Walking, Running, Swimming: An Analysis of the Effects of Land and Water Aerobic Exercises on Cognitive Functions and Neural Substrates

n the brain and cognitive reserves framework, aerobic exercise is considered as a protective lifestyle factor able to induce positive effects on both brain structure and function. However, speci c aspects of such a bene cial effect still need to be completely clari ed. To this aim, the present narrative review focused on the potential brain/cognitive/neural reserve–construction mechanisms triggered by different aerobic exercise types (land activities; such as walking or running; vs. water activities; such as swimming), by considering human and animal studies on healthy subjects over the entire lifespan. The literature search was conducted in PubMed database. The studies analyzed here indicated that all

this aim, the present narrative review focused on the potential brain/cognitive/neural reserve–construction mechanisms triggered by different aerobic exercise types (land activities; such as walking or running; vs. water activities; such as swimming), by considering human and animal studies on healthy subjects over the entire lifespan. The literature search was conducted in PubMed database. The studies analyzed here indicated that all the considered kinds of activities exert a bene cial effect on cognitive/behavioral functions and on the underlying brain neurobiological processes. In particular, the main effects observed involve the cognitive domains of memory and executive functions. These effects appear related to structural and functional changes mainly involving the fronto-hippocampal axis. The present review supports the requirement of further studies that investigate more speci cally and systematically the effects of each type of aerobic activity, as a basis to plan more effective and personalized interventions on individuals as well as prevention and healthy promotion policies for the general population. Keywords: physical activity; motor activity; health behaviour; brain/cognitive/neural reserve; humans; animal models; neuroplasticity 1. Introduction In the last two decades the relationship between brain damage and clinical symptoms has appeared to be more complex previously thought. Additionally, it has becoming clearer that healthy elderly individuals can recruit larger or additional brain regions than healthy young individuals to perform the same cognitive tasks [1]. Reserve mechanisms have been hypothesized as acting to make the brain more resilient to injuries by using pre-existent neural resources or by using neural and cognitive compensatory processes. In this frame- work, thereserve hypothesishas been developed, which posits that not only in aging, but also across the entire lifespan, exposure to stimulating activities is able to equip individuals with high-level resilience that can be spent in case of damage [2,3]. Thereserveconcept basically encompasses: thebrain reserve, consisting in a very powerful cerebral structure, both at molecular and supra-molecular levels; thecognitive reserve, consisting in a high-level functional capacity to ef ciently engage cognitive processes; theneural reserve, consisting in a high-level ability to recruit alternative cognitive strategies [4–6]. Int. J. Environ. Res. Public Health2022,19, 16310.

Thereserveconcept basically encompasses: thebrain reserve, consisting in a very powerful cerebral structure, both at molecular and supra-molecular levels; thecognitive reserve, consisting in a high-level functional capacity to ef ciently engage cognitive processes; theneural reserve, consisting in a high-level ability to recruit alternative cognitive strategies [4–6]. Int. J. Environ. Res. Public Health2022,19, 16310.

Int. J. Environ. Res. Public Health2022,19, 16310 2 of 21 It is well known that several kinds of stimuli, including education, occupation, and leisure activities, such as cognitive, social and physical activities and exercises, contribute to the development of reserves. Namely, engagement in physical exercise has been associated with successful aging [7], and adequate motor function in the elderly has been considered as evidence of reserve occurrence [8]. Indeed, education has been found to be directly associated with walking speed and indirectly associated with white matter lesion load in the elderly [8]. In this context, the World Health Organization [9] released the global recommen- dation on physical activity for health, establishing a minimum level of physical activity (in terms of frequency, duration, type and total amount of exercise) during the entire lifespan. In fact, physical inactivity is the fourth risk factor for global mortality and the WHO promotes physical activity as a modi able factor to prevent diseases and to pro- mote general health in population. Anaerobic/aerobic exercise has been considered as an important protective factor for physical and psychological wellbeing [10]. Anaerobic activities include fast and short high-intensity exercises (such as sprinting and jumping) that do not require any oxygen consumption during their performance. Conversely, aerobic activities imply a moderate effort for a prolonged period (typical examples are walking or swimming) that allows the body to receive constant amounts of oxygen to produce energy during performance. A large number of studies focusing on the neuroplastic effects of lifespan enriched experience have been conducted also in animal models, demonstrating that enhanced stim- ulations support the construction of brain/cognitive/neural reserve [11–14]. In animals, a multidimensional high-level stimulation is modeled by the experimental paradigm of environmental enrichment [15–17]. However, several studies have speci cally focused on the analysis of the effects of physical activity in animal models, both in physiological and pathological conditions [18–20]. The use of rodent-based exercise models provides a number of advantages in comparison to human studies, because of their shorter gesta- tional period and lifespan, more numerous progenies, superior genetical and physiological homogeneity, higher control in experimental procedure

