The effects of an exercise intervention on neuroelectric activity and executive function in children with overweight/obesity: The ActiveBrains randomized controlled trial.

OBJECTIVE: To investigate whether a 20-week aerobic and resistance exercise program induces changes in brain current density underlying working memory and inhibitory control in children with overweight/obesity. METHODS: A total of 67 children (10.00 ± 1.10 years) were randomized into an exercise or control group. Electroencephalography (EEG)-based current density (µA/mm2 ) was estimated using standardized low-resolution brain electromagnetic tomography (sLORETA) during a working memory task (Delayed non-matched-to-sample task, DNMS) and inhibitory control task (Modified flanker task, MFT). In DNMS, participants had to memorize four stimuli (Pokemons) and then select between two of them, one of which had not been previously shown. In MFT, participants had to indicate whether the centered cow (i.e., target) of five faced the right or left. RESULTS: The exercise group had significantly greater increases in brain activation in comparison with the control group during the encoding phase of DNMS, particularly during retention of second stimuli in temporal and frontal areas (peak t = from 3.4 to 3.8, cluster size [k] = from 11 to 39), during the retention of the third stimuli in frontal areas (peak t = from 3.7 to 3.9, k = from 15 to 26), and during the retention of the fourth stimuli in temporal and occipital areas (peak t = from 2.7 to 4.3, k = from 13 to 101). In MFT, the exercise group presented a lower current density change in the middle frontal gyrus (peak t = -4.1, k = 5). No significant change was observed between groups for behavioral performance (p ≥ 0.05). CONCLUSION: A 20-week exercise program modulates brain activity which might provide a positive influence on working memory and inhibitory control in children with overweight/obesity.

Which indices of cardiorespiratory fitness are more strongly associated with brain health in children with overweight/obesity?

PURPOSE: To compare the strength of associations between different indices of cardiorespiratory fitness (CRF) and brain health outcomes in children with overweight/obesity. METHODS: Participants were 100 children aged 8-11 years. CRF was assessed using treadmill exercise test (peak oxygen uptake [V̇O2peak ], treadmill time, and V̇O2 at ventilatory threshold) and 20-metre shuttle run test (20mSRT, laps, running speed, estimated V̇O2peak using the equations by Léger et al., Mahar et al., and Matsuzaka et al.). Intelligence, executive functions, and academic performance were assessed using validated methods. Total gray matter and hippocampal volumes were assessed using structural MRI. RESULTS: V̇O2peak /body mass (ß = 0.18, 95% CI = 0.01-0.35) and treadmill time (ß = 0.18-0.21, 95% CI = 0.01-0.39) were positively associated with gray matter volume. 20mSRT laps were positively associated with executive functions (ß = 0.255, 95% CI = 0.089-0.421) and academic performance (ß = 0.199-0.255, 95% CI = 0.006-0.421), and the running speed was positively associated with executive functions (ß = 0.203, 95% CI = 0.039-0.367). Estimated V̇O2peak/Léger et al. was positively associated with intelligence, executive functions, academic performance, and gray matter volume (ß = 0.205-0.282, 95% CI = 0.013-0.500). Estimated V̇O2peak/Mahar et al. and V̇O2peak/Matsuzaka et al. (speed) were positively associated with executive functions (ß = 0.204-0.256, 95% CI = 0.031-0.436). CONCLUSION: Although V̇O2peak is considered the gold standard indicator of CRF in children, peak performance (laps or running speed) and estimated V̇O2peak/Léger et al. derived from 20mSRT had stronger and more consistent associations with brain health outcomes than other indices of CRF in children with overweight/obesity.

Fitness, Gray Matter Volume, and Executive Function in Cognitively Normal Older Adults: Cross-Sectional Findings From the AGUEDA Trial.

