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Importance: Sleep disturbances are common among older adults and have been associated with the development of Alzheimer disease (AD), such as amyloid-β (Aβ) pathology. For effective AD prevention, it is essential to pinpoint the specific disturbances in sleep and the underlying 24-hour activity rhythms that confer the highest risk of Aβ deposition., Objective: To determine the associations of 24-hour activity rhythms and sleep with Aβ deposition in adults without dementia, to evaluate whether disrupted 24-hour activity and sleep may precede Aβ deposition, and to assess the role of the apolipoprotein E ε4 (APOE4) genotype., Design, Setting, and Participants: This was an observational cohort study using data from the Rotterdam Study. Of 639 participants without dementia who underwent Aβ positron emission tomography (PET) from September 2018 to November 2021, 319 were included in the current study. Exclusion criteria were no APOE genotyping and no valid actigraphy data at the baseline visits from 2004 to 2006 or from 2012 to 2014. The mean (SD) follow-up was 7.8 (2.4) years. Data were analyzed from March 2023 to April 2024., Exposures: Actigraphy (7 days and nights, objective sleep, and 24-hour activity rhythms), sleep diaries (self-reported sleep), Aβ42/40, phosphorylated tau (p-tau)181 and p-tau217 plasma assays, 18F-florbetaben PET (mean standard uptake value ratio [SUVR] in a large cortical region of interest), and APOE4 genotype., Main Outcomes and Measures: Association of objective and self-reported sleep and 24-hour activity rhythms at baseline with brain Aβ PET burden at follow-up., Results: The mean (range) age in the study population was 61.5 (48-80) years at baseline and 69.2 (60-88) years at follow-up; 150 (47%) were women. Higher intradaily variability at baseline, an indicator of fragmented 24-hour activity rhythms, was associated with higher Aβ PET burden at follow-up (β, 0.15; bootstrapped 95% CI, 0.04 to 0.26; bootstrapped P = .02, false discovery rate [FDR] P = .048). APOE genotype modified this association, which was stronger in APOE4 carriers (β, 0.38; bootstrapped 95% CI, 0.05 to 0.64; bootstrapped P = .03) compared to noncarriers (β, 0.07; bootstrapped 95% CI, -0.04 to 0.18; bootstrapped P = .19). The findings remained largely similar after excluding participants with AD pathology at baseline, suggesting that a fragmented 24-hour activity rhythm may have preceded Aβ deposition. No other objective or self-reported measure of sleep was associated with Aβ., Conclusions and Relevance: Among community-dwelling adults included in this study, higher fragmentation of the 24-hour activity rhythms was associated with greater subsequent Aβ burden, especially in APOE4 carriers. These results suggest that rest-activity fragmentation could represent a modifiable risk factor for AD.

Physical activity is a protective factor against brain atrophy, while loss of brain volume could also be a determinant of physical activity. Therefore, we aimed to explore the bidirectional association of physical activity with brain structures in middle-aged and older adults from the UK Biobank. Overall, 3027 participants (62.45 ± 7.27 years old, 51.3% females) had data at two time points. Hippocampal volume was associated with total (β=0.048, p FDR =0.016) and household (β=0.075, p FDR <0.001) physical activity. Global fractional anisotropy (β=0.042, p FDR =0.028) was also associated with household physical activity. In the opposite direction, walking was negatively associated with white matter volume (β=-0.026, p FDR =0.008). All these associations were confirmed by the linear mixed models. Interestingly, sports at baseline were linked to hippocampal and frontal cortex volumes at follow-up but these associations disappeared after adjusting for multiple comparisons (p all >0.104). In conclusion, we found more consistent evidence that a healthier brain structure predicted higher physical activity levels than for the inverse, more established relationship., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

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: The dual-factor model of mental health (i.e., the presence of psychological well-being along with the absence of distress) and its association with academic performance over time has been barely studied in the adolescent population, as most of the prior research focuses on psychological well-being or distress indicators in isolation. The current study analyzed the bidirectional longitudinal association between the dual-factor model of mental health and academic performance in adolescents, comprising a longitudinal assessment 2 years apart., Methods: A total of 266 secondary school students (13.9 ± 0.3 years at baseline) from Deporte, ADOlescencia y Salud study were assessed. Mental health was assessed through the Behavior Assessment System for Children and Adolescents. Academic performance was assessed through academic grades and the Test of Educational Abilities. A cross-lagged modeling approach was used to examine the bidirectional longitudinal association between mental health and academic performance., Results: Higher academic performance at baseline was associated with better mental health over time, but not vice versa, since this association was not bidirectional., Conclusion: Results suggest that academic performance is an important target for developing educational interventions, as it shapes adolescents' mental health at 2 years of follow-up., Impact: The overall picture of students' mental health and academic performance was analyzed. Academic performance may be a predictor of adolescents' mental health status. Mental health may not be a predictor of adolescents' academic performance. Good mental health should be promoted among youth with low academic performance., (© 2023. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

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.)

