Aging is associated with heightened systemic inflammation, decline in selective aspects of cognition, and an increase in white matter lesions (WMLs). Both WMLs and systemic inflammation have been related to cognition. However, it is not clear how they interdependently relate to cognitive aging. In this study we examined whether WMLs mediate the relation between markers of systemic inflammation and cognition in late adulthood. Baseline data from the randomized clinical trial “Investigating Gains in Neurocognition in an Intervention Trial of Exercise” (IGNITE) were used, which included 598 healthy older adults (mean age=69.9±3.75 years). Interleukin 6 (IL-6) and Tumor Necrosis Factor Alpha (TNF-α) were included as markers of systemic inflammation. A confirmatory factor analysis of cognitive performance resulted in factors measuring episodic memory (EM), processing speed (PS), working memory (WM), attentional control (AC), and visuospatial function (VF). WML volumes were computed from FLAIR and T1 scans using UBO detector. Mediation models were run with age, sex, years of education, and study site included as covariates. Higher levels of IL-6 were associated with more WMLs (b = 0.12, p < 0.001) as well as lower scores on all cognitive factors (all p < 0.03). In contrast, higher levels of TNF- α were associated with more WMLs (b = 0.10, p < 0.05) but not with any of the cognitive measures (all p > 0.3). More WMLs were associated with poorer PS, WM, AC, and VF (all p < 0.03), but not EM (all p > 0.05). Further, associations between IL-6 and measures of PS, WM, AC, and VF were statistically mediated by WMLs (all b = -0.01, all p < 0.05). These findings suggest that markers of systemic inflammation might lead to poorer cognitive performance by impacting WMLs. The differences between IL-6 and TNF-α with cognition highlight the need for more research to understand how different cytokine pathways relate to cognition. Our results are important for building a mechanistic framework to understand the interplay between inflammation, WMLs, and cognition and could inform the development of targeted interventions focusing on regulating cytokines to support brain health and cognitive aging.

OBJECTIVES:To evaluate the association between cardiorespiratory fitness (CRF) and cognition in a large sample of older adults, and to examine clinical and demographic factors that might moderate these associations. METHODS:CRF was measured with a graded exercise test performed on a motorised treadmill. A confirmatory factor analysis was conducted using data from a comprehensive neuropsychological battery to obtain latent factors reflecting core cognitive domains. Linear regression models evaluated the association between CRF and each of the cognitive composites, and potential moderators including demographic factors (age, sex, education), apolipoprotein E ε4 (APOE4) carriage, beta-blocker use and components of maximal effort criteria during CRF testing. RESULTS:The sample consisted of 648 adults (mean (SD) age 69.88 (3.75)), including 461 women (71.1%). The highest oxygen consumption obtained during testing (VO2max) was mean (SD) = 21.68 (5.06) mL/kg/min. We derived a five-factor model composed of episodic memory, processing speed, working memory, executive function/attentional control and visuospatial function. Higher CRF was associated with better performance across all five cognitive domains after controlling for covariates. Age and APOE4 carriage did not moderate observed associations. The relationship between CRF and cognitive performance was greater in women, those with fewer years of education and those taking beta-blockers in the domains of processing speed (sex: β=-0.447; p=0.015; education: β=-0.863; p=0.018) and executive function/attentional control (sex: β=-0.417; p=0.022; education β=-0.759; p=0.034; beta-blocker use: β=0.305; p=0.047). CONCLUSION:Higher CRF in older adulthood is associated with better cognitive performance across multiple domains susceptible to age-related cognitive decline. Sex, education and use of beta-blockers moderated observed associations within select cognitive domains.

ObjectivePhysical exercise may increase brain volume and cortical thickness in late adulthood. However, few studies have examined the possibility for exercise to influence brain morphology in women treated for breast cancer. We conducted a nested sub-study within a randomized clinical trial to examine whether 6 months of moderate-intensity aerobic exercise in postmenopausal women with early-stage breast cancer influences brain morphology.MethodsWe included twenty-eight postmenopausal women newly diagnosed with Stage 0-IIIa breast cancer (M age = 62.96 ± 5.40) who were randomized to either 45–60 min of supervised aerobic exercise 3 days/week (n = 16) or usual care (n = 12). Before beginning aromatase inhibitor aromatase inhibitor therapy, and the exercise intervention, and again at 6-month follow-up, volumetric and cortical thickness measures were derived from magnetic resonance imaging scans.ResultsThere were no significant intervention effects on brain volume and cortical thickness. However, greater average exercise intensity (%) during the intervention was associated with greater post-intervention cortical volume, mean cortical thickness, precentral gyrus thickness, and superior parietal thickness (all p < 0.05). Finally, total supervised exercise time was associated with higher precentral gyrus thickness after the intervention (p = 0.042, R2 = 0.263).ConclusionThe exercise intervention did not significantly affect brain volumes and cortical thickness compared to the control group. However, positive associations were found between exercise intensity and brain morphology changes after the 6-month intervention, indicating that exercise may reduce the vulnerability of the brain to the deleterious effects of breast cancer and its treatment.

