Aims/hypothesis There is debate about increased mortality risk associated with low levels of glycaemia. To address this issue, we examined the shape of the risk relationship between glycated haemoglobin and mortality in a UK population. 16-1.80]). Spline regression suggested no increased risk at the low end of the distribution. Indeed, the HR for all-cause mortality was virtually constant in the low range and only started to rise when the level was approximately 5.5%. There were similar associations of glycated haemoglobin with cause-specific mortality, with the strongest association being seen for cardiovascular mortality. Conclusions/interpretation Our findings in a large nondiabetic population do not support the concern about increased mortality risk with low glycated haemoglobin. Differences in population characteristics might explain contrary results of earlier studies and need further exploration.

Objective Stressful life events (SLE) have been associated with increased dementia risk, but their association with cognitive decline has been inconsistent. In a longitudinal population-based study of elderly individuals, we examined the association between SLE and cognitive decline, and the role of potential effect modifiers. Methods A total of 2665 non-demented participants of the Cache County Memory Study completed a stress life events questionnaire at Wave 2, and were revisited 4 and 7 years later. The events were represented via several scores: total number, subjective rating (negative, positive, unexpected), and a weighted summary based on their impact. Cognition was assessed at each visit with the modified Mini-Mental State Exam. General linear models were used to examine the association between SLE scores and cognition. Effect modification by age, education, and APOE genotype was tested. Results Years of formal education (p = 0.006) modified the effect of number of SLE, and age (p = 0.009) modified the effect of negative SLE on the rate of cognitive decline. Faster decline was observed among those with fewer years of education experiencing more SLE and also among younger participants experiencing more negative SLE. There was no association between other indicators of SLE and cognitive decline. APOE genotype did not modify any of the above associations. Conclusions The effects of SLE on cognition in late life are complex and vary by individual factors such as age and education. These results may explain some of the contradictory findings in the literature.

BACKGROUND Maternal folate intake and related biomarkers have been inconsistently associated with a risk of oral clefts. METHODS Maternal concentrations of plasma folate (PF) and erythrocyte folate (EF), plasma pyridoxal-5′-phosphate (PLP; active vitamin B6) and total plasma homocysteine (tHcy) were measured in a Utah study with 347 cases and 469 controls. RESULTS Risk of all clefts combined, including cleft lip with or without cleft palate (CL/P) and cleft palate only (CP), was 65% lower in the highest versus lowest PF quartile (odds ratio [OR], 0.35; 95% confidence interval [CI], 0.23–0.53; p-trend < 0.001). Results remained significant in the subgroups with isolated CL/P and CP (p-trend < 0.001 in each). EF results were similar. In the highest versus lowest PLP quartile, risk of CP with other malformations was lower (OR, 0.25; 95% CI, 0.07–0.95); however, no other associations were significant for PLP or tHcy. Differences in mean bio-marker levels between cases and controls widened with an increasing interval between delivery and maternal blood collection. Decreased cleft risk with increasing quartiles of PF, EF, and PLP and decreasing tHcy was more apparent in mothers with a longer versus shorter interval between the index child delivery and blood collection. CONCLUSION Low maternal blood folate concentration was associated with an increased risk of clefts, and the differences in mean case and control PF, EF, PLP, and tHcy concentrations widened over time. Additional mechanistic studies are warranted to elucidate whether an acquired or inherited disorder of folate metabolism plays a role in the etiology of clefts.

These results suggest that depression may be less prevalent in populations of dementia caregivers than in clinic-based samples, but that the correlates of depression are similar for both population and convenience samples. Interventions targeting individuals with small support networks, emotion-focused coping styles, poorer health, low quality of life, and those caring for persons with higher numbers of behavioral problems need development and testing.