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.)

Background: Body composition between prepubertal children and adolescents varies, and it is unclear how physical activity and sedentary behaviour affect adolescent body composition., Objectives: This study aimed to examine the associations of physical activity and screen time with overall and specific fat depots in the general adolescent population., Methods: In a population-based prospective cohort study, among 3258 adolescents aged 13 years, physical activity and screen time were assessed via self-report questionnaires. Body mass index, dual-energy X-ray absorptiometry-based measures (i.e. fat mass and lean body mass) and magnetic resonance imaging-based measures (i.e. abdominal subcutaneous and visceral fat mass) were obtained., Results: After adjusting for social-demographic and growth-related factors, each additional hour of daily physical activity was associated with lower fat mass, abdominal visceral fat mass and higher lean body mass (all p < 0.05). However, these associations were not observed in the longitudinal analyses. Each additional hour of daily screen time was associated with higher body mass index, fat mass, abdominal subcutaneous and visceral fat mass (all p < 0.05), which were consistent with the longitudinal analyses., Conclusion: Adolescents with higher physical activity and lower screen time had lower levels of adiposity both at the general and visceral levels., (© 2023 World Obesity Federation.)

Importance: Physical activity may promote healthy brain development in children, but previous research was predominantly cross-sectional and included small samples, providing limited knowledge., Objective: To investigate the longitudinal associations of physical activity with brain morphology changes., Design, Setting, and Participants: A 4-year longitudinal population-based cohort study in Rotterdam, the Netherlands, embedded in Generation R, a cohort from fetal life onward. From the women enrolled during pregnancy, children who had repeated measures of brain structure at ages 10 (range 8 to 12) years and 14 (range 13 to 15) years were included. Data were collected from March 2013 to November 2015 (baseline) and from October 2016 to January 2020 (follow-up). Data were analyzed from April to December 2022., Exposure: At age 10 years, both the child and their primary caregiver reported the child's levels of physical activity with regard to sport participation, outdoor play, and total physical activity. Primary analyses were based on an average multi-informant report., Main Outcomes and Measures: Brain morphology was quantified by magnetic resonance imaging. Hypothesized regions of interest were the bilateral amygdala and hippocampal volumes. Global brain measures were studied to test the specificity of the hypothesis., Results: Data were available for 1088 children (566 girls [52%]; 693 [64%] Dutch). Their mean (SD) age at baseline was 10.1 (0.6) years. For amygdala volume change, positive associations with multi-informant reports of total physical activity (β = 2.6; 95% CI, 0.3-4.9) were found. Total physical activity was associated with hippocampal volume increases only when reported by the child (β = 3.1; 95% CI, 0.4-5.8). No robust associations with global brain measures were found., Conclusions and Relevance: In this cohort study of 1088 children, more physical activity at 10 years was consistently associated with an increase in amygdala volume in children aged 10 to 14 years. Physical activity and increases in hippocampal volume were found using child reports of physical activity only. These findings suggest physical activity in late childhood was prospectively associated with volumetric changes in specific subcortical structures, but not to global brain development, from late childhood to early adolescence. These findings may inform the design of future public health interventions to best facilitate neurodevelopment with physical activity.

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.

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.)

