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Background It is a priority to understand that physical activity behaviour over time is a priority in Down syndrome population in order to design and promote succesfull interventions to maintain or increase levels of physical activity. We aimed to study 1 and 2-year changes in objectively measured physical activity among a relatively large sample of adolescents with Down syndrome. Methods This study comprised a total of 99 adolescents with Down syndrome (38 girls) aged from 11 to 20 years old at baseline. Participants with valid accelerometer data at baseline and at least one of the follow-up visits were included in the analysis. Results Overall, levels of physical activity observed in adolescents with Down syndrome declined from baseline to follow-ups, but these changes were not significant (all P > 0.05). Moderate-to-moderately high tracking of physical activity was observed in adolescents with Down syndrome (all P < 0.001). Youths who met physical activity guidelines at baseline demonstrated a greater decline in physical activity in 1 and 2-year changes ( P < 0.05), although they were also more likely to meet physical activity guidelines at 1 and 2-year follow-ups ( P < 0.05). Conclusions Adolescents with Down syndrome do not change their levels of physical activity at 2-year follow-ups, but those who met physical activity guidelines presented stronger declines in physical activity over time. [ABSTRACT FROM AUTHOR]

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 (β from 0.6 to 0.8 and k from 106 to 1927) and knee extension strength in three regions (β 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 (β = -0.3, k = 1102 and k = 152) and the 2-km walking test in one region (β = -0.4, k = 99). Only handgrip strength-related GMV was associated with cognitive flexibility (p = 0.039, β = 0.215) and spatial working memory (p < 0.03, β 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., (© 2024 The Author(s). Scandinavian Journal of Medicine & Science In Sports published by John Wiley & Sons Ltd.)

High-performance, resource-efficient methods for plasma amyloid-β (Aβ) 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 (r 2 >0.99) and precision (< 10% coefficient of variation), low quantification limits (Aβ1-40: 12.5 pg/ml; Aβ1-42: 3.125 pg/ml), and high signal correlation (r 2 ~0.7) with the two-step immunoprecipitation assay. The novel single-step assay showed more efficient recovery of Aβ 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 Aβ-PET individuals. The new method enables simplified yet robust evaluation of plasma Aβ biomarkers in Alzheimer's disease., Competing Interests: Conflict of Interest YC, XZ, NAY and TKK are inventors on a University of Pittsburgh patent filed on the method described in this manuscript.

Introduction: Patients with coronary artery disease (CAD) have a higher risk of developing cognitive impairment and mental health disorders compared to the general population. Physical exercise might improve their brain health. The overall goal of the HEART-BRAIN randomized controlled trial (RCT) is to investigate the effects of different types of exercise on brain health outcomes in patients with CAD, and the underlying mechanisms., Methods: This three-arm, single-blinded RCT will include 90 patients with CAD (50-75 years). Participants will be randomized into: (1) control group-usual care ( n  = 30), (2) aerobic high-intensity interval training (HIIT) ( n  = 30), or (3) HIIT combined with resistance exercise training ( n  = 30). The 12-week intervention includes 3 supervised sessions (45-min each) per week for the exercise groups. Outcomes will be assessed at baseline and post-intervention. The primary outcome is to determine changes in cerebral blood flow assessed by magnetic resonance imaging. Secondary outcomes include changes in brain vascularization, cognitive measures (i.e., general cognition, executive function and episodic memory), and cardiorespiratory fitness. Additional health-related outcomes, and several potential mediators and moderators will be investigated (i.e., brain structure and function, cardiovascular and brain-based biomarkers, hemodynamics, physical function, body composition, mental health, and lifestyle behavior)., Conclusion: The HEART-BRAIN RCT will provide novel insights on how exercise can impact brain health in patients with CAD and the potential mechanisms explaining the heart-brain connection, such as changes in cerebral blood flow. The results may have important clinical implications by increasing the evidence on the effectiveness of exercise-based strategies to delay cognitive decline in this high-risk population., Clinical Trial Registration: ClinicalTrials.gov, identifier [NCT06214624]., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Toval, Solis-Urra, Bakker, Sánchez-Aranda, Fernández-Ortega, Prieto, Alonso-Cuenca, González-García, Martín-Fuentes, Fernandez-Gamez, Olvera-Rojas, Coca-Pulido, Bellón, Sclafani, Sanchez-Martinez, Rivera-López, Herrera-Gómez, Peñafiel-Burkhardt, López-Espinosa, Corpas-Pérez, García-Ortega, Vega-Cordoba, Barranco-Moreno, Morales-Navarro, Nieves, Caro-Rus, Amaro-Gahete, Mora-Gonzalez, Vidal-Almela, Carlén, Migueles, Erickson, Moreno-Escobar, García-Orta, Esteban-Cornejo and Ortega.)

