Logo of japPublished ArticleArchivesSubscriptionsSubmissionsContact UsJournal of Applied PhysiologyAmerican Physiological Society
J Appl Physiol (1985). 2011 Nov; 111(5): 1505–1513.
Published online 2011 Apr 28. doi:  10.1152/japplphysiol.00210.2011
PMCID: PMC3220305
Physiology and Pathophysiology of Physical Inactivity

Exercise, brain, and cognition across the life span


This is a brief review of current evidence for the relationships between physical activity and exercise and the brain and cognition throughout the life span in non-pathological populations. We focus on the effects of both aerobic and resistance training and provide a brief overview of potential neurobiological mechanisms derived from non-human animal models. Whereas research has focused primarily on the benefits of aerobic exercise in youth and young adult populations, there is growing evidence that both aerobic and resistance training are important for maintaining cognitive and brain health in old age. Finally, in these contexts, we point out gaps in the literature and future directions that will help advance the field of exercise neuroscience, including more studies that explicitly examine the effect of exercise type and intensity on cognition, the brain, and clinically significant outcomes. There is also a need for human neuroimaging studies to adopt a more unified multi-modal framework and for greater interaction between human and animal models of exercise effects on brain and cognition across the life span.

Keywords: physical activity, aerobic training, strength training, brain function, brain structure, mental health

it is increasingly prevalent in the print media, television, and the internet to be bombarded with advertisements for products and programs to enhance mental and physical health in a relatively painless fashion through miracle elixirs, computer-based training or gaming programs, or brief exercise programs. Although there is little convincing scientific evidence for many such claims (46), there have been some promising developments in the scientific literature with regard to physical activity and exercise effects on cognitive and brain health. In fact, a number of our forefathers appear to have anticipated some of the potential benefits of an active lifestyle. For example, Thomas Jefferson argued, “a strong body makes the mind strong.” Hugh Blair, a Scottish Theologian from the 18th century suggested that, “Exercise is the chief source of improvement in our faculties.” One of the first noted scientist/physicians, Hippocrates, opinioned, “If we could give every individual the right amount of nourishment and exercise, we would have found the safest way to health.”

Indeed, there is an increasing amount of research, much of it epidemiological, that argues for numerous long-term health benefits of regular physical activity and exercise. For example, studies have reported an inverse relationship between physical activity and the risk of type II diabetes (58), cardiovascular-related disease and death (89), osteoporosis (52), colon and breast cancer (62), and mental disorders (29). Despite this increasing wealth of knowledge concerning the relationship between physical activity and health we have become an increasingly sedentary society. For example, it has been estimated that less than 50% of children (6–11 yr) and only 8% of adolescents (12–19 yr) are active the recommended 60 min most days of the week, whereas only less than 5% of adults (20–59 yr) and elderly (60+ yr) are active the recommended 30 min a day for this age group (99). Furthermore, it has been suggested that our current sedentary nature represents a maladaptation of our evolutionary history in which high levels of physical activity were required for survival (6).

In the present brief review we focus on the relationship between physical activity and cognitive and brain health. We briefly review molecular and cellular exercise-related changes in our discussion of the animal literature. However, the majority of our review will focus on aerobic and strength training effects on human cognition and brain health across the life span in healthy populations. Finally, we conclude with prescriptions for additional research on this important topic.


As we progress from elementary to high school, our brains rapidly develop structural and functional circuitry that support higher-level cognitive abilities, such as our ability to regulate and inhibit behavior, multi-task, and resist distraction (13). Consequently, behaviors that affect brain function play a vital role in facilitating optimal cognitive development during childhood. Physical activity is no exception. Research indicates that childhood physical inactivity, and subsequently reduced aerobic fitness, is associated with poorer academic achievement (15, 19) and lower performance on standard neuropsychological tests (9, 90). The majority of scientific literature supports a general benefit of aerobic fitness on childhood cognitive performance. For example, a meta-analysis that aggregated results across 44 studies found an overall effect size of 0.32 for the association between childhood physical activity and fitness and cognition, with significant effects across a range of abilities, such as perceptual skills (0.49), creativity and concentration (0.40), academic readiness (0.39) and achievement (0.30), IQ (0.34), and math (0.20) and verbal (0.17) tests (90).

Still some studies have shown selective benefits of exercise on childhood cognition (for review, see Ref. 97). For example, one study increased task difficulty and thus pushed the limits of prefrontal function beyond what other studies have done (77). This is consistent with a training study that found 3 mo of aerobic exercise training improved prefrontally mediated executive function abilities in 7- to 11-year-old overweight children (27). Other studies demonstrating a selective association have shown, in agreement with a large animal literature, that aerobic fitness is preferentially associated with a type of memory supported by the hippocampus, relational memory, rather than item memory (17, 18). Unlike item memory, relational memory requires forming associations, such as remembering not only the face of a person you met last week, but also remembering his name, what you talked about, and where you met him. Finally, overall there is stronger support for aerobic fitness benefits on accuracy rather than speed of processing (9, 17, 18, 47, 77), which is consistent with the idea that accuracy may be a better measure of cognitive development than speed (26). Yet the majority of literature on physical activity, aerobic fitness, and childhood cognition is cross-sectional in nature, therefore more training studies with temporally extended follow-up testing are needed for stronger support of these summarized findings.

Nevertheless, neuroimaging research provides additional evidence for both general and selective effects of exercise on childhood cognition. Functional brain imaging studies using event-related potentials (ERPs) have shown that more aerobically fit children have larger P300s during information processing (47, 48, 77), an ERP component whose amplitude is associated with our ability to effectively focus attention and that is thought to emerge, in part, from the temporoparietal cortex (76). ERP brain recordings also indicate that aerobically fit children better regulate and monitor their mistakes, or processing errors, abilities made possible by the anterior cingulate and prefrontal cortices (47, 77). For example, Hillman and colleagues (47) found that higher-fit children who outperformed lower-fit children on the Eriksen flanker task (a test of conflict resolution) showed a smaller error-related negativity (ERN) on error trials, an ERP component thought to index conflict monitoring and error evaluation; higher-fit children also showed a larger positivity error (Pe) component, thought to index awareness of one's mistakes. Overall, higher-fit children were more accurate in trials following errors of commission, while showing a smaller ERN and larger Pe, suggesting higher-fit children's brains monitor conflict more efficiently (see also 77). Neuroanatomically, childhood aerobic fitness is associated with more brain volume in structures important for demanding information processing and relational memory, such as the dorsal striatum (16) and the hippocampus (17), respectively.

In sum, cross-sectional and longitudinal training studies support a positive association between aerobic fitness and enhanced performance in both the classroom and laboratory (for reviews, see Refs. 90, 97). Furthermore, neuroimaging evidence supports a beneficial association between childhood aerobic fitness and improved brain function and structure.