Importance: Childhood obesity is a risk factor associated with type 2 diabetes, cardiovascular disease, and mental disorders later in life. Investigation of the parallel effects of a defined exercise program on cardiometabolic and mental health in children with overweight or obesity may provide new insights on the potential benefits of exercise on overall health., Objective: To investigate the effects of a 20-week exercise program on cardiometabolic and mental health in children with overweight or obesity., Design, Setting, and Participants: This secondary analysis of a parallel-group randomized clinical trial was conducted in Granada, Spain, from November 1, 2014, to June 30, 2016. Data analyses were performed between February 1, 2020, and July 14, 2022. Children with overweight or obesity aged 8 to 11 years were eligible, and the study was performed in an out-of-school context., Intervention: The exercise program included 3 to 5 sessions/wk (90 min/session) of aerobic plus resistance training for 20 weeks. The wait-list control group continued with their usual routines., Main Outcomes and Measures: Cardiometabolic outcomes as specified in the trial protocol included body composition (fat mass, fat-free mass, and visceral adipose tissue), physical fitness (cardiorespiratory, speed-agility, and muscular), and traditional risk factors (waist circumference, blood lipid levels, glucose levels, insulin levels, and blood pressure). Cardiometabolic risk score (z score) was calculated based on age and sex reference values for levels of triglycerides, inverted high-density lipoprotein cholesterol, and glucose, the mean of systolic and diastolic blood pressure, and waist circumference. An additional cardiometabolic risk score also included cardiorespiratory fitness. Mental health outcomes included an array of psychological well-being and ill-being indicators., Results: The 92 participants included in the per-protocol analyses (36 girls [39%] and 56 boys [61%]) had a mean (SD) age of 10.0 (1.1) years. The exercise program reduced the cardiometabolic risk score by approximately 0.38 (95% CI, -0.74 to -0.02) SDs; decreased low-density lipoprotein cholesterol level by -7.00 (95% CI, -14.27 to 0.37) mg/dL (to convert to mmol/L, multiply by 0.0259), body mass index (calculated as weight in kilograms divided by height in meters squared) by -0.59 (95% CI, -1.06 to -0.12), fat mass index by -0.67 (95% CI, -1.01 to -0.33), and visceral adipose tissue by -31.44 (95% CI, -58.99 to -3.90) g; and improved cardiorespiratory fitness by 2.75 (95% CI, 0.22-5.28) laps in the exercise group compared with the control group. No effects were observed on mental health outcomes., Conclusions and Relevance: In this secondary analysis of a randomized clinical trial, an aerobic plus resistance exercise program improved cardiometabolic health in children with overweight or obesity but had no effect on mental health., Trial Registration: ClinicalTrials.gov Identifier: NCT02295072.

Importance: Understanding the mechanisms by which physical activity is associated with a lower risk of psychiatric symptoms may stimulate the identification of cost-efficient strategies for preventing and treating mental illness at early life stages., Objective: To examine neurobiological, psychosocial, and behavioral mechanisms that mediate associations of physical activity with psychiatric symptoms in youth by testing an integrated model., Design, Setting, and Participants: Generation R is an ongoing prospective population-based cohort study collecting data from fetal life until young adulthood in a multiethnic urban population in the Netherlands. Pregnant women living in Rotterdam with an expected delivery date between April 2002 and January 2006 were eligible for participation along with their children born during this time. Data were collected at a single research center in the Erasmus Medical Center Sophia Children's Hospital. For the current study, data were analyzed from 4216 children with complete data on both exposure and outcome at ages 6, 10, and 13 years. Data were analyzed from January 2021 to November 2022., Exposures: Physical activity was ascertained at age 6 years (visit 1) via parent report and included weekly frequency and duration of walking or cycling to or from school, physical education at school, outdoor play, swimming, and sports participation., Main Outcomes and Measures: Psychiatric symptoms (internalizing and externalizing symptoms) were assessed at age 6 years (visit 1) and at age 13 years (visit 3) using the Child Behavior Checklist. Several mechanisms were explored as mediators, measured at age 10 years (visit 2). Neurobiological mechanisms included total brain volume, white matter microstructure, and resting-state connectivity assessed using a 3-T magnetic resonance imaging scanner. Psychosocial mechanisms included self-esteem, body image, and friendship. Behavioral mechanisms included sleep quality, diet quality, and recreational screen time. Pearson correlations between physical activity measures and psychiatric symptoms were calculated, with false discovery rate correction applied to account for the number of tests performed. Mediation analyses were performed when a correlation (defined as false discovery rate P < .05) between exposure and outcome was observed and were adjusted for confounders., Results: Among the 4216 children included in this study, the mean (SD) age was 6.0 (0.4) years at visit 1, and 2115 participants (50.2%) were girls. More sports participation was associated with fewer internalizing symptoms (β for direct effect, -0.025; SE, 0.078; P = .03) but not externalizing symptoms. Self-esteem mediated the association between sports participation and internalizing symptoms (β for indirect effect, -0.009; SE, 0.018; P = .002). No evidence was found for associations between any other neurobiological, psychosocial, or behavioral variables. No association was found between other types of physical activity and psychiatric symptoms at these ages., Conclusions and Relevance: The integrated model presented in this cohort study evaluated potential mechanisms mediating associations between physical activity and psychiatric symptoms in youth. Self-esteem mediated an association between sports participation in childhood and internalizing symptoms in adolescence; other significant mediations were not observed. Further studies might explore whether larger effects are present in certain subgroups (eg, children at high risk of developing psychiatric symptoms), different ages, or structured sport-based physical activity interventions.

