions.
They discovered that compared to healthy participants, individuals with liver fibrosis showed reduced cognitive abilities and a decrease in gray matter volume in several brain regions, including the hippocampus, thalamus, striatum, and brain stem.
Inflammation: A Potential Mediator?
Although the study could not establish a cause-and-effect relationship, only correlations, the team was able to explore potential mediators of the connection between liver disease and brain health.
They focused on inflammation, which is implicated in many liver and brain diseases.
Using a systemic inflammation marker, the C-reactive protein, the team found that levels were higher in participants with liver fibrosis than those without.
They also uncovered a small but significant mediating effect of C-reactive protein on the association between liver fibrosis, cognitive function, and brain volume.
These findings suggest inflammation may contribute, in part, to the link between liver and brain health.
Early Surveillance and Prevention
The results of the study emphasize the importance of early surveillance and prevention of liver disease.
According to Rongtao Jiang, a postdoctoral associate in Scheinost’s lab and lead author of the study, early-stage liver fibrosis is reversible, and early intervention could potentially reduce cognitive decline and brain volume loss.
Moreover, since inflammation seems to play a role in this connection, targeting inflammation with specific drugs or interventions might help to prevent the disease burden of liver fibrosis.
Implications for Alzheimer’s Disease
The study also offers evidence that preventing liver disease could help delay the progression of neurodegenerative diseases like Alzheimer’s.
Previous research has demonstrated a link between liver disease and Alzheimer’s, showing that amyloid-beta deposits implicated in Alzheimer’s originate in and are cleared from the blood by the liver.
Liver dysfunction could, therefore, lead to insufficient amyloid-beta clearance and accumulation in the brain.
Notably, the brain regions most strongly associated with liver fibrosis in the study – the hippocampus, thalamus, and striatum – are often among the first to suffer volume loss in aging and early Alzheimer’s disease.
Scheinost summarizes the impact of the study by highlighting the profound interconnection of physical, mental, and brain health.
“In some ways, it’s about taking care of yourself as a whole. Any piece of the puzzle you can address is probably going to have other downstream effects and benefits.”
If you care about liver health, please read studies about a diet that can treat fatty liver disease and obesity, and coffee drinkers may halve their risk of liver cancer.
For more information about liver health, please see recent studies that anti-inflammatory diet could help prevent fatty liver disease, and results showing vitamin D could help prevent non-alcoholic fatty liver disease.
The study was published in eBioMedicine.
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