The influence of aerobic fitness on cerebral white matter integrity and cognitive function in older adults: results of a one-year exercise intervention.

Cerebral white matter (WM) degeneration occurs with increasing age and is associated with declining cognitive function. Research has shown that cardiorespiratory fitness and exercise are effective as protective, even restorative, agents against cognitive and neurobiological impairments in older adults. In this study, we investigated whether the beneficial impact of aerobic fitness would extend to WM integrity in the context of a one-year exercise intervention. Further, we examined the pattern of diffusivity changes to better understand the underlying biological mechanisms. Finally, we assessed whether training-induced changes in WM integrity would be associated with improvements in cognitive performance independent of aerobic fitness gains. Results showed that aerobic fitness training did not affect group-level change in WM integrity, executive function, or short-term memory, but that greater aerobic fitness derived from the walking program was associated with greater change in WM integrity in the frontal and temporal lobes, and greater improvement in short-term memory. Increases in WM integrity, however, were not associated with short-term memory improvement, independent of fitness improvements. Therefore, while not all findings are consistent with previous research, we provide novel evidence for correlated change in training-induced aerobic fitness, WM integrity, and cognition among healthy older adults.

Neurobiological markers of exercise-related brain plasticity in older adults.

The current study examined how a randomized one-year aerobic exercise program for healthy older adults would affect serum levels of brain-derived neurotrophic factor (BDNF), insulin-like growth factor type 1 (IGF-1), and vascular endothelial growth factor (VEGF) - putative markers of exercise-induced benefits on brain function. The study also examined whether (a) change in the concentration of these growth factors was associated with alterations in functional connectivity following exercise, and (b) the extent to which pre-intervention growth factor levels were associated with training-related changes in functional connectivity. In 65 participants (mean age=66.4), we found that although there were no group-level changes in growth factors as a function of the intervention, increased temporal lobe connectivity between the bilateral parahippocampus and the bilateral middle temporal gyrus was associated with increased BDNF, IGF-1, and VEGF for an aerobic walking group but not for a non-aerobic control group, and greater pre-intervention VEGF was associated with greater training-related increases in this functional connection. Results are consistent with animal models of exercise and the brain, but are the first to show in humans that exercise-induced increases in temporal lobe functional connectivity are associated with changes in growth factors and may be augmented by greater baseline VEGF.

Caudate Nucleus Volume Mediates the Link between Cardiorespiratory Fitness and Cognitive Flexibility in Older Adults.

The basal ganglia play a central role in regulating the response selection abilities that are critical for mental flexibility. In neocortical areas, higher cardiorespiratory fitness levels are associated with increased gray matter volume, and these volumetric differences mediate enhanced cognitive performance in a variety of tasks. Here we examine whether cardiorespiratory fitness correlates with the volume of the subcortical nuclei that make up the basal ganglia and whether this relationship predicts cognitive flexibility in older adults. Structural MRI was used to determine the volume of the basal ganglia nuclei in a group of older, neurologically healthy individuals (mean age 66 years, N = 179). Measures of cardiorespiratory fitness (VO(2max)), cognitive flexibility (task switching), and attentional control (flanker task) were also collected. Higher fitness levels were correlated with higher accuracy rates in the Task Switching paradigm. In addition, the volume of the caudate nucleus, putamen, and globus pallidus positively correlated with Task Switching accuracy. Nested regression modeling revealed that caudate nucleus volume was a significant mediator of the relationship between cardiorespiratory fitness, and task switching performance. These findings indicate that higher cardiorespiratory fitness predicts better cognitive flexibility in older adults through greater grey matter volume in the dorsal striatum.

Beyond vascularization: aerobic fitness is associated with N-acetylaspartate and working memory.