The aim of the study is to investigate the association of cardiorespiratory fitness (CRF) and muscular strength indicators with gray matter volume (GMV) and to study whether fitness-related regions of GMV are associated to executive function (EF) in cognitively normal older adults. Ninety-one cognitively normal older adults (71.69 ± 3.91 years; 57.14% females) participated in this study from the AGUEDA trial. CRF was measured by a 2-km walking test and a 6-min walking test. Muscular strength was measured by handgrip, biceps curl, squats, and isokinetic strength tests. T1-weigthed images were obtained through a magnetic resonance scan. GMV was determined by voxel-based morphometric analysis. Standardized EF tests were performed. CRF did not show any positive association with GMV. Handgrip strength was positively associated with GMV (p < 0.001) in nine regions (ß from 0.6 to 0.8 and k from 106 to 1927) and knee extension strength in three regions (ß from 0.4 to 0.5 and k from 76 to 2776). Squats strength was negatively associated with GMV (p < 0.001) in two regions (ß = -0.3, k = 1102 and k = 152) and the 2-km walking test in one region (ß = -0.4, k = 99). Only handgrip strength-related GMV was associated with cognitive flexibility (p = 0.039, ß = 0.215) and spatial working memory (p < 0.03, ß 0.247-0.317), but not with EF score (p > 0.05). Muscular strength, but no CRF, may be positively related to GMV in cortical and subcortical regions, with implications for specific cognitive domains rather than the overall EF score. Specifically, handgrip strength was the indicator most associated with higher GMV, while squats strength and CRF were negatively related to GMV. ClinicalTrials.gov identifier: NCT05186090.

Early life factors and structural brain network in children with overweight/obesity: The ActiveBrains project.

BACKGROUND: The aims of this study were to investigate the association of early life factors, including birth weight, birth length, and breastfeeding practices, with structural brain networks; and to test whether structural brain networks associated with early life factors were also associated with academic performance in children with overweight/obesity (OW/OB). METHOD: 96 children with OW/OB aged 8-11 years (10.03 ± 1.16) from the ActiveBrains project were included. Early life factors were collected from birth records and reported by parents as weight, height, and months of breastfeeding. T1-weighted images were used to identify structural networks using a non-negative matrix factorization (NNMF) approach. Academic performance was evaluated by the Woodcock-Muñoz standardized test battery. RESULTS: Birth weight and birth length were associated with seven networks involving the cerebellum, cingulate gyrus, occipital pole, and subcortical structures including hippocampus, caudate nucleus, putamen, pallidum, nucleus accumbens, and amygdala. No associations were found for breastfeeding practices. None of the networks linked to birth weight and birth length were linked to academic performance. CONCLUSIONS: Birth weight and birth length, but not breastfeeding, were associated with brain structural networks in children with OW/OB. Thus, early life factors are related to brain networks, yet a link with academic performance was not observed. IMPACT: Birth weight and birth length, but not breastfeeding, were associated with several structural brain networks involving the cerebellum, cingulate gyrus, occipital pole, and subcortical structures including hippocampus, caudate, putamen, pallidum, accumbens and amygdala in children with overweight/obesity, playing a role for a normal brain development. Despite no academic consequences, other behavioral consequences should be investigated. Interventions aimed at improving optimal intrauterine growth and development may be of importance to achieve a healthy brain later in life.

Association of muscular strength and targeted proteomics involved in brain health in children with overweight/obesity.