Following the rapid cognitive development in childhood, young adulthood (i.e., 18–35 yr) is characterized by relative stability and peak cognitive performance. This may be one reason that comparatively fewer studies examine cognitive enhancements associated with physical activity and aerobic fitness training during this part of the life span. This may also be the reason that studies have generally found mixed support for the association between aerobic fitness and cognition in young adulthood (1, 85, 88). Yet several neuroimaging studies have shown evidence for increased efficiency of brain function without differences in behavioral performance (51, 95, 96). For example, similar to the findings of Hillman and colleagues (47) with children, one study showed that higher-fit young adults also had smaller ERNs coupled with larger Pe amplitude, specific to trials with errors of commission (95). Despite these neuroelectric differences, there were no differences in behavioral performance between lower- and higher-fit adults. Studies like these suggest that aerobic fitness effects on behavior may only emerge in this high-functioning group when the task is extremely difficult or that young adults have a greater range of compensatory strategies compared with children and older adults to achieve enhanced performance. There are very few training studies with young adults; however, some studies do support the effectiveness of aerobic training for improving cognition at this age (74, 92), particularly for those with a genetic predisposition for impaired cognition due to lower dopamine levels in the brain (93). Thus overall, whereas cross-sectional behavioral results are mixed with young adults, neuroimaging and training results seem to support a positive association between greater aerobic fitness and brain function. Future research that examines the effect of task difficulty, uses more diverse imaging techniques, and examines the long-term effects of aerobic fitness during adulthood will help clarify many unanswered questions for this age group.

Older adulthood mirrors childhood in some interesting ways, when brain structure and function again enter a period of high interindividual variability and lifestyle factors, such as physical activity, increasingly impact mental health. Although epidemiological and prospective studies largely support the role of physical activity and aerobic fitness in healthy cognitive (80, 109) and brain (83) aging and preventing the onset of all types of dementia (60, 64), it is less clear from training studies whether increased aerobic fitness per se is the key ingredient for improved brain and cognition from behavior changes associated with this lifestyle factor (22, 35). Much evidence, however, does support the notion that aerobic exercise benefits cognitive performance (22, 32, 57), brain function (10, 23, 108), and brain structure (21, 68) in elderly adults.

Specifically, aerobic training in late life preferentially benefits executive functions, including brain processes such as multi-tasking, planning, and inhibition, all largely supported by the prefrontal cortex (22, 23, 57). Several fMRI studies have examined the effects of aerobic training on brain function. Colcombe and colleagues (23) examined the effects of a 6-mo, three times weekly aerobic training program for sedentary adults on task-related brain activation during the Eriksen flanker task. Aerobically trained older adults had greater increases in brain activity in the frontal and parietal cortices from pre- to postintervention, brain areas involved in processes important for task performance, such as conflict resolution and selective attention. Aerobically trained adults also had greater reduction in anterior cingulate cortex activation, a brain area involved in conflict and error monitoring. This pattern of activation changes suggests that aerobic training led to increased efficiency of conflict and error monitoring and enhanced regulatory response from the prefrontal cortex following signals of conflict from the anterior cingulate (8). In line with this theoretical account, functional improvements were coupled with improvement in conflict regulation performance. This study demonstrated that participating in an aerobic training program improves the aging brain's ability to effectively engage task-relevant resources, particularly under cognitively challenging conditions. Thus aerobic training had a selective rather than general effect on task-related brain function.

Another way to assess brain function is to examine not how much the brain activates under controlled cognitive conditions, but rather how different areas of the brain communicate under little to no cognitive demand. The benefit of the latter is an absence of group differences in behavioral performance or strategy that could potentially confound differences in task-related brain activation. Voss and colleagues (108) examined changes in functional communication, or connectivity, in sedentary older adults following a 1-yr, three times weekly aerobic training program. The study examined whether aerobic training would enhance communication in the Default Network (a network whose dysfunction is proposed to be a biomarker for normal cognitive decline and Alzheimer's Disease), as well as brain networks involved in higher-level executive functions, spatial attention, motor control, and audition. Of all the networks examined, the Default Network was the primary brain network showing enhanced connectivity following aerobic training, in addition to increased connectivity between the left and right prefrontal cortices in an Executive Control network. Thus aerobic fitness training benefits not only task-related magnitude of brain activation, but also the resting coherence of brain networks important for cognition and neurological disease status.

In addition to functional brain changes, studies also support significant changes in regional brain volume following aerobic training. Following a 6-mo, three times weekly aerobic program, Colcombe and colleagues (21) found gray matter increases in the lateral prefrontal anterior cingulate and lateral temporal cortices and increased anterior white matter volume. Furthermore, another study found that a 1-yr, three times weekly aerobic training program increased volume of the anterior hippocampus, which houses the dentate gyrus subregion linked to neurogenesis in animal studies (38, 74, 103); whereas there were no volumetric benefits for the posterior hippocampus, thalamus, or caudate nucleus (33). Also consistent with the animal literature, increased anterior hippocampus volume was associated with increased peripheral brain-derived neurotrophic factor (BDNF) for only the aerobic group. The significance of BDNF will be discussed in more depth below. Finally, while this study found memory improvements for the aerobic and nonaerobic control group, increased anterior hippocampal volume was associated with improved memory for only the aerobic group, trends not shown in the caudate or thalamus. However, change in BDNF was not associated with changes in memory. Thus one caveat of most human studies is the inability to unequivocally determine the nature of the cellular and molecular changes that underlie the observed changes in brain volume and cognitive function. Although one study indicated that cerebral blood volume, potentially an in vivo marker of neurogenesis, is at least one factor that may be involved with increased hippocampal volume and corresponding increases in learning performance (74). Nevertheless, these studies provide continuing support that beginning an aerobic exercise program in late life can still translate into meaningful benefits for the brain and cognition.


Although resistance training has a broad range of systemic benefits (7, 61), very few studies to date have specifically focused on the role of resistance training in promoting cognitive health across the life span. To our knowledge, no studies have specifically assessed the effect of resistance training on cognitive and brain function in children. A lack of such studies may be partly due to the common misperception that resistance training is unsafe for children. Likewise, there is a general void in the literature regarding the role of chronic resistance training in promoting cognitive and brain function in young adults.

For older adults, evidence regarding whether resistance training has cognitive benefit has been equivocal. However, we note that the trials with negative results were limited by small sample sizes (i.e., 13–23 participants per experimental group) or short intervention periods (i.e., 8–16 wk) (32, 55, 75, 100). For example, Tsutsumi and colleagues (100) demonstrated no cognitive benefit of resistance training in their 12-wk randomized controlled trial that compared the effect of high-intensity/low-volume resistance training and low-intensity/high-volume resistance training with no exercise controls on cognitive function in 42 community-dwelling older adults (i.e., 14 participants per group). Recently, Kimura and colleagues (55) also demonstrated no effect of resistance training on the executive process of task switching despite including 119 participants in their 12-wk training study. In addition to sufficient duration of resistance training, the intensity or load of training appears to be a key requirement to produce cognitive benefits. For example, Lachman and colleagues (59) conducted a 6-mo randomized controlled trial of home-based resistance training among 210 sedentary community-dwelling older adults and found no significant between-group differences in memory. The home-based resistance training program was a 35-min videotaped program of 10 exercises using elastic bands. Participants were instructed to use bands of greater resistance when they could complete greater than 10 repetitions of an exercise without significant fatigue. This is a lower intensity protocol compared with three recent randomized controlled trials with positive findings that used loading protocols ranging from 50 to 80% of a single-repetition maximum lift (i.e., 1 RM) (14). It is important to highlight that while there were no significant between-group differences in cognitive performance, Lachman and colleagues (59) found that the change in resistance used by those in the intervention group was positively associated with change in memory performance, after controlling for baseline age, education, sex, and disability level. Hence, the investigators suggested that resistance training can benefit memory among older adults, especially when using higher resistance levels.