speci cally focused on the analysis of the effects of physical activity in animal models, both in physiological and pathological conditions [18–20]. The use of rodent-based exercise models provides a number of advantages in comparison to human studies, because of their shorter gesta- tional period and lifespan, more numerous progenies, superior genetical and physiological homogeneity, higher control in experimental procedure choices, and the larger possibility of investigation in the nervous system [21]. Moreover, rodent models provide the possibility of carrying out speci c studies on the effects of anaerobic and aerobic physical activities by using speci cal exercise tools and animals housed in conventional cages (without speci cal exercise tools) as control subjects. Human anaerobic activities are modeled in animal resis- tance training designed to increase muscular strength and power and physical capacity [22]. Among the various models, an example of widely used procedures is ladder climbing, in which the animal is progressively trained to climb a ladder with a xed load to the tail [23]. Another example is weightlifting performed by the animal standing upright with the weight typically added by means of a belt or a shoulder harness [24]. On the other hand, human aerobic activities are modeled in animals by means of voluntary or forced walking, running, and swimming (for details, see below). The effects of aerobic exercise on cognitive functions and neuroplasticity have been more widely investigated in animal models compared to studies involving anaerobic exercise [25]. On the basis of the described evidence, the aim of the present review was to offer an overview of physical activity, with particular attention to aerobic activities, as a potential builder of brain, cognitive, and neural reserves. To this aim, we considered human and animal studies on healthy subjects. The review rst presents a general section on the effects of aerobic exercise on cognitive functions and neural substrates by taking into account the evidence provided by animal and human studies. The following two sections focus on the potential brain/cognitive/neural reserve development mechanisms elicited by different aerobic exercise types: (1) land activities such as walking or running; and (2) water

The review rst presents a general section on the effects of aerobic exercise on cognitive functions and neural substrates by taking into account the evidence provided by animal and human studies. The following two sections focus on the potential brain/cognitive/neural reserve development mechanisms elicited by different aerobic exercise types: (1) land activities such as walking or running; and (2) water activities, such as swimming. Human and animal models were considered separately in these analyses.

Int. J. Environ. Res. Public Health2022,19, 16310 3 of 21 2. Aerobic Exercise Effects on Cognitive Functions and Neural Substrates 2.1. Humans In humans, it has been observed that aerobic exercise enhances both the mood and cognitive functioning (mainly, the executive functions) [26,27]. A recent study on young fe- male artistic gymnasts compared with age/gender-matched sedentary children highlighted the bene cial effect of endurance and controlled aerobic training on working memory and learning abilities [28]. Studies showed that aerobic training performed for 3 days per week for at least one year limited the hippocampal decline due to normal aging processes [29–32]. Other studies showed an increase of hippocampal and entorhinal volumes after regular aerobic exercises [33,34]. Several studies have demonstrated the long-term effects of physical exercise on brain functioning, especially in the prefrontal areas and consequently on executive functions (see [35] for a review). The long-lasting bene cial effects of physical exercise on attention, working memory, cognitive exibility, inhibition mechanisms and affective state, persisting up to 2 h after exercise cessation have also been demonstrated [35,36]. More recently, physical exercise has been found to be associated with better cogni- tive functioning in older adults, with increased serum neuro lament concentrations [37]. Some studies investigating the effect of different kinds of physical exercises not only on cognition [35,38] but also on the mood and emotional states, reported bene cial effects in individuals practicing sports [35,39]. Moreover, it has been shown that open skill sports (e.g., tennis) trained not only motor but also cognitive functions, in particular, in- hibitory control [40,41]. Interestingly, a study investigating the effect of physical exercise on brain functional connectivity in Olympic athletes showed the strongest connections in the thalamo-sensorimotor network of the swimmers reporting the highest world rankings [42]. Recently, a study focusing on aerobic exercise associated this activity with less age- related gray and white matter loss [43]. By using functional magnetic resonance imaging (f-MRI) Vivar and colleagues [44] showed that higher- t older adults achieved better results than low- t adults on attentional tests. Interestingly, this nding was associated to increased BOLD signals in the

