Potential use of other starch sources in the treatment of glycogen storage disease type Ia - an in vitro study.

BACKGROUND: Glycogen storage disease type Ia (GSD-Ia) is one of the most common hepatic GSD. Its treatment mainly consists of a diet including a high intake of slow-digestion carbohydrates such as raw cornstarch and the restriction of simple sugars. This enables the maintenance of euglycemia and prevents secondary metabolic disorders. Starch is a glucose polymer formed by amylose and amylopectin, which can be obtained from distinct sources. Although uncooked cornstarch has been successfully used in the treatment of GSD-Ia, it can lead to hyperglycemia and weight gain. in vitro andin vivo tests indicated that sweet manioc starch can be potentially used in the treatment of GSD-Ia. RESULTS: The moisture analysis revealed a variation from 10.3 to 12.8% in the sweet manioc starch samples, whereas the moisture content of uncooked cornstarch ranged from 7.3 to 11.1%. Quantifiable sugar was detected in 3/5 samples of sweet manioc starch and 1/3 samples of uncooked cornstarch. Notably, this uncooked cornstarch brand is widely employed in GSD-Ia treatment in Brazil. Products B and E had higher values of amylopectin and undetectable levels of sugars. A clinical trial is warranted to compare samples F and G and determine the impact of sugar trace in the same dietary source of starch. CONCLUSIONS: Collectively, the results demonstrated possible therapeutic alternatives for GSD-Ia in addition to traditional uncooked cornstarch.

The potential of robot eyes as predictive cues in HRI-an eye-tracking study.

Robots currently provide only a limited amount of information about their future movements to human collaborators. In human interaction, communication through gaze can be helpful by intuitively directing attention to specific targets. Whether and how this mechanism could benefit the interaction with robots and how a design of predictive robot eyes in general should look like is not well understood. In a between-subjects design, four different types of eyes were therefore compared with regard to their attention directing potential: a pair of arrows, human eyes, and two anthropomorphic robot eye designs. For this purpose, 39 subjects performed a novel, screen-based gaze cueing task in the laboratory. Participants' attention was measured using manual responses and eye-tracking. Information on the perception of the tested cues was provided through additional subjective measures. All eye models were overall easy to read and were able to direct participants' attention. The anthropomorphic robot eyes were most efficient at shifting participants' attention which was revealed by faster manual and saccadic reaction times. In addition, a robot equipped with anthropomorphic eyes was perceived as being more competent. Abstract anthropomorphic robot eyes therefore seem to trigger a reflexive reallocation of attention. This points to a social and automatic processing of such artificial stimuli.

Overview of the Incorporation of Legumes into New Food Options: An Approach on Versatility, Nutritional, Technological, and Sensory Quality.

Consumers are more aware and demanding of healthy food options, besides being concerned with environment-friendly consumption. This paper aims to evaluate nutritional, technological, and sensory characteristics of legumes and their products' quality and versatility, considering potential applications in new food options. Legumes are foods that have a recognized nutritional group since they have high protein and fiber content. However, their consumption is still somehow limited for some reasons: in some countries it is not easy to find all the species or cultivars, they need an organization and planning before preparation since they need soaking, and there is the presence of antinutritional factors. Due to the different functionalities of legume proteins, they can be applied to a variety of foods and for different purposes, as grains themselves, aquafaba, extracts, flours, brans, and textured proteins and sprouts. These products have been inserted as ingredients in infant food formulations, gluten-free foods, vegetarian diets, and in hybrid products to reduce food costs as well. Foods such as bread, cakes, cookies, meat analogues, and other baked or cooked products have been elaborated with nutritional, technological and sensory quality. Further development of formulations focused on improving the quality of legume-based products is necessary because of their potential and protein quality.

Biodegradable sodium alginate films incorporated with lycopene and ß-carotene for food packaging purposes.