Randomized controlled trials of resistance training that are 6 mo or greater in duration and delivered high-loading protocols collectively provide emerging evidence that resistance training has cognitive benefits. Cassilhas and colleagues (14) demonstrated that 6 mo of either three times weekly moderate or high-intensity resistance training improved memory performance and verbal concept formation among 62 community-dwelling senior men ages 65 to 75 yr. Moderate intensity was defined as 50% of 1 RM and high intensity was defined as 80% of 1 RM. Using a protocol similar to Cassilhas (14), recent work by Busse and colleagues (11) suggests that resistance training may also be beneficial for sedentary older adults at greater risk for Alzheimer's disease—those with objective mild memory impairment.

The work of Cassilhas and colleagues (14) also provides valuable insight into the possible mechanisms underlying the benefit of resistance training on cognitive performance. They found serum insulin-like growth factor-1 (IGF-1) levels were higher in the resistance training groups than in the control group. IGF-1 promotes neuronal growth, survival, and differentiation and improves cognitive performance (24), which will be discussed further below. In older adults, resistance training also reduces serum homocysteine (107). Increased homocysteine levels are associated with impaired cognitive performance (84), Alzheimer's Disease (87), and cerebral white matter lesions (106), although the cognitive relevance of reductions in homocysteine in longitudinal study remain unclear (e.g., 3).

Finally, Liu-Ambrose and colleagues (65) demonstrated that 12 mo of either once weekly or twice weekly progressive resistance training improved selective attention and conflict resolution performance among 155 community-dwelling senior women aged 65 to 75 yr. Enhanced selective attention and conflict resolution was also associated with increased gait speed. Clinically, improved gait speed predicts a substantial reduction in both morbidity (82) and mortality (31, 45). These results illustrate the clinical significance of cognitive gains induced by resistance training. Davis and colleagues (28) also provided novel evidence that cognitive benefits associated with resistance training are sustained for 1 yr after the intervention has ended.

Thus, while there is less literature across the life span on the effects of resistance training on brain and cognition, compared with aerobic training, preliminary evidence highlights its importance for future study.


Animal models of exercise effects on brain physiology and structure have indicated several key pathways through which aerobic and resistance training may enhance brain function. These pathways include improvement in both the structural integrity of the brain (i.e., growth of new neurons and blood vessels) and increased production of neurochemicals that promote growth, differentiation, survival, and repair of brain cells. In addition, animal models have begun to shed light on how aging interacts with these molecular and cellular models of exercise effects on brain and cognition.

Many studies now suggest that aerobic training results in neurogenesis, or the generation of new neurons, in the hippocampus (102, 103), which has been subsequently linked to improved hippocampal function (25, 74). To our knowledge hippocampal neurogenesis has not been studied in animal models in the context of other forms of exercise programs (e.g., aerobic vs. exercise analogous to resistance training in rodents), therefore future research is needed to understand the specificity of neurogenesis following different forms of exercise. Furthermore, although the rate of hippocampal neurogenesis declines with normal aging, animal studies generally support some protection from such decline with aerobic exercise training (54, 104). Age does appear to attenuate the effect of aerobic exercise on neurogenesis compared with young adult animals and for 15- and 19-mo-old animals, respectively (54, 104). One study showed no training-induced neurogenesis in old (22 mo) animals despite some improvement on a spatial pattern separation task and positive evidence for young animals (25). Other studies have also found that neurogenesis is not necessary for improved performance (e.g., 53) or that neurogenesis is associated with improvement in some tasks (e.g., spatial memory) and not others (e.g., motor performance, conditioning) (20). Therefore, while hippocampal neurogenesis is a highly replicable effect following aerobic exercise, there are still some questions about how it supports behavioral improvements following aerobic exercise compared with other exercise-related factors.

For example, another consistent effect in animal models is exercise-induced increases in angiogenesis, or the growth of new blood vessels (25, 74, 104), which has in turn been linked to improved learning and memory (53, 74). Like neurogenesis, no studies to our knowledge have examined the specificity of angiogenesis following different types of exercise. Unlike neurogenesis, aerobic training produces angiogenesis outside of just the hippocampus, including areas directly activated by locomotion such as the cerebellum (4, 50) and primary motor cortex (56, 94). Furthermore, at least two studies have shown aerobic training-related increases in hippocampal angiogenesis in young but not aged mice (22 and 19 mo, respectively) (25, 104). Similar to effects described above, the study by Creer and colleages (25) showed that despite no significant hippocampal angiogenesis (or neurogenesis), aerobically trained old rodents still showed moderate improvements in performance. Thus while angiogenesis is consistently found in response to aerobic exercise in young animals, the role of training-induced angiogenesis in cognitive improvements across the life span is also a topic in need of future study.

Animal models have also indicated several candidates for circulating neurochemicals that may mediate effects of exercise on brain health. Two that have received the most empirical support include BDNF and IGF-1. BDNF is endogenously produced throughout the brain, with particularly high concentrations in the hippocampus (71), and in animals is known to increase in the brain during single acute bouts (79) and following chronic aerobic exercise training (72, 73). While BDNF is also produced in the periphery, some studies have suggested that peripheral BDNF in humans at rest and during an acute bout of aerobic exercise is predominantly brain-derived (estimated from arterial-to-venous difference of radial artery and the internal jugular vein), although it may dip during recovery (79). Also, at least one training study from the same group has shown that 3 mo of aerobic training increases human resting peripheral brain-derived BDNF but did not affect peripheral estimates of brain-derived BDNF during aerobic exercise (86). Another study showed that peripheral BDNF in blood serum was selectively increased following 30 min of high intensity (∼85% of heart rate max) compared with lower intensity (∼70% of heart rate max) aerobic exercise (39). Finally, it is interesting to note that there is evidence that resting peripheral serum BDNF is selectively upregulated in humans following chronic aerobic (111) but not resistance training (63). Overall, these studies suggest that BDNF release in the human cortex and hippocampus during exercise and at rest can be estimated in the periphery from blood plasma or serum and demonstrate that examining the effects of acute bouts of exercise on the brain may help build links to animal models and (although it is unknown whether the mechanisms are the same) may inform how the brain adapts to cumulative changes in different types of exercise behavior. A noted limitation of these studies, however, is small sample sizes of young adults; thus, it will be important for these results to be replicated with larger samples of a broader age range.

Understanding how exercise affects BDNF production is important because BDNF is considered a critical factor in exercise-induced benefits on learning and memory. For example, Farmer and colleagues (38) demonstrated that BDNF is associated with aerobic exercise-induced increases in long-term potentiation (LTP), which facilitates synaptic plasticity and is considered a cellular model of learning and memory. Furthermore, blocking BDNF receptors during exercise abolishes downstream effects on metabolic factors (43) and cognitive performance (43, 44, 105). Although there is overwhelming evidence in support of BDNF as an important factor in exercise-induced improvement in brain and cognition, more research is needed that investigates how age interacts with these results. For example, Garza and colleagues (41) showed that aged rodents (22 mo) had increased hippocampal BDNF mRNA following short (i.e., 2 days) and chronic (i.e., 20 days) bouts of running; however, there were substantial differences in the regional pattern of sensitivity for exercise-induced increases in BDNF, which the authors suggested may reflect age-related shifts in hippocampal physiology that in turn impact how exercise affects hippocampal structure and function in old age. Another study found that chronic aerobic exercise was not associated with increases in hippocampal BDNF protein for aged rodents (24 mo), despite positive results for young rodents (2).