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.

Background: Emerging research supports the idea that exercise positively affects neurodevelopment. However, the mechanisms linking exercise with brain health are largely unknown. We aimed to investigate the effect of exercise on (a) blood biomarkers selected based on previous evidence (brain-derived neurotrophic factor, β-hydroxybutyrate (BHB), cathepsin B (CTSB), kynurenine, fibroblast growth factor 21 (FGF21), soluble vascular cell adhesion molecule-1 (sVCAM-1)); and (b) a panel of 92 neurology-related proteins (discovery analysis). We also investigated whether changes in these biomarkers mediate the effects of exercise on brain health (hippocampal structure and function, cognitive performance, and mental health)., Methods: We randomized 81 overweight/obese children (10.1 ± 1.1 years, 41% girls) into 2 groups: either 20 weeks of aerobic plus resistance exercise or control. Candidate biomarkers were assessed using enzyme-linked immunosorbent assay (ELISA) for kynurenine, FGF21, and CTSB; colorimetry for β-hydroxybutyrate; and XMap for brain-derived neurotrophic factor and soluble vascular cell adhesion molecule-1. The 92 neurology-related proteins were analyzed by an antibody-based proteomic analysis., Results: Our intervention had no significant effect on candidate biomarkers (all p > 0.05). In the discovery analysis, a reduction in circulating macrophage scavenger receptor type-I was observed (standardized differences between groups = -0.3, p = 0.001). This effect was validated using ELISA methods (standardized difference = -0.3, p = 0.01). None of the biomarkers mediated the effects of exercise on brain health., Conclusions: Our study does not support a chronic effect of exercise on candidate biomarkers. We observed that while chronic exercise reduced the levels of macrophage scavenger receptor type-I, it did not mediate the effects of exercise on brain health. Future studies should explore the implications of this novel biomarker for overall health., (Copyright © 2023. Production and hosting by Elsevier B.V.)

