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