Muscular strength has been positively associated with better brain health indicators during childhood obesity. However, the molecular mechanisms underlying the positive impact of muscular strength in brain health are poorly understood. We aimed to study the association of muscular strength with neurology-related circulating proteins in plasma in children with overweight/obesity and to explore the role of cardiorespiratory fitness (CRF) as a confounder. The participants were 86 Caucasian children (10.1 ± 1.1 years old; 41% girls) from the ActiveBrains project. Muscular strength was measured by field and laboratory tests. CRF was assessed with an incremental treadmill test. Olink's technology was used to quantify 92 neurology-related proteins in plasma. Protein-protein interactions were computed using the STRING website. Muscular strength was positively associated with 12 proteins (BetaNGF, CDH6, CLEC10A, CLM1, FcRL2, HAGH, IL12, LAIR2, MSR1, SCARB2, SMOC2, and TNFRSF12A), and negatively associated with 12 proteins (CLEC1B, CTSC, CTSS, gal-8, GCP5, NAAA, NrCAM, NTRK2, PLXNB3, RSPO1, sFRP3, and THY1). After adjustment for CRF, muscular strength was positively associated with eight proteins (BetaNGF, CDH6, CLEC10A, FcRL2, LAIR2, MSR1, SCARB2, and TNFRSF12A) and negatively associated with two proteins (gal-8 and NrCAM). After applying FDR correction, only CLEC10A remained statistically significant. In conclusion, muscular strength was associated with blood circulating proteins involved in several biological processes, particularly anti-inflammatory response, lipid metabolism, beta amyloid clearance, and neuronal action potential propagation. More powered studies are warranted in pediatric populations to contrast or confirm our findings.

Genome Editing and Protein Energy Malnutrition.

Protein-energy malnutrition is a state of disordered catabolism resulting from metabolic derangements or starvation. It is associated with chronic disease, hypoglycemia, hypothermia, serious infections, and even an increased prevalence of morbidity and mortality in countries with poor socioeconomic or environmental factors. Adequate food administration is essential to satisfy the main caloric and nutritional demands of humans. The most significant factors seen in the development of protein-energy malnutrition in areas of high incidence, such as underdeveloped countries, are inadequate food and nutrient supplies. It has been well established that one of the strategies to alleviate undernourishment is the biofortification of staple crops. This is because vegetables and plants are significant sources of crucial nutrients for human growth and development. To enhance plant nutrition, recent tactics aim to formulated balanced and diverse diets with acceptable levels of vitamins and minerals that benefit human health. New advances in plant biotechnology and animal productivity could control key enzymes in several metabolic pathways, enriching important nutrients such as iron and vitamins and decreasing the content of disadvantageous compounds such as acrylamide-forming amino acids and phytic acids. Numerous biofortified crops such as rice, maize, and wheat have been created to resolve the problem of nutrition deficiencies. Some examples of these methodologies are genome editing engineered nucleases, transcriptional activator-like effector nucleases, zinc finger nucleases, and clustered regularly interspaced short palindromic repeats and associated Cas9 endonuclease which have been created and widely studied for their application, efficiency, and specificity.

Physical fitness and brain source localization during a working memory task in children with overweight/obesity: The ActiveBrains project.

The present study aims (i) to examine the association of physical fitness components (i.e., cardiorespiratory fitness, speed-agility, and muscular fitness) with brain current source density during working memory; and (ii) to examine whether fitness-related current density was associated to working memory performance and academic achievement. Eighty-five children with overweight/obesity aged 8-11 years participated in this cross-sectional study. Physical fitness components were assessed using the ALPHA test battery. Electroencephalography recordings were performed during a Delayed Non-Match-to-Sample task that assessed working memory. Brain source analysis was carried out using sLORETA to estimate regional current source density differences between high and low (H-L) working memory loads. Academic achievement was measured by the Spanish version of the Woodcock-Johnson III test battery. The main results showed that higher cardiorespiratory fitness was associated with higher H-L current density differences in frontal, limbic, and occipital regions during encoding and maintenance task's phases (ß≥0.412, p ≤ 0.019). A limbic area was further related to better working memory performance (ß=0.267, p = 0.005). During retrieval, higher cardiorespiratory fitness was also associated with higher current density in temporal regions (ß=0.265, p = 0.013), whereas lower muscular fitness was associated with higher current density in frontal regions (ß=-0.261, p = 0.016). Our results suggest that cardiorespiratory fitness, but not speed-agility nor muscular fitness, is positively associated with brain current source density during working memory processes in children with overweight/obesity. Fitness-related current density differences in limbic regions were associated with better working memory.