Physical activity has been suggested as modifiable factor that might contribute to improving cognitive and brain function during aging. However, previous studies were mainly of cross-sectional design and did not consider effects of time or potential reverse causality. We aimed to investigate the bidirectional associations of physical activity with brain structure in middle-aged and older adults. Overall, 4365 participants (64.01 ± 10.82 years; 56% women) from the Rotterdam Study had physical activity and brain structure assessed on at least one of 2 timepoints ('baseline': 2006-2012 or 'follow-up': 2012-2017, median duration between visits: 5 years). Physical activity was assessed through the LASA Physical Activity Questionnaire. T1-weighted MRI and diffusion tensor imaging were used to quantify brain volumes and white matter microstructure, respectively. Cross-lagged panel models were performed to estimate bidirectional associations, and linear mixed-effects models to investigate the consistency of findings. Larger total brain volume (β = 0.067, 95%-confidence interval 0.035;0.099, p FDR  = 0.001), gray matter volume (β = 0.063, 0.031;0.096, p FDR  = 0.002), and white matter volume (β = 0.051, 0.020;0.083, p FDR = 0.013) at baseline were associated with higher levels of sports at follow-up. Lower global mean diffusivity at baseline was associated with higher levels of walking at follow-up (β = -0.074, -0.111;-0.037, p FDR = 0.001). No associations were found between physical activity levels at baseline and brain metrics at follow-up. In conclusion, larger brain volumes and white matter microstructure at baseline were associated with individuals remaining more physically active at follow-up. Overall, this study identified older adults with potentially advanced brain aging status as being at higher risk of physical inactivity over time, and therefore as potential target group for prevention and novel intervention strategies., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Importance: Pediatric overweight and obesity are highly prevalent across the world, with implications for poorer cognitive and brain health. Exercise might potentially attenuate these adverse consequences., Objectives: To investigate the effects of an exercise program on brain health indicators, including intelligence, executive function, academic performance, and brain outcomes, among children with overweight or obesity and to explore potential mediators and moderators of the main effects of exercise., Design, Setting, and Participants: All preexercise and postexercise data for this 20-week randomized clinical trial of 109 children aged 8 to 11 years with overweight or obesity were collected from November 21, 2014, to June 30, 2016, with neuroimaging data processing and analyses conducted between June 1, 2017, and December 20, 2021. All 109 children were included in the intention-to-treat analyses; 90 children (82.6%) completed the postexercise evaluation and attended 70% or more of the recommended exercise sessions and were included in per-protocol analyses., Interventions: All participants received lifestyle recommendations. The control group continued their usual routines, whereas the exercise group attended a minimum of 3 supervised 90-minute sessions per week in an out-of-school setting., Main Outcomes and Measures: Intelligence, executive function (cognitive flexibility, inhibition, and working memory), and academic performance were assessed with standardized tests, and hippocampal volume was measured with magnetic resonance imaging., Results: The 109 participants included 45 girls (41.3%); participants had a mean (SD) body mass index of 26.8 (3.6) and a mean (SD) age of 10.0 (1.1) years at baseline. In per-protocol analyses, the exercise intervention improved crystallized intelligence, with the exercise group improving from before exercise to after exercise (mean z score, 0.62 [95% CI, 0.44-0.80]) compared with the control group (mean z score, -0.10 [95% CI, -0.28 to 0.09]; difference between groups, 0.72 SDs [95% CI, 0.46-0.97]; P < .001). Total intelligence also improved significantly more in the exercise group (mean z score, 0.69 [95% CI, 0.48-0.89]) than in the control group (mean z score, 0.07 [95% CI, -0.14 to 0.28]; difference between groups, 0.62 SDs [95% CI, 0.31-0.91]; P < .001). Exercise also positively affected a composite score of cognitive flexibility (mean z score: exercise group, 0.25 [95% CI, 0.05-0.44]; control group, -0.17 [95% CI, -0.39 to 0.04]; difference between groups, 0.42 SDs [95% CI, 0.13-0.71]; P = .005). These main effects were consistent in intention-to-treat analyses and after multiple-testing correction. There was a positive, small-magnitude effect of exercise on total academic performance (mean z score: exercise group, 0.31 [95% CI, 0.18-0.44]; control group, 0.10 [95% CI, -0.04 to 0.24]; difference between groups, 0.21 SDs [95% CI, 0.01-0.40]; P = .03), which was partially mediated by cognitive flexibility. Inhibition, working memory, hippocampal volume, and other brain magnetic resonance imaging outcomes studied were not affected by the exercise program. The intervention increased cardiorespiratory fitness performance as indicated by longer treadmill time to exhaustion (mean z score: exercise group, 0.54 [95% CI, 0.27-0.82]; control group, 0.13 [95% CI, -0.16 to 0.41]; difference between groups, 0.42 SDs [95% CI, 0.01-0.82]; P = .04), and these changes in fitness mediated some of the effects (small percentage of mediation [approximately 10%-20%]). The effects of exercise were overall consistent across the moderators tested, except for larger improvements in intelligence among boys compared with girls., Conclusions and Relevance: In this randomized clinical trial, exercise positively affected intelligence and cognitive flexibility during development among children with overweight or obesity. However, the structural and functional brain changes responsible for these improvements were not identified., Trial Registration: ClinicalTrials.gov Identifier: NCT02295072.

