Life expectancy has been increasing over the past decades (United Nations, 2013). As a result, a growing number of individuals are subject to age-related cognitive decline (Prince et al., 2015). Executive functions, processing speed, and memory are typically mostly affected (Hedden and Gabrieli, 2004). Pathological progression of memory impairments resulting in, for example, Alzheimer’s disease, have been reported to be one of the greatest worries of the population about living beyond the age of 75 (Anderson and McConnell, 2007). Thus, there is growing interest in interventions that potentially counteract age-related memory decline.

Regular cardiovascular exercise has been reported to positively influence memory and to induce structural and functional changes in brain regions associated with memory, e.g., the hippocampus. Several weeks or months of regular cardiovascular training were shown to increase performance in a face-name matching task (Griffin et al., 2011), visuospatial short-term memory (Stroth et al., 2009), and immediate and delayed memory for wordlists (Chapman et al., 2013). The increase in cardiovascular fitness after physical exercise training has been found to correlate positively with improvements in episodic memory (Hötting et al., 2012). Moreover, increased hippocampus volume (Erickson et al., 2011; Niemann et al., 2014; Thomas A. G. et al., 2016) and increased hippocampal cerebral blood volume (Pereira et al., 2007) have been reported after a period of regular cardiovascular training. However, evidence in humans concerning the effects of long-term aerobic exercise on memory and associated brain structures in the medial temporal lobe is contradictory. Some studies reported positive effects of an exercise intervention on memory (Stroth et al., 2009; Griffin et al., 2011), while others failed to find a difference in memory between an aerobic exercise group and a control group (Gourgouvelis et al., 2018). In a meta-analysis, Roig et al. (2013) concluded that the positive effects of regular cardiovascular training on long-term memory were not reliably found. Participants’ age, training intensity, training duration, and the type of memory tested have been discussed to in part account for the differing results. A better understanding of possible mediators underlying the effects of cardiovascular exercise on memory may resolve some of the observed inconsistencies and shed light on why some training studies yield more consistent exercise-induced memory effects than others.

Similar to chronic cardiovascular exercise, results for single bouts of exercise on memory functions are inconsistent. On the one hand, a single bout of cardiovascular exercise has been shown to positively affect memory (Roig et al., 2013; Bosch et al., 2017b; Dal Maso et al., 2018). On the other hand, other researchers did not find an acute effect of exercise on memory (Hopkins et al., 2012; Basso et al., 2015), or reported enhancements of specific aspects of memory (Coles and Tomporowski, 2008; Suwabe et al., 2017). Inconsistencies in results from human studies are potentially caused by variations in the type of memory tested, exercise intensity, as well as the timing of the exercise session in relation to memory encoding (Roig et al., 2013).

To date, only a few studies have tested the effects of cardiovascular exercise on memory after encoding, i.e., during memory consolidation, and their results have been inconclusive. Beneficial outcomes have been reported for procedural memory when retention was measured 24 h (Roig et al., 2012; Dal Maso et al., 2018) or several days after encoding (Roig et al., 2012; McNerney and Radvansky, 2015). Additionally, an EEG study revealed that better skill retention after exercising was associated with greater beta-band event-related desynchronization in sensorimotor areas, indicating that exercise may improve motor memory by modulating neuronal processing in motor cortices in the early stages of memory consolidation (Dal Maso et al., 2018). However, the effects of cardiovascular exercise after encoding on declarative memory are more equivocal. In one study, participants performed an aerobic exercise session either before or after exposure to a word list which they were instructed to memorize. Memory was tested 60 min and 24 h after learning (Labban and Etnier, 2018). At neither time point did the results indicate a beneficial effect of exercising compared to a no-exercising condition during the consolidation phase. In another study, 6 min of either cycling or relaxing after encoding of emotional images resulted in better memory performance in the cycling group when assessed 60 min after exercise, and thus suggested a beneficial effect of cardiovascular exercise on memory consolidation (Segal et al., 2012). Other researchers compared the effects of 30 min of cycling at low or high intensity to the effects of relaxing after vocabulary learning (Hötting et al., 2016). Cycling after encoding did not enhance the absolute number of recalled words tested 60 min and 24 h after learning. However, participants who exercised at high intensity showed less forgetting between the 60-min and 24-h measurements than participants in the relaxation group. These findings suggested a benefit of cardiovascular exercise directly after encoding on memory consolidation. van Dongen et al. (2016) demonstrated that cycling with a 4-h delay after encoding revealed better performance in a hippocampus-dependent picture-location association task, compared to a group cycling directly after encoding, and a no-exercise control group. In the same study, fMRI data revealed that participants who cycled 4 h after learning showed more distinctive hippocampal representations for the learned associations during retrieval, compared to participants of the other two groups. Furthermore, higher hippocampal pattern similarity correlated with better memory retention across participants. These data suggested that cardiovascular exercise might enhance later stages of memory consolidation more than early phases. In summary, current data on the effects of cardiovascular exercise after encoding on memory performance are ambiguous. Most studies reporting beneficial effects of a single bout of exercise on memory consolidation used sensorimotor tasks. Studies assessing declarative memory are rare and their findings are inconsistent.