Aerobic exercise is a promising form of prevention for cognitive decline; however, little is known about the molecular mechanisms by which exercise and fitness impacts the human brain. Several studies have postulated that increased regional brain volume and function are associated with aerobic fitness because of increased vascularization rather than increased neural tissue per se. We tested this position by examining the relationship between cardiorespiratory fitness and N-acetylaspartate (NAA) levels in the right frontal cortex using magnetic resonance spectroscopy. NAA is a nervous system specific metabolite found predominantly in cell bodies of neurons. We reasoned that if aerobic fitness was predominantly influencing the vasculature of the brain, then NAA levels should not vary as a function of aerobic fitness. However, if aerobic fitness influences the number or viability of neurons, then higher aerobic fitness levels might be associated with greater concentrations of NAA. We examined NAA levels, aerobic fitness, and cognitive performance in 137 older adults without cognitive impairment. Consistent with the latter hypothesis, we found that higher aerobic fitness levels offset an age-related decline in NAA. Furthermore, NAA mediated an association between fitness and backward digit span performance, suggesting that neuronal viability as measured by NAA is important in understanding fitness-related cognitive enhancement. Since NAA is found exclusively in neural tissue, our results indicate that the effect of fitness on the human brain extends beyond vascularization; aerobic fitness is associated with neuronal viability in the frontal cortex of older adults.

Childhood aerobic fitness predicts cognitive performance one year later.

Aerobically fit children outperform less fit peers on cognitive control challenges that involve inhibition, cognitive flexibility, and working memory. The aim of this study was to determine whether, compared with less fit children, more fit 9- and 10-year-old pre-adolescents exhibit superior performance on a modified compatible and incompatible flanker task of cognitive control at the initial time of fitness testing and approximately one year later. We found that more fit children demonstrated increased flanker accuracy at both test sessions, coupled with a superior ability to flexibly allocate strategies during task conditions that required different amounts of cognitive control, relative to less fit children. More fit children also gained a speed benefit at follow-up testing. Structural MRI data were also collected to investigate the relationship between basal ganglia volume and task performance. Bilateral putamen volumes of the dorsal striatum and globus pallidus volumes predicted flanker performance at initial and follow-up testing one year later. The present findings suggest that childhood aerobic fitness and basal ganglia volumes relate to cognitive control at the time of fitness testing and may play a role in cognitive performance in the future. We hope that this research will encourage public health and educational changes that will promote a physically active lifestyle in children.

The association between aerobic fitness and executive function is mediated by prefrontal cortex volume.

Aging is marked by a decline in cognitive function, which is often preceded by losses in gray matter volume. Fortunately, higher cardiorespiratory fitness (CRF) levels are associated with an attenuation of age-related losses in gray matter volume and a reduced risk for cognitive impairment. Despite these links, we have only a rudimentary understanding of whether fitness-related increases in gray matter volume lead to elevated cognitive function. In this cross-sectional study, we examined whether the association between higher aerobic fitness levels and elevated executive function was mediated by greater gray matter volume in the prefrontal cortex (PFC). One hundred and forty-two older adults (mean age=66.6 years) completed structural magnetic resonance imaging (MRI) scans, CRF assessments, and performed Stroop and spatial working memory (SPWM) tasks. Gray matter volume was assessed using an optimized voxel-based morphometry approach. Consistent with our predictions, higher fitness levels were associated with: (a) better performance on both the Stroop and SPWM tasks, and (b) greater gray matter volume in several regions, including the dorsolateral PFC (DLPFC). Volume of the right inferior frontal gyrus and precentral gyrus mediated the relationship between CRF and Stroop interference while a non-overlapping set of regions bilaterally in the DLPFC mediated the association between CRF and SPWM accuracy. These results suggest that specific regions of the DLPFC differentially relate to inhibition and spatial working memory. Thus, fitness may influence cognitive function by reducing brain atrophy in targeted areas in healthy older adults.

A functional MRI investigation of the association between childhood aerobic fitness and neurocognitive control.

We used functional magnetic resonance imaging (fMRI) to examine brain activity of higher fit and lower fit children during early and late task blocks of a cognitive control flanker paradigm. For congruent trials, all children showed increased recruitment of frontal and parietal regions during the early block when the task was unfamiliar, followed by a decrease in activity in the later block. No within-group changes in congruent accuracy were reported across task blocks, despite a decline in performance across all participants, likely due to fatigue. During incongruent trials, only higher fit children maintained accuracy across blocks, coupled with increased prefrontal and parietal recruitment in the early task block and reduced activity in the later block. Lower fit children showed a decline in incongruent accuracy across blocks, and no changes in activation. We suggest that higher fit children are better at activating and adapting neural processes involved in cognitive control to meet and maintain task goals.