Introduction: Persistent psychiatric symptomatology during childhood and adolescence predicts vulnerability to experience mental illness in adulthood. Physical activity is well-known to provide mental health benefits across the lifespan. However, the underlying mechanisms linking physical activity and psychiatric symptoms remain underexplored. In this context, we aim to systematically synthesise evidence focused on the mechanisms through which physical activity might reduce psychiatric symptoms across all ages., Methods and Analysis: With the aid of a biomedical information specialist, we will develop a systematic search strategy based on the predetermined research question in the following electronic databases: MEDLINE, Embase, Web of Science, Cochrane and PsycINFO. Two independent reviewers will screen and select studies, extract data and assess the risk of bias. In case of inability to reach a consensus, a third person will be consulted. We will not apply any language restriction, and we will perform a qualitative synthesis of our findings as we anticipate that studies are scarce and heterogeneous., Ethics and Dissemination: Only data that have already been published will be included. Then, ethical approval is not required. Findings will be published in a peer-reviewed journal and presented at conferences. Additionally, we will communicate our findings to healthcare providers and other sections of society (eg, through regular channels, including social media)., Prospero Registration Number: CRD42021239440., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background & Aims: Exposure to a suboptimal environment during the fetal and early infancy period's results in long-term consequences for brain morphology and function. We investigated the associations of early life factors such as anthropometric neonatal data (i.e., birth length, birth weight and birth head circumference) and breastfeeding practices (i.e., exclusive and any breastfeeding) with white matter (WM) microstructure, and ii) we tested whether WM tracts related to early life factors are associated with academic performance in children with overweight/obesity., Methods: 96 overweight/obese children (10.03 ± 1.16 years; 38.7% girls) were included from the ActiveBrains Project. WM microstructure indicators used were fractional anisotropy (FA) and mean diffusivity (MD), derived from Diffusion Tensor Imaging. Academic performance was evaluated with the Battery III Woodcock-Muñoz Tests of Achievement. Regression models were used to examine the associations of the early life factors with tract-specific FA and MD, as well as its association with academic performance., Results: Head circumference at birth was positively associated with FA of the inferior fronto-occipital fasciculus tract (0.441; p = 0.005), as well as negatively associated with MD of the cingulate gyrus part of cingulum (-0.470; p = 0.006), corticospinal (-0.457; p = 0.005) and superior thalamic radiation tract (-0.476; p = 0.001). Association of birth weight, birth length and exclusive breastfeeding with WM microstructure did not remain significant after false discovery rate correction. None tract related to birth head circumference was associated with academic performance (all p > 0.05)., Conclusions: Our results highlighted the importance of the perinatal growth in WM microstructure later in life, although its possible academic implications remain inconclusive., Competing Interests: Conflict of Interest The authors declare no conflicts of interest., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Adolescence is a critical period for neurodevelopment, it is characterised by the establishment of behavioural patterns that can affect children's physical, mental and cognitive health, both immediately and later in life., Objective: The aim of the present research was to examine the association between adherence to the Mediterranean diet (MeD) and academic performance, as well as to analyze the moderating role of body mass index (BMI) status in this relationship., Methods: This cross-sectional study had a total 1290 adolescents (13.07 ± 0.82 years old, 714 boys and 576 girls) aged 12-14 years were included in this study. Adherence to the MeD was assessed using the Mediterranean Diet Quality Index. Academic performance was assessed through school records using four subjects: language, mathematics, English and grade point average (GPA)., Results: Results showed a positive association between adherence to the MeD and all academic indicators after adjusting for potential confounders (β ranging from 0.165 to 0.213, all p < 0.001). The group of good adherence to the MeD had significantly higher scores in all the academic indicators compared with the poor/average group (p < 0.01). No interaction was found between BMI status and adherence to MeD in relation to academic indicators (all p > 0.340). These differences remained significant for both normal weight and overweight/obesity groups (p < 0.01)., Conclusions: Our results suggest that adherence to the MeD may be positively associated academic performance on adolescents regardless, of BMI status., Competing Interests: Conflict of interest The authors declare that they have no conflict of interest., (Copyright © 2021 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Purpose: To find modifiable factors that are related to subjective well-being would be valuable for improving interventions in fibromyalgia. Physical activity, sedentary behaviour, and physical fitness may represent potential areas to optimize treatment regimens. In fibromyalgia, there is a discordance between clinical observations and patient-reported outcomes (objective and subjective assessments). Therefore, the present study aims at analyzing the associations of objective and subjective evaluations of physical activity, sedentary behaviour, and physical fitness with subjective well-being and determine if and how objective and subjective associations differ., Methods: In this population-based cross-sectional study participated 375 women with fibromyalgia from the al-Ándalus project (Spain). Physical activity, sedentary behaviour, and physical fitness were objectively (accelerometers and performance testing) and subjectively (questionnaires) measured. Participants self-reported their levels of positive affect, negative affect, and life satisfaction., Results: In the most conservative multivariate analysis, we found independent associations of the objective measures of physical activity with positive affect and life satisfaction and sedentary behaviour with positive affect. No such relationship was seen with subjective measures of the same behaviours. Moreover, we observed that objective and subjective physical fitness evaluations were independent of each other related to subjective well-being., Conclusions: Independent associations of the objective measures (but not the subjective assessments) of physical activity with positive affect and life satisfaction, and of sedentary behaviour with positive affect were observed. However, objective measures and subjective appraisals of physical fitness appear to be independently related to well-being, which should be considered when developing physical exercise interventions for fibromyalgia.Implications for rehabilitationThe analysis of concurrent associations of objective and subjective evaluations of physical functioning with subjective well-being offers indications for modifiable targets in rehabilitation that can improve well-being in fibromyalgia.Exercise-based rehabilitation may help women with fibromyalgia to improve subjective well-being, particularly positive affect.Rehabilitation should focus on both the objective physical performance of women with fibromyalgia and on their perceptions of what they can do physically.When rehabilitation aims at enhancing positive affect or life satisfaction by changing the lifestyle of women with fibromyalgia, physical activity and sedentary behaviour should be objectively monitored.