Cardiovascular exercise has been proposed to affect memory by increasing levels of neurochemical substances, such as hormones, neurotransmitters, and neurotrophic factors known to be involved in the formation of memories on the neuronal level (Basso and Suzuki, 2017). It has been suggested that early stages of memory consolidation, when the memory trace has most likely not yet reached a stable state, may be particularly susceptible to external influences, such as exercise (Nader and Hardt, 2009). Accordingly, research in both rodents and humans has shown that early memory traces can be altered by stress, physical activity, and pharmacological treatments (McGaugh, 1966; Siette et al., 2014; Vogel et al., 2016).

One of the neurochemical pathways postulated to mediate the effects of cardiovascular exercise on memory involves the exercise-induced alteration of neurotrophic factor levels, such as brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), and insulin-like growth factor 1 (IGF-1; Cotman et al., 2007). In rodents, BDNF, VEGF, and IGF-1 have been shown to be elevated after wheel running (Cetinkaya et al., 2013; Uysal et al., 2015). Moreover, they have been shown to be involved in processes underlying memory formation (Cotman et al., 2007; Voss et al., 2013). BDNF, for instance, is involved in the morphological changes of dendritic spines, long-term potentiation (LTP), and increases neurogenesis by promoting cell survival and proliferation (Bekinschtein et al., 2014; Miranda et al., 2019). LTP is one of the primary mechanisms of synaptic plasticity underlying memory and learning processes. As a key regulator of LTP, BDNF has become a particularly prominent target of research (Miranda et al., 2019). VEGF has been proposed to modulate memory by being involved in angiogenesis and neurogenesis (Fabel et al., 2003; Greenberg and Jin, 2005). IGF-1 is thought to have a neuroprotective function, to play a role in neurogenesis, angiogenesis, synaptic plasticity, and to interact with VEGF to enhance neurogenesis after exercise (Cotman et al., 2007; Fernandez and Torres-Alemán, 2012). Inhibiting BDNF and VEGF action in rodents has been shown to prevent running-induced memory benefits (Vaynman et al., 2004) and neurogenesis (Fabel et al., 2003), respectively. While blocking of IGF-1 activity did not alter the positive effect of exercise on learning, it prevented exercise-induced memory benefits when tested 2 days after learning (Ding et al., 2006). In addition, exercise-induced increases in BDNF, VEGF, and IGF-1 have been shown to correlate with improved spatial learning and memory (Cetinkaya et al., 2013; Uysal et al., 2015). Thus, the results of rodent research suggested that BDNF, VEGF, and IGF-1 mediate the beneficial effects of physical activity on neuroplasticity and memory.

In contrast to rodents, neurotrophic factors cannot be measured directly in the living human brain. Measures are usually taken from blood serum or plasma. In some studies, BDNF, VEGF, and IGF-1 have been shown to cross the blood-brain barrier, indicating a transferability from peripheral to central levels (Pan et al., 1998; Nishijima et al., 2010; Rich et al., 2017; but see Lanz et al., 2012). In humans, a single bout of moderate to intense aerobic exercise has been shown to transiently increase BDNF levels (Ferris et al., 2007; Winter et al., 2007; Hötting et al., 2016; Tsai et al., 2018). In contrast, the evidence for changes in VEGF and IGF-1 levels after cardiovascular exercise in humans is limited in number, and results are equivocal (Griffin et al., 2011; Skriver et al., 2014). Only a few studies reported increases in VEGF and IGF-1 after acute exercise (Kraemer et al., 2004; Kraus et al., 2004; Skriver et al., 2014; Tsai et al., 2018). Associations between the change in neurotrophic factor levels and memory, which might indicate an involvement of neurotrophic factors in memory processes, have not reliably been shown in human studies. Some researchers have demonstrated that increased BDNF levels after exercising correlate with vocabulary learning (Winter et al., 2007) and motor memory (Skriver et al., 2014), while others did not find a relationship with performance in episodic memory tasks (Schmidt-Kassow et al., 2014; Etnier et al., 2016). So far, human studies have failed to find correlations between acute increases in VEGF and IGF-1 after exercising and memory measures (Skriver et al., 2014; Tsai et al., 2018). Hence, a relationship between changes in neurotrophic factors and exercise-induced memory improvements in humans has not been reliably demonstrated to date.