Physical fitness and its association with cognitive performance in Chilean schoolchildren: The Cogni-Action Project.

This study aimed to establish the association and differences in a diversity of cognitive domains according to cardiorespiratory fitness (CRF), muscular fitness (MF), and speed-agility fitness (S-AF) level in a large sample of Chilean schoolchildren. 1171 Chilean schoolchildren aged 10-14 years participated. CRF, MF, and S-AF were assessed through the ALPHA-fitness test battery. Cognition was evaluated through the NeuroCognitive Performance Test, which involved eight tests related to four main domains: cognitive flexibility (CF), working memory (WM), inhibitory control (IC), and intelligence (IN). Both global (multivariate) and individual (univariate) analyses were performed to determine the differences in cognitive functioning according to low-, middle-, and high-fitness level. The global analyses showed a significant main effect for CRF, F(16,940)  = 3.08, p ≤ .001 and MF groups, F(16,953)  = 2.30, p = .002, but not for S-AF, F(16,948)  = 1.37, p = .105. CRF shows a significant main effect in seven of eight tests, involving CF, WM, IC, and IN domains, whereas MF shows a significant main effect in five of eight tests without association with IN. SA-F shows a significant main effect only with IC. Statistical differences were found between the low- and middle/high-fitness groups but not between the middle- and high-fitness groups. At a global level, both CRF and MF seem to be associated with a higher cognitive profile in scholars; however, at an individual level, all fitness components show a favorable relationship to some cognitive domine. Then, future cognitive developing strategies should consider all fitness components, prioritizing those low-fitness schoolchildren.

The Gut Barrier, Intestinal Microbiota, and Liver Disease: Molecular Mechanisms and Strategies to Manage.

Liver disease encompasses pathologies as non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, alcohol liver disease, hepatocellular carcinoma, viral hepatitis, and autoimmune hepatitis. Nowadays, underlying mechanisms associating gut permeability and liver disease development are not well understood, although evidence points to the involvement of intestinal microbiota and their metabolites. Animal studies have shown alterations in Toll-like receptor signaling related to the leaky gut syndrome by the action of bacterial lipopolysaccharide. In humans, modifications of the intestinal microbiota in intestinal permeability have also been related to liver disease. Some of these changes were observed in bacterial species belonging Roseburia, Streptococcus, and Rothia. Currently, numerous strategies to treat liver disease are being assessed. This review summarizes and discusses studies addressed to determine mechanisms associated with the microbiota able to alter the intestinal barrier complementing the progress and advancement of liver disease, as well as the main strategies under development to manage these pathologies. We highlight those approaches that have shown improvement in intestinal microbiota and barrier function, namely lifestyle changes (diet and physical activity) and probiotics intervention. Nevertheless, knowledge about how such modifications are beneficial is still limited and specific mechanisms involved are not clear. Thus, further in-vitro, animal, and human studies are needed.

Early life factors, gray matter brain volume and academic performance in overweight/obese children: The ActiveBrains project.