Incorporating carotenoids into sodium alginate films can give them functional properties for food packaging applications. The lycopene and ß-carotene were included in the biopolymer matrix at 0.1%, 0.3%, and 0.5% (g carotenoid/g polymer). There was no significant difference (p > 0.05) in film thickness (45 ± 1 µm) of sodium alginate films with carotenoids. Nevertheless, the low quantity of carotenoids was enough to promote significant variations in the tensile properties of films. The films with lycopene or ß-carotene showed lower tensile strength and elongation at break than control films. The carotenoid incorporation promoted a reduction (p < 0.05) in water vapor permeability, mainly by adding 0.5%. In the same way, it improved the light transmission and thermal stability of films and did not affect the water solubility of films. The scanning electron microscopy of films showed a homogeneous surface, but the films with lycopene or ß-carotene showed a more compact structure than the control film. The sodium alginate films incorporated with 0.3% lycopene or ß-carotene showed a remarkable protective effect on sunflower oil against oxidation compared with traditional commercial plastic packaging under accelerated storage conditions (heat and light). Therefore, they can be considered a potential material for food packaging purposes.

Effects of meditation on pain intensity, physical function, quality of life and depression in adults with low back pain - A systematic review with meta-analysis.

BACKGROUND: Low back pain (LBP) is a common biopsychosocial health problem. Meditation may provide a complementary treatment option for LBP patients. OBJECTIVES: The aim of this systematic review with meta-analysis was to examine the effects of meditation on pain intensity, functional disability, quality of life, and depression in LBP populations. METHODS: This systematic review was conducted according to the PRISMA Guidelines. PubMed, Web of Science, CENTRAL, CamQuest and PubPsych were searched up to a publication date of June 2020. Inclusion criteria were RCTs or non-RCTs with LBP patients, aged at least 18 years, the application of a specific meditation technique, and pain intensity and/or functional disability as outcomes. Pooled SMDs were calculated at post-treatment and follow up. The Cochrane risk-of-bias tool was used to estimate risk of bias. The overall quality of evidence was assessed using the GRADE approach. RESULTS: 12 studies with a total of 1005 participants were included in this review. Compared to controls, meditation solely showed a significant positive effect on pain intensity (SMD = -0.27 [CI -0.43; -0.11]; p = 0.001; based on 10 studies with 934 participants) and physical quality of life (SMD = 0.21 [CI 0.07; 0.36]; p = 0.005; based on 5 studies with 756 participants) at post-treatment. At follow up (mean 20 weeks, range 4-52) there were no significant effects anymore. The quality of the evidence was moderate due to study limitations and imprecision. CONCLUSIONS: Meditation seems to be promising with regard to reducing short-term pain intensity in patients with LBP. However, additional well-designed and large trials are required in order to draw more reliable conclusions.

Common Benign Melanocytic and Non-Melanocytic Skin Tumors among the Elderly: Results of the Graz Study on Health and Aging.

BACKGROUND AND OBJECTIVES: Benign skin tumors are the most common skin findings and contribute to the major reasons for consulting a dermatologist. However, the frequency of benign skin tumors concerning different body areas and their relationship with sun-related behavior have not been sufficiently characterized. We aimed to improve knowledge about the anatomic distribution of the most frequently occurring benign skin tumors among a healthy predominant elderly population. Furthermore, we investigated associations with sun-related habits. METHODS: In total, 100 participants, 37 men, and 63 women (mean age: 67.2 years; range: 46-86 years) were enrolled in the Graz Study on Health and Aging (GSHA) cohort. Full body images were investigated for melanocytic nevi, seborrheic keratoses, hemangiomas, dermatofibromas, and lentigines. Information on the phenotypic trait, sun exposure, use of sun-protective measures, and history of sunburns was collected in a questionnaire. RESULTS: Common melanocytic nevi were the most frequently encountered skin lesions. Male sex was associated with multiple common nevi on the abdomen and the presence of atypical nevi. High sun exposure in central European latitudes during adolescence was positively associated with multiple common nevi on the total body. Multiple common nevi and atypical nevi on the back correlated with frequent use of sunscreens with SPF during young adulthood and adolescence, respectively. CONCLUSION: Our study adds new knowledge about the most frequently occurring benign skin tumors, considering all visible body areas. This research may serve as a reference basis for following epidemiological studies.