A known neurotrophic factor important for both aerobic and resistance training is IGF-1. IGF-1 is produced both in the central nervous system and in the periphery in response to aerobic (12, 30, 98) and resistance (14) exercise. Furthermore, studies have shown that blocking entry of peripheral IGF-1 into the brain during aerobic training also blocks exercise-induced hippocampal neurogenesis (98), angiogenesis (66), and exercise-facilitated brain injury recovery (12). Studies have also supported a dependence between IGF-1 and exercise-induced increases in BDNF (12, 30). For example, one study demonstrated that blocking IGF-1 receptors in the hippocampus during exercise abolished exercise effects on increased hippocampal BDNF mRNA and protein expression, and similar effects were found for hippocampal levels of markers of synaptic plasticity that are presumed to be end-products of BDNF action (exercise-induced increases in synapsin I, p-CAMKII, p-MAPKII) (30). In turn, researchers that have found attenuated exercise-related enhancement of BDNF in aged rodents have speculated that this may be partly due to the reduction in IGF-1 associated with aging (2, 67).

Thus animal models have shown that BDNF and IGF-1 play important roles in mediating the effects of exercise on brain health and performance. Other neurotrophic factors and neuropeptides shown to change with exercise behavior include nerve growth factor (70), fibroblast growth factor type 2 (42), vascular endothelial growth factor (36), and VGF growth factor (49) and galanin (101). Furthermore, aerobic exercise also enhances several neurotransmitter systems in the brain, including increasing circulating dopamine (78), serotonin (5), and acetylcholine (40). Relatively less research has been done on the mechanisms by which exercise affects production of these neurochemicals with links to cognition and learning and memory. Therefore, the extent to which these neurochemicals also contribute to benefits of exercise across the life span deserves future study.

In summary, animal models have revealed much about the potential neurobiological mechanisms of exercise effects on brain and cognition across the life span. Aerobic exercise has a concentrated benefit on the hippocampus, increasing the growth of new neurons and new blood vessels, and increasing synaptic plasticity, which helps facilitate the integration of hippocampal neurons into existing brain networks. Several important neurotrophins are integral to the effects of exercise on brain and cognition. While aerobic exercise seems to selectively upregulate central BDNF, both aerobic and resistance exercise upregulate central and peripheral IGF-1. Both are key players in exercise-induced increases in learning and memory, and IGF-1 may be particularly important in mediating the effects of BDNF and promoting exercise-induced neurogenesis and angiogenesis. However, it should be noted that animal models often use cognitive measures of learning and memory that rarely conceptually overlap with the cognitive paradigms used in human research. Thus the extent to which the reviewed potential mechanisms account for benefits of exercise on executive function in humans is a topic that deserves future consideration. In addition, future research is needed to clarify the role of these molecular and cellular pathways in models of aging and exercise. Research has generally supported the idea that aerobic exercise attenuates age-related declines in neurogenesis and learning and memory, but it is still unclear how much overlap there is between the exercise model for young and aged animals.


The reviewed literature provides an overview of the effects of exercise on brain and cognition throughout the life span. Whereas research has focused primarily on the benefits of aerobic exercise in youth and young adult populations, there is growing evidence that both aerobic and resistance training are important for maintaining cognitive and brain health in old age. Our review also points out gaps in the literature and important future directions for the field.

Clearly there is a need for more research that investigates the effect of exercise type on the brain and cognition, and in turn, clinically significant outcomes such as quality of life, memory complaints, mobility, falls risk, and mortality. While standard neuropsychological tests and brain imaging data provide valuable data for characterizing the specific brain systems affected by exercise behavior, the translation of these results into clinically relevant outcomes is also important for building a more interactive relationship between basic research findings and clinical practice. Also important for translating research into practice will be a greater understanding of how individual differences mediate or moderate the effects of different exercise types on brain and cognition. For instance, it is possible that aerobic training will be more effective for some individuals whereas resistance training would benefit others more, and their combination may be best for yet another group. Some factors important to examine may include (but not be limited to) genetics, personality, and personal health history or disease status. Greater understanding of the role of these factors in the effects of exercise training on brain and cognitive health may also help clarify the relative importance of aerobic fitness gains compared with engaging in physical activity without focus on fitness gains per se. These issues have important practical significance for affecting public health recommendations for physical activity behavior to improve brain and cognition.

Within the realm of brain imaging, when comparing the effects of different exercise types, it will be important for future research to incorporate more of a multi-modal framework. Currently our knowledge of exercise effects in childhood and young adulthood is based primarily from neuroelectric methods, whereas training studies with older adults have used primarily hemodynamic measures of brain function. Therefore, it will be important for future research to incorporate multiple methods of measuring brain function across the life span. Along these lines, additional methods that will be important for future research include measures of blood volume and blood flow such as arterial spin labeling (ASL) and measures of white matter microstructure, including diffusion tensor imaging (DTI). For example, a recent study demonstrated the feasibility of measuring resting and task-related cerebral blood flow with ASL following an acute bout of exercise, which will be important for studies examining effects of acute exercise on fMRI activation (91). In addition, we know of only one study (10) that has used ASL to examine effects of chronic exercise exposure, which suggested increased hippocampal blood flow following an aerobic exercise program. Given the increasing reports of effects of chronic exercise on fMRI activation, this is an important gap to fill. Other cross-sectional research has used DTI to show preliminary evidence for an association between aerobic fitness and white matter integrity in the uncinate fasciculus (connecting ventral frontal and temporal lobes) and cingulum bundle (transversing the midline between anterior and posterior areas) (68, 69). Finally, near-infrared spectroscopy is another technology that could be applied during exercise, making it another useful tool to compare effects of acute and chronic exercise on brain and cognition (81, 110). Overall, while these studies generally have relatively small sample sizes and have examined targeted age groups, they represent a starting point for future studies to expand on in both sample size and diversity, and in longitudinal designs.

Finally, it will be important for future research to try to integrate animal and human work. For example, more animal studies that incorporate a life span perspective could help characterize potential similarities and differences of neurobiological mechanisms for exercise effects on brain and cognition at different points in the developmental timeline. On the other hand, it will be important for more human studies to incorporate measures of neurobiological markers such as peripheral measures of BDNF and IGF-1 both during acute exercise and following chronic exercise exposure. More work of this nature will help build an understanding of how acute effects are similar to or different from chronic benefits on brain and cognition across the life span, ultimately furthering our understanding of the mechanisms for how different types of cumulated exercise behaviors affect the brain and cognition. In this spirit, future studies with humans may also gain valuable insight from animal models about optimal methods for combining interventions based on different exercise types and/or exercise and cognitive training programs or diets. For example, a study by Fabel and colleagues (37) supports the idea that the functional significance of hippocampal neurogenesis resulting from aerobic exercise is further promoted if followed by environmental enrichment or cognitive training. This suggests that while aerobic exercise would be a good starting point for intervention programs, beneficial effects for brain and cognition may be further enhanced if followed by the addition of other activity types, such as resistance training, cognitive training, or some combination thereof.