Early life factors may influence brain and academic outcomes later in life, especially during childhood. Here we investigate the associations of early life factors (i.e., birth weight, birth length, and breastfeeding) with gray matter volume, adjusted for body mass index and cardiorespiratory fitness, and ii) we test whether early-life factor-related differences in gray matter volume are associated with academic performance in overweight/obese children. 96 children with overweight/obesity aged 8-11 years participated. Birth weight, birth length and gestational age were collected from birth records, and breastfeeding practices were asked to parents. T1-weighted images were acquired with a 3.0 T Magnetom Tim Trio system. Academic performance was assessed with the Bateria III Woodcock-Muñoz Tests of Achievement. Whole-brain voxel-wise multiple regressions were used to test the associations of each early life factor with gray matter volume. Higher birth weight and birth length were associated with greater gray matter volume in 9 brain regions including the middle frontal gyrus, rectal gyrus, thalamus, putamen, middle temporal gyrus, lingual gyrus, middle occipital gyrus, calcarine cortex and cerebellum bilaterally (ß ranging from 0.361 to 0.539, t ranging from 3.46 to 5.62 and cluster size from 82 to 4478 voxels; p < 0.001); and greater duration of any breastfeeding was associated with greater gray matter volume in 3 regions including the bilateral inferior frontal gyrus and rolandic operculum (ß ranging from 0.359 to 0.408, t ranging from 4.01 to 4.32 and cluster size from 64 to 171 voxels; p < 0.001). No associations were found for duration of exclusive breastfeeding. Additionally, none of the gray matter regions that were associated with the early life factors were associated with academic performance (all p > 0.05). Our results demonstrate that birth weight, birth length, and breastfeeding are predictive of gray matter volume of numerous brain structures that are involved in higher order cognition and emotion regulation, but how these results relate to measures of academic achievement remain a matter of speculation.

Inflammatory biomarkers and brain health indicators in children with overweight and obesity: The ActiveBrains project.

INTRODUCTION: Chronic inflammation plays an important role on the pathogenesis of several cardiovascular and metabolic diseases, as well as on brain function and behaviour. The aim of the present study was to examine the associations between inflammatory biomarkers and a wide range of brain health indicators (i.e., academic performance, executive function, behavioural and emotional functioning, and brain volume) in children with overweight/obesity. METHODS: A total of 107 children (10.0 ±â€¯1.1 years, 41% girls) from the ActiveBrains project were included in the analysis. Five inflammatory biomarkers were analysed in plasma: white blood cell (WBC) count, interleukin-6 (IL-6), interleukin-1ß, tumor necrosis factor-α (TNF-α), and C-reactive protein (CRP). Academic performance was assessed by Woodcock-Muñoz Tests of Achievement. Executive function was assessed through the Design Fluency Test for cognitive flexibility, the Stroop test for cognitive inhibition, and the Delayed Non-Match-to-Sample task for working memory. Behavioural and emotional functioning was evaluated through the Behavior Assessment System for Children (BASC) questionnaire. Total and regional brain volume was assessed by magnetic resonance imaging. RESULTS: IL-6 was inversely associated with adaptive skills (ß = -0.228; p = 0.030), while TNF-α was related to mathematics (ß = -0.198; p = 0.034). In addition, CRP was positively associated with externalizing (ß = 0.246; p = 0.046) and internalizing problems (ß = 0.234; p = 0.039), as well as the behavioural symptoms index (ß = 0.236; p = 0.047). However, these significant associations disappeared after multiple comparisons correction. Inflammatory biomarkers were not associated with executive function and total brain volumes. Regarding regional brain analyses, WBC was positively associated with gray matter volume in the left middle temporal gyrus (ß = 0.387; p < 0.001, k = 44), and CRP was positively associated with gray matter volume in the right superior temporal gyrus (ß = 0.439; p < 0.001, k = 29). Additionally, when adjusting by total brain volume, CRP was positively associated with gray matter volume in the right supplementary motor cortex (ß = 0.453; p < 0.001, k = 51). Moreover, both, IL-6 (ß = 0.366; p < 0.001, k = 81) and TNF-α (ß = 0.368; p < 0.001, k = 62) were positively associated with white matter volume around the right inferior frontal gyrus pars opercularis, while CRP was inversely associated with white matter volume around the left superior frontal gyrus (ß = -0.482; p < 0.001, k = 82). After adjusting by total brain volume, CRP was also inversely associated with white matter volume in 3 additional clusters (ß ranging from -0.473 to -0.404; p < 0.001, k = 87). CONCLUSIONS: Inflammation was slightly associated with brain health (i.e., academic performance, behavioural and emotional functioning and regional brain volume) in children with overweight or obesity. Further larger longitudinal and interventional studies are warranted to elucidate the short-term and long-term effect of systemic low-grade inflammation on children's brain health.

