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Among children with moderate acute malnutrition (MAM) the level of serum cobalamin (SC) and effect of food supplements are unknown. We aimed to assess prevalence and correlates of low SC in children with MAM, associations with hemoglobin and development, and effects of food supplements on SC. A randomized 2 × 2 × 3 factorial trial was conducted in Burkina Faso. Children aged 6 to 23 months with MAM received 500 kcal/d as lipid-based nutrient supplement (LNS) or corn-soy blend (CSB), containing dehulled soy (DS) or soy isolate (SI) and 0%, 20%, or 50% of total protein from milk for 3 months. Randomization resulted in baseline equivalence between intervention groups. Data on hemoglobin and development were available at baseline. SC was available at baseline and after 3 and 6 months. SC was available from 1,192 (74.1%) of 1,609 children at baseline. The mean (±SD) age was 12.6 (±5.0) months, and 54% were females. Low mid-upper arm circumference (MUAC; <125 mm) was found in 80.4% (958) of the children and low weight-for-length z-score (WLZ; <-2) in 70.6% (841). Stunting was seen in 38.2% (456). Only 5.9% were not breastfed. Median (IQR) SC was 188 (137; 259) pmol/L. Two-thirds had SC ≤222 pmol/L, which was associated with lower hemoglobin. After age and sex adjustments, very low SC (<112 pmol/L) was associated with 0.21 (95% CI: 0.01; 0.41, p = 0.04) and 0.24 (95% CI: 0.06; 0.42, p = 0.01) z-score lower fine and gross motor development, respectively. SC data were available from 1,330 (85.9%) of 1,548 children followed up after 3 months and 398 (26.5%) of the 1,503 children after 6 months. Based on tobit regression, accounting for left censored data, and adjustments for correlates of missing data, the mean (95% CI) increments in SC from baseline to the 3- and 6-month follow-up were 72 (65; 79, p < 0.001) and 26 (16; 37, p < 0.001) pmol/L, respectively. The changes were similar among the 310 children with SC data at all 3 time points. Yet, the increase was 39 (20; 57, p < 0.001) pmol/L larger in children given LNS compared to CSB if based on SI (interaction, p < 0.001). No effect of milk was found. Four children died, and no child developed an allergic reaction to supplements. The main limitation of this study was that only SC was available as a marker of status and was missing from a quarter of the children. Low SC is prevalent among children with MAM and may contribute to impaired erythropoiesis and child development. The SC increase during supplementation was inadequate. The bioavailability and adequacy of cobalamin in food supplements should be reconsidered. ISRCTN Registry ISRCTN42569496.

Our group has completed an exercise study of 200 patients with mild Alzheimer's disease. We found improvements in cognitive, neuropsychiatric, and physical measures in the participants who adhered to the protocol. Epidemiological studies in healthy elderly suggest that exercise preserves cognitive and physical abilities to a higher extent in APOE ε4 carriers. In this post hoc subgroup analysis study, we investigated whether the beneficial effect of an exercise intervention in patients with mild AD was dependent on the patients' APOE genotype. We found that patients who were APOE ε4 carriers benefitted more from the exercise intervention by preservation of cognitive performance and improvement in physical measures. This exploratory study establishes a possible connection between the beneficial effects of exercise in AD and the patients' APOE genotype. These findings, if validated, could greatly impact the clinical management of patients with AD and those at risk for developing AD.

This trial showed no significant difference in the percentage of patients who died or had severe disability or coma when higher or lower blood-pressure targets were used after an out-of-hospital cardiac arrest.

SARS-CoV-2 vaccines are crucial in controlling COVID-19, but knowledge of which factors determine waning immunity is limited. We examined antibody levels and T-cell gamma-interferon release after two doses of BNT162b2 vaccine or a combination of ChAdOx1-nCoV19 and BNT162b2 vaccines for up to 230 days after the first dose. Generalized mixed models with and without natural cubic splines were used to determine immunity over time. Antibody responses were influenced by natural infection, sex, and age. IgA only became significant in naturally infected. A one-year IgG projection suggested an initial two-phase response in those given the second dose delayed (ChAdOx1/BNT162b2) followed by a more rapid decrease of antibody levels. T-cell responses correlated significantly with IgG antibody responses. Our results indicate that IgG levels will drop at different rates depending on prior infection, age, sex, T-cell response, and the interval between vaccine injections. Only natural infection mounted a significant and lasting IgA response. This study investigates the dynamics of immunological markers after first SARS-CoV-2 vaccination dose in cohort of healthcare professionals in Denmark. Natural infection was associated with higher antibody responses, and IgG decline varied by age, sex, T-cell response, previous infection, and interval between vaccine doses.

