Gymnastik- och idrottshögskolan, GIH

Brain-derived neurotrophic factor (BDNF) is essential for neuroplasticity. Exercise caninduce increases in forearm venous plasma and serum BDNF, often assumed to be indicativeof release from the brain. We investigated the effects of exercise on circulating levels of matureBDNF (mBDNF) and its precursor proBDNF. Sixteen healthy, physically fit adults (20–40 years old)cycled for 20 min at 40, 60 and 80% of V˙O2 max, separated by 30 min of rest. BDNF was analysed in blood samples from the brachial artery, internal jugular vein, femoral vein and antecubital vein. Brain/skeletal muscle exchange of BDNF, calculated as arterial-venous differences in BDNF multiplied by blood flow in the middle cerebral artery/common femoral artery, was measured simultaneously with blood sampling. Exercise intensity-dependent increases were observed in blood platelet count, forearm venous serum mBDNF and plasma proBDNF, but not in forearm venous plasma mBDNF. Brain release (or uptake) was not detected for either plasma mBDNF, serum mBDNF or plasma proBDNF. However, muscle uptake of plasma mBDNF and release of plasma proBDNF were observed after high-intensity exercise. Our findings demonstrate that exercise-dependent increases in serum mBDNF are not derived from the brain or the exercised skeletal muscle. Rather, the source of the increase appears to be the increase in platelets that are enriched with mBDNF. Furthermore, in physically fit adults, BDNF is not released from the brain into the bloodstream, after exercise, regardless of exercise intensity. Finally, changes in plasma proBDNF after exercise appear to be dependent on exercised skeletal muscle rather than brain release. KEY POINTS: Previously shown exercise-induced increases in forearm venous brain-derived neurotrophic factor (BDNF) are often assumed to be indicative of release from the brain. We investigated whether exercise-induced changes in forearm venous mature BDNF (mBDNF) and precursor proBDNF are paralleled by concomitant changes in BDNF exchange over the brain and skeletal muscle. We observed exercise intensity-dependent increases in platelet count, forearm venous serum mBDNF and plasma proBDNF, but not in forearm venous plasma mBDNF. We found muscle uptake of plasma mBDNF and release of plasma proBDNF after high-intensity exercise but no exercise intensity-dependent brain exchange of either plasma mBDNF, serum mBDNF or plasma proBDNF. Our findings suggest that acute exercise-induced increases in circulating serum mBDNF may be solely a result of increased platelet count, probably due to splenic platelet release; and that exercised skeletal muscle, and not the brain, responds to high-intensity exercise by releasing plasma proBDNF.

PURPOSE: The transition phase between childhood and adolescence is critical, given the observation of increased mental health issues during this period, coupled with the absence of efficient intervention tools. This study aims to examine a possible effect of physical activity on mental health symptoms in adolescents during this transitional age.

METHODS: We used data from a large-scale population-based Swedish twin sample of 14,083 individuals to investigate cross-sectional and longitudinal associations between physical activity and mental health problems during childhood and adolescence. We examine different aspects of mental health symptoms, including internalizing and externalizing symptoms. We applied generalized estimating equations to investigate the associations and explored potential familial confounding using within-twin pair analysis.

RESULTS: We found high physical activity intensity and frequency to be associated with better mental health throughout childhood and adolescence, cross-sectionally and longitudinally. Compared to those who reported low, those reporting high physical activity intensity and frequency in both childhood and/or adolescence had significantly lower symptoms of mental health at age 15. This association was statistically significant for both internalizing and externalizing symptoms. The within-twin pair analysis showed that familial confounding factors can largely explain the association with the externalizing scale, but not the internalizing scale.

DISCUSSION: Physical activity in childhood and adolescence may play an essential role in reducing the risk of developing mental health problems, especially internalizing symptoms. Implementing acceptable, low-risk, and cost-effective interventions to promote physical activity could effectively safeguard young individuals from these symptoms.

