Dementia in Celiac Disease

Abstract & Commentary

By Gunnar Gouras, MD, Associate Professor of Neurology and Neuroscience, Weill Medical College, Cornell University. Dr. Gouras reports no financial relationship relevant to this field of study.

Synopsis: Clinical-pathological study of patients with onset of dementia within 2 years of gastrointestinal symptom onset in Celiac disease.

Source: Hu WT et al. Cognitive Impairment and Celiac Disease. Arch Neurol. 2006;63:1440-1446.

An association between Celiac disease (CD) and cognitive decline has been described mainly in case reports; therefore, the 13 patients identified by Hu and colleagues from the medical records of the Mayo Clinic between 1970 and 2005 represent the largest study on CD and dementia. The authors provide comprehensive clinical-pathological descriptions of these 13 patients who were selected because they both had intestinal biopsy confirmed CD and developed dementia within 2 years of the onset of gastrointestinal symptoms (median age at onset 64; range 45–79). Ataxia was the most common additional neurological symptom seen in 10 of the patients; 2 patients had dementia as their only neurological symptom.

Remarkably, patients had an insidious subacute onset of cognitive decline with scores on cognitive testing consistent with moderate dementia. Indeed, 3 patients were given a diagnosis of possible Creutzfeldt-Jakob disease (CJD) because of initially rapid onset of dementia in association with ataxia, with 2 of 3 cases also having myoclonus and seizures. CJD was subsequently ruled out by neuropathological examination. Amnesia, acalculia, confusion, and personality changes were the most common initial cognitive features. The investigators noted that patients with onset of cognitive impairment within the first year after onset of GI symptoms had lower average cognitive scores than those with onset of cognitive decline in the second year. Neuropathological studies were carried out in 5 of 13 patients and showed non-specific gliosis, although one patient had ubiquitin-positive inclusions consistent with frontotemporal lobar degeneration with ubiquitin-only immunoreactive changes; the authors speculated that this might have been coincidence. Focal or generalized slowing was seen in 6 of 9 patients who had an EEG. The most common MRI abnormalities among the 7 patients who had brain MRIs were generalized atrophy (6 patients); frontal atrophy was seen in the remaining patient). Non-specific scattered or confluent white matter T2 hyperintensities on MRI were also common.

The authors discuss the possible pathophysiological cause of this association, supporting an autoimmune mechanism in CD-associated dementia, analogous to CD-associated ataxia. The possibility of nutritional deficiency in CD is discussed, although the authors point out that in the 6 patients found to have reduced vitamin B12, folate or vitamin E, subsequent supplementation and normalization did not lead to cognitive improvement.

Commentary

Finding additional causes of dementia and awareness of neurological symptoms associated with systemic diseases are important. Neurological symptoms are estimated to occur in about 10% of patients with celiac disease. Although ataxia and peripheral neuropathy are the most frequently described neurological symptoms, cognitive dysfunction needs to be considered.

Caveats in interpreting this interesting study linking dementia to CD include that 13 patients is still a small number. It is also not fully clear when cognitive testing was performed and how much progression there was in the cognitive decline of these patients. Encouraging improvement or stabilization with a gluten-free diet was noted in 3 of the patients in this study, although more information on the adherence to a gluten-free diet among all the patients studied might have been helpful. The authors justifiably argue that the association between CD and cognitive impairment is unlikely only due to chance, especially since onset of GI and neurological symptoms occurred simultaneously in 5 patients. Further studies on this interesting association will be necessary.