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 metaanalyses 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.

High-intensity interval training (HIIT) is a time-efficient strategy to improve fitness and performance. Whereas the multiple and negative effects of high intake of alcohol have been widely studied, the effect of moderate alcohol doses after exercise is not clear, and it is currently under debate. For that, a total of 80 young healthy adults are studied and allocated into 5 groups, each including 16 participants. Four groups follow a HIIT program, while the fifth group is a control non-training group. The training groups will be randomized according to the characteristics of the ingested beverage (alcohol beer, beer 0.0%, sparkling water, or ethanol). The effects of HIIT on several aspects of physical performance and mental health in young healthy adults are evaluated, also the concomitant effect of daily and moderate alcohol consumption. The novelty of this study lies in the continuous measurement of the psychological parameters associated with carrying out a highly demanding training program in conjunction with alcohol consumption in moderate quantities, reflecting real-life conditions.

Background. The main purpose of this study was to determine the effects of a high-intensity interval training (HIIT) intervention in the context of moderate alcohol consumption on cognitive performance in healthy young adults. Methods. We conducted a 10-week HIIT program along with four types of beverages with/without alcohol content. A total of 75 healthy adults (18–40 years old; 46% female) were allocated to either a control Non-Training group or an HIIT program group (2 days/week). Using block randomization, participants in the HIIT group were further allocated to an HIIT-Alcohol group (alcohol beer or sparkling water with vodka added, 5.4%) or an HIIT-NonAlcohol group (sparkling water or non-alcohol beer, 0.0%). The control group was instructed to maintain an active lifestyle but did not undergo any regular training. A comprehensive neuropsychological battery was used to evaluate cognitive performance (i.e., memory, working memory, processing speed, inhibitory control, and verbal fluency). Changes from baseline to week 10 were included in the main analyses. Results. All groups improved in all neuropsychological measures (all p ≤ 0.001), independent of sex and alcohol consumption, with no statistical differences between groups (all p > 0.05). Furthermore, larger increases in maximal oxygen uptake were associated with greater improvements in processing speed, inhibitory control, and verbal fluency (all p < 0.050). Conclusions. Although the improvements found in cognitive performance cannot be attributed to the HIIT intervention, no significant impairments in cognitive functions were noted due to moderate alcohol intake. Furthermore, our results confirmed that exercise-induced physical fitness improvements were associated with cognitive performance enhancements in young healthy adults.

Pregnancy involves various physiological, physical, and social changes that can impact the mental health of the woman, causing her to have a stressful experience. Physical fitness (PF) is postulated as a powerful marker of health in this population. Therefore, this longitudinal study examined the association of PF with maternal emotional well-being and ill-being outcomes at 16th and 34th gestational weeks (g.w.) in a sample of 158 pregnant women (32.9 ± 4.7 years old). Self-reported PF was assessed with the valid and feasible International Fitness Scale [i.e., overall PF, cardiorespiratory fitness (CRF), muscular strength, speed–agility, and flexibility]; positive and negative affect, emotional intelligence, and resilience were measured using validated questionnaires specifically designed for this purpose. The results showed that women with greater overall PF and its components showed higher positive affect and lower negative affect (all, p < 0.05); greater emotional intelligence (all, p < 0.05); and greater resilience (all, p < 0.05), with similar results both in the 16th and the 34th g.w. These findings underscore the pivotal role of PF in promoting emotional health and resilience during pregnancy, thereby highlighting the need for integrating PF enhancement strategies in prenatal care programs.