Chemical, Technological, and Sensory Quality of Pasta and Bakery Products Made with the Addition of Grape Pomace Flour.

Grapes are one of the most cultivated fruits in the world. Concomitantly, a large amount of waste is generated from this product. Grape pomace (GP) flour can be used as an increment for making new food products. GP is rich in fibers and phenolic compounds, and in addition could be used to reduce agro-industrial residues. Thus, the objective of this study was to evaluate the influence of the addition of different percentages of grape pomace (GP) on the chemical, technological, and sensory characteristics in pasta and bakery products. An integrative review was conducted. The selection of papers was carried out by searching studies in databases. An improvement in chemical quality with the addition of GP was observed, such as fiber, anthocyanin, and micronutrient content. Biscuits, cookies, cakes, breads, and pasta did not show any impairment in terms of acceptability. However, biscuits and cookies had the best global acceptance. The degree of acceptance still seems to be low for the use of GP to be included in high quantities in successful products. Samples with a maximum of 10% addition of GP flour seem to be accepted. On the other hand, the higher the percentage of GP flour, the healthier benefits they seem to promote.

Heritability of R2* iron in the basal ganglia and cortex.

BACKGROUND: While iron is essential for normal brain functioning, elevated concentrations are commonly found in neurodegenerative diseases and are associated with impaired cognition and neurological deficits. Currently, only little is known about genetic and environmental factors that influence brain iron concentrations. METHODS: Heritability and bivariate heritability of regional brain iron concentrations, assessed by R2* relaxometry at 3 Tesla MRI, were estimated with variance components models in 130 middle-aged to elderly participants of the Austrian Stroke Prevention Family Study. RESULTS: Heritability of R2* iron ranged from 0.46 to 0.82 in basal ganglia and from 0.65 to 0.76 in cortical lobes. Age and BMI explained up to 12% and 9% of the variance of R2* iron, while APOE ε4 carrier status, hypertension, diabetes, hypercholesterolemia, sex and smoking explained 5% or less. The genetic correlation of R2* iron among basal ganglionic nuclei and among cortical lobes ranged from 0.78 to 0.87 and from 0.65 to 0.97, respectively. R2* rates in basal ganglia and cortex were not genetically correlated. CONCLUSIONS: Regional brain iron concentrations are mainly driven by genetic factors while environmental factors contribute to a certain extent. Brain iron levels in the basal ganglia and cortex are controlled by distinct sets of genes.

Telomere length and brain aging: A systematic review and meta-analysis.

The current evidence on the association of leukocyte telomere length (LTL) with age-related structural and cognitive changes in the brain is mixed. Herein conforming to PRISMA 2020 guidelines, we performed a systematic review and meta-analysis using data from 27 observational studies in non-demented individuals. We used effect size and p-value based meta-analysis methods considering marked heterogeneity among studies. We found that the longer LTL was associated with higher brain volume (ß = 0.43, 95%CI: 0.36-0.50%, p = 0.008, N = 1102) and with higher global cognition (ß = 0.01; 95%CI: 0.00-0.02, p = 0.03, N = 19609) by effect size based meta-analysis and with brain volume, hippocampal volume, global cognition, cognitive domains of attention/speed as well as executive functions by p-value based meta-analysis. No significant association of LTL with brain white matter hyperintensities was detected. Furthermore, the evidence strongly suggests a subgroup-specific canonical effect of telomeres, notably in older individuals and females. In conclusion, we provide meta-analytic evidence on the beneficial effect of telomeres on brain structure as well as cognition and advocate for a beneficial subgroup-specific effect that warrants further attention.

Influence of cultivar and season on carotenoids and phenolic compounds from red lettuce influence of cultivar and season on lettuce.

