Mayo Clinic discovers potential link between celiac disease and cognitive decline

ROCHESTER, Minn. -- Mayo Clinic researchers have uncovered a new link between celiac disease, a digestive condition triggered by consumption of gluten, and dementia or other forms of cognitive decline. The investigators' case series analysis -- an examination of medical histories of a group of patients with a common problem -- of 13 patients will be published in the October issue of Archives of Neurology.

"There has been very little known about this connection between celiac disease and cognitive decline until now," says Keith Josephs, M.D., Mayo Clinic neurologist and study investigator. "This is the largest case series to date of patients demonstrating cognitive decline within two years of the onset of celiac disease symptom onset or worsening."

Says Joseph Murray, M.D., Mayo Clinic gastroenterologist and study investigator, "There has been a fair amount written before about celiac disease and neurological issues like peripheral neuropathy (nerve problems causing numbness or pain) or balance problems, but this degree of brain problem -- the cognitive decline we've found here -- has not been recognized before. I was not expecting there would be so many celiac disease patients with cognitive decline."

The next step in the research will be to investigate the measure and nature of the connection between the two conditions.

"It's possible it's a chance connection, but given the temporal link between the celiac symptoms starting or worsening and the cognitive decline within a two-year time span, especially the simultaneous occurrence in five patients, this is unlikely a chance connection," says Dr. Josephs. "Also, these patients are relatively young to have dementia."

Theories to explain the connection between celiac disease and cognitive decline include the following, according to Dr. Murray:

  • Nutritional deficiency
  • Inflammatory cytokines -- chemical messengers of inflammation that could contribute to problems in the brain
  • An immune attack on the brain that may occur in some patients with celiac disease

The cognitive decline that occurred in three of the celiac disease patients studied, according to Dr. Josephs, is relatively unique in its reversal in two of the patients and stabilization in one patient. Typically, cognitive decline continues to worsen, he says. "This is key that we may have discovered a reversible form of cognitive impairment," he says.

William Hu, M.D., Ph.D., Mayo Clinic neurology resident and study investigator, says that the reversal or stabilization of the cognitive symptoms in some patients when they underwent gluten withdrawal also argues against chance as an explanation of the link between celiac disease and cognitive decline.

Currently, the investigators do not know which celiac disease patients are at risk for cognitive decline; this deserves future investigation, says Dr. Hu.

Dr. Murray suggests that recognizing and treating celiac disease early will likely prevent most consequences of the disease, including symptoms in the gut or the brain. For celiac disease patients who have already developed cognitive decline, closely following a gluten-free diet may result in some symptom improvement, he says. For those with cognitive decline without a confirmed diagnosis of celiac disease, he does not recommend a gluten-free diet, however.

Physicians can play an important role in keeping alert to a potential celiac disease and cognitive decline connection, says Dr. Hu.

"For patients who come in with atypical forms of dementia, we need to consider checking for celiac disease, especially if the patients have diarrhea, weight loss or a younger age of onset -- under age 70," he says.

To conduct this case series analysis, the researchers identified 13 Mayo Clinic patients with documented cognitive impairment within two years of onset of symptoms or severe exacerbation of adult celiac disease. All celiac disease had been confirmed by small-bowel biopsy, and any patients for whom an alternate cause of cognitive decline could be identified were excluded from the analysis. Patients included five women and eight men, with a median onset of cognitive decline at age 64 that coincided with onset or worsening of symptoms of diarrhea, the presence of excess fat in the stools and abdominal cramping in five patients. The most common reasons for seeking medical help were amnesia, confusion and personality changes. The average score on the Short Test of Mental Status among the 13 patients was 28 out of 38 possible total, indicating moderate cognitive impairment. Ten patients experienced loss of coordination and four experienced symptoms of peripheral neuropathy. Four patients demonstrated deficiency in folate, vitamin B-12, vitamin E or a combination of these deficiencies, although supplementation did not improve the patients' cognitive decline. Three patients' cognitive decline either improved or stabilized when they completely withdrew from gluten consumption. A brain autopsy or biopsy was completed in five patients, and there was no evidence of Alzheimer's disease or any other well-known causes for dementia.

Celiac disease occurs in 1 out of 133 people and predominantly affects Caucasians, according to Dr. Murray. Symptoms can include intermittent diarrhea, abdominal pain and bloating, or no gastrointestinal symptoms at all. It can also manifest in weight loss, fatigue, anemia, general weakness, foul-smelling or grayish stools that may be fatty or oily, osteoporosis or stunted growth (in children only). The condition may also cause symptoms far outside of the gut. Nine out of 10 times, the disease is not discovered due to the vague nature of the symptoms, according to Dr. Murray. The treatment for celiac disease is a gluten-free diet. For further information on celiac disease, see http://www.mayoclinic.com/health/celiac-disease/DS00319.

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Last reviewed: By John M. Grohol, Psy.D. on 21 Feb 2009
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