Aim: Insufficient physical activity among adolescents, combined with poorer well-being and mental health, are worrying societal problems. Adolescents with ADHD encounter daily challenges and are more prone to experiencing mental and physical health issues compared to their peers. The aim was to investigate associations between moderate-to-vigorous physical activity, sedentary time, screen-time, psychosomatic problems, and ADHD symptoms in adolescents. Method: Data came from a cross-sectional study. Participants (N = 1139) were seventh-grade students who answered questionnaires on screen-time, psychosomatic problems, hyperactivity, and ADHD and were assigned an accelerometer, worn for seven consecutive days. Data were analyzed using linear regression. Results: A negative association was found between moderate to vigorous physical activity and psychosomatic problems in the entire sample. Moderate-to-vigorous physical activity was more strongly associated with psychosomatic problems for adolescents with self-reported ADHD symptoms (B = -0.14 (-0.24, -0.04)) than adolescents without ADHD symptoms (B: -0.03 (-0.05, -0.01)). Conclusions: Moderate-to-vigorous physical activity, sedentary time, and screen-time were all significantly associated with psychosomatic problems among all participants. Moderate-to-vigorous physical activity showed a stronger association with psychosomatic problems among participants with ADHD. This indicates that this group may be particularly responsive to interventions attempting to promote mental health through physical activity.

Background: Poor-quality sleep has been linked to increased dementia risk. We investigated the relationship between healthy sleep pattern and older brain age, and the extent to which this is mediated by systemic inflammation.

Methods: The study included 27,500 adults from the UK Biobank (mean age 54.7 y, 54.0% female). The presence of five self-reported healthy sleep characteristics (early chronotype, 7-8 h daily sleep, no insomnia, no snoring, no excessive daytime sleepiness) were summed into a healthy sleep score (0-5 pts) and used to define three sleep patterns: healthy (≥4 pts), intermediate (2-3 pts), and poor (≤1 pt). Low-grade inflammation was estimated using the INFLA-score, a composite index of inflammatory biomarkers. After a mean follow-up of 8.9 y, brain age was estimated using a machine learning model based on 1079 brain MRI phenotypes and used to calculate brain age gap (BAG; i.e., brain age minus chronological age). Data were analysed using linear regression and generalised structural equation models.

Findings: At baseline, 898 (3.3%) participants had poor sleep, 15,283 (55.6%) had intermediate sleep, and 11,319 (41.2%) had healthy sleep. Compared to healthy sleep, intermediate (β = 0.25 [0.11, 0.40], P = 0.010) and poor (β = 0.46 [0.05, 0.87], P < 0.001) sleep were associated with significantly higher BAG. In mediation analysis, INFLA-score mediated 6.81% and 10.42% of the associations between intermediate and poor sleep and higher BAG.

Interpretation: Poor sleep health may accelerate brain ageing. This may be driven by higher levels of systemic inflammation.

It remains unknown whether dietary nitrate and breakfast may enhance working memory (WM) performance by augmenting physiological mechanisms and subjective psychological well-being. We performed a 3-arm randomised within-subject crossover study, with pretest-posttest comparisons, to test whether nitrate consumption via breakfast with a beetroot juice shot or regular breakfast compared to no breakfast improved WM (measured with n-back tests) and cognitive task-related changes in prefrontal cortical haemodynamic response (oxygenated- and deoxygenated-haemoglobin derived from functional near-infrared spectroscopy). In addition, effects on peripheral vascular function and self-reported psychological factors were assessed. In 60 adolescents (13-15 years old; 66% girls), WM improved in all conditions, with no intervention effects. Intervention effects were seen for oxygenated-haemoglobin changes, such that it increased after the breakfast with a nitrate shot during the WM tests and decreased after the regular breakfast. Thus, different neurophysiological mechanisms may be at play to preserve WM in adolescents depending on their breakfast composition. The trial was registered in the ISRCTN registry (ISRCTN16596056) on 21/02/2022.