rankings [42]. Recently, a study focusing on aerobic exercise associated this activity with less age- related gray and white matter loss [43]. By using functional magnetic resonance imaging (f-MRI) Vivar and colleagues [44] showed that higher- t older adults achieved better results than low- t adults on attentional tests. Interestingly, this nding was associated to increased BOLD signals in the prefrontal regions and by decreased signals in the anterior cingulate cortex. Details on the original studies cited in this section are provided in Table. Table 1. Studies on aerobic exercise effects on cognitive functions and neural substrates of healthy human subjects. Authors Sample Size Design Physical Exercises Cognitive/ Behavioural Effects Brain Effects Aerobic physical activity Elbaz et al., 2013 [8] n= 4010; M/F% = 39%/61% Age [range] = 65–85 years Longitudinal study over 10 years Walking speed measured at baseline and after 4 years as 6 m by time - White matter lesions (deep, periventricular and total volumes assessed on structural MRI scans) Hyodo et al., 2019 [27] n= 21 M/F = 10/11 Age [range] = 65–74 years Cross-sectional study with repeated measure Single session: Cycling exercises (intensity = 60% of the individual ventilatory threshold; duration = 10 0 ) vs. dance exercises (intensity = 3 different movements [twisting the upper body; swinging the arms side to side; swinging the arms back] duration = 3 0 .20 0 for each) Improvement in the executive functions (by Stroop task, before the training and after 5 min at the end of the training) and in the mood (vitality, stability, pleasure, arousal) (by Two dimensional mood scale before and immediately after the exercises) -

Int. J. Environ. Res. Public Health2022,19, 16310 4 of 21 Table 1.Cont. Authors Sample Size Design Physical Exercises Cognitive/ Behavioural Effects Brain Effects Serra et al., 2021 [28] n= 28 M/F = 0/28 Age [range] = 7–10 years Cross-sectional study Artistic gymnastics (Intensity = 3 sessions a week for 2 years minimum; duration = 90 0 for session) vs. no gym Improvement in the memory functions measured by the Table Radial Arm Maze task and in the schooling achievements assessed by BVN5-11 - Erickson et al., 2009 [29] n= 165 M/F = 56/109 Age [range] = 59–81 years Correlational study Aerobic exercises (by motor driven treadmill) Improvement in the cardiorespiratory aerobic tness assessed by VO2peak Increase of hippocampal volumes measured by manual segmentation on T1-weighted images obtained on 3T scan Erickson et al., 2011 [30] n= 120 Age [mean SD] = 66.5 5.6 years M%/F% = 33.5%/66.5% Cross-sectional study Aerobic exercises (by motor driven treadmill; Intensity = 30–100 m/min with increments of 2% every 2 min; duration = 10 0 –40 0 in seven weeks) vs. Stretching and toning exercise (four muscle toning exercises using dumbbells or resistance bands; two exercises for balance; one yoga sequences and one free exercise; Intensity = increasing the weight or repetitions; duration = seven weeks) Improvement in the memory function by computerized spatial memory task preformed before, after 6 months and at the end of the trainings Increase of hippocampal volumes measured by manual segmentation on T1-weighted images obtained on 3T scan. Scans were performed before, during and after trainings Maass et al., 2015 [31] n= 40 M%/F% = 45%/55% Age [mean SD] = 68.4 4.3 years Cross-sectional study Aerobic exercises in terms of running/walking by stationary treadmills (Intensity = 30-min interval training 3 times per week; duration = 12 weeks) vs. Stretching exercise by progressive muscle relaxation (Intensity = twice a week; Duration = 45 0 each session for 12 weeks) Improvement in the recognition memory functions by the verbal learning memory test (free recall, 30-min delayed recall and recognition). Cognition was assessed before and after trainings Increase of hippocampal volumes assessed by