Thus, while all exercise might not be painless or provide the “easy fix” to enhance brain and cognition across the life span, there is ample evidence to support it as one of the most effective means available to improve mental and physical health, without the side effects of many pharmacological treatments. In this review we highlighted some of the best evidence in support of exercise benefits for nonpathological populations, but also pointed out important areas for future research to advance the field. It is our hope that this will encourage greater diversity of approaches and methodologies, applied to a larger diversity of populations, in the field of exercise neuroscience. Such advancements promise to improve translation of positive findings in the research laboratory to improved quality of life from childhood to late life.


Preparation for this manuscript was supported by funding from the National Institute on Aging at the National Institutes of Health (Grant Numbers 05-R370-AG025667, RO1-AG25032) for private investigator A. Kramer. T. Liu-Ambrose is a Canadian Institute Health Research New Investigator, and Michael Smith is a Foundation for Health Research Scholar.


No conflicts of interest, financial or otherwise, are declared by the authors.


1. Aberg MAI, Pedersen NL, Torén K, Svartengren M, Bäckstrand B, Johnsson T, Cooper-Kuhn CM, Aberg ND, Nilsson M, Kuhn HG. Cardiovascular fitness is associated with cognition in young adulthood. Proc Natl Acad Sci USA 106: 20906–20911, 2009 [PMC free article] [PubMed]
2. Adlard PA, Perreau VM, Cotman CW. The exercise-induced expression of BDNF within the hippocampus varies across life-span. Neurobiol Aging 26: 511–520, 2005 [PubMed]
3. Aisen PS, Schneider LS, Sano M, Diaz-Arrastia R, van Dyck CH, Weiner MF, Bottiglieri T, Jin S, Stokes KT, Thomas RG, Thal LJ, Study ADC. High-dose B vitamin supplementation and cognitive decline in Alzheimer disease: a randomized controlled trial. JAMA 300: 1774–1783, 2008 [PMC free article] [PubMed]
4. Black JE, Isaacs KR, Anderson BJ, Alcantara AA, Greenough WT. Learning causes synaptogenesis, whereas motor activity causes angiogenesis, in cerebellar cortex of adult rats. Proc Natl Acad Sci USA 87: 5568–5572, 1990 [PMC free article] [PubMed]
5. Blomstrand E, Perret D, Parry-Billings M, Newsholme EA. Effect of sustained exercise on plasma amino acid concentrations on 5-hydroxytryptamine metabolism in six different brain regions in the rat. Acta Physiol Scand 136: 473–481, 1989 [PubMed]
6. Booth FW, Laye MJ. The future: genes, physical activity and health. Acta Physiol (Oxf) 199: 549–556, 2010 [PubMed]
7. Borst SE. Interventions for sarcopenia and muscle weakness in older people. Age Ageing 33: 548–555, 2004 [PubMed]
8. Botvinick MM, Braver TS, Barch DM, Carter CS, Cohen JD. Conflict monitoring and cognitive control. Psychol Rev 108: 624–652, 2001 [PubMed]
9. Buck SM, Hillman CH, Castelli DM. The relation of aerobic fitness to stroop task performance in preadolescent children. Med Sci Sports Exercise 40: 166–172, 2008 [PubMed]
10. Burdette JH, Laurienti PJ, Espeland MA, Morgan A, Telesford Q, Vechlekar CD, Hayasaka S, Jennings JM, Katula JA, Kraft RA, Rejeski WJ. Using network science to evaluate exercise-associated brain changes in older adults. Front Aging Neurosci 2: 23, 2010 [PMC free article] [PubMed]
11. Busse AL, Filho WJ, Magaldi RM, Coelho VA, Melo AC, Betoni RA, Santarem JM. Effects of resistance training exercise on cognitive performance in elderly individuals with memory impairment: results of a controlled trial. Einstein 6: 402–407, 2008
12. Carro E, Trejo JL, Busiguina S, Torres-Aleman I. Circulating insulin-like growth factor I mediates the protective effects of physical exercise against brain insults of different etiology and anatomy. J Neurosci 21: 5678–5684, 2001 [PubMed]
13. Casey BJ, Tottenham N, Liston C, Durston S. Imaging the developing brain: what have we learned about cognitive development? Trends Cognitive Sci 9: 104–110, 2005 [PubMed]
14. Cassilhas RC, Viana VAR, Grassmann V, Santos RT, Santos RF, Tufik S, Mello MT. The impact of resistance exercise on the cognitive function of the elderly. Med Sci Sports Exercise 39: 1401–1407, 2007 [PubMed]
15. Castelli DM, Hillman CH, Buck SM, Erwin HE. Physical fitness and academic achievement in third- and fifth-grade students. J Sport Exercise Psychol 29: 239–252, 2007 [PubMed]
16. Chaddock L, Erickson K, Prakash R, Vanpatter M, Voss M, Pontifex M, Raine L, Hillman C, Kramer A. Basal ganglia volume is associated with aerobic fitness in preadolescent children. Dev Neurosci 32: 249–256, 2010 [PMC free article] [PubMed]
17. Chaddock L, Erickson KI, Prakash RS, Kim JS, Voss MW, Vanpatter M, Pontifex MB, Raine LB, Konkel A, Hillman CH, Cohen NJ, Kramer AF. A neuroimaging investigation of the association between aerobic fitness, hippocampal volume, and memory performance in preadolescent children. Brain Res 1358: 172–183, 2010 [PMC free article] [PubMed]
18. Chaddock L, Hillman CH, Buck SM, Cohen NJ. Aerobic fitness and executive control of relational memory in preadolescent children. Med Sci Sports Exerc 43: 344–329, 2010 [PubMed]
19. Chomitz VR, Slining MM, McGowan RJ, Mitchell SE, Dawson GF, Hacker KA. Is there a relationship between physical fitness and academic achievement? Positive results from public school children in the northeastern. US J Sch Health 79: 30–37, 2009 [PubMed]
20. Clark PJ, Brzezinska WJ, Thomas MW, Ryzhenko NA, Toshkov SA, Rhodes JS. Intact neurogenesis is required for benefits of exercise on spatial memory but not motor performance or contextual fear conditioning in C57BL/6J mice. Neuroscience 155: 1048–1058, 2008 [PubMed]
21. Colcombe S, Erickson K, Scalf P, Kim J, Prakash R, Mcauley E, Elavsky S, Marquez D, Hu L, Kramer A. Aerobic exercise training increases brain volume in aging humans. J Gerontol A Biol Med Sci 61: 1166, 2006 [PubMed]
22. Colcombe SJ, Kramer AF. Fitness effects on the cognitive function of older adults: a meta-analytic study. Psychol Sci 14: 125–130, 2003 [PubMed]
23. Colcombe SJ, Kramer AF, Erickson KI, Scalf P, McAuley E, Cohen NJ, Webb A, Jerome GJ, Marquez DX, Elavsky S. Cardiovascular fitness, cortical plasticity, aging. Proc Natl Acad Sci USA 101: 3316–3321, 2004 [PMC free article] [PubMed]