The goal of the present study was to test whether one bout of cardiovascular exercise after encoding had beneficial effects on hippocampus-dependent memory compared to a non-cardiovascular exercise bout after the same memory task. Moreover, we examined whether memory effects were related to exercise-induced changes in neurotrophic factor levels. Young participants were randomized to either a cycling (BIKE) or a stretching and toning training (STRETCH). Immediately after the encoding of an artificial vocabulary, that is during an early stage of memory consolidation, participants engaged in a single bout of physical exercise. Memory was assessed 1–2 weeks after the initial vocabulary acquisition. Blood samples were taken at rest (baseline) and directly after an acute bout of physical exercise to measure serum levels of BDNF and VEGF. We hypothesized that cardiovascular exercise after encoding would result in enhanced memory for the encoded vocabulary compared to stretching and toning. Moreover, it was assumed that cardiovascular exercise, compared to stretching and toning, increased BDNF and VEGF levels. Exercise-induced increases in both neurotrophic factor levels were thought to positively correlate with memory performance.

Data were analyzed using the statistical software R (version 3.5.1, R Core Team, 2018). Independent samples t-tests were used to compare the BIKE and the STRETCH group at pre-assessment. The lme4 package (Bates et al., 2015) was used to analyze performance in the vocabulary learning task and neurotrophic factor levels with linear mixed effect models (LMMs). Group was inserted as a factor in all models, with the STRETCH group serving as reference level. The fixed and random effects of each model are described in detail below. If not stated otherwise, all models included the covariates gender and age, which was centered at the mean. The package parameters (Lüdecke et al., 2020) were used for obtaining p-values and confidence intervals, using Wald-test approximation. Post hoc tests were performed with pairwise comparisons of estimated marginal means and the package emmeans (Lenth, 2019). Corrections for multiple comparisons were conducted following the Tukey method. The significance level was set to p < 0.05 for all analyses.

The BIKE and STRETCH groups did not differ in age, cardiorespiratory fitness (VO₂peak), body mass index (BMI), and depression score at baseline (Table 3).

In the first learning-exercise session, the BIKE group trained with a significantly higher heart rate (M = 143 beats/min, SD = 13.83) compared to the STRETCH group (M = 92 beats/min, SD = 8.55); t_(40.26) = 15.42, 95% CI: [43.8, 57.0], p < 0.001.

Comparing d’ in block 1 and within-session learning in the first learning-exercise session revealed no significant difference between the BIKE and the STRETCH group (Table 3; no significant group × block interaction (ß = −0.02, 95% CI [−0.21, 0.17], p = 0.838).

The aim of this study was to test whether a single bout of cardiovascular exercise carried out in the early stages of memory consolidation improves memory as assessed with an artificial vocabulary learning task. In addition, the effects of physical exercise on serum levels of BDNF and VEGF were determined in order to explore whether they mediate exercise-induced memory changes. Results did not indicate a beneficial effect of cycling on memory measured 1–2 weeks after initial acquisition compared to stretching and toning. Analyses of serum neurotrophic factor levels revealed significantly larger BDNF and VEGF increases after physical exercise in the cycling group compared to the stretching and toning group. Exercise-induced changes in BDNF levels tended to positively correlate with memory measures in the BIKE group, but not in the STRETCH group.