Study protocol and rationale of the "Cogni-action project" a cross-sectional and randomized controlled trial about physical activity, brain health, cognition, and educational achievement in schoolchildren.

BACKGROUND: Education and health are crucial topics for public policies as both largely determine the future wellbeing of the society. Currently, several studies recognize that physical activity (PA) benefits brain health in children. However, most of these studies have not been carried out in developing countries or lack the transference into the education field. The Cogni-Action Project is divided into two stages, a cross-sectional study and a crossover-randomized trial. The aim of the first part is to establish the associations of PA, sedentarism, and physical fitness with brain structure and function, cognitive performance and academic achievement in Chilean schoolchildren (10-13 years-old). The aim of the second part is to determinate the acute effects of three PA protocols on neuroelectric indices during a working memory and a reading task. METHODS: PA and sedentarism will be self-reported and objectively-assessed with accelerometers in a representative subsample, whilst physical fitness will be evaluated through the ALPHA fitness test battery. Brain structure and function will be assessed by magnetic resonance imaging (MRI) in a randomized subsample. Cognitive performance will be assessed through the NeuroCognitive Performance Test, and academic achievement by school grades. In the second part 32 adolescents (12-13 year-old) will be cross-over randomized to these condition (i) "Moderate-Intensity Continuous Training" (MICT), (ii) "Cooperative High-Intensity Interval Training" (C-HIIT), and (iii) Sedentary condition. Neuroelectric indices will be measures by electroencephalogram (EEG) and eye-tracking, working memory by n-back task and reading comprehension by a reading task. DISCUSSION: The main strength of this project is that, to our knowledge, this is the first study analysing the potential association of PA, sedentarism, and physical fitness on brain structure and function, cognitive performance, and academic achievement in a developing country, which presents an important sociocultural gap. For this purpose, this project will use advanced technologies in neuroimaging (MRI), electrophysiology (EEG), and eye-tracking, as well as objective and quality measurements of several physical and cognitive health outcomes. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03894241 Date of register: March 28, 2019. Retrospectively Registered.

Variations of body composition, physical activity and caloric intake in schoolchildren during national holidays.

UNLABELLED: Scientific literature has described that a significant body weight increase in schoolchildren occurs during some holiday periods (summer, winter, and thanksgiving holidays), harming their health. In this regard, it is thought that this phenomenon is mainly due to changes in eating habits and the variation in levels of physical activity; however, this approach has not yet been explored during national holidays (NAH) in Chile. PURPOSE: To determine any changes in body composition, physical activity and caloric intake during NAH. METHODS: A total of 46 schoolchildren (24 boys, age 10.5 ± 0.5; BMI 21.7 ± 4.7) participated. Measurements were performed 2 days before and after the NAH (9 days). Weight was measured and fat percentage was established using the Slaughter formula. Levels of physical activity were measured with accelerometers, validating 3 weekdays and 1 weekend; caloric intake was established through a 24-h recall. RESULTS: Weight, percentage of fat and caloric intake increased significantly (250 g, 2.2 % and 733.3 kcal, respectively; p < 0.05); however, none of the variables of physical activity showed significant changes. CONCLUSION: The change in caloric intake seems to be the main cause of weight and fat gain during the NAH.

Physical Exercise and Mechanism Related to Alzheimer's Disease: Is Gut-Brain Axis Involved?