24. Cotman CW, Berchtold NC, Christie LA. Exercise builds brain health: key roles of growth factor cascades and inflammation. Trends Neurosci 30: 464–472, 2007 [PubMed]
25. Creer DJ, Romberg C, Saksida LM, van Praag H, Bussey TJ. Running enhances spatial pattern separation in mice. Proc Natl Acad Sci USA 107: 2367–2372, 2010 [PMC free article] [PubMed]
26. Davidson MC, Amso D, Anderson LC, Diamond A. Development of cognitive control and executive functions from 4 to 13 years: evidence from manipulations of memory, inhibition, and task switching. Neuropsychologia 44: 2037–2078, 2006 [PMC free article] [PubMed]
27. Davis CL, Tomporowski PD, McDowell JE, Austin BP, Miller PH, Yanasak NE, Allison JD, Naglieri JA. Exercise improves executive function and achievement and alters brain activation in overweight children: a randomized, controlled trial. Health Psychol 30: 91–98, 2011 [PMC free article] [PubMed]
28. Davis JC, Marra CA, Beattie BL, Robertson MC, Najafzadeh M, Graf P, Nagamatsu LS, Liu-Ambrose T. Sustained cognitive and economic benefits of resistance training among community-dwelling senior women: a 1-year follow-up study of the Brain Power study. Arch Intern Med 170: 2036–2038, 2010 [PubMed]
29. DHHS Physical Activity Guidelines Advisory Committee Report. Washington, DC: US Department of Health and Human Services, edited by Services DoHaH, 2008
30. Ding Q, Vaynman S, Akhavan M, Ying Z, Gomez-Pinilla F. Insulin-like growth factor I interfaces with brain-derived neurotrophic factor-mediated synaptic plasticity to modulate aspects of exercise-induced cognitive function Neuroscience 140: 823–833, 2006 [PubMed]
31. Dumurgier J, Elbaz A, Ducimetière P, Tavernier B, Alpérovitch A, Tzourio C. Slow walking speed and cardiovascular death in well functioning older adults: prospective cohort study. BMJ 339: b4460, 2009 [PMC free article] [PubMed]
32. Dustman R, Ruhling R, Russell E, Shearer DE, Bonekat HW, Shigeoka JW, Wood JS, Bradford DC. Aerobic exercise training and improved neuropsychological function of older individuals. Neurobiol Aging 5: 35–42, 1984 [PubMed]
33. Erickson KI, Voss MW, Prakash RS, Bsak C, Szabo A, Chaddock L, Kim JS, Heo S, Alves H, White SM, Wojcicki TR, Mailey E, Vieira VJ, Martin SA, Pence BD, Woods JA, McAuley E, Kramer AF. Exercise training increases size of hippocampus and improves memory. Proc Natl Acad Sci USA 108: 3017–3022, 2011 [PMC free article] [PubMed]
35. Etnier J, Nowell P, Landers D, Sibley B. A meta-regression to examine the relationship between aerobic fitness and cognitive performance. Brain Res Rev 52: 119–130, 2006 [PubMed]
36. Fabel K, Fabel K, Tam B, Kaufer D, Baiker A, Simmons N, Kuo CJ, Palmer TD. VEGF is necessary for exercise-induced adult hippocampal neurogenesis. Eur J Neurosci 18: 2803–2812, 2003 [PubMed]
37. Fabel K, Wolf SA, Ehninger D, Babu H, Leal-Galicia P, Kempermann G. Additive effects of physical exercise and environmental enrichment on adult hippocampal neurogenesis in mice. Front Neurosci 10: 3: 50, 2009 [PMC free article] [PubMed]
38. Farmer J, Zhao X, Van Praag H, Wodtke K, Gage FH, Christie BR. Effects of voluntary exercise on synaptic plasticity and gene expression in the dentate gyrus of adult male Sprague-Dawley rats in vivo. Neuroscience 124: 71–79, 2004 [PubMed]
39. Ferris LT, Williams JS, Shen CL. The effect of acute exercise on serum brain-derived neurotrophic factor levels and cognitive function. Med Sci Sports Exerc 39: 728–734, 2007 [PubMed]
40. Fordyce DE, Farrar RP. Enhancement of spatial learning in F344 rats by physical activity and related learning-associated alterations in hippocampal and cortical cholinergic functioning. Behav Brain Res 46: 123–133, 1991 [PubMed]
41. Garza AA, Ha TG, Garcia C, Chen MJ, Russo-Neustadt AA. Exercise, antidepressant treatment, and BDNF mRNA expression in the aging brain. Pharmacol Biochem Behav 77: 209–220, 2004 [PubMed]
42. Gómez-Pinilla F, Dao L, So V. Physical exercise induces FGF-2 and its mRNA in the hippocampus. Brain Res 764: 1–8, 1997 [PubMed]
43. Gomez-Pinilla F, Vaynman S, Ying Z. Brain-derived neurotrophic factor functions as a metabotrophin to mediate the effects of exercise on cognition. Eur J Neurosci 28: 2278–2287, 2008 [PMC free article] [PubMed]
44. Griesbach GS, Hovda DA, Gomez-Pinilla F. Exercise-induced improvement in cognitive performance after traumatic brain injury in rats is dependent on BDNF activation. Brain Res 1288: 105–115, 2009 [PMC free article] [PubMed]
45. Hardy SE, Perera S, Roumani YF, Chandler JM, Studenski SA. Improvement in usual gait speed predicts better survival in older adults. J Am Geriatr Soc 55: 1727–1734, 2007 [PubMed]
46. Hertzog C, Kramer AF, Wilson RS, Lindenberger U. Enrichment effects on adult cognitive development: Can the functional capacity of older adults be preserved and enhanced? Psychol Sci Public Interest 9: 1–65, 2009
47. Hillman CH, Buck SM, Themanson JR, Pontifex MB, Castelli DM. Aerobic fitness and cognitive development: Event-related brain potential and task performance indices of executive control in preadolescent children. Dev Psychol 45: 114–129, 2009 [PubMed]
48. Hillman CH, Castelli DM, Buck SM. Aerobic fitness and neurocognitive function in healthy preadolescent children. Med Sci Sports Exerc 37: 1967–1974, 2005 [PubMed]
49. Hunsberger JG, Newton SS, Bennett AH, Duman CH, Russell DS, Salton SR, Duman RS. Antidepressant actions of the exercise-regulated gene VGF. Nat Med 13: 1476–1482, 2007 [PubMed]
50. Isaacs KR, Anderson BJ, Alcantara AA, Black JE, Greenough WT. Exercise and the brain: angiogenesis in the adult rat cerebellum after vigorous physical activity and motor skill learning. J Cereb Blood Flow Metab 12: 110–119, 1992 [PubMed]
51. Kamijo K, O'Leary KC, Pontifex MB, Themanson JR, Hillman CH. The relation of aerobic fitness to neuroelectric indices of cognitive and motor task preparation. Psychophysiology 47: 814–821, 2010 [PMC free article] [PubMed]
52. Kelley GA. Exercise and regional bone mineral density in postmenopausal women: a meta-analytic review of randomized trials. Am J Phys Med Rehabil 77: 76–87, 1998 [PubMed]