Introduction. Executive functions (EF) is essential for cognitive aging and vascular cognitive impairment. Habitual physical activity (PA) has been shown to yield positive effects on EF in aging. In this study, we aim (1) to investigate the relationship between EF and time spent in sedentary behaviour (SED), light-PA (LIPA), moderate-PA (MPA), and vigorous-PA (VPA), respectively; and (2) to examine the potential beneficial effect of combined movement behaviours.

Methods. The study consisted of 4592 participants (women: 52.6%), aged 50 to 65 years, from the Swedish CArdioPulmonary bioImage Study(SCAPIS) in Gothenburg region (data collection: 2013-2017). The Trail Making Tests (A and B) were applied to evaluate the EF. ActiGraph accelerometer was employed to evaluate the daily movement patterns objectively. After adjusting for covariates in demographic factors, cardiorespiratory fitness, and vascular risk factors, piecewise linear and linear regression models were used to examine the relationship between movement patterns and EF.

Results. In the fully adjusted model, when daily sedentary time was less than 10 hours, an increased SED time was positively associated with EF score. However, a negative association was observed between SED time and EF score when daily sedentary time exceeded 10 hours. When daily LIPA time exceeded 4 hours, LIPA time was found to have a negative association with EF score. An increase in MPA time was positively associated with EF score when daily MPA was less than 45 minutes. A significant positive association was observed between conducting daily VPA within 20 minutes and EF score. The majority of participants in our study demonstrated a movement pattern characterized by high levels of cardiorespiratory fitness, sedentary time within 10 hours, LPA more than 4 hours, MPA more than 45 minutes, and VPA more than 20 minutes. This particular movement pattern was significantly and positively associated with EF scores compared to other groups.

Discussion. The association between EF and specific movement behaviours varied depending on their daily duration. In this study, the majority of middle-aged and older adults demonstrated an active movement pattern, which was positively associated with EF. Further research is needed to investigate the underlying pathways that explain this

Insulin resistance (IR) is a risk factor for the development of several major metabolic diseases. Muscle fiber composition is established early in life and is associated with insulin sensitivity. Hence, muscle fiber composition was used to identify early defects in the development of IR in healthy young individuals in the absence of clinical manifestations. Biopsies were obtained from the thigh muscle, followed by an intravenous glucose tolerance test. Indices of insulin action were calculated and cardiovascular measurements, analyses of blood and muscle were performed. Whole-body insulin sensitivity (SI_galvin) was positively related to expression of type I muscle fibers (r=0.49; P<0.001) and negatively related to resting heart rate (HR, r=-0.39; P<0.001), which was also negatively related to expression of type I muscle fibers (r=-0.41; P<0.001). Muscle protein expression of endothelial nitric oxide synthase (eNOS), whose activation results in vasodilation, was measured in two subsets of subjects expressing a high percentage of type I fibers (59±6%; HR = 57±9 beats/min; SI_galvin = 1.8±0.7 units) or low percentage of type I fibers (30±6%; HR = 71±11; SI_galvin = 0.8±0.3 units; P<0.001 for all variables vs. first group). eNOS expression was: 1. higher in subjects with high type I expression; 2. almost two-fold higher in pools of type I vs. II fibers; 3. only detected in capillaries surrounding muscle fibers; and 4. linearly associated with SI_galvin. These data demonstrate that an altered function of the autonomic nervous system and a compromised capacity for vasodilation in the microvasculature occur early in the development of IR.

Background: We have previously reported on the design and efficacy of two cluster-randomized multi-level workplace interventions, attempting to decrease sedentary behavior (SED) or increase moderate to vigorous physical activity (MVPA) among office workers to improve mental health outcomes. The aim of this study was to investigate intervention effects on mental health outcomes, i.e., mental wellbeing, depression or anxiety symptoms, and stress immediately after the 6-month intervention period.

Methods: Teams of 263 office workers were cluster-randomized to one of two interventions or a waitlist control group. The PA intervention (iPA) focused on increasing MVPA and the SED intervention (iSED) on reducing SED. Both multi-level interventions targeted individual office workers and their social, physical, and organizational work environment, incorporating counseling based on cognitive behavioral therapy and motivational interviewing. Mental health outcomes were assessed using validated questionnaires before and immediately after the intervention. Intervention effects were analyzed using linear mixed effects models.