PURPOSE: Breast cancer and obesity negatively affect brain health, but we know little about whether obesity in the context of breast cancer is related to brain health outcomes. Here, we assessed associations of BMI and body weight with brain volume, cortical thickness, inflammatory biomarkers, and objective cognitive function in postmenopausal women recently diagnosed with Stage I-IIIa breast cancer. METHODS: Twenty-three women (mean age = 62.92 ± 5.84 years) underwent magnetic resonance imaging (MRI), weight and height assessments for calculation of body mass index (BMI), neuropsychological testing, and blood extractions. FreeSurfer was used for calculation of regional volumes and cortical thickness from the MRI anatomical scan. Linear regressions were conducted to analyse the associations of BMI and weight with brain variables, cognitive performance, and inflammatory biomarkers. RESULTS: Higher BMI was associated with reduced cortical thickness of the paracentral gyrus (β = -0.492, p = .015) and posterior cingulate cortex (β = -0.407, p = .048). Similarly, greater weight was associated with reduced cortical thickness of the cuneus, entorhinal cortex, paracentral gyrus, and posterior cingulate cortex (all p < .05). These associations persisted after controlling for age and estimated total intracranial volume (eTIV). In contrast, higher BMI was associated with better performance on the two measures of processing speed (β = 0.546, p = .006; β = 0.542, p = .006) and greater weight was associated with better learning and memory, verbal memory, and processing speed (all p < .05). These associations persisted after adjusting for age and education. As hypothesized, higher BMI and weight was associated with greater levels of inflammation as measured by IL-6 (all p < .05) and TNF-alpha (β = 0.629, p < .001, and β = 0.419, p = .042, respectively). The associations were still observed after adjusting for age. CONCLUSIONS: Our results might be in line with the “obesity paradox” such that late-life obesity is associated with better cognitive performance. The associations with inflammatory markers indicate a possible mechanism for the cortical findings but more research is needed to understand the links with cognition.Supported by the National Cancer Institute [R01CA196762].

Introduction Physical activity (PA) has beneficial effects on brain health and cardiovascular disease (CVD) risk. Yet, we know little about whether PA-induced changes to physiological mediators of CVD risk influence brain health and whether benefits to brain health may also explain PA-induced improvements to CVD risk. This study combines neurobiological and peripheral physiological methods in the context of a randomised clinical trial to better understand the links between exercise, brain health and CVD risk.Methods and analysis In this 12-month trial, 130 healthy individuals between the ages of 26 and 58 will be randomly assigned to either: (1) moderate-intensity aerobic PA for 150 min/week or (2) a health information control group. Cardiovascular, neuroimaging and PA measurements will occur for both groups before and after the intervention. Primary outcomes include changes in (1) brain structural areas (ie, hippocampal volume); (2) systolic blood pressure (SBP) responses to functional MRI cognitive stressor tasks and (3) heart rate variability. The main secondary outcomes include changes in (1) brain activity, resting state connectivity, cortical thickness and cortical volume; (2) daily life SBP stress reactivity; (3) negative and positive affect; (4) baroreflex sensitivity; (5) pulse wave velocity; (6) endothelial function and (7) daily life positive and negative affect. Our results are expected to have both mechanistic and public health implications regarding brain–body interactions in the context of cardiovascular health.Ethics and dissemination Ethical approval has been obtained from the University of Pittsburgh Institutional Review Board (IRB ID: 19020218). This study will comply with the NIH Data Sharing Policy and Policy on the Dissemination of NIH-Funded Clinical Trial Information and the Clinical Trials Registration and Results Information Submission rule.Trial registration number NCT03841669.

BACKGROUND:Accumulation of amyloid-β (Aβ) plaques is one of the main features of Alzheimer's disease (AD). Physical performance has been related to dementia risk and Aβ, and it has been hypothesized as one of the mechanisms leading to greater accumulation of Aβ. Yet, no evidence synthesis has been performed in humans.OBJECTIVE:To investigate the association of physical performance with Aβ in humans, including Aβ accumulation on brain, and Aβ abnormalities measured in cerebrospinal fluid (CSF) and blood.METHODS:A systematic review with multilevel meta-analysis was performed from inception to June 16th, 2022. Studies were eligible if they examined the association of physical performance with Aβ levels, including the measure of physical performance as a predictor and the measure of Aβ as an outcome in humans.RESULTS:7 articles including 2,619 participants were included in the meta-analysis. The results showed that physical performance was not associated with accumulation of Aβ in the brain (ES = 0.01; 95% CI -0.21 to 0.24; I2 = 69.9%), in the CSF (ES = -0.28; 95% CI -0.98 to 0.41; I2 = 91.0%) or in the blood (ES = -0.19; 95% CI -0.61 to 0.24; I2 = 99.75%). Significant heterogeneity was found across the results , which posed challenges in arriving at consistent conclusions; and the limited number of studies hindered the opportunity to conduct a moderation analysis.CONCLUSIONS:The association between physical performance and Aβ is inconclusive. This uncertainly arises from the limited number of studies, study design limitations, and heterogeneity of measurement approaches. More studies are needed to determine whether physical performance is related to Aβ levels in humans.