This paper presents complete HPLC profiles and MS spectrometric data of bioactive compounds from four cultivars of red lettuce produced in winter and summer and their antioxidant capacity. The experiment was carried out in a greenhouse, where red curly lettuce was cultivated: Mila, Maira, Carmin and Scarlet. The cultivar and season have not influenced the qualitative profile of carotenoids (CAR) and phenolic compounds (PC) of red lettuce. Instead, the season influenced the concentration of these components in all cultivars. The levels of phenolic compounds were significantly higher in winter, while the levels of carotenoids were higher in summer. Ten anthocyanins were identified (cyanidins and delphinidins). The main carotenoid found was the all-trans-ß-carotene (45-48%), followed by lutein (13-20%) and zeaxanthin (11-15%). Major phenolic compounds include 5-caffeoylquinic acid, rutin and amentoflavone. Red lettuce cultivars have their main bioactive compounds described and compared within the variety and within the growing season. Different season and different lettuce cultivars may differ in the content of their bioactive compounds and in their antioxidant capacity.

Association of low-frequency and rare coding variants with information processing speed.

Measures of information processing speed vary between individuals and decline with age. Studies of aging twins suggest heritability may be as high as 67%. The Illumina HumanExome Bead Chip genotyping array was used to examine the association of rare coding variants with performance on the Digit-Symbol Substitution Test (DSST) in community-dwelling adults participating in the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. DSST scores were available for 30,576 individuals of European ancestry from nine cohorts and for 5758 individuals of African ancestry from four cohorts who were older than 45 years and free of dementia and clinical stroke. Linear regression models adjusted for age and gender were used for analysis of single genetic variants, and the T5, T1, and T01 burden tests that aggregate the number of rare alleles by gene were also applied. Secondary analyses included further adjustment for education. Meta-analyses to combine cohort-specific results were carried out separately for each ancestry group. Variants in RNF19A reached the threshold for statistical significance (p = 2.01 × 10-6) using the T01 test in individuals of European descent. RNF19A belongs to the class of E3 ubiquitin ligases that confer substrate specificity when proteins are ubiquitinated and targeted for degradation through the 26S proteasome. Variants in SLC22A7 and OR51A7 were suggestively associated with DSST scores after adjustment for education for African-American participants and in the European cohorts, respectively. Further functional characterization of its substrates will be required to confirm the role of RNF19A in cognitive function.

RNA Expression of DNA Damage Response Genes in Muscle-Invasive Bladder Cancer: Influence on Outcome and Response to Adjuvant Cisplatin-Based Chemotherapy.

BACKGROUND: Perioperative cisplatin-based chemotherapy (CBC) can improve the outcome of patients with muscle-invasive bladder cancer (MIBC), but it is still to be defined which patients benefit. Mutations in DNA damage response genes (DDRG) can predict the response to CBC. The value of DDRG expression as a marker of CBC treatment effect remains unclear. MATERIAL AND METHODS: RNA expression of the nine key DDRG (BCL2, BRCA1, BRCA2, ERCC2, ERCC6, FOXM1, RAD50, RAD51, and RAD52) was assessed by qRT-PCR in a cohort of 61 MICB patients (median age 66 y, 48 males, 13 females) who underwent radical cystectomy in a tertiary care center. The results were validated in the The Cancer Genome Atlas (TCGA) cohort of MIBC (n = 383). Gene expression was correlated with disease-free survival (DFS) and overall survival (OS). Subgroup analyses were performed in patients who received adjuvant cisplatin-based chemotherapy (ACBC) (Mannheim n = 20 and TCGA n = 75). RESULTS: Low expression of RAD52 was associated with low DFS in both the Mannheim and the TCGA cohorts (Mannheim: p = 0.039; TCGA: p = 0.017). This was especially apparent in subgroups treated with ACBC (Mannheim: p = 0.0059; TCGA: p = 0.012). Several other genes showed an influence on DFS in the Mannheim cohort (BRCA2, ERCC2, FOXM1) where low expression was associated with poor DFS (p < 0.05 for all). This finding was not fully supported by the data in the TCGA cohort, where high expression of FOXM1 and BRCA2 correlated with poor DFS. CONCLUSION: Low expression of RAD52 correlated with decreased DFS in the Mannheim and the TCGA cohort. This effect was especially pronounced in the subset of patients who received ACBC, making it a promising indicator for response to ACBC on the level of gene expression.

