Public release date: 9-Oct-2006
Contact: Lisa Lucier
newsbureau@mayo.edu
507-284-5005
Mayo Clinic

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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