times per week; duration = 12 weeks) vs. Stretching exercise by progressive muscle relaxation (Intensity = twice a week; Duration = 45 0 each session for 12 weeks) Improvement in the recognition memory functions by the verbal learning memory test (free recall, 30-min delayed recall and recognition). Cognition was assessed before and after trainings Increase of hippocampal volumes assessed by manual segmentation using a 7T T1-weighted images and increase in the cerebral blood ow by 3T high resolution perfusion-weighted images. Scans were performed before and after tranings Brinke et al., 2015 [32] n= 86 M/F = 0/86 Age [range] = 70–80 years Cross-sectional study with repeated measure Resistance Training (Keiser-based exercises; Intensity = 6–8 repetitions for two sets; Duration = 60 0 daily) vs. Aerobic Training (outdoor walking program; Intensity = 40–80% of individual age-speci c target heart rate; duration = 12 weeks) vs. Balance and tone Training by using stretching, motion exercises, balance exercises, functional and relaxation techniques Improvement in the memory functions assessed by the Rey Auditory Verbal Learning test (immediate and 20-min delayed recall) Increase of hippocampal volumes assessed by automated segmentation of 3T T1-weighted images

Int. J. Environ. Res. Public Health2022,19, 16310 5 of 21 Table 1.Cont. Authors Sample Size Design Physical Exercises Cognitive/ Behavioural Effects Brain Effects Whiteman et al., 2016 [34] n= 33 M/F = 13/20 Age [range] = 18–30 years Correlational study Aerobic exercises by treadmill (Intensity = speed 0.8 m/s and incline of 10%, increasing speed of 0.35% m/sec and incline of 2% grade every 3 min; Duration = volitional exhaustion criterium Improvement in the cardiorespiratory aerobic tness by VO2max and in memory functions by an inside/outside MRI scanner visual memory recognition test Increase of entorhinal volumes assessed on 3T T1-weighed images by using the voxel-based morphometry approach Chiu et al., 2017 [36] n= 31 M/F = 15/16 Age [mean SD] = 22.2 4.3 years Cross-sectional study with repeated measure Open skills sports (Volleyball) vs. Closed skills (Exercise) sports Improvement in the cognitive processing speed by anker task; improvement in aerobic physical tness by VO2 max after PACER test - Desai et al., 2022 [37] n= 1158 M/F = 430/728 Age [mean SD] = 77.4 4.3 years Correlational study Physical activity assessed by US Health Interview Survey and divided in little activity (0 min of activity participation per week), medium activity (<150 min activity participation per week), high activity (>150 min activity participation per week) Decrease of cognitive decline assessed by the East Boston Memory test; the Mini Mental state Examination and the Symbol digit modalities test. Association with neuro lament concentration was tested - Aly et al., 2019 [38] n= 33 Age [mean SD] = 19.7 1.5 years Cross-sectional study Swimming vs. Karate vs. generic physical activity assessed by the International Physical Activity Questionnaire and divided in vigorous, moderate and light intensity Increase of attentional resources by the auditory oddball task Changes in neurophysiological activity by EEG measurement Zhang et al., 2022 [39] n= 1117 M/F = 554/563 Age [mean SD] = 18.9 1.2 years Correlational study Swimming vs. Karate vs. generic physical activity assessed by the International Physical Activity Questionnaire and divided in vigorous, moderate and light intensity Improvement in the cardiorespiratory aerobic tness by VO2Max and decrease of

task Changes in neurophysiological activity by EEG measurement Zhang et al., 2022 [39] n= 1117 M/F = 554/563 Age [mean SD] = 18.9 1.2 years Correlational study Swimming vs. Karate vs. generic physical activity assessed by the International Physical Activity Questionnaire and divided in vigorous, moderate and light intensity Improvement in the cardiorespiratory aerobic tness by VO2Max and decrease of negative emotional states assessed by Depression Anxiety Stress scale and by Connor-Davidson resilience scale - Wang et al., 2013 [40] n= 60 M/F = 60/0 Age [mean SD] = 20.2 2.9 years Cross-sectional study Open skills: Tennis vs. Closed skills: swimming vs. no physical activity assessed by a 7-day physical activity recall questionnaire divided in light, moderate, high, intense and sleep of PA Improvement in the inhibitory control assessed by Stop-signal task and in the Aerobic tness assessed by VO2Max - Montuori et al., 2019 [41] n= 27 M/F = 27/0 Age [mean SD] = 25.3 5.2 years Cross-sectional study Volleyball (Intensity = 2–4 h for session 5 times a week; duration = about 13 years of experience) Improvement in the executive functioning (Reaction time and accuracy in terms of `switch costs' and errors in a switching task) -

This review analyzes the effects of aerobic exercises on cognitive functions and neural substrates.