Influence of thickening agents on rheological properties and sensory attributes of dysphagic diet.

Dysphagia is the difficulty during the progression of the bolus from the mouth to the stomach. Modifying the texture of the food is a fundamental factor for safe swallowing in patients with dysphagia since inadequate consistency can result in complications. To personalize and develop diets for dysphagia, understanding, and controlling the rheological and sensory properties of thickeners is useful. This review examines the different types of thickeners used to modify the texture of foods, as well as their influence on rheological properties and sensory attributes to efficiently manage the diet in dysphagia. The study discusses characteristics such as: hardness, viscosity, viscoelasticity, as well as sensory attributes related to rheology. The thickeners xanthan gum, methylcellulose, carboxymethylcellulose, guar gum, linseed, and chia, carboxymethylated curdlan, and konjac glucomannan were reviewed in this work. Sensory evaluations of different foods have already been carried out on some products such as: meats, carrots, soups, pates, and timbales with their modified textures. The sensory attributes measured among hydrocolloids are strongly correlated with rheological parameters. Dysphagic diets should have less hardness and adherence, but with adequate cohesiveness to facilitate chewing, swallowing to protect from aspiration and reduction of residues in the oropharynx. The use of a single type of thickener may not be ideal, their mixtures and synergistic effect can improve the viscous and elastic characteristics of foods, to obtain safe food to swallow and to improve the sensory interest of dysphagic patients. Personalized recommendations with follow-up on swallowing approaches, respecting patient's individuality, explaining thickening agents' differences would be pertinent.

Phenolic compounds and antioxidant activity in vitro and in vivo of Butia and Opuntia fruits.

Despite the consumption recommendations and the potential health benefits, Brazilian biodiversity has a large number of fruit species that are still unexplored, such as Butia catarinensis (Butiá da Praia), Butia eriospatha (Butiá da Serra) and Opuntia elata (Arumbeva). The phenolic compounds of these fruits were determined by HPLC-DAD-MS/MS. Morever, in vitro assays of antioxidant capacity on hydroethanolic extracts against hydrogen peroxide (H2O2), hydroxyl (OH), peroxyl (ROO) and ABTS radicals were evaluated. In vivo assays evaluating the survival of worms and reactive oxygen species (ROS) generation were performed using the nematode Caenorhabditis elegans. Eighteen, twenty-eight and seventeen phenolic compounds were identified in Butiá da Praia, Butiá da Serra and Arumbeva, respectively. The main groups of phenolic compounds found in the fruits were hydroxybenzoic acids (60.5, 26.5 and 96.1% of the total phenolic compounds for Butiá da Praia, Butiá da Serra and Arumbeva, respectively), flavan-3-ols (23.6 and 61.2% of the total phenolic compounds for Butiá da Praia and Butiá da Serra) and flavonols (2.6% of the total phenolic compounds for Arumbeva). The hydroethanolic extracts of these fruits were free radical scavenger, sources of phenolic compounds and did not cause toxic effects in vivo. In hydroethanolic extracts of Butiá da Praia and Arumbeva, the total phenolic content increased by around 67% and 35%, respectively. Besides the health benefits, these proved to be promising sources of natural antioxidants, with phenolic composition variating among species and collection site. The obtained results enable future applications of studied fruits extracts in food and/or pharmaceutical products, encouraging and valuing the sustainable use of biodiversity.

New insights into the phenolic compounds and antioxidant capacity of feijoa and cherry fruits cultivated in Brazil.