Role of childhood aerobic fitness in successful street crossing.

UNLABELLED: Increased aerobic fitness is associated with improved cognition, brain health, and academic achievement during preadolescence. PURPOSE: In this study, we extended these findings by examining the relationship between aerobic fitness and an everyday real-world task: street crossing. Because street crossing can be a dangerous multitask challenge and is a leading cause of injury in children, it is important to find ways to improve pedestrian safety. METHODS: A street intersection was modeled in a virtual environment, and higher-fit (n = 13, 7 boys) and lower-fit (n = 13, 5 boys) 8- to 10-yr-old children, as determined by V˙O(2max) testing, navigated trafficked roads by walking on a treadmill that was integrated with an immersive virtual world. Child pedestrians crossed the street while undistracted, listening to music, or conversing on a hands-free cellular phone. RESULTS: Cell phones impaired street crossing success rates compared with the undistracted or music conditions for all participants (P = 0.004), a result that supports previous research. However, individual differences in aerobic fitness influenced these patterns (fitness × condition interaction, P = 0.003). Higher-fit children maintained street crossing success rates across all three conditions (paired t-tests, all P > 0.4), whereas lower-fit children showed decreased success rates when on the phone, relative to the undistracted (P = 0.018) and music (P = 0.019) conditions. CONCLUSIONS: The results suggest that higher levels of childhood aerobic fitness may attenuate the impairment typically associated with multitasking during street crossing. It is possible that superior cognitive abilities of higher-fit children play a role in the performance differences during complex real-world tasks.

A review of the relation of aerobic fitness and physical activity to brain structure and function in children.

A growing number of schools have increasingly de-emphasized the importance of providing physical activity opportunities during the school day, despite emerging research that illustrates the deleterious relationship between low levels of aerobic fitness and neurocognition in children. Accordingly, a brief review of studies that link fitness-related differences in brain structure and brain function to cognitive abilities is provided herein. Overall, the extant literature suggests that childhood aerobic fitness is associated with higher levels of cognition and differences in regional brain structure and function. Indeed, it has recently been found that aerobic fitness level even predicts cognition over time. Given the paucity of work in this area, several avenues for future investigations are also highlighted.

Do athletes excel at everyday tasks?

PURPOSE: Cognitive enhancements are associated with sport training. We extended the sport-cognition literature by using a realistic street crossing task to examine the multitasking and processing speed abilities of collegiate athletes and nonathletes. METHODS: Pedestrians navigated trafficked roads by walking on a treadmill in a virtual world, a challenge that requires the quick and simultaneous processing of multiple streams of information. RESULTS: Athletes had higher street crossing success rates than nonathletes, as reflected by fewer collisions with moving vehicles. Athletes also showed faster processing speed on a computer-based test of simple reaction time, and shorter reaction times were associated with higher street crossing success rates. CONCLUSIONS: The results suggest that participation in athletics relates to superior street crossing multitasking abilities and that athlete and nonathlete differences in processing speed may underlie this difference. We suggest that cognitive skills trained in sport may transfer to performance on everyday fast-paced multitasking abilities.

Aerobic fitness and response variability in preadolescent children performing a cognitive control task.

OBJECTIVE: To investigate the relationship between aerobic fitness and cognitive variability in preadolescent children. METHOD: Forty-eight preadolescent children (25 males, 23 females, mean age = 10.1 years) were grouped into higher- and lower-fit groups according to their performance on a test of aerobic capacity (VO2max). Cognitive function was measured via behavioral responses to a modified flanker task. The distribution in reaction time was calculated within each participant to assess intraindividual variability of performance. Specifically, the standard deviation and coefficient variation of reaction time were used to represent cognitive variability. RESULTS: Preadolescent children, regardless of fitness, exhibited longer reaction time, increased response variability, and decreased response accuracy to incongruent compared to congruent trials. Further, higher-fit children were less variable in their response time and more accurate in their responses across conditions of the flanker task, while no group differences were observed for response speed. CONCLUSION: These findings suggest that fitness is associated with better cognitive performance during a task that varies cognitive control demands, and extends this area of research to suggest that intraindividual variability may be a useful measure to examine the relationship between fitness and cognition during preadolescence.