Objectives: This study aimed to investigate the associations between portion sizes (PSs) from different food groups and energy, as well as nutrient intakes in European adolescents. Methods: A sample of 1631 adolescents (54.2 % girls) were included from the Healthy Lifestyle in Europe by Nutrition in Adolescence Cross-Sectional (HELENA) study. Mean food PS was calculated by dividing the total intake of the items by the number of eating occasions of these consumed items. To determine the key items for analysis, foods were ranked by frequency of consumption. A one-way between-groups analysis of covariance was used to test for significant differences in means across tertiles. A multivariable linear regression analysis was carried out, adjusting for age, sex, maternal education, body mass index, and using country as a level. Results: Energy intake increased with elevated intakes of energy-dense foods. Large portions of rice and other grains, starch roots and potatoes, and meat substitutes, nuts, and pulses were associated with increased car-bohydrate and fiber intake. Larger portions of cheese and butter and animal fat were significantly associated with a higher fat intake. Lower intakes of some vitamins and micronutrients were noticed with consumption of larger portions of high energy-dense foods, such as desserts and pudding, margarine and vegetable oil, and butter and animal fat. Conclusions: Large food PSs may be associated with positive energy, as well as macro-and micronutrient intake. Moreover, the findings from this study may help the future development of dietary guidance in gen-eral and specific to PSs, and support targeted strategies to address intakes of certain nutrients in European adolescents. (c) 2022 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)

We aimed to investigate the effect of three types of exercise interventions on memory (i.e., immediate memory (IM), long-term memory (LTM), and recognition). We also investigated whether exercise-induced changes in circulating S-Klotho and 1,25-dihydroxivitamin D (1,25(OH)2 D) levels were related to those observed in memory in healthy middle-aged sedentary adults. A 12-week randomized controlled trial was performed with a parallel-group design. Seventy-four participants (45-65 years old: 53% women) were randomly assigned to (1) no exercise (control) group, (2) concurrent training based on the international physical activity recommendations (PAR) group, (3) high-intensity interval training (HIIT) group, or (4) HIIT plus whole-body electromyostimulation (HIIT-EMS) group. Memory outcomes were assessed using the Wechsler Memory Scale-third edition. S-Klotho plasma levels were determined according to a solid-phase sandwich enzyme-linked immunosorbent assay kit while 1,25(OH)2 D plasma levels were measured using a DiaSorin-Liaison immunochemiluminometric analyzer. IM-Verbal Paired Associates (IM-VPA) and IM-Logical Memory (IM-LM) were improved in both the HIIT and HIIT-EMS groups compared with the control group (all p ≤ 0.045). Exercise-induced changes in S-Klotho plasma levels were positively associated with those observed in IM, LTM, and recognition (all p ≤ 0.007), whereas exercise-induced changes in 1,25(OH)2 D plasma levels were directly related to changes in IM and LTM (all p ≤ 0.048). In conclusion, a 12-week HIIT intervention with or without WB-EMS seems to be the most effective exercise program to improve IM. The significant and positive associations between exercise-induced changes in S-Klotho and 1,25(OH)2 D levels with those observed in memory outcomes suggest that these factors may be potentially related to exercise-induced improvements of memory in middle-aged adults.

Physical activity (PA) in the form of aerobic exercise (AE) preserves and improves neurocognitive function across the lifespan. However, a mechanistic understanding of the pathways by which aerobic exercise impacts brain health is still lacking, particularly with respect to stress-related pathways. One mechanistic hypothesis is that AE improves neurocognitive health in part by modifying circulating levels of stress-related hormones and signaling factors associated with the hypothalamic-pituitary-adrenal (HPA) axis and autonomic nervous system (ANS), as commonly measured by the biomarkers cortisol (CORT) and salivary α-amylase (sAA). Thus, this hypothesis predicts that changes in stress biomarkers, such as CORT and sAA, are possible explanatory pathways mediating the positive effects of AE on neurocognitive health. In the present review article, we provide a summary of available studies examining the possibility that exercise-induced changes to stress biomarkers could partly account for exercise-related improvements in neurocognitive health. Our review indicates that despite the intuitive appeal of this hypothesis, there is insufficient evidence available to conclude that chronic and habitual AE affects neurocognitive health by altering stress biomarker pathways. The cross-sectional nature of the majority of reviewed studies highlights the need for well-controlled studies to adequately test this hypothesis.