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., (© 2023. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Background: Overweight and obesity affect more than 18% of children and adolescents in the world. Obesity-related associations with brain morphology might be associated with reduced efficiency of inhibitory control. This association highlights a possible mechanism by which obesity impacts intelligence and academic achievement. Prior work indicates a mediating effect of inhibitory control on the relationship between body mass index (BMI) and intelligence and academic achievement. However, although obesity is associated with impaired math performance, we do not know whether inhibitory control also mediates the relationship between BMI and math performance. This study tests the hypothesis that inhibitory control statistically mediates the relationship between BMI and math performance., Methods: 161 children (9 to 13 years old, 80 female) participated in the present study. We evaluated BMI; math performance, in a test composed of 20 arithmetic equations of the type x = (a × b) - c; and inhibitory control through the Flanker test. We carried out Spearman correlation tests, hierarchical multiple linear regression, and tested the confidence of the model where inhibitory control statistically mediates the indirect association between BMI and math performance. Mediation analysis in this cross-sectional study aimed to improve understanding of indirect relationships and offer insights into possible causal connections., Results: Better math performance and lower BMI were associated with greater accuracy on the inhibitory control test and greater accuracy on the inhibitory control test was associated with better performance on math test. We found an indirect association between higher BMI in children and impairments in math performance, that was mediated by inhibitory control (a: -0.008, p = 0.025; b: 7.10, p = 0.0004; c: 0.05, p = 0.592; c': 0.11, p = 0.238; Indirect Effect: -0.0599, 95% CI: -0.13, -0.005)., Conclusions: An indirect association between higher body mass indices in children and impairments in math performance was detected, through the impact that BMI has on inhibitory control., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Cordeiro et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: To examine the associations between muscular strength and mental health., Design: We used baseline data of 91 cognitively healthy older adults (71.69 ± 3.91 years old, 57 % women) participating in the AGUEDA randomized controlled trial., Methods: Muscular strength was assessed using both objective (i.e., handgrip strength, biceps curl, squats, and isokinetic test) and perceived (i.e., International Fitness Scale) indicators. Psychological ill-being indicators: anxiety, depression, stress, and loneliness; and psychological well-being indicators: satisfaction with life, self-esteem, and emotional well-being) were assessed using a set of valid and reliable self-reported questionnaires. Linear regression analyses were performed adjusting for sex, age, years of education, body mass index , alcohol, diet, and smoking (model 1), and additionally by cardiorespiratory fitness (model 2)., Results: Elbow extension was positively associated with stress in model 1 ( β = 0.252, 95 % Confidence Interval [95 % CI] = 0.007 to 0.497, p = 0.044), and even after further adjustment for cardiorespiratory fitness ( β = 0.282, 95 % CI = 0.032 to 0.532, p = 0.028). Perceived strength was negatively associated with depressive symptoms in model 1 ( β = -0.271, 95 % CI = -0.491 to -0.049, p = 0.017) and model 2 reported associations tending towards significant ( β = -0.220, 95 % CI = -0.445 to 0.005, p = 0.055). Handgrip strength was positively associated with self-esteem in model 1 ( β = 0.558, 95 % CI = 0.168 to 0.949, p = 0.006) and model 2 ( β = 0.546, 95 % CI = 0.135 to 0.956, p = 0.010). No further associations were found among other muscular strength and mental health variables., Conclusion: Handgrip had a moderate association with self-esteem and there was a small association between perceived strength with depressive symptoms and elbow extension with stress. No other associations were observed between muscular strength and mental health outcomes in cognitively normal older adults., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier B.V.)