It has been hypothesized that physical exercise might enhance memory, possibly through the acute exercise-induced release of neuromodulatory factors, such as dopamine, norepinephrine, cortisol, and BDNF, which are known to be involved in memory consolidation (McGaugh, 2000; Siette et al., 2014; van Dongen et al., 2016; Miranda et al., 2019). In the present study, participants exercised immediately after encoding a new vocabulary. Thus, encoding conditions were held constant across groups, but the activity of the groups differed in the early stages of memory consolidation. Yet, the results of the present study did not provide evidence that cycling directly after the encoding phase was beneficial for memory consolidation, compared to stretching and toning. The timing of exercise relative to memory encoding has been discussed as a crucial factor modulating the benefits of acute exercise on memory processes (Roig et al., 2016). A meta-analysis reported larger effect sizes for memory improvements when exercise was implemented before than after learning (Roig et al., 2013). The larger effect sizes might be due to the combined effect of exercise on encoding and consolidation processes because the physiological adaptations induced by a bout of cardiovascular exercise performed before encoding are likely to persist into the early stages of memory consolidation. Roig et al. (2016) suggested that a close temporal coupling of exercise with memory processes is the key factor for memory improvements to occur. This is supported by studies that systematically varied the timing of exercise relative to a memory task. Results showed beneficial effects of an acute bout of cardiovascular exercise on visuo-motor memory regardless of whether exercise was performed immediately before or after motor learning, but not when exercise and learning were separated by 1 h longer time intervals (Statton et al., 2015; Thomas et al., 2016a). van Dongen et al. (2016) did not report beneficial effects of cardiovascular exercise on memory for picture-location associations and hippocampal pattern separation when exercise was performed immediately after learning. However, exercise improved memory when performed 4 h after learning, thus, in the late stages of memory consolidation (van Dongen et al., 2016). The authors discussed that levels of neurotrophins supporting synaptic plasticity might be naturally lower several hours after learning and thus, exercise upregulating the release of these factors might have a larger impact on memory outcomes during late consolidation stages. However, these explanations are still speculative and a possible more pronounced effect of delayed exercise relative to encoding on memory consolidation needs replication in further studies.

Moreover, studies differed with regard to the memory tasks used and thus, the addressed underlying neuronal networks. In the present study, we assessed the retention of items encoded in an implicit paired association task. fMRI data suggested that successful learning in this task is associated with hippocampal activity and increased functional coupling between the left hippocampus and cortical association areas as the left fusiform gyrus and the left inferior parietal lobe (Breitenstein et al., 2005). Results of previous acute exercise studies assessing memory in associative learning tasks have yielded inconsistent results with some studies showing better memory for associations encoded prior to exercise (van Dongen et al., 2016; Bosch et al., 2017a), while others did not find better memory for associations learned before exercise (McNerney and Radvansky, 2015; Hötting et al., 2016). Findings seemed to be more consistent for motor learning tasks. For instance, several studies reported positive effects of a single cardiovascular exercise session after practicing visuo-motor tracking tasks (Roig et al., 2012; Thomas et al., 2016b; Dal Maso et al., 2018). Learning in visuo-motor tasks has been shown to activate the basal ganglia, cerebellum, and motor cortices (Doyon et al., 2009) and have been found to be spared after hippocampal lesions (Corkin, 1968). Therefore, one could speculate that in humans, the brain structures responsible for motor learning are in particular sensitive to the beneficial effects of acute cardiovascular exercise. Yet, this is contradictory to results in rodents reporting very reliable exercise-induced functional and structural changes in the hippocampus after exercise (reviewed in Cotman et al., 2007; van Praag, 2008). Moreover, fMRT results in humans showed task-dependent modulations of hippocampal activity after acute exercise (Bosch et al., 2020). Future studies contrasting hippocampus-dependent learning tasks and hippocampus-independent learning tasks in humans might shed light on the question of whether there is a task-dependent effect of physical exercise in phases of early memory consolidation (McNerney and Radvansky, 2015).

In addition, studies analyzing the effects of acute cardiovascular exercise on memory differed in the intensity of the physical exercise and the fitness status of participants (Roig et al., 2013). In the present study, the BIKE group received cardiovascular training of moderate intensity. The training heart rates of participants in the BIKE group were adjusted to the individual aerobic-anaerobic threshold. Thus, the relative training intensity was similar for all participants and we made sure that participants trained within the aerobic range. Moreover, the heart rate was measured in the STRETCH group as well, confirming a significant mean difference of 44 beats/min between groups. Some recent studies have suggested that higher physical exercise intensities more reliably improve memory performance in acute exercise designs compared to low or moderate intensity exercise (Winter et al., 2007; Etnier et al., 2016; Thomas et al., 2016b). However, the effect of training intensity is additionally dependent on individuals’ baseline fitness and age.