Exercise training increases size of hippocampus and improves memory.

The hippocampus shrinks in late adulthood, leading to impaired memory and increased risk for dementia. Hippocampal and medial temporal lobe volumes are larger in higher-fit adults, and physical activity training increases hippocampal perfusion, but the extent to which aerobic exercise training can modify hippocampal volume in late adulthood remains unknown. Here we show, in a randomized controlled trial with 120 older adults, that aerobic exercise training increases the size of the anterior hippocampus, leading to improvements in spatial memory. Exercise training increased hippocampal volume by 2%, effectively reversing age-related loss in volume by 1 to 2 y. We also demonstrate that increased hippocampal volume is associated with greater serum levels of BDNF, a mediator of neurogenesis in the dentate gyrus. Hippocampal volume declined in the control group, but higher preintervention fitness partially attenuated the decline, suggesting that fitness protects against volume loss. Caudate nucleus and thalamus volumes were unaffected by the intervention. These theoretically important findings indicate that aerobic exercise training is effective at reversing hippocampal volume loss in late adulthood, which is accompanied by improved memory function.

Cardiorespiratory fitness and attentional control in the aging brain.

A growing body of literature provides evidence for the prophylactic influence of cardiorespiratory fitness on cognitive decline in older adults. This study examined the association between cardiorespiratory fitness and recruitment of the neural circuits involved in an attentional control task in a group of healthy older adults. Employing a version of the Stroop task, we examined whether higher levels of cardiorespiratory fitness were associated with an increase in activation in cortical regions responsible for imposing attentional control along with an up-regulation of activity in sensory brain regions that process task-relevant representations. Higher fitness levels were associated with better behavioral performance and an increase in the recruitment of prefrontal and parietal cortices in the most challenging condition, thus providing evidence that cardiorespiratory fitness is associated with an increase in the recruitment of the anterior processing regions. There was a top-down modulation of extrastriate visual areas that process both task-relevant and task-irrelevant attributes relative to the baseline. However, fitness was not associated with differential activation in the posterior processing regions, suggesting that fitness enhances attentional function by primarily influencing the neural circuitry of anterior cortical regions. This study provides novel evidence of a differential association of fitness with anterior and posterior brain regions, shedding further light onto the neural changes accompanying cardiorespiratory fitness.

Cardiorespiratory fitness and the flexible modulation of cognitive control in preadolescent children.

The influence of cardiorespiratory fitness on the modulation of cognitive control was assessed in preadolescent children separated into higher- and lower-fit groups. Participants completed compatible and incompatible stimulus-response conditions of a modified flanker task, consisting of congruent and incongruent arrays, while ERPs and task performance were concurrently measured. Findings revealed decreased response accuracy for lower- relative to higher-fit participants with a selectively larger deficit in response to the incompatible stimulus-response condition, requiring the greatest amount of cognitive control. In contrast, higher-fit participants maintained response accuracy across stimulus-response compatibility conditions. Neuroelectric measures indicated that higher-fit, relative to lower-fit, participants exhibited global increases in P3 amplitude and shorter P3 latency, as well as greater modulation of P3 amplitude between the compatible and incompatible stimulus-response conditions. Similarly, higher-fit participants exhibited smaller error-related negativity (ERN) amplitudes in the compatible condition, and greater modulation of the ERN between the compatible and incompatible conditions, relative to lower-fit participants who exhibited large ERN amplitudes across both conditions. These findings suggest that lower-fit children may have more difficulty than higher-fit children in the flexible modulation of cognitive control processes to meet task demands.

Aerobic fitness and executive control of relational memory in preadolescent children.