BACKGROUND: Alzheimer's disease is a progressive neurodegenerative disease characterized by structural changes in the brain, including hippocampal atrophy, cortical thinning, amyloid plaques, and tau tangles. Due to the aging of the global population, the burden of Alzheimer's disease is expected to increase, making the exploration of non-pharmacological interventions, such as physical exercise, an urgent priority. RESULTS: There is emerging evidence that regular physical exercise may mitigate the structural and functional declines associated with Alzheimer's disease. The underlying mechanisms, however, remain poorly understood. Gut-brain axis research is a promising area for further investigation. This system involves bidirectional communication between the gut microbiome and the brain. According to recent studies, the gut microbiome may influence brain health through modulating neuroinflammation, producing neuroactive compounds, and altering metabolic processes. Exercise has been shown to alter the composition of the gut microbiome, potentially impacting brain structure and function. In this review, we aim to synthesize current research on the relationship between physical exercise, structural brain changes in Alzheimer's disease, and the gut-brain axis. CONCLUSIONS: In this study, we will investigate whether changes in the gut microbiome induced by physical exercise can mediate its neuroprotective effects, offering new insights into the prevention and treatment of Alzheimer's disease. By integrating findings from neuroimaging studies, clinical trials, and microbiome research, this review will highlight potential mechanisms. It will also identify key gaps in the literature. This will pave the way for future research directions.

Neurological-related proteomic profiling in plasma of children with metabolic healthy and unhealthy overweight/obesity.

OBJECTIVE: Children with overweight/obesity (OW/OB) exhibit poor cardiometabolic health, yet mechanisms influencing brain health remain unclear. We examined the differences in neurological-related circulating proteins in plasma among children with metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO) and the association with metabolic syndrome markers. METHODS: In this cross-sectional study, we included 84 Caucasian children (39% girls), aged 10.1 ± 1.1 years, from the ActiveBrains project (NCT02295072). A ninety-two-protein targeted approach using Olink's® technology was used. RESULTS: We identified distinct concentrations of CD38, LAIR2, MANF and NRP2 proteins in MHO compared with MUO. Moreover, individual metabolic syndrome (MS) markers were linked to nine proteins (CD38, CPM, EDA2R, IL12, JAMB, KYNU, LAYN, MSR1 and SMOC2) in children with OW/OB. These proteins play crucial roles in diverse biological processes (e.g., angiogenesis, cholesterol transport, nicotinamide adenine dinucleotide (NAD+) catalysis and maintenance of blood-brain barrier) related to brain health. CONCLUSION: Our proteomics study suggests that cardiometabolic health (represented by MHO/MUO or individual MS markers) is associated with the concentration in plasma of several proteins involved in brain health. Larger-scale studies are needed to contrast/confirm these findings, with CD38 standing out as a particularly noteworthy and robust discovery.

The effects of physical activity on white matter microstructure in children with overweight or obesity: The ActiveBrains randomized clinical trial.

Background: Emerging research supports the idea that physical activity benefits brain development. However, the body of evidence focused on understanding the effects of physical activity on white matter microstructure during childhood is still in its infancy, and further well-designed randomized clinical trials are needed. Aim: This study aimed: (i) to investigate the effects of a 20-week physical activity intervention on global white matter microstructure in children with overweight or obesity, and (ii) to explore whether the effect of physical activity on white matter microstructure is global or restricted to a particular set of white matter bundles. Methods: In total, 109 children aged 8 to 11 years with overweight or obesity were randomized and allocated to either the physical activity program or the control group. Data were collected from November 2014 to June 2016, with diffusion tensor imaging (DTI) data processing and analyses conducted between June 2017 and November 2021. Images were pre-processed using the Functional Magnetic Resonance Imaging (MRI) of the Brain´s Software Library (FSL) and white matter properties were explored by probabilistic fiber tractography and tract-based spatial statistics (TBSS). Results: Intention-to-treat analyses were performed for all children who completed the pre-test and post-test DTI assessment, with good quality DTI data (N = 89). Of them, 83 children (10.06±1.11 years, 39 % girls, intervention group=44) met the per-protocol criteria (attended at least 70 % of the recommended sessions). Our probabilistic fiber tractography analysis did not show any effects in terms of global and tract-specific fractional anisotropy (FA) and mean diffusivity (MD) in the per-protocol or intention-to-treat analyses. Additionally, we did not observe any effects on the voxel-wise DTI parameters (i.e., FA and MD) using the most restricted TBSS approach (i.e., per protocol analyses and p-corrected image with a statistical threshold of p < 0.05). In the intention-to-treat analysis, we found that our physical activity program had a borderline effect (p-corrected image with a statistical threshold of p < 0.1) on 7 different clusters, including a cluster in the corpus callosum. Conclusion: We conclude that a 20-week physical activity intervention was not enough to induce changes in global and tract-specific white matter during childhood. The effects of physical activity on white matter microstructure could be restricted to local changes in several white matter tracts (e.g., the body of the corpus callosum). However, our results were not significant, and more interventions are needed to determine whether and how physical activity affects white matter microstructure during childhood.