Purpose: This study was aimed to analyze the associations of objectively measured physical activity (PA), sedentary time, and physical fitness with mental health in the early second trimester (16 ± 2 gestational weeks) of pregnancy., Methods: From 229 women initially contacted, 124 pregnant women participated in the present cross-sectional study. Data were collected between November 2015 and March 2017. The participants wore Actigraph GT3X+ Triaxial accelerometers for 9 consecutive days to objectively measure their PA levels and sedentary time. A performance-based test battery was used to measure physical fitness. Self-report questionnaires assessed psychological ill-being (i.e., negative affect, anxiety, and depression), and psychological well-being (i.e., emotional intelligence, resilience, and positive affect). Linear regression analyses were adjusted for age, educational level, accelerometer wear time, miscarriages, and low back pain., Results: Moderate-to-vigorous PA was negatively associated with depression (β = -0.222, adjusted R 2  = 0.050, p = 0.041). Higher levels of sedentary time were negatively associated with positive affect (β = -0.260, adjusted R 2  = 0.085, p = 0.017). Greater upper-body flexibility was positively associated with better emotional regulation (β = 0.195, adjusted R 2 = 0.030, p = 0.047). The remaining associations were not significant (all p > 0.05)., Conclusion: An active lifestyle characterized by higher levels of moderate-to-vigorous PA and lower levels of sedentary time during pregnancy might modestly improve the mental health of pregnant women. Although previous research has focused on the benefits of cardiorespiratory exercise, the present study shows that only upper-body flexibility is related to emotional regulation in early pregnant women. If the present findings are corroborated in further experimental research, physical exercise programs should focus on enhancing flexibility to promote improvements in emotional regulation during early second-trimester of pregnancy., Competing Interests: Competing interests The authors declare that they have no competing interests., (Copyright © 2021. Production and hosting by Elsevier B.V.)

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 (β≥0.412, p ≤ 0.019). A limbic area was further related to better working memory performance (β=0.267, p = 0.005). During retrieval, higher cardiorespiratory fitness was also associated with higher current density in temporal regions (β=0.265, p = 0.013), whereas lower muscular fitness was associated with higher current density in frontal regions (β=-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., (© 2020 John Wiley & Sons Ltd.)

Objectives: To determine the effects of exercise on fatigue and sleep quality in fibromyalgia (primary aim) and to identify which type of exercise is the most effective in achieving these outcomes (secondary aim)., Data Sources: PubMed and Web of Science were searched from inception until October 18, 2018., Study Selection: Eligible studies contained information on population (fibromyalgia), intervention (exercise), and outcomes (fatigue or sleep). Randomized controlled trials (RCT) testing the effectiveness of exercise compared with usual care and randomized trials (RT) comparing the effectiveness of 2 different exercise interventions were included for the primary and secondary aims of the present review, respectively. Two independent researchers performed the search, screening, and final eligibility of the articles. Of 696 studies identified, 17 RCTs (n=1003) were included for fatigue and 12 RCTs (n=731) for sleep. Furthermore, 21 RTs compared the effectiveness of different exercise interventions (n=1254)., Data Extraction: Two independent researchers extracted the key information from each eligible study., Data Synthesis: Separate random-effect meta-analyses were performed to examine the effects from RCTs and from RTs (primary and secondary aims). Standardized mean differences (SMD) effect sizes were calculated using Hedges' adjusted g. Effect sizes of 0.2, 0.4, and 0.8 were considered small, moderate, and large. Compared with usual care, exercise had moderate effects on fatigue and a small effect on sleep quality (SMD, -0.47; 95% confidence interval [CI], -0.67 to -0.27; P<.001 and SMD, -0.17; 95% CI, -0.32 to -0.01; P=.04). RTs in which fatigue was the primary outcome were the most beneficial for lowering fatigue. Additionally, meditative exercise programs were the most effective for improving sleep quality., Conclusions: Exercise is moderately effective for lowering fatigue and has small effects on enhancing sleep quality in fibromyalgia. Meditative exercise programs may be considered for improving sleep quality in fibromyalgia., (Copyright © 2020 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