It has been shown that more fit and regularly active participants showed stronger increases in cognitive functions after acute cardiovascular exercise compared to less fit and untrained peers (Chang et al., 2012; Hopkins et al., 2012). Participants in the present study were sedentary and had relatively low cardiovascular fitness levels (average peak oxygen uptake volume, VO₂peak, of 34 ml/kg/min) compared to normative samples in that age range (Laukkanen and Held, 1999). Most other studies reporting positive effects of acute cardiovascular exercise on memory included participants with higher fitness levels of above a VO₂peak of 40 ml/kg/min (Winter et al., 2007; Etnier et al., 2016; Thomas et al., 2016b; Bosch et al., 2017b). It remains a task of future research to further elucidate the extent to which variables such as prior physical activity, intensity of the physical exercise, or the interaction of both factors influence the effect of acute cardiovascular exercise on memory.

Due to the general study design of the larger project, memory for the pseudoword-picture pairs of the implicit vocabulary learning task was assessed 1–2 weeks after initial encoding and was spread over three separate sessions that took place on different days. Moreover, participants were exposed to further pseudoword-picture pairs between initial encoding and memory assessment, possibly causing interference effects. It is, therefore, possible that the study design may have masked potential effects on the behavioral level.

Exercise-induced changes in neurotrophic factor levels have been suggested to at least partly mediate the positive effects of cardiovascular exercise on memory (Cotman et al., 2007; El-Sayes et al., 2019). Consistent with the literature, BDNF levels increased significantly more after acute cardiovascular exercise compared with non-cardiovascular exercise (Winter et al., 2007; Hötting et al., 2016; Tsai et al., 2018). So far, only a few studies have investigated the response of VEGF levels to acute cardiovascular exercise and reported mixed findings (Landers-Ramos et al., 2014; Skriver et al., 2014; Tsai et al., 2018; Kujach et al., 2020). The present results indicated an increase of VEGF levels after cycling, but not after stretching and toning. Thus, a bout of moderate intensity cardiovascular exercise seems to increase both BDNF and VEGF levels in young, untrained adults.

Regarding the relationship between exercise-induced changes in BDNF levels and memory, results yielded significant differences between the BIKE and STRETCH groups. Follow-up analyses of the present study showed marginally significant associations between a larger increase in BNDF and better performance in measures of memory (memory performance in block 1 and within-session learning in the recognition sessions) only in the BIKE group. Correlation coefficients were of moderate strength. The sample size calculation for the present study was based on the main hypothesis of the larger project predicting a group difference in memory improvements across multiple learning sessions. Thus, the relatively small sample size in the BIKE group was not sufficient to test for significant correlations in such a range and needs replication in larger samples. Nonetheless, results of the present study add to the literature showing a positive relationship between the increase in BDNF and memory performance, suggesting that BDNF may be related to memory improvement after exercise (Schmidt-Kassow et al., 2014; Skriver et al., 2014; but see Etnier et al., 2016; Bosch et al., 2017a,b).

Although BDNF correlated with memory in the BIKE group, there was no difference in memory parameters between the BIKE and the STRETCH group. It has been assumed that higher levels of neuromodulatory substances (BDNF, VEGF) after encoding might facilitate memory consolidation (Miranda et al., 2019; van Dongen et al., 2016). BDNF levels in response to cardiovascular exercise have been shown to increase in an intensity-dependent manner, with higher intensities inducing larger increases (Ferris et al., 2007; Winter et al., 2007; Etnier et al., 2016; Hötting et al., 2016). Moreover, exercising with higher intensity than in the present study is known to increase levels of further neuromodulators, such as noradrenalin, adrenalin, and lactate (Winter et al., 2007; Skriver et al., 2014; Basso and Suzuki, 2017). It could, thus, be speculated that the cycling intensity in the present study did not sufficiently enhance BDNF levels and did not induce the secretion of neurochemical substances which would have been required for behavioral benefits after acute cardiovascular exercise (but see Bosch et al., 2017b for contrasting evidence).

In line with earlier research, the increase in VEGF did not correlate with memory and no group differences were found for the relationship between acute exercise-induced changes in VEGF levels and memory (Skriver et al., 2014). However, literature relating to exercise-induced VEGF changes and memory in both chronic and acute study designs is limited, and results are equivocal (Skriver et al., 2014; Woost et al., 2018). In observational studies, higher VEGF levels have been positively associated with larger hippocampal volume, less hippocampal atrophy, and less cognitive decline over time (Hohman et al., 2015) as well as with a decreased risk for Alzheimer’s disease (Mateo et al., 2007), indicating that VEGF might be beneficial for memory-related processes.