Acca sellowiana (feijoa) and Eugenia involucrata (cherry) are fruits species of Brazilian biodiversity (Myrtaceae family). In this study, a sampling process was used with three different harvesting sites. The composition of phenolic compounds of these fruits was determined by HPLC-DAD-MS/MS. Moreover, the antioxidant capacity of hydroethanolic extracts against hydrogen peroxide (H2O2), hydroxyl (OH), peroxyl (ROO-) and ABTS radicals was evaluated. Thirty and twenty-seven phenolic compounds were identified in feijoa and cherry, respectively. The major phenolic compounds found were pedunculagin isomer (5040.87, 3443.66 and 1324.95 µg·g-1) in feijoa and procyanidin (1406.54, 1888.00 and 1380.64 µg·g-1) in cherry. Hydroethanolic extract of these fruits was a potent scavenger of free radicals and excellent source of phenolic compounds. In hydroethanolic extracts of feijoa, the phenolic content increased by around 50%, while in the cherry the content was similar to that found in the fruit. For ORAC method, sample 2 of feijoa and cherry showed values of 383 and 126 µM·TE·g-1, respectively, featuring the highest antioxidant capacity. This study is the first to report the identification of castalagin, catechin and epicatechin in feijoa, and rutin in cherry. Besides, the health benefits, these fruits can contribute to biodiversity conservation.

Genetically Elevated LDL Associates with Lower Risk of Intracerebral Hemorrhage.

OBJECTIVE: Observational studies point to an inverse correlation between low-density lipoprotein (LDL) cholesterol levels and risk of intracerebral hemorrhage (ICH), but it remains unclear whether this association is causal. We tested the hypothesis that genetically elevated LDL is associated with reduced risk of ICH. METHODS: We constructed one polygenic risk score (PRS) per lipid trait (total cholesterol, LDL, high-density lipoprotein [HDL], and triglycerides) using independent genomewide significant single nucleotide polymorphisms (SNPs) for each trait. We used data from 316,428 individuals enrolled in the UK Biobank to estimate the effect of each PRS on its corresponding trait, and data from 1,286 ICH cases and 1,261 matched controls to estimate the effect of each PRS on ICH risk. We used these estimates to conduct Mendelian Randomization (MR) analyses. RESULTS: We identified 410, 339, 393, and 317 lipid-related SNPs for total cholesterol, LDL, HDL, and triglycerides, respectively. All four PRSs were strongly associated with their corresponding trait (all p < 1.00 × 10-100 ). While one SD increase in the PRSs for total cholesterol (odds ratio [OR] = 0.92; 95% confidence interval [CI] = 0.85-0.99; p = 0.03) and LDL cholesterol (OR = 0.88; 95% CI = 0.81-0.95; p = 0.002) were inversely associated with ICH risk, no significant associations were found for HDL and triglycerides (both p > 0.05). MR analyses indicated that 1mmol/L (38.67mg/dL) increase of genetically instrumented total and LDL cholesterol were associated with 23% (OR = 0.77; 95% CI = 0.65-0.98; p = 0.03) and 41% lower risks of ICH (OR = 0.59; 95% CI = 0.42-0.82; p = 0.002), respectively. INTERPRETATION: Genetically elevated LDL levels were associated with lower risk of ICH, providing support for a potential causal role of LDL cholesterol in ICH. ANN NEUROL 2020 ANN NEUROL 2020;88:56-66.

Global and Regional Development of the Human Cerebral Cortex: Molecular Architecture and Occupational Aptitudes.

We have carried out meta-analyses of genome-wide association studies (GWAS) (n = 23 784) of the first two principal components (PCs) that group together cortical regions with shared variance in their surface area. PC1 (global) captured variations of most regions, whereas PC2 (visual) was specific to the primary and secondary visual cortices. We identified a total of 18 (PC1) and 17 (PC2) independent loci, which were replicated in another 25 746 individuals. The loci of the global PC1 included those associated previously with intracranial volume and/or general cognitive function, such as MAPT and IGF2BP1. The loci of the visual PC2 included DAAM1, a key player in the planar-cell-polarity pathway. We then tested associations with occupational aptitudes and, as predicted, found that the global PC1 was associated with General Learning Ability, and the visual PC2 was associated with the Form Perception aptitude. These results suggest that interindividual variations in global and regional development of the human cerebral cortex (and its molecular architecture) cascade-albeit in a very limited manner-to behaviors as complex as the choice of one's occupation.

