ABSTRACT
BACKGROUND: Metabolites involved in one-carbon metabolism (OCM) may predict cognitive prognosis in dementia. The link between OCM, apolipoprotein E (APOE), and DNA methylation creates a biologically plausible mechanism of interaction. AIM: To assess OCM metabolites as predictors of 5-year cognitive prognosis in patients with mild dementia, and in subgroups defined by the APOEε4 allele variant. METHODS: We followed one-hundred and fifty-two patients with mild dementia (86 with Alzheimer's disease, 66 with Lewy body dementia, including 90 with at least one APOEε4 allele) for 5â¯years with annual Mini-Mental State Examinations (MMSE). Total homocysteine, methionine, choline, betaine, dimethylglycine, sarcosine, folate, cobalamin and pyridoxal 5'-phoshate were measured in serum at baseline. We used linear mixed models to assess metabolite-MMSE associations, including 3-way interactions between metabolites, time, and APOEε4. False-discovery rate adjusted p-values (Q-values) are reported. RESULTS: Metabolite concentrations were not different in patients with dementia according to the presence of APOEε4. Overall, serum concentration of total homocysteine was inversely associated with MMSE performance, while betaine was positively associated with MMSE (Qâ¯<â¯0.05), but neither was associated with MMSE decline. Serum concentrations of betaine, dimethylglycine and sarcosine, however, were associated with slower MMSE decline in patients with APOEε4, but with faster MMSE decline in patients without the allele (all 3-way interactions: Qâ¯<â¯0.05). CONCLUSION: Components of the choline oxidation pathway are associated with a better cognitive prognosis in APOEε4 carriers and a worse cognitive prognosis in non-carriers. Further research investigating targeted metabolic interventions according to APOE allele status is warranted.
Subject(s)
Apolipoprotein E4/genetics , Choline/metabolism , Dementia/genetics , Dementia/metabolism , Aged , Alzheimer Disease/diagnosis , Alzheimer Disease/genetics , Alzheimer Disease/metabolism , Cognitive Dysfunction/diagnosis , Cognitive Dysfunction/genetics , Cognitive Dysfunction/metabolism , Dementia/diagnosis , Female , Humans , Lewy Body Disease/diagnosis , Lewy Body Disease/genetics , Lewy Body Disease/metabolism , MaleABSTRACT
BACKGROUND: Describing vitamin D status and its predictors in various populations is important in order to target public health measures. OBJECTIVES: To describe the status and predictors of vitamin D status in healthy Nepalese mothers and infants. METHODS: 500 randomly selected Nepalese mother and infant pairs were included in a cross-sectional study. Plasma 25(OH)D concentrations were measured by LC-MS/MS and multiple linear regression analyses were used to identify predictors of vitamin D status. RESULTS: Among the infants, the prevalence of vitamin D insufficiency (25(OH)D <50 nmol/L) and deficiency (<30 nmol/L) were 3.6% and 0.6%, respectively, in contrast to 59.8% and 14.0% among their mothers. Infant 25(OH)D concentrations were negatively associated with infant age and positively associated with maternal vitamin D status and body mass index (BMI), explaining 22% of the variability in 25(OH)D concentration. Global solar radiation, maternal age and BMI predicted maternal 25(OH)D concentration, explaining 9.7% of its variability. CONCLUSION: Age and maternal vitamin D status are the main predictors of vitamin D status in infants in Bhaktapur, Nepal, who have adequate vitamin D status despite poor vitamin D status in their mothers.
Subject(s)
Infant Nutritional Physiological Phenomena , Maternal Health , Nutritional Status , Vitamin D Deficiency/epidemiology , Vitamin D/analogs & derivatives , Adolescent , Adult , Biomarkers/blood , Body Mass Index , Chromatography, Liquid , Cross-Sectional Studies , Female , Humans , Infant , Lactation/blood , Linear Models , Male , Maternal Age , Nepal/epidemiology , Prevalence , Risk Factors , Sunlight , Tandem Mass Spectrometry , Vitamin D/blood , Vitamin D Deficiency/blood , Vitamin D Deficiency/diagnosis , Young AdultABSTRACT
BACKGROUND: Neopterin levels and kynurenine/tryptophan ratios (KTRs) increase with IFN-γ stimulation, indicating TH1 immunity, and thus might be inversely associated with asthma. OBJECTIVE: We sought to examine the association of maternal neopterin levels and KTRs during pregnancy with asthma in the offspring. METHODS: We analyzed the associations of maternal plasma total neopterin levels and KTRs in midpregnancy with asthma at age 7 years among 2883 children in the Norwegian Mother and Child Cohort Study. Asthma was classified either based on registered dispensed asthma medications in the Norwegian Prescription Database or maternal report. We calculated adjusted relative risks using log-binomial regression. RESULTS: The median gestational week of blood sampling was 18 weeks (interquartile range, 17-19 weeks). The risk of dispensed asthma medications at age 7 years was highest among children of mothers in the highest quartile of neopterin levels, whereas the risk was similar in the 3 lowest quartiles. The adjusted relative risk of dispensed asthma medications was 1.66 (95% CI, 1.16-2.38) when comparing children of mothers in the highest quartile with those in the 3 lowest quartiles. A similar association was observed for maternal report of asthma at age 7 years. When we evaluated allergic versus nonallergic asthma, neopterin levels tended to be associated with nonallergic asthma. Maternal KTR was not associated with asthma development. CONCLUSIONS: Our findings indicate that high maternal levels of neopterin, a marker of cellular immune activation, during pregnancy were positively associated with asthma in offspring. Experimental studies would be needed to further elucidate underlying mechanisms.
