Cognitive impairment in celiac disease improves on a gluten-free diet and correlates with histological and serological indices of disease severity

Celiac disease, typically thought of as a gastrointestinal disease, has a wide variety of symptoms that can affect other parts of the body including the mind. Many people with celiac disease report having “brain fog”, a form of cognitive impairment can encompass disorientation, problems with staying focused and paying attention, and lapses in short-term memory. There have only been a few studies that have investigated the link between cognitive function and celiac disease, but those few have supported a possible relationship. This article reports on a recent pilot study looking to further flesh out the possibility of untreated celiac disease causing cognitive impairment.

The study, titled “Cognitive impairment in coeliac disease improves on a gluten-free diet and correlates with histological and serological indices of disease severity” was first published online by Alimentary Pharmacology and Therapeutics on May 28, 2014. The researchers, led by first authors I. T. Lichtwark and E. D. Newnham selected 16 confirmed celiac patients out of a celiac clinic in Melbourne, Australia. Of those, 5 eventually withdrew and were excluded from the study. Various biological and psychological tests were completed by the remaining 11 participants from the start of the study, to the end at 52 weeks.

As expected, the patients showed physical signs of recovery after starting a gluten-free diet. Blood serum levels of tissue transglutaminase (tTG) decreased in every patient, and normalized in 7 patients by the 52nd week. Normalization of tTG was associated with mucosal healing.

Of the eight psychological tests, four showed significant improvement in the patients’ performances over the course of the experiment. The other four tests demonstrated improvement as well but failed to reach statistical significance. Several of the tests also correlated with level of mucosal healing, as determined by Marsh score, as well as blood serum tTG levels. There was no correlation found between cognitive test performance and serum levels of vitamin B12, vitamin D, hemoglobin, or ferritin.

A “foggy” mind or “brain fog” is a very common symptom associated with celiac disease but it has no strict definition and its exact cause is unknown. The level of impairment for patients in this study was comparable to the level of impairment of people with a blood alcohol level of 0.05.

In this pilot study, the authors investigated how this symptom may be related to celiac disease. They offer three possible explanations: One, that micronutrient deficiencies, caused by untreated celiac disease, caused the cognitive impairment. Deficiencies in iron, vitamin D, and folate are known to be associated with cognitive impairment. However, the authors found no correlation between micronutrient deficiency and performance on the battery of psychological tests.

Two, systemic inflammation, caused by untreated celiac disease, leads to high levels of circulating cytokines. Having high levels of circulating cytokines is associated with various mental issues, such as changes in mood and behavior, as well as cognition.

And lastly, three, gluten itself may be directly affecting the cognition of the patients. In animals, studies have shown that gluten in the diet can reduce the amount of brain tryptophan which is used to make serotonin, an important neurotransmitter. Certain opioid proteins can be formed from partially digested gluten. These opioid peptides, called “exorphins” because they come from the outside (as opposed to endorphins, which come from your own body) are known to affect brain function in animals. Getting rid of gluten from the diet might also have effects on the bacteria in the gut, which, in rats, has been demonstrated to change behavior.

More studies are needed to determine the exact mechanism for a how untreated celiac disease leads to cognitive impairment, but it is clear from just this one relatively small study that there is significant impairment and that it is very correlated with intestinal healing.The authors even offer the possibility of using psychological tests in the future to measure how celiac patients intestines’ are healing after being treated with a gluten-free diet.