Results: Participants were mostly female and highly educated, with a mean age of 42 years and had favorable levels of mental health at baseline. Mental wellbeing improved for the iSED group (β = 8, 95% CI 1 to 15, p = 0.030) but not for the iPA group (β = 6, 95% CI -1 to 12, p = 0.072) compared to the control group. No effects were found for depression or anxiety symptoms or stress.

Conclusions: The multi-level interventions improved mental wellbeing among this population of office workers, reaching statistical significance in the iSED group. The size of the effect can be regarded meaningful, considering favorable mental health and high PA level at baseline. Thus, workplace interventions that provide support on multiple levels appear to have potential for improving mental wellbeing, but not reducing ill-health variables, among healthy office workers. More research is needed to understand the mechanisms through which such improvements can be achieved and to identify the most effective intervention components.

Blood-based biomarkers of neurodegeneration demonstrate great promise for the diagnosis and prognosis of Alzheimer's disease. Ultra-sensitive plasma assays now allow for quantification of the lower concentrations in cognitively unimpaired older adults, making it possible to investigate whether these markers can provide insight also into the early neurodegenerative processes that affect cognitive function and whether the markers are influenced by modifiable risk factors. Adopting an exploratory approach in 93 healthy older adults (65-75 years), we used structural equation modelling to investigate cross-sectional associations between multiple latent cognitive abilities (working memory, episodic memory, spatial and verbal reasoning) and plasma amyloid beta (Aβ42/Aβ40 ratio), phosphorylated-tau 181 (ptau-181), glial fibrillary acidic protein (GFAP), and neurofilament light (NfL), as well as the influence of device-measured habitual physical activity on these associations. The results showed that NfL was negatively associated with working memory, and that NfL interacted with moderate-to-vigorous physical activity in its association with episodic memory. The study has thereby demonstrated the potential of neurodegenerative plasma markers for improving understanding of normative cognitive aging and encourages future research to test the hypothesis that high levels of NfL, indicative of white matter pathology, limit the beneficial effect of physical activity on episodic memory in healthy aging.

Exercise promotes brain plasticity partly by stimulating increases in mature brain-derived neurotrophic factor (mBDNF), but the role of the pro-BDNF isoform in the regulation of BDNF metabolism in humans is unknown. We quantified the expression of pro-BDNF and mBDNF in human skeletal muscle and plasma at rest, after acute exercise (+/- lactate infusion), and after fasting. Pro-BDNF and mBDNF were analyzed with immunoblotting, enzyme-linked immunosorbent assay, immunohistochemistry, and quantitative polymerase chain reaction. Pro-BDNF was consistently and clearly detected in skeletal muscle (40-250 pg mg^-1 dry muscle), whereas mBDNF was not. All methods showed a 4-fold greater pro-BDNF expression in type I muscle fibers compared to type II fibers. Exercise resulted in elevated plasma levels of mBDNF (55%) and pro-BDNF (20%), as well as muscle levels of pro-BDNF (∼10%, all P < 0.05). Lactate infusion during exercise induced a significantly greater increase in plasma mBDNF (115%, P < 0.05) compared to control (saline infusion), with no effect on pro-BDNF levels in plasma or muscle. A 3-day fast resulted in a small increase in plasma pro-BDNF (∼10%, P < 0.05), with no effect on mBDNF. Pro-BDNF is highly expressed in human skeletal muscle, particularly in type I fibers, and is increased after exercise. While exercising with higher lactate augmented levels of plasma mBDNF, exercise-mediated increases in circulating mBDNF likely derive partly from release and cleavage of pro-BDNF from skeletal muscle, and partly from neural and other tissues. These findings have implications for preclinical and clinical work related to a wide range of neurological disorders such as Alzheimer's, clinical depression, and amyotrophic lateral sclerosis.