PURPOSE: the neurocognitive benefits of an active lifestyle in childhood have public health and educational implications, especially as children in today's technological society are becoming increasingly overweight, unhealthy, and unfit. Human and animal studies show that aerobic exercise affects both prefrontal executive control and hippocampal function. This investigation attempts to bridge these research threads by using a cognitive task to examine the relationship between aerobic fitness and executive control of relational memory in preadolescent 9- and 10-yr-old children. METHOD: higher-fit and lower-fit children studied faces and houses under individual item (i.e., nonrelational) and relational encoding conditions, and the children were subsequently tested with recognition memory trials consisting of previously studied pairs and pairs of completely new items. With each subject participating in both item and relational encoding conditions, and with recognition test trials amenable to the use of both item and relational memory cues, this task afforded a challenge to the flexible use of memory, specifically in the use of appropriate encoding and retrieval strategies. Hence, the task provided a test of both executive control and memory processes. RESULTS: lower-fit children showed poorer recognition memory performance than higher-fit children, selectively in the relational encoding condition. No association between aerobic fitness and recognition performance was found for faces and houses studied as individual items (i.e., nonrelationally). CONCLUSIONS: the findings implicate childhood aerobic fitness as a factor in the ability to use effective encoding and retrieval executive control processes for relational memory material and, possibly, in the strategic engagement of prefrontal- and hippocampal-dependent systems.

Plasticity of brain networks in a randomized intervention trial of exercise training in older adults.

Research has shown the human brain is organized into separable functional networks during rest and varied states of cognition, and that aging is associated with specific network dysfunctions. The present study used functional magnetic resonance imaging (fMRI) to examine low-frequency (0.008 < f < 0.08 Hz) coherence of cognitively relevant and sensory brain networks in older adults who participated in a 1-year intervention trial, comparing the effects of aerobic and non-aerobic fitness training on brain function and cognition. Results showed that aerobic training improved the aging brain's resting functional efficiency in higher-level cognitive networks. One year of walking increased functional connectivity between aspects of the frontal, posterior, and temporal cortices within the Default Mode Network and a Frontal Executive Network, two brain networks central to brain dysfunction in aging. Length of training was also an important factor. Effects in favor of the walking group were observed only after 12 months of training, compared to non-significant trends after 6 months. A non-aerobic stretching and toning group also showed increased functional connectivity in the DMN after 6 months and in a Frontal Parietal Network after 12 months, possibly reflecting experience-dependent plasticity. Finally, we found that changes in functional connectivity were behaviorally relevant. Increased functional connectivity was associated with greater improvement in executive function. Therefore the study provides the first evidence for exercise-induced functional plasticity in large-scale brain systems in the aging brain, using functional connectivity techniques, and offers new insight into the role of aerobic fitness in attenuating age-related brain dysfunction.

Basal ganglia volume is associated with aerobic fitness in preadolescent children.

The present investigation is the first to explore the association between childhood aerobic fitness and basal ganglia structure and function. Rodent research has revealed that exercise influences the striatum by increasing dopamine signaling and angiogenesis. In children, higher aerobic fitness levels are associated with greater hippocampal volumes, superior performance on tasks of attentional and interference control, and elevated event-related brain potential indices of executive function. The present study used magnetic resonance imaging to investigate if higher-fit and lower-fit 9- and 10-year-old children exhibited differential volumes of other subcortical brain regions, specifically the basal ganglia involved in attentional control. The relationship between aerobic fitness, dorsal and ventral striatum volumes and performance on an attention and inhibition Eriksen flanker task was also examined. The results indicated that higher-fit children showed superior flanker task performance compared to lower-fit children. Higher-fit children also showed greater volumes of the dorsal striatum, and dorsal striatum volume was negatively associated with behavioral interference. The results support the claim that the dorsal striatum is involved in cognitive control and response resolution and that these cognitive processes vary as a function of aerobic fitness. No relationship was found between aerobic fitness, the volume of the ventral striatum and flanker performance. The findings suggest that increased childhood aerobic fitness is associated with greater dorsal striatal volumes and that this is related to enhanced cognitive control. Because children are becoming increasingly overweight, unhealthy and unfit, understanding the neurocognitive benefits of an active lifestyle during childhood has important public health and educational implications.