53. Kerr AL, Steuer EL, Pochtarev V, Swain RA. Angiogenesis but not neurogenesis is critical for normal learning and memory acquisition. Neuroscience 171: 214–226, 2010 [PubMed]
54. Kim YP, Kim H, Shin MS, Chang HK, Jang MH, Shin MC, Lee SJ, Lee HH, Yoon JH, Jeong IG, Kim CJ. Age-dependence of the effect of treadmill exercise on cell proliferation in the dentate gyrus of rats. Neurosci Lett 355: 152–154, 2004 [PubMed]
55. Kimura K, Obuchi S, Arai T, Nagasawa H, Shiba Y, Watanabe S, Kojima M. The influence of short-term strength training on health-related quality of life and executive cognitive function. J Physiol Anthropol 29: 95–101, 2010 [PubMed]
56. Kleim JA, Cooper NR, VandenBerg PM. Exercise induces angiogenesis but does not alter movement representations within rat motor cortex. Brain Res 934: 1–6, 2002 [PubMed]
57. Kramer AF, Hahn S, Cohen NJ, Banich MT, McAuley E, Harrison CR, Chason J, Vakil E, Bardell L, Boileau RA, Colcombe A. Ageing, fitness and neurocognitive function. Nature 400: 418–419, 1999 [PubMed]
58. Laaksonen DE, Lindström J, Lakka TA, Eriksson JG, Niskanen L, Wikström K, Aunola S, Keinänen-Kiukaanniemi S, Laakso M, Valle TT, Ilanne-Parikka P, Louheranta A, Hämäläinen H, Rastas M, Salminen V, Cepaitis Z, Hakumäki M, Kaikkonen H, Härkönen P, Sundvall J, Tuomilehto J, Uusitupa M.; and study Fdp Physical activity in the prevention of type 2 diabetes: the Finnish diabetes prevention study. Diabetes 54: 158–165, 2005 [PubMed]
59. Lachman ME, Neupert SD, Bertrand R, Jette AM. The effects of strength training on memory in older adults. J Aging Phys Act 14: 59–73, 2006 [PubMed]
60. Larson EB, Wang L, Bowen JD, McCormick WC, Teri L, Crane P, Kukull W. Exercise is associated with reduced risk for incident dementia among persons 65 years of age and older. Ann Intern Med 144: 73–81, 2006 [PubMed]
61. Layne JE, Nelson ME. The effects of progressive resistance training on bone density: a review. Med Sci Sports Exerc 31: 25–30, 1999 [PubMed]
62. Lee IM. Physical activity and cancer prevention–data from epidemiologic studies. Med Sci Sports Exerc 35: 1823–1827, 2003 [PubMed]
63. Levinger I, Goodman C, Matthews V, Hare DL, Jerums G, Garnham A, Selig S. BDNF, metabolic risk factors, and resistance training in middle-aged individuals. Med Sci Sports Exerc 40: 535–541, 2008 [PubMed]
64. Lindsay J, Laurin D, Verreault R, Hébert R, Helliwell B, Hill GB, McDowell I. Risk factors for Alzheimer's disease: a prospective analysis from the Canadian Study of Health and Aging. Am J Epidemiol 156: 445–453, 2002 [PubMed]
65. Liu-Ambrose T, Nagamatsu LS, Graf P, Beattie BL, Ashe MC, Handy TC. Resistance training and executive functions: a 12-month randomized controlled trial. Arch Intern Med 170: 170–178, 2010 [PMC free article] [PubMed]
66. Lopez-Lopez C, LeRoith D, Torres-Aleman I. Insulin-like growth factor I is required for vessel remodeling in the adult brain. Proc Natl Acad Sci USA 101: 9833–9838, 2004 [PMC free article] [PubMed]
67. Markowska AL, Mooney M, Sonntag WE. Insulin-like growth factor-1 ameliorates age-related behavioral deficits. Neuroscience 87: 559–569, 1998 [PubMed]
68. Marks B, Katz L, Styner M, Smith J. Aerobic fitness and obesity: relationship to cerebral white matter integrity in the brain of active and sedentary older adults. Br J Sports Med 2010. June 17 [Epub ahead of print] [PubMed]
69. Marks BL, Madden DJ, Bucur B, Provenzale JM, White LE, Cabeza R, Huettel SA. Role of aerobic fitness and aging on cerebral white matter integrity. Ann NY Acad Sci 1097: 171–174, 2007 [PubMed]
70. Molteni R, Ying Z, Gómez-Pinilla F. Differential effects of acute and chronic exercise on plasticity-related genes in the rat hippocampus revealed by microarray. Eur J Neurosci 16: 1107–1116, 2002 [PubMed]
71. Murer MG, Yan Q, Raisman-Vozari R. Brain-derived neurotrophic factor in the control human brain and in Alzheimer's disease and Parkinson's disease. Prog Neurobiol 63: 71–124, 2001 [PubMed]
72. Neeper SA, Gómez-Pinilla F, Choi J, Cotman C. Exercise and brain neurotrophins. Nature 373: 109, 1995 [PubMed]
73. Neeper SA, Gómez-Pinilla F, Choi J, Cotman CW. Physical activity increases mRNA for brain-derived neurotrophic factor and nerve growth factor in rat brain. Brain Res 726: 49–56, 1996 [PubMed]
74. Pereira AC, Huddleston DE, Brickman AM, Sosunov AA, Hen R, McKhann GM, Sloan R, Gage FH, Brown TR, Small SA. An in vivo correlate of exercise-induced neurogenesis in the adult dentate gyrus. Proc Natl Acad Sci USA 104: 5638–5643, 2007 [PMC free article] [PubMed]
75. Perrig-Chiello P, Perrig WJ, Ehrsam R, Staehelin HB, Krings F. The effects of resistance training on well-being and memory in elderly volunteers. Age Ageing 27: 469–475, 1998 [PubMed]
76. Polich J. Updating P300: an integrative theory of P3a and P3b. Clin Neurophysiol 118: 2128–2148, 2007 [PMC free article] [PubMed]
77. Pontifex MB, Raine LB, Johnson CR, Chaddock L, Voss MW, Cohen NJ, Kramer AF, Hillman CH. Cardiorespiratory fitness and the flexible modulation of cognitive control in preadolescent children. J Cogn Neurosci 23: 1332–1345, 2011 [PubMed]
78. Poulton NP, Muir GD. Treadmill training ameliorates dopamine loss but not behavioral deficits in hemi-parkinsonian rats. Exp Neurol 193: 181–197, 2005 [PubMed]
79. Rasmussen P, Brassard P, Adser H, Pedersen MV, Leick L, Hart E, Secher NH, Pedersen BK, Pilegaard H. Evidence for a release of brain-derived neurotrophic factor from the brain during exercise. Exp Physiol 94: 1062–1069, 2009 [PubMed]
80. Richards M, Hardy R, Wadsworth MEJ. Does active leisure protect cognition? Evidence from a national birth cohort. Soc Sci Med 56: 785–792, 2003 [PubMed]
81. Rooks CR, Thom NJ, McCully KK, Dishman RK. Effects of incremental exercise on cerebral oxygenation measured by near-infrared spectroscopy: a systematic review. Prog Neurobiol 92: 134–150, 2010 [PubMed]
82. Rosano C, Newman AB, Katz R, Hirsch CH, Kuller LH. Association between lower digit symbol substitution test score and slower gait and greater risk of mortality and of developing incident disability in well-functioning older adults. J Am Geriatr Soc 56: 1618–1625, 2008 [PMC free article] [PubMed]
