Natural history of celiac disease-associated antibodies and progression to overt disease in children at increased genetic risk

Background: Celiac disease is a lifelong, gluten-sensitive, autoimmune-mediated chronic enteropathy, tightly associated with risk alleles at the HLA class II genes. Aims: This study was carried out as a part of the population-based Type 1 Diabetes Prediction and Prevention (DIPP) Project. The first aim was to study the natural history of celiac disease-associated antibodies before the diagnosis of celiac disease was made. The second aim was to describe when and in which order celiac disease-associated and type 1 diabetes-associated antibodies appeared in children with genetic risk for both diseases. Subjects and Methods: Antibodies against tissue transglutaminase (TGA) and other celiac disease-associated antibodies were measured in serum samples collected at 3- to 12-month intervals of children at genetic risk for celiac disease who participated in the DIPP project. Celiac disease was confirmed by duodenal biopsy. Type 1 diabetes-associated antibodies were measured in all samples that had been collected. Overt disease was diagnosed according to World Health Organization criteria. Follow-up continued until a diagnosis of type 1 diabetes or until the end of a defined follow-up period. Results: TGA appeared in children at genetic risk for celiac disease only after the first year of life, but anti-gliadin antibodies often emerged significantly earlier, at age 6 months. The data show that spontaneous disappearance of celiac disease-associated antibodies, transient or persisting, is a common phenomenon, at least in prepubertal children. In children with genetic susceptibility to type 1 diabetes and celiac disease, celiac disease-associated antibodies usually develop earlier than the type 1 diabetes-associated antibodies. Conclusions: The transient nature of celiac disease-associated antibodies emphasizes the significance of establishing seropositivity repeatedly in screening detected celiac disease before gastroscopy and duodenal biopsy are considered and emphasized the importance of duodenal biopsy for diagnosing celiac disease.

Genetically Determined Hypometabolism in Alzheimer’s Disease and Midlife Risk Factors for Cognitive Impairment

The role of genetic factors in the pathogenesis of Alzheimer’s disease (AD) is not completely understood. In order to improve this understanding, the cerebral glucose metabolism of seven monozygotic and nine dizygotic twin pairs discordant for AD was compared to that of 13 unrelated controls using positron emission tomography (PET). Traditional region of interest analysis revealed no differences between the non-demented dizygotic co-twins and controls. In contrast, in voxel-level and automated region of interest analyses, the non-demented monozygotic co-twins displayed a lower metabolic rate in temporal and parietal cortices as well as in subcortical grey matter structures when compared to controls. Again, no reductions were seen in the non-demented dizygotic co-twins. The reductions seen in the non-demented monozygotic co-twins may indicate a higher genetically mediated risk of AD or genetically mediated hypometabolism possibly rendering them more vulnerable to AD pathogenesis. With no disease modifying treatment available for AD, prevention of dementia is of the utmost importance. A total of 2 165 at least 65 years old twins of the Finnish Twin Cohort with questionnaire data from 1981 participated in a validated telephone interview assessing cognitive function between 1999 and 2007. Those subjects reporting heavy alcohol drinking in 1981 had an elevated cognitive impairment risk over 20 years later compared to light drinkers. In addition, binge drinking was associated with an increased risk even when total alcohol consumption was controlled for, suggesting that binge drinking is an independent risk factor for cognitive impairment. When compared to light drinkers, also non-drinkers had an increased risk of cognitive impairment. Midlife hypertension, obesity and low leisure time physical activity but not hypercholesterolemia were significant risk factors for cognitive impairment. The accumulation of risk factors increased cognitive impairment risk in an additive manner. A previously postulated dementia risk score based on midlife demographic and cardiovascular factors was validated. The risk score was found to well predict cognitive impairment risk, and cognitive impairment risk increased significantly as the score became higher. However, the risk score is not accurate enough for use in the clinic without further testing.