A neuroimaging investigation of the association between aerobic fitness, hippocampal volume, and memory performance in preadolescent children.

Because children are becoming overweight, unhealthy, and unfit, understanding the neurocognitive benefits of an active lifestyle in childhood has important public health and educational implications. Animal research has indicated that aerobic exercise is related to increased cell proliferation and survival in the hippocampus as well as enhanced hippocampal-dependent learning and memory. Recent evidence extends this relationship to elderly humans by suggesting that high aerobic fitness levels in older adults are associated with increased hippocampal volume and superior memory performance. The present study aimed to further extend the link between fitness, hippocampal volume, and memory to a sample of preadolescent children. To this end, magnetic resonance imaging was employed to investigate whether higher- and lower-fit 9- and 10-year-old children showed differences in hippocampal volume and if the differences were related to performance on an item and relational memory task. Relational but not item memory is primarily supported by the hippocampus. Consistent with predictions, higher-fit children showed greater bilateral hippocampal volumes and superior relational memory task performance compared to lower-fit children. Hippocampal volume was also positively associated with performance on the relational but not the item memory task. Furthermore, bilateral hippocampal volume was found to mediate the relationship between fitness level (VO(2) max) and relational memory. No relationship between aerobic fitness, nucleus accumbens volume, and memory was reported, which strengthens the hypothesized specific effect of fitness on the hippocampus. The findings are the first to indicate that aerobic fitness may relate to the structure and function of the preadolescent human brain.

Brain-derived neurotrophic factor is associated with age-related decline in hippocampal volume.

Hippocampal volume shrinks in late adulthood, but the neuromolecular factors that trigger hippocampal decay in aging humans remains a matter of speculation. In rodents, brain-derived neurotrophic factor (BDNF) promotes the growth and proliferation of cells in the hippocampus and is important in long-term potentiation and memory formation. In humans, circulating levels of BDNF decline with advancing age, and a genetic polymorphism for BDNF has been related to gray matter volume loss in old age. In this study, we tested whether age-related reductions in serum levels of BDNF would be related to shrinkage of the hippocampus and memory deficits in older adults. Hippocampal volume was acquired by automated segmentation of magnetic resonance images in 142 older adults without dementia. The caudate nucleus was also segmented and examined in relation to levels of serum BDNF. Spatial memory was tested using a paradigm in which memory load was parametrically increased. We found that increasing age was associated with smaller hippocampal volumes, reduced levels of serum BDNF, and poorer memory performance. Lower levels of BDNF were associated with smaller hippocampi and poorer memory, even when controlling for the variation related to age. In an exploratory mediation analysis, hippocampal volume mediated the age-related decline in spatial memory and BDNF mediated the age-related decline in hippocampal volume. Caudate nucleus volume was unrelated to BDNF levels or spatial memory performance. Our results identify serum BDNF as a significant factor related to hippocampal shrinkage and memory decline in late adulthood.

Functional connectivity: a source of variance in the association between cardiorespiratory fitness and cognition?

Over the next 20 years the number of Americans diagnosed with dementia is expected to more than double (CDC, 2007). It is, therefore, an important public health initiative to understand what factors contribute to the longevity of a healthy mind. Both default mode network (DMN) function and increased aerobic fitness have been associated with better cognitive performance and reduced incidence of Alzheimer's disease among older adults. Here we examine the association between aerobic fitness, functional connectivity in the DMN, and cognitive performance. Results showed significant age-related deficits in functional connectivity in both local and distributed DMN pathways. However, in a group of healthy elderly adults, almost half of the age-related disconnections showed increased functional connectivity as a function of aerobic fitness level. Finally, we examine the hypothesis that functional connectivity in the DMN is one source of variance in the relationship between aerobic fitness and cognition. Results demonstrate instances of both specific and global DMN connectivity mediating the relationship between fitness and cognition. We provide the first evidence for functional connectivity as a source of variance in the association between aerobic fitness and cognition, and discuss results in the context of neurobiological theories of cognitive aging and disease.