83. Rovio S, Spulber G, Nieminen LJ, Niskanen E, Winblad B, Tuomilehto J, Nissinen A, Soininen H, Kivipelto M. The effect of midlife physical activity on structural brain changes in the elderly. Neurobiol Aging 31: 1927–1936, 2010 [PubMed]
84. Schafer JH, Glass TA, Bolla KI, Mintz M, Jedlicka AE, Schwartz BS. Homocysteine and cognitive function in a population-based study of older adults. J Am Geriatr Soc 53: 381–388, 2005 [PubMed]
85. Scisco JL, Leynes PA, Kang J. Cardiovascular fitness and executive control during task-switching: an ERP study. Int J Psychophysiol 69: 52–60, 2008 [PubMed]
86. Seifert T, Brassard P, Wissenberg M, Rasmussen P, Nordby P, Stallknecht B, Adser H, Jakobsen AH, Pilegaard H, Nielsen HB, Secher NH. Endurance training enhances BDNF release from the human brain. Am J Physiol Regul Integr Comp Physiol 298: R372–R377, 2010 [PubMed]
87. Seshadri S, Beiser A, Selhub J, Jacques PF, Rosenberg IH, D'Agostino RB, Wilson PWF, Wolf PA. Plasma homocysteine as a risk factor for dementia and Alzheimer's disease. N Engl J Med 346: 476–483, 2002 [PubMed]
88. Shay KA, Roth DL. Association between aerobic fitness and visuospatial performance in healthy older adults. Psychol Aging 7: 15–24, 1992 [PubMed]
89. Shiroma EJ, Lee IM. Physical activity and cardiovascular health: lessons learned from epidemiological studies across age, gender, and race/ethnicity. Circulation 122: 743–752, 2010 [PubMed]
90. Sibley B, Etnier J. The relationship between physical activity and cognition in children: A meta-analysis. Pediatr Exerc Sci 15: 243–256, 2003
91. Smith JC, Paulson ES, Cook DB, Verber MD, Tian Q. Detecting changes in human cerebral blood flow after acute exercise using arterial spin labeling: implications for fMRI. J Neurosci Methods 191: 258–262, 2010 [PubMed]
92. Stroth S, Hille K, Spitzer M, Reinhardt R. Aerobic endurance exercise benefits memory and affect in young adults. Neuropsychol Rehabil 19: 223–243, 2009 [PubMed]
93. Stroth S, Reinhardt RK, Thöne J, Hille K, Schneider M, Härtel S, Weidemann W, Bös K, Spitzer M. Impact of aerobic exercise training on cognitive functions and affect associated to the COMT polymorphism in young adults. Neurobiol Learning Memory 94: 364–372, 2010 [PubMed]
94. Swain RA, Harris AB, Wiener EC, Dutka MV, Morris HD, Theien BE, Konda S, Engberg K, Lauterbur PC, Greenough WT. Prolonged exercise induces angiogenesis and increases cerebral blood volume in primary motor cortex of the rat. Neuroscience 117: 1037–1046, 2003 [PubMed]
95. Themanson JR, Hillman CH. Cardiorespiratory fitness and acute aerobic exercise effects on neuroelectric and behavioral measures of action monitoring. Neuroscience 141: 757–767, 2006 [PubMed]
96. Themanson JR, Pontifex MB, Hillman CH. Fitness and action monitoring: evidence for improved cognitive flexibility in young adults. Neuroscience 157: 319–328, 2008 [PMC free article] [PubMed]
97. Tomporowski PD, Davis CL, Miller PH, Naglieri JA. Exercise and children's intelligence, cognition, and academic achievement. Ed Psychol Rev 20: 111–131, 2008 [PMC free article] [PubMed]
98. Trejo JL, Carro E, Torres-Aleman I. Circulating insulin-like growth factor I mediates exercise-induced increases in the number of new neurons in the adult hippocampus. J Neurosci 21: 1628–1634, 2001 [PubMed]
99. Troiano RP, Berrigan D, Dodd KW, Mâsse LC, Tilert T, McDowell M. Physical activity in the United States measured by accelerometer. Med Sci Sports Exerc 40: 181–188, 2008 [PubMed]
100. Tsutsumi T, Don BM, Zaichkowsky LD, Delizonna LL. Physical fitness and psychological benefits of strength training in community dwelling older adults. Appl Human Sci 16: 257–266, 1997 [PubMed]
101. Van Hoomissen JD, Holmes PV, Zellner AS, Poudevigne A, Dishman RK. Effects of beta-adrenoreceptor blockade during chronic exercise on contextual fear conditioning and mRNA for galanin and brain-derived neurotrophic factor. Behav Neurosci 118: 1378–1390, 2004 [PubMed]
102. Van Praag H, Christie BR, Sejnowski TJ, Gage FH. Running enhances neurogenesis, learning, and long-term potentiation in mice. Proc Natl Acad Sci USA 96: 13427–13431, 1999 [PMC free article] [PubMed]
103. Van Praag H, Kempermann G, Gage F. Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus. Nat Neurosci 2: 266–270, 1999 [PubMed]
104. Van Praag H, Shubert T, Zhao C, Gage FH. Exercise enhances learning and hippocampal neurogenesis in aged mice. J Neurosci 25: 8680–8685, 2005 [PMC free article] [PubMed]
105. Vaynman S, Ying Z, Gomez-Pinilla F. Hippocampal BDNF mediates the efficacy of exercise on synaptic plasticity and cognition. Eur J Neurosci 20: 2580–2590, 2004 [PubMed]
106. Vermeer SE, Van Dijk EJ, Koudstaal PJ, Oudkerk M, Hofman A, Clarke R, Breteler MMB. Homocysteine, silent brain infarcts, and white matter lesions: The Rotterdam Scan Study. Ann Neurol 51: 285–289, 2002 [PubMed]
107. Vincent KR, Braith RW, Bottiglieri T, Vincent HK, Lowenthal DT. Homocysteine and lipoprotein levels following resistance training in older adults. Prev Cardiol 6: 197–203, 2003 [PubMed]
108. Voss MW, Prakash RS, Erickson KI, Basak C, Chaddock L, Kim JS, Alves H, Heo S, Szabo A, White SM, Wojcicki TR, Mailey EL, Gothe N, Olson EA, McAuley E, Kramer AF. Plasticity of brain networks in a randomized intervention trial of exercise training in older adults. Front Aging Neurosci 2: 1–17, 2010 [PMC free article] [PubMed]
109. Yaffe K, Fiocco AJ, Lindquist K, Vittinghoff E, Simonsick EM, Newman AB, Satterfield S, Rosano C, Rubin SM, Ayonayon HN, Harris TB, Study HA. Predictors of maintaining cognitive function in older adults: the Health ABC study. Neurology 72: 2029–2035, 2009 [PMC free article] [PubMed]
110. Yanagisawa H, Dan I, Tsuzuki D, Kato M, Okamoto M, Kyutoku Y, Soya H. Acute moderate exercise elicits increased dorsolateral prefrontal activation and improves cognitive performance with Stroop test. NeuroImage 50: 1702–1710, 2010 [PubMed]
111. Zoladz JA, Pilc A, Majerczak J, Grandys M, Zapart-Bukowska J, Duda K. Endurance training increases plasma brain-derived neurotrophic factor concentration in young healthy men. J Physiol Pharmacol 59, Suppl 7: 119–132, 2008 [PubMed]

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