This study aimed to analyze the associations of activity-rest pattern indicators with academic achievement, executive function, and intelligence and to explore whether these associations are mediated by the total gray matter volume among children with overweight/obesity. Ninety-five children (10 ± 1 year, 37 girls) with overweight/obesity (based on the World Obesity Federation body mass index cutoff points) were included in this cross-sectional study. Hip- and wrist-worn ActiGraph GT3X + accelerometers were used to assess the activity-rest pattern. Interdaily stability (IS), intradaily variability (IV), the mean value of the lowest 5 hours (L5), and the mean value of the maximum 10 hours (M10) of activity and their respective timing (TL5, TM10) were used as indicators of the activity-rest pattern throughout the day. Chronotype and social jetlag were used as indicators of circadian preference. Academic achievement, executive function, and intelligence were assessed with standardized tests. Gray matter volume was acquired by magnetic resonance imaging (MRI). IS was positively associated with executive function (β = 0.244, P = .014). IV was negatively associated with mathematics and academic applications (β: -0.211 to -0.238, P's ≤ .026). Later TM10 in the day was related to lower writing, academic skills, and intelligence (β: -0.229 to -0.271, P's ≤ .025). None of the associations found were mediated by gray matter volume. A non-fragmented and stable activity-rest pattern and earlier physical activity in the day were associated with better academic achievement, executive function, and intelligence in children with overweight/obesity. Further studies are required to corroborate or contrast our findings., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Children with overweight/obesity have poorer sleep and smaller gray matter volume (GMV) than normal-weight children. No studies have investigated the associations of objectively-assessed sleep and GMV in children with overweight/obesity, or their implications for academic and cognitive outcomes., Objectives: To explore the associations of sleep behaviors with GMV in the whole brain and particularly the hippocampus as a region of interest independent of sedentary time (SED) and physical activity; and to assess whether GMV in the associated regions was related to academic achievement, executive function and intelligence quotient (IQ)., Methods: Ninety-six children with overweight/obesity (10 ± 1 year) were included. Sleep behaviors were assessed with accelerometers. GMV was acquired by magnetic resonance imaging. Academic achievement, executive function and IQ were assessed with separate tests. Analyses were adjusted for sex, peak height velocity and parent education as well as SED and physical activity., Results: Earlier wake time, less time in bed, wakening after sleep onset (WASO) and WASO occurrences were associated with higher GMV in eight cortical brain regions (k:56-448, P's < .001). Longer total sleep time, higher sleep efficiency and less WASO time were associated with higher GMV in the right hippocampus (β:0.187-0.220, P's < .05). The inferior temporal, fusiform, supramarginal, and postcentral gyri, the superior parietal cortex, precuneus and hippocampus associated with academic achievement and/or IQ. Associations remained after adjustments for SED and physical activity., Conclusions: Sleep behaviors are associated with GMV in multiple cortical regions including the right hippocampus in children with overweight/obesity, which in turn, were associated with academic achievement and IQ., (© 2020 World Obesity Federation.)

Objectives: Physical fitness is a modifiable factor associated with enhanced brain health during childhood. To our knowledge, the present study is the first to examine: (i) whether physical fitness components (i.e., cardiorespiratory, motor and muscular fitness) are associated with resting state functional connectivity of hippocampal seeds to different cortical regions in children with overweight/obesity, and (ii) whether resting state hippocampal functional connectivity is coupled with better academic performance., Patients and Methods: In this cross-sectional study, a total of 99 children with overweight/obesity aged 8-11 years were recruited from Granada, Spain (November 2014 to February 2016). The physical fitness components were assessed following the ALPHA health-related fitness test battery. T1-weighted and resting-state fMRI images were acquired with a 3.0 Tesla Siemens Magnetom Tim Trio system. Academic performance was assessed by the Woodcock-Muñoz standardized test. Hippocampal seed-based procedures with post-hoc regression analyses were performed., Results: In the fully adjusted models, cardiorespiratory fitness was independently associated with greater hippocampal connectivity between anterior hippocampus and frontal regions (β ranging from 0.423 to 0.424, p < 0.001). Motor fitness was independently associated with diminished hippocampal connectivity between posterior hippocampus and frontal regions (β ranging from -0.583 to -0.694, p < 0.001). However, muscular fitness was not independently associated with hippocampal functional connectivity. Positive resting state hippocampal functional connectivity was related to better written expression (β ranging from 0.209 to 0.245; p < 0.05)., Conclusions: Physical fitness components may associate with functional connectivity between hippocampal subregions and frontal regions, independent of hippocampal volume, in children with overweight/obesity. Particularly, cardiorespiratory fitness may enhance anterior hippocampal functional connectivity and motor fitness may diminish posterior hippocampal functional connectivity. In addition, resting state hippocampal functional connectivity may relate to better written expression., (Copyright © 2020 Elsevier Inc. All rights reserved.)