The background of this study is to examine the associations of individual and combined early morning patterns (i.e., active commuting to school, physical activity before school, having breakfast and good sleep) with white matter microstructure (WMM) and, whether the associated white mater microstructure outcomes were related to mental health outcomes in children with overweight or obesity. 103 children with overweight or obesity (10.0 ± 1.1 years old, 42 girls) from the ActiveBrains project participated in this cross-sectional study. Early morning patterns and mental health indicators (i.e., self-esteem, optimism, positive and negative affect, stress, depression and anxiety) were self-reported by the children using validated questionnaires. WMM was assessed by magnetic resonance imaging using diffusion tensor imaging. When examined independently, early morning patterns were not related with WMM (all P > 0.05). However, the combination of early morning patterns was related with WMM (P < 0.05). Specifically, physically active early morning patterns (i.e., active commuting to school and physical activity before school) were associated with global fractional anisotropy (FA) (β = 0.298, P = 0.013) and global radial diffusivity (RD) (β = - 0.272, P = 0.021), as well as with tract-specific FA (β = 0.314, P = 0.004) and RD (β = - 0.234, P = 0.032) in the superior longitudinal fasciculus (SLF). Furthermore, combined physically active early morning pattern-associated global (i.e., FA and RD) and tract-specific (i.e., FA and RD in the SLF) WMM indicators were positively associated with happiness (β absolute value range from 0.252 to 0.298, all P < 0.05). A combination of physically active early morning patterns may positively relate to white matter microstructure in children with overweight or obesity, and, in turn, happiness., (© 2023. The Author(s).)

Background: One of the pathological hallmarks distinguishing Alzheimer's disease from other dementias is the accumulation of amyloid beta (Aβ). Higher physical activity is associated with decreased dementia risk, and one potential path could be through Aβ levels modulation. We aimed to explore the relationship between physical activity and Aβ 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 Aβ 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 Aβ 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 Aβ was medium (pooled standardized mean difference = -0.69, 95% confidence interval (95%CI): -1.41 to 0.03; I 2  = 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 Aβ. Data from observational studies were examined based on measurements of Aβ in the brain using positron emission tomography scans, CSF, and blood. Higher physical activity was positively associated with Aβ only in the CSF (Estimate r = 0.12; 95%CI: 0.05-0.18; I 2  = 38.00%)., Conclusion: Physical activity might moderately reduce blood Aβ 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 Aβ only in CSF. Therefore, further research is needed to understand the modulating role of physical activity in the brain, CSF, and blood Aβ, as well as its implication for cognitive health., (Copyright © 2023. Production and hosting by Elsevier B.V.)

Preschool children spend a large part of their day at school, and a large part of that time they spend in sedentary time. Although sedentary time negatively affects regions of the brain responsible for cognition, it is believed that the type of sedentary time performed can favor executive functions' performance. The present study explored the associations between sedentary time inside and outside preschools with executive function (EF) tasks in preschoolers. Seventy-three preschool children (60% girls; 55.0 ± 9.1 months of age) were objectively assessed for sedentary time and physical activity (PA) using accelerometers (wGT3X). EF was evaluated using the Go/No-Go paradigm through the Early Years Toolbox - YET. Go's inverse efficiency (IE) and the No-Go accuracy were analyzed. To establish possible associations between EF and sedentary time, a structural equation model was conducted after adjustments for sex, age, body mass index, and moderate-to-vigorous PA. A significant and positive association between sedentary time on weekend days and IE (b = 0.61; p  < .001) was observed. The general model explained 52% of the variation in IE and 2.1% in the accuracy of No-Go. The sedentary time on weekend days seems to be related to worse EI. This result emphasizes a context-dependent association between time being sedentary and preschoolers' EF. Further investigations should focus on exploring the type of sedentary behavior children are engaged in different contexts.

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., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

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/mm 2 ) 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., (© 2023 The Authors. Scandinavian Journal of Medicine & Science In Sports published by John Wiley & Sons Ltd.)