Abstract Background Risk factors for atherosclerotic cardiovascular disease such as smoking, hypertension, physical inactivity, and diabetes have also been associated with risk of dementia. Whether hypertriglyceridemia represents a shared risk factor as well remains unknown. We tested the hypothesis that hypertriglyceridemia is associated with increased risk of non-Alzheimer dementia, Alzheimer disease, and ischemic stroke. Methods Using the Copenhagen General Population Study and the Copenhagen City Heart Study, we examined the association between increased plasma triglycerides and risk of non-Alzheimer dementia, Alzheimer disease, and ischemic stroke with Cox regression. Results On a continuous scale, higher concentrations of plasma triglycerides were associated with increased risk of non-Alzheimer dementia and ischemic stroke, but not with Alzheimer disease. In age, sex, and cohort adjusted models, the highest percentile of triglycerides (median 629 mg/dL; 7.1 mmol/L) versus the 1–50th percentiles (median 89 mg/dL; 1.0 mmol/L) was associated with hazard ratios of 1.75 (95% confidence interval: 1.17–2.63) for non-Alzheimer dementia, 1.18 (0.73–1.91) for Alzheimer disease, and of 1.89 (1.50–2.38) for ischemic stroke. Corresponding hazard ratios were 1.62 (1.08–2.44), 1.25 (0.77–2.02), and 1.57 (1.24–1.98) in models adjusted multifactorially, and 1.79 (1.16–2.87), 1.18 (0.73–1.92), and 1.46 (1.10–1.95) in models adjusted multifactorially and additionally for apolipoprotein E (APOE) genotype, respectively. Results were similar after excluding individuals who had an event within 2 years after study entry. Conclusions Moderate hypertriglyceridemia was associated with increased risk of both non-Alzheimer dementia and ischemic stroke, highlighting plasma triglycerides as a shared risk factor between dementia and atherosclerotic cardiovascular disease.

Dementia is a major cause of disability, and risk-factor reduction may have the potential to delay or prevent the disease. Our aim was to determine the absolute 10-year risk of dementia, by age, sex and apolipoprotein E (APOE) genotype. We obtained data from the Copenhagen General Population Study (from 2003 to 2014) and the Copenhagen City Heart Study (from 1991 to 1994 and 2001 to 2003). Participants underwent a questionnaire, physical examination and blood sampling at baseline. Diagnoses of dementia and cerebrovascular disease were obtained from the Danish National Patient Registry up to Nov. 10, 2014. Among 104 537 individuals, the absolute 10-year risk of Alzheimer disease in 3017 women and men who were carriers of the APOE ɛ44 genotype was, respectively, 7% and 6% at age 60–69 years, 16% and 12% at age 70–79 years, and 24% and 19% at age 80 years and older. Corresponding values for all dementia were 10% and 8%, 22% and 19%, and 38% and 33%, respectively. Adjusted hazard ratios (HRs) for all dementia increased by genotype, from genotype ɛ22 to ɛ32 to ɛ33 to ɛ42 to ɛ43 to ɛ44 (p for trend < 0.001). Compared with ɛ33 carriers, ɛ44 carriers were more likely to develop Alzheimer disease (adjusted HR 8.74, 95% confidence interval [CI] 7.08–10.79), vascular dementia (adjusted HR 2.87, 95% CI 1.54–5.33), unspecified dementia (adjusted HR 4.68, 95% CI 3.74–5.85) and all dementia (adjusted HR 5.77, 95% CI 4.89–6.81). Age, sex and APOE genotype robustly identify high-risk groups for Alzheimer disease and all dementia. These groups can potentially be targeted for preventive interventions.

The heterogeneity of the SARS-CoV-2 immune responses has become considerably more complex over time and diverse immune imprinting is observed in vaccinated individuals. Despite vaccination, following the emergence of the Omicron variant, some individuals appear more susceptible to primary infections and reinfections than others, underscoring the need to elucidate how immune responses are influenced by previous infections and vaccination. IgG, IgA, neutralizing antibodies and T-cell immune responses in 1,325 individuals (955 of which were infection-naive) were investigated before and after three doses of the BNT162b2 vaccine, examining their relation to breakthrough infections and immune imprinting in the context of Omicron. Our study shows that both humoral and cellular responses following vaccination were generally higher after SARS-CoV-2 infection compared to infection-naive. Notably, viral exposure before vaccination was crucial to achieving a robust IgA response. Individuals with lower IgG, IgA, and neutralizing antibody responses postvaccination had a significantly higher risk of reinfection and future Omicron infections. This was not observed for T-cell responses. A primary infection before Omicron and subsequent reinfection with Omicron dampened the humoral and cellular responses compared to a primary Omicron infection, consistent with immune imprinting. These results underscore the significant impact of hybrid immunity for immune responses in general, particularly for IgA responses even after revaccination, and the importance of robust humoral responses in preventing future infections. In this study, the authors investigate immune responses following a third (booster) SARS-CoV-2 vaccination dose in a cohort of healthcare professionals in Denmark. They find stronger immune responses among those with a prior infection, and correlation between lower antibody responses and higher risk of subsequent breakthrough infection.