Public health messaging calls for individuals to be more physically active and less sedentary, yet these lifestyle behaviors have been historically studied independently. Both physical activity (PA) and sedentary behavior (SB) are linked through time-use in a 24-hour day and are related to health outcomes, such as neurocognition. While the benefits of PA on brain health in late adulthood have been well-documented, the influence of SB remains to be understood. The purpose of this paper was to critically review the evolving work on SB and brain health in late adulthood and emphasize key areas of consideration to inform potential research. Overall, the existing literature studying the impact of SB on the components and mechanisms of brain health are mixed and inconclusive, provided largely by cross-sectional and observational work employing a variety of measurement techniques of SB and brain health outcomes. Further, many studies did not conceptually or statistically account for the role of PA in the proposed relationships. Therefore, our understanding of the way in which SB may influence neurocognition in late adulthood is limited. Future efforts should include more prospective longitudinal and randomized clinical trials with intentional methodological approaches to better understand the relationships between SB and the brain in late adulthood, and how these potential links are differentiated from PA.

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.

Adolescence is recognized as a time of rapid physiological and behavioral change. In this transition, eating behavior is still being formed and remains an integral part of a person’s lifestyle throughout his or her life. This study aims to assess eating behavior and associations with food intake in European adolescents. We included 2194 adolescents (45.9% boys), aged 12.5 to 17.5 years, from the cross-sectional HELENA study, with two completed 24 h recalls and complete questionnaire data on their eating behavior (Eating Behavior and Weight Problems Inventory for Children- EWI-C). Three subscales of the EWI were evaluated; they measured Strength and motivation to eat (EWI 1), Importance and impact of eating (EWI 2), and Eating as a means of coping with emotional stress (EWI 3). Since these subscales were specially focused on eating behavior, participants were classified as either Low (≤P75) or High (>P75) on each of the subscales. Our results showed a higher consumption of different types of food, in the EWI 1 scales, linked to the hunger and interest in eating, and we observed a relationship with the consumption of energy-dense products. This result was repeated in EWI 3, the subscale linked to emotional eating, where we also found higher consumption of energy-dense products. This study suggests that special features of eating behavior are associated with food intake in adolescents.

AimTo study the acute effect of a dietary multi-ingredient nootropic on cognitive performance in young healthy adults. We also analyzed the influence of the dietary multi-ingredient nootropic on emotional state, heart rate (HR), and heart rate variability (HRV).MethodsThis is a randomized, triple-blinded, placebo-controlled, crossover trial. In total, 26 young healthy adults (50% women; 24.9 ± 3.3 years old) ingested 10 g of a dietary multi-ingredient nootropic [Evo-Gamers®; Harrison Sport Nutrition (HSN), Granada, Spain] or placebo (maltodextrin) in a randomized order (clinicaltrials.gov No. NCT04790188). After 30 min of the ingestion, participants performed a battery of cognitive performance tests to measure the processing speed, inhibitory control, working memory, cognitive flexibility, creativity, and verbal fluency. The emotional status was assessed through questionnaires, and HR and HRV were measured using a heart rate monitor.ResultsIn comparison with placebo, the acute ingestion of the nootropic showed a significantly better response time in several cognitive tests (i.e., processing speed, inhibitory control, spatial working memory, and cognitive flexibility, all P < 0.05 and effect size range of 0.4–0.6). It also displayed a higher accuracy in the processing speed, the inhibitory control, and cognitive flexibility tests (all P < 0.05; effect size ranged from 0.4 to 0.6). Furthermore, the nootropic showed a higher creativity and positive emotions and lower sadness-depression emotions, whereas HR and HRV remained similar between placebo vs. nootropic conditions. However, there were no differences between the nootropic and placebo in verbal fluency, motivation, or anxiety (all P > 0.05).ConclusionAn acute ingestion of a dietary multi-ingredient nootropic enhances cognitive performance in comparison with placebo without negatively influencing HR or HRV in young healthy adults.