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 [V̇O 2peak ], treadmill time, and V̇O 2 at ventilatory threshold) and 20-metre shuttle run test (20mSRT, laps, running speed, estimated V̇O 2peak 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: V̇O 2peak /body mass (β = 0.18, 95% CI = 0.01-0.35) and treadmill time (β = 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 (β = 0.255, 95% CI = 0.089-0.421) and academic performance (β = 0.199-0.255, 95% CI = 0.006-0.421), and the running speed was positively associated with executive functions (β = 0.203, 95% CI = 0.039-0.367). Estimated V̇O 2peak/Léger et al. was positively associated with intelligence, executive functions, academic performance, and gray matter volume (β = 0.205-0.282, 95% CI = 0.013-0.500). Estimated V̇O 2peak/Mahar et al. and V̇O 2peak/Matsuzaka et al. (speed) were positively associated with executive functions (β = 0.204-0.256, 95% CI = 0.031-0.436)., Conclusion: Although V̇O 2peak is considered the gold standard indicator of CRF in children, peak performance (laps or running speed) and estimated V̇O 2peak/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., (© 2023 The Authors. Scandinavian Journal of Medicine & Science In Sports published by John Wiley & Sons Ltd.)

Cardiorespiratory fitness (CRF) is inversely associated with cardiovascular disease (CVD) risk factors and brain health impairments. However, the molecular mechanisms linking CRF to health in children are poorly understood. We aimed to examine protein levels related to brain health and CVD in plasma of fit compared to unfit children with overweight/obesity (OW/OB). Eighty-seven children with OW/OB (10.08 ± 1.1 years, 59% boys) from the ActiveBrains project were included. CRF was measured by performing a treadmill test, and children were categorized into fit or unfit. Targeted proteomics in plasma was performed using Olink's proximity extension assay technology of Neurology panel in the whole sample and of Cardiovascular panel in a subsample. Sixteen proteins (PLXNB3, sFRP3, CLEC1B, RSPO1, Gal8, CLEC10A, GCP5, MDGA1, CTSC, LAT, IL4RA, PRSS27, CXCL1, Gal9, MERTK, and GT) were differentially expressed between fit and unfit children with OW/OB after adjusting for sex, maturational status, and body mass index. However, statistically significant differences disappeared after applying FDR correction. Potential candidate proteins related to CRF levels in children with OW/OB were detected, being involved in several biological processes such as neurogenesis, immune/inflammatory response, signal transduction, platelet activation. Nevertheless, these preliminary findings should be confirmed or contrasted in future studies using larger sample sizes, longitudinal and experimental designs. Highlights The molecular mechanisms underlying the link of cardiorespiratory fitness (CRF) with cardiovascular and brain health in children with overweight/obesity (OW/OB) are poorly understood.Targeted proteomic analysis revealed differentially expressed proteins (PLXNB3, sFRP3, CLEC1B, RSPO1, Gal8, CLEC10A, GCP5, MDGA1, CTSC, LAT, IL4RA, PRSS27, CXCL1, Gal9, MERTK, and GT) in plasma of "Fit" compared to "Unfit" children with OW/OB. These proteins are involved in several biological processes such as immune/inflammatory response, neurogenesis, signal transduction, and cellular metabolic process.Longitudinal and experimental studies are warranted to reveal how improvements in CRF are related to changes in circulating levels of the abovementioned proteins and how they might reduce cardiovascular diseases risk factors and brain health impairments later in life.

We investigated the interaction between a genetic score and an exercise intervention on brain health in children with overweight/obesity. One hundred one children with overweight/obesity (10.0 ± 1.5 yr, 59% girls) were randomized into a 20-wk combined exercise intervention or a control group. Several cognitive and academic outcomes were measured with validated tests. Hippocampal volume was quantified using magnetic resonance imaging. Six brain health-related polymorphisms [rs6265 ( BDNF ), rs2253206 ( CREB1 ), rs2289656 ( NTRK2 ), rs4680 ( COMT ), rs429358, and rs7412 ( APOE )] were genotyped. Cognitive flexibility and academic skills improved significantly more in the exercise than in the control group only in the children with a "favorable" genetic profile [mean z -score, 0.41-0.67 (95% CI 0.11 to 1.18)], yet not in those with "less favorable" genetic profile. An individual response analysis showed that children responded to exercise in cognitive flexibility only in the "genetically favorable" group [i.e., 62% of them had a meaningful (≥0.2 Cohen d ) increase in the exercise group compared with only 25% in the control group]. This finding was consistent in per-protocol and intention-to-treat analyses ( P = 0.01 and P = 0.03, respectively). The results were not significant or not consistent for the rest of outcomes studied. Our findings suggest that having a more favorable genetic profile makes children with overweight/obesity more responsive to exercise, particularly for cognitive flexibility. NEW & NOTEWORTHY Interindividual differences have been reported in brain health-related outcomes in response to exercise interventions in adults, which could be partially explained by genetic background differences. However, the role of genetic polymorphisms on brain health-related outcomes in response to exercise interventions remains unexplored in pediatric population. The current study in children with overweight/obesity showed that a genetic score composed of six brain health-related polymorphisms ( BDNF , CREB1 , NTRK2 , COMT , and APOE ) regulated the exercise-induced response on several brain health outcomes, yet mainly and more consistently on cognitive flexibility.