Leukocyte Telomere Length Is Related to Brain Parenchymal Fraction and Attention/Speed in the Elderly: Results of the Austrian Stroke Prevention Study.

There are controversial results if leukocyte telomere length (LTL) is related to structural brain changes and cognitive decline in aging. Here, we investigated the association between LTL and 1) global MRI correlates of brain aging such as brain parenchymal fraction (BPF) and white matter hyperintensities (WMH) load and Fazekas score as well as 2) global (g-factor) and domain-specific cognition such as attention/speed, conceptualization, memory, and visuopractical skills. In total, 909 participants of the Austrian Stroke Prevention Study with LTL, MRI, and cognitive tests were included. There were 388 (42.7%) men, and the mean age was 65.9 years. Longer LTL was significantly associated with larger BPF (ß = 0.43, p < 0.001), larger WMH load (ß = 0.03, p = 0.04), and score (ß = 0.05, p = 0.04) after adjusting for age, sex, vascular risk factors, and ApoE4 carrier status. The effect on BPF was more significant in the subgroups of women (ß = 0.51, p = 0.001), age >65 years (ß = 0.58, p = 0.002), BMI ≥ 25 (ß = 0.40, p = 0.004), education ≤10 years (ß = 0.42, p = 0.002), hypertensives (ß = 0.51, p = 0.001), cardiovascular disease (CVD) (ß = 0.58, p = 0.005), non-diabetics (ß = 0.42, p < 0.001), and Apoe4 non-carriers (ß = 0.49, p < 0.001). The effect on WMH was significant within the hypertensives (load: ß = 0.04, p = 0.02), non-diabetics (load:ß = 0.03, p = 0.01; score: ß = 0.06, p = 0.02), in those with education ≤10 years (load: ß = 0.03, p = 0.04; score: ß = 0.07, p = 0.02), in ApoE4 non-carriers (load: ß = 0.03, p = 0.02; score: ß = 0.07, p = 0.01) and in subjects without CVD (score: ß = 0.06, p = 0.05). We only observed a significant association between LTL and the cognitive domain of attention/speed, which was confined to the subgroups of BMI ≥ 25 (ß = 0.04, p = 0.05) and education ≤10 years (ß = 0.04, p = 0.05). The effect of LTL on attention/speed was partly mediated in both subgroups by BPF (ß = 0.02, 95% CI = 0.01:0.03) when tested by bootstrapping. Our results support a strong protective role of longer LTL on global brain volume which in turn may contribute to better cognitive functions, especially in the attention/speed domain in the elderly.

Corticosteroids and Regional Variations in Thickness of the Human Cerebral Cortex across the Lifespan.

Exposures to life stressors accumulate across the lifespan, with possible impact on brain health. Little is known, however, about the mechanisms mediating age-related changes in brain structure. We use a lifespan sample of participants (n = 21 251; 4-97 years) to investigate the relationship between the thickness of cerebral cortex and the expression of the glucocorticoid- and the mineralocorticoid-receptor genes (NR3C1 and NR3C2, respectively), obtained from the Allen Human Brain Atlas. In all participants, cortical thickness correlated negatively with the expression of both NR3C1 and NR3C2 across 34 cortical regions. The magnitude of this correlation varied across the lifespan. From childhood through early adulthood, the profile similarity (between NR3C1/NR3C2 expression and thickness) increased with age. Conversely, both profile similarities decreased with age in late life. These variations do not reflect age-related changes in NR3C1 and NR3C2 expression, as observed in 5 databases of gene expression in the human cerebral cortex (502 donors). Based on the co-expression of NR3C1 (and NR3C2) with genes specific to neural cell types, we determine the potential involvement of microglia, astrocytes, and CA1 pyramidal cells in mediating the relationship between corticosteroid exposure and cortical thickness. Therefore, corticosteroids may influence brain structure to a variable degree throughout life.