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Brain images show celiac disease related damage

March 25, 2020

Brain injury, cognitive deficiency and mental health issues tied to gluten exposure, study finds

A DTI scan of the brain

By Amy Ratner, Medical and Science News Analyst

People with celiac disease have a greater risk of brain damage and mental health issues, according to a new study based on brain images and cognitive test scores.

Researchers from the University of Sheffield, Sheffield, UK, attributed the neurological damage to gluten exposure, including inadvertent exposure in those following the gluten-free diet.

The study concluded that patients with celiac disease had “had cognitive deficit, worsened mental health and white matter changes based on analysis of brain images.”

“For the first time, the study offers some clarity on the fact that there does appear to be the risk of neurological damage for people living with celiac disease, driven by their autoimmune response to gluten exposure,” said Iain Croall, PhD, a study author and research fellow in the academic unit of radiology at Royal Hallamshire Hospital.

“Neuropsychological impairment in people with celiac disease has been overlooked for too long, despite accumulating anecdotal reports,” said Salvatore Alesci, MD, Beyond Celiac chief scientist and strategy officer. “The Sheffield study provides the first scientifically robust and objective evidence that significant brain changes occur in celiac disease as a result of gluten exposure.”

Researchers hope the study will alert physicians to even mild cognitive changes in patients, which previously were likely overlooked. Additionally, the study should motivate physicians to advise that patients strictly follow the gluten-free diet since it is the best way to limit progression of brain injury, according to the authors.

“While gastrointestinal injury is generally understood to recover on a [gluten-free diet], the brain is far less capable of this and acquired neurological deficits will accumulate and persist for the rest of the patient’s life,” says the study, which was published in the journal Gastroenterology.

Alesci noted that while the results need to be validated through continued investigation, the study clearly points to the important link between the gut, immune response and the brain. “This calls for increased awareness among physicians of the need to consistently incorporate mental health evaluation in the diagnosis and follow-up of celiac disease,” he said.

Measuring neurological damage

The study is based on a comparison of samples from 105 celiac disease patients and healthy controls collected through the National UK Biobank. The Biobank contains medical data from 500,000 adult volunteers. Sheffield researchers obtained results of cognitive test scores and surveys about mental health, as well as MRI brain imagining analysis from Biobank participants identified as having celiac disease. These were compared to matched healthy controls.

Bias in research: any tendency which prevents unprejudiced consideration of a question 6. In research, bias occurs when systematic error is introduced into sampling or testing by selecting or encouraging one outcome or answer over others. It can occur in study design or data collection data analysis and publication.


“All this means that the data was collected entirely independently,” Croall said. Use of the biobank data removes bias and validates previous research that has shown that celiac disease involves some level of injury to the brain and subsequently some cognitive problems, he noted. Limitations of earlier studies included the possibility that bias accounts for the wide range of prevalence estimates of neurological symptoms in those with celiac disease. Some research has found these symptoms in up to 50 percent of newly diagnosed patients, while other investigations have found none.

The Sheffield study suggests the variation in findings is due to research being done by groups that are focused on either gastroenterology or neurology. “This study, which has found a range of neurological findings in an independent cohort of patients with celiac disease is an important addition to the discussion,” the study authors write.

Brain scans

A brain scan designed to detect very small changes in the brain’s white matter found that people with celiac disease appeared to have suffered some injury in locations including the brainstem, thalamus and corpus callosum, Croall said.

The scan is very sensitive in detecting changes to the white matter that can’t be seen on more conventional kinds of imaging. Researchers use computer processing to produce Diffusion Tensor Imaging (DTI) values for different parts of the brain, which give an indication of its health. “We found in the study that people with celiac disease consistently had different DTI values in the parts of the brain previously mentioned when compared to controls, which in research is a sign of injury to those parts of the brain’s white matter tracts,” Croall explained.

Cognitive and mental health

Additionally, those with celiac disease also had slower reaction time in 12 rounds of a test similar to a popular card game in which players react quickly to spot pairs of cards of the same rank. Significant differences were not found in several other tests of cognitive health. The study also found higher anxiety, depression, thoughts of self-harm and health related unhappiness in those with celiac disease based on questionnaires filled out as part of participation in the biobank.

Related: Beyond Celiac brain fog study

When MRI evidence and survey responses were both considered, they provided evidence of physical injury to the brain as well as meaningful impacts on patients’ psychological health and wellbeing, the study concludes.

Neurological symptoms not trivial

Although the neurological consequences of celiac disease may not be readily apparent, they should not be considered trivial, according to study authors.  In fact, the lower level of severity leads to these symptoms going unrecognized, the study says. “The [study results] highlight the importance of awareness of neurological involvement in celiac disease and the ways in which these can meaningfully affect patients,” the authors wrote.

Study limitations include the lack of information including how long patients had been diagnosed, how well they were following the gluten-free diet and the results of blood tests for antibodies to gluten. Additionally, the patients studied were likely to be healthier due to some study exclusion criteria and to represent a similar, or heterogeneous, group. Study authors said they are confident in results but note that they might under represent the scale of neurological problems in celiac disease. Also, more investigation is needed in those with gluten sensitivity and undiagnosed celiac disease.

You can find the study here.


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