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., (© 2023 The Authors. Scandinavian Journal of Medicine & Science In Sports published by John Wiley & Sons Ltd.)

Alzheimer's disease is currently the leading cause of dementia and one of the most expensive, lethal and severe diseases worldwide. Age-related decline in executive function is widespread and plays a key role in subsequent dementia risk. Physical exercise has been proposed as one of the leading non-pharmaceutical approaches to improve executive function and ameliorate cognitive decline. This single-site, two-arm, single-blinded, randomized controlled trial (RCT) will include 90 cognitively normal older adults, aged 65-80 years old. Participants will be randomized to a 24-week resistance exercise program (3 sessions/week, 60 min/session, n = 45), or a wait-list control group ( n = 45) which will be asked to maintain their usual lifestyle. All study outcomes will be assessed at baseline and at 24-weeks after the exercise program, with a subset of selected outcomes assessed at 12-weeks. The primary outcome will be indicated by the change in an executive function composite score assessed with a comprehensive neuropsychological battery and the National Institutes of Health Toolbox Cognition Battery. Secondary outcomes will include changes in brain structure and function and amyloid deposition, other cognitive outcomes, and changes in molecular biomarkers assessed in blood, saliva, and fecal samples, physical function, muscular strength, body composition, mental health, and psychosocial parameters. We expect that the resistance exercise program will have positive effects on executive function and related brain structure and function, and will help to understand the molecular, structural, functional, and psychosocial mechanisms involved., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Solis-Urra, Molina-Hidalgo, García-Rivero, Costa-Rodriguez, Mora-Gonzalez, Fernandez-Gamez, Olvera-Rojas, Coca-Pulido, Toval, Bellón, Sclafani, Martín-Fuentes, Triviño-Ibañez, de Teresa, Huang, Grove, Hillman, Kramer, Catena, Ortega, Gómez-Río, Erickson and Esteban-Cornejo.)

ABSTRACT Neurotrophic factors and cardiorespiratory fitness are both considered important in developmental trajectories but their link to brain health remains poorly understood. The aims of the study were to examine whether levels of plasma-derived neurotrophic factors were associated with brain health indicators in children with overweight or obesity; and to test whether these associations were moderated by cardiorespiratory fitness. 100 children (41% girls) were included in this analysis. Plasma levels of brain-derived neurotrophic factor, insulin-like growth factor-1, vascular endothelial growth factor A, and epidermal growth factor were determined by XMap technology. Academic performance and executive function were assessed using validated neuropsychological tests. Hippocampal volume was measured using magnetic resonance imaging. Cardiorespiratory fitness was assessed using the 20-m Shuttle Run Test. Insulin-like growth factor-1 was positively associated with cognitive flexibility. Stratified analyses by fitness categories (i.e. unfit vs. fit) showed that brain-derived neurotrophic factor was positively associated with right posterior hippocampal volume in fit children, and epidermal growth factor was negatively associated with right hippocampal, and right anterior hippocampal volumes in their unfit peers, with a moderating role of cardiorespiratory fitness in these associations. However, all these significant associations disappeared after correction for multiple comparisons. The association between neurotrophic factors and brain health indicators in children with overweight/obesity was neither strong nor consistent. These results could help enhance our understanding of determinants of brain health in children with overweight/obesity. Highlights This study provides novel findings on the associations between neurotrophic factors and a wide range of brain health indicators in children.This study additionally explored the role of cardiorespiratory fitness in these associations.The association between neurotrophic factors and brain health in children with overweight/obesity was neither strong nor consistent.Cardiorespiratory fitness moderated the associations of brain-derived neurotrophic factor and epidermal growth factor with right hippocampal volume.