Physical activity and amyloid beta in middle-aged and older adults: A systematic review and meta-analysis.

BACKGROUND: One of the pathological hallmarks distinguishing Alzheimer's disease from other dementias is the accumulation of amyloid beta (Aß). Higher physical activity is associated with decreased dementia risk, and one potential path could be through Aß levels modulation. We aimed to explore the relationship between physical activity and Aß in middle-aged and older adults. METHODS: A systematic search of PubMed, Web of Science, PsycINFO, Cochrane Central Register of Controlled Trials, and SPORTDiscus was performed from inception to April 28, 2022. Studies were eligible if they included physical activity and Aß data in adults aged 45 years or older. Multi-level meta-analyses of intervention and observational studies were performed to examine the role of physical activity in modulating Aß levels. RESULTS: In total, 37 articles were included (8 randomized controlled trials, 3 non-randomized controlled trials, 4 prospective longitudinal studies, and 22 cross-sectional studies). The overall effect size of physical activity interventions on changes in blood Aß was medium (pooled standardized mean difference = -0.69, 95% confidence interval (95%CI): -1.41 to 0.03; I2 = 74.6%). However, these results were not statistically significant, and there were not enough studies to explore the effects of physical activity on cerebrospinal fluid (CSF) and brain Aß. Data from observational studies were examined based on measurements of Aß in the brain using positron emission tomography scans, CSF, and blood. Higher physical activity was positively associated with Aß only in the CSF (Estimate r = 0.12; 95%CI: 0.05-0.18; I2 = 38.00%). CONCLUSION: Physical activity might moderately reduce blood Aß in middle-aged and older adults. However, results were only near statistical significance and might be interpreted with caution given the methodological limitations observed in some of the included studies. In observational studies, higher levels of physical activity were positively associated with Aß only in CSF. Therefore, further research is needed to understand the modulating role of physical activity in the brain, CSF, and blood Aß, as well as its implication for cognitive health.

A streamlined, resource-efficient immunoprecipitation-mass spectrometry method for quantifying plasma amyloid-ß biomarkers in Alzheimer's disease.

High-performance, resource-efficient methods for plasma amyloid-ß (Aß) quantification in Alzheimer's disease are lacking; existing mass spectrometry-based assays are resource- and time-intensive. We developed a streamlined mass spectrometry method with a single immunoprecipitation step, an optimized buffer system, and ≤75% less antibody requirement. Analytical and clinical performances were compared with an in-house reproduced version of a well-known two-step assay. The streamlined assay showed high dilution linearity (r2>0.99) and precision (< 10% coefficient of variation), low quantification limits (Aß1-40: 12.5 pg/ml; Aß1-42: 3.125 pg/ml), and high signal correlation (r2~0.7) with the two-step immunoprecipitation assay. The novel single-step assay showed more efficient recovery of Aß peptides via fewer immunoprecipitation steps, with significantly higher signal-to-noise ratios, even at plasma sample volumes down to 50 pl. Both assays had equivalent performances in distinguishing non-elevated vs. elevated brain Aß-PET individuals. The new method enables simplified yet robust evaluation of plasma Aß biomarkers in Alzheimer's disease.