Results from rodent studies have supported the involvement of BNDF and VEGF in exercise-induced memory improvements and their associated structural changes in the brain, such as synaptogenesis, neurogenesis, and angiogenesis (Fabel et al., 2003; Vaynman et al., 2004; Cotman et al., 2007; Uysal et al., 2015; El-Sayes et al., 2019). While VEGF has mainly been related to neurogenesis and the growth and protection of the vasculature (Greenberg and Jin, 2005; El-Sayes et al., 2019), BDNF, in particular, has received a lot of attention due to its role in long-term potentiation, that is synaptic plasticity essential for memory consolidation (Miranda et al., 2019). Methodological differences between rodent and human research may partially explain inconsistent results found with respect to associations between neurotrophic factor levels and memory in humans (Schmidt-Kassow et al., 2014; Skriver et al., 2014). In contrast to rodents, invasive procedures to manipulate or measure levels of neurotrophic factors in the brain cannot be applied in humans. Therefore, they are typically measured peripherally in serum or plasma. It is unclear how these peripherally measured neurotrophic factors are related to the levels in the brain (Pan et al., 1998; Lanz et al., 2012; Rich et al., 2017). Moreover, local increases, for example in the hippocampus, cannot be determined by peripheral measures. Therefore, systemic measurements in humans might not reliably capture changes in neurotrophic factors and their relationship to memory, as they may increase and act particularly at the local level in the brain.

Among the limitations of the present study is the blood sampling procedure. Serum BDNF levels were increased after lightly exercising in the STRETCH group (average heart rate of 94 beats/min). Previous studies did not report BDNF increases after exercising at comparable intensity (Schmidt-Kassow et al., 2014; Hötting et al., 2016). For organizational and technical reasons, blood samples collected after exercise were stored at room temperature until they were transported to the centrifuge. This storage possibly caused the release of BDNF from platelets and may be responsible for the unexpected increase of BDNF levels in the STRETCH group (Webb et al., 1998; Gejl et al., 2019). Thus, the absolute values of neurotrophic factors in the present study should be interpreted with caution, in particular when comparing absolute serum values to those reported in previous studies. Nevertheless, given that the sampling procedure and storage time were the same for both groups, it is possible to unequivocally interpret group differences in BDNF change. Additionally, taking blood samples on different days and at different times might have introduced additional variance in the levels of neurotrophic factors due to time- and day-dependent fluctuations (Hetland et al., 2008; Piccinni et al., 2008). However, the time difference and number of days between baseline and post-exercise blood sampling were similar between the BIKE and STRETCH groups, rendering it highly unlikely that circadian fluctuations accounted for group differences.

The present data show no beneficial effect of a single cardiovascular exercise session compared with a single stretching and toning session on early stages of memory consolidation in young adults. However, acute cardiovascular exercise increased both BDNF and VEGF levels in comparison to non-cardiovascular exercise. Moreover, positive correlations between changes in BDNF and memory measures were compatible with the idea and previous findings (Skriver et al., 2014; Bosch et al., 2017b) that BDNF contributed to memory enhancement after acute cardiovascular exercise.

The raw data analyzed in this study are available on request from the corresponding author. The data are not publicly available due to privacy concerns.

The studies involving human participants were reviewed and approved by the Local Ethics Committee of the Faculty of Psychology and Human Movement Science, University of Hamburg. The participants provided their written informed consent to participate in this study.

LK contributed to the study concept and design, recruitment of participants, implementation, data management, data analysis, interpretation of results, and drafted the manuscript. A-MK contributed to the sports medical data collection, data management, data analysis, and to the critical review of the manuscript. K-MB and RR contributed to the study concept and critical review of the manuscript. TJ contributed to the study concept, analysis of BDNF and VEGF data and interpretation, and critical review of the manuscript. BR contributed to the study concept and design, interpretation of results, critical review of the manuscript, and secured funding for the study. KH contributed to the study concept and design, data analysis, interpretation of results, and critical review of the manuscript. All authors contributed to the article and approved the submitted version.

Cyberfitness.tv and FitnessRaum.de provided the training videos used in the physical exercise sessions free of charge. The companies were not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication.

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