Context:Recently, data on 2,000,000 people established that low body mass index (BMI) is associated with increased risk of dementia. Whether this observational association reflects a causal effect remains to be clarified.Objective:We tested the hypothesis that there is a causal association between low BMI and high risk of Alzheimer’s disease.Design, Setting, and Participants:Using a Mendelian randomization approach, we studied 95,578 individuals from the Copenhagen General Population Study (CGPS) with up to 36 years of follow-up and consortia data on 303,958 individuals from the Genetic Investigation of Anthropometric Traits (GIANT) and the International Genomics of Alzheimer's Project (IGAP).Main Outcome Measure:Risk of Alzheimer’s disease.Results:The causal odds ratio for a 1-kg/m2 genetically determined lower BMI was 0.98 [95% confidence interval (CI), 0.77 to 1.23] for a weighted allele score in the CGPS. Using 32 BMI-decreasing variants from GIANT and IGAP the causal odds ratio for Alzheimer’s disease for a 1-standard deviation (SD) lower genetically determined BMI was 1.02 (95% CI, 0.86 to 1.22). Corresponding observational hazard ratios from the CGPS were 1.07 (95% CI, 1.05 to 1.09) and 1.32 (95% CI, 1.20 to 1.46) for a 1-kg/m2 and a 1-SD lower BMI, respectively.Conclusions:Genetic and hence lifelong low BMI is not associated with increased risk of Alzheimer’s disease in the general population. These data suggest that low BMI is not a causal risk factor for Alzheimer’s disease and that the corresponding observational association likely is explained by reverse causation or confounding.In this Mendelian randomization study of 399,536 individuals, genetic and hence lifelong lower BMI was not associated with higher risk of Alzheimer’s disease, in contrast to observational associations.

Environmental enteropathy (EE) may increase the risk of diabetes, but data are limited. We assessed the role of EE on markers of glucose metabolism. Cross-sectional study among Tanzanian adults assessing EE and diabetes was conducted between 2019 and 2021. Data on demography, body mass index (BMI), Human immunodeficiency virus (HIV), EE (i.e., fecal myeloperoxidase, lipopolysaccharide binding protein, and markers of intestinal permeability and absorption capacity), glucose and insulin were collected. Data reduction using principal components analysis produced two components: sugar uptake and inflammatory EE. Tertiles were used to define EE severity as: lower, middle, and upper. The main outcome, combined prediabetes and diabetes, was defined as 2-hour oral glucose tolerance test (OGTT) glucose ≥7.8 mmol/L. Lower homeostatic model assessment (HOMA)-β and insulinogenic index, higher HOMA-insulin resistance (HOMA-IR), and lower Matsuda index were secondary outcomes. Logistic regression assessed the associations and HIV and BMI groups were tested as effect modifiers. A total of 612 participants were included. The mean (±SD) age was 42.0 (±11.6) years and 57.2% (350) were females. Eighty (13%) were underweight, 367 (60%) normal weight, 165 (27%) overweight, and 357 (58%) were HIV-infected. We found no overall association of EE on the main outcome, but BMI and HIV modified the associations. Compared to lower tertile of sugar uptake EE, the upper tertile was associated with marginally significant higher odds of prediabetes and diabetes (OR=2.1 (95% CI: 0.9, 4.9; P = 0.06)) and marginally significant higher HOMA-IR (OR=2.6 (1.0, 6.8; P = 0.06)) among overweight and obese participants. Similarly, compared to the lower tertile, the upper tertile of inflammatory EE was associated with higher odds of prediabetes and diabetes (OR=2.1 (1.1, 4.1; P = 0.03)) among HIV-uninfected participants, whereas among HIV-infected participants those in the middle tertile compared to those in the lower tertile had higher odds of lower Matsuda index (OR=2.3 (1.1, 4.7; P = 0.03)). EE may increase the risk of prediabetes and diabetes among those who are overweight and in individuals who are not HIV-infected. Longitudinal studies on the role of EE on diabetes are needed to confirm these results to provide the basis for developing and testing novel interventions to combat diabetes in Africa.

The increased burden of non-communicable diseases (NCDs) is fueled by lifestyle factors including diet. This cross-sectional study explored among Tanzanian adults whether unhealthy dietary patterns are associated with intestinal and systemic inflammation which could increase the risk of NCDs. The study included 574 participants, with both diet and inflammatory markers data. Dietary patterns were derived using principal component analysis and reduced rank regression, revealing three main patterns: vegetable-rich, vegetable-poor, and carbohydrate-dense diets. Fecal myeloperoxidase (MPO) and neopterin (NEO) were markers of intestinal inflammation whereas plasma lipopolysaccharide-binding protein (LBP) and C-reactive protein (CRP) were assessed as markers of systemic inflammation. Ordinal logistic regression was used to assess associations between terciles of dietary patterns and quintiles of the inflammatory markers adjusting for potential confounders. High adherence to a vegetable-poor dietary pattern was associated with elevated MPO (adjusted OR, 1.7 95% CI 1.1, 2.8). NEO tended to be higher in people with high adherence to both vegetable-poor pattern (adjusted OR, 2.6 95% CI 1.0, 6.4) and vegetable-rich pattern (adjusted OR, 2.7, 95% CI 1.1, 6.5). No associations were found between dietary patterns and systemic inflammation markers (LBP and CRP). We found links between dietary vegetable intake and intestinal inflammation but not systemic inflammation. However, the cross-sectional nature of the study limits establishing causality and the sample size for some variables may have been inadequate, emphasizing the need for further studies to understand how dietary habits influence inflammation in this population.