Neuroscience, Exercise, and Cognitive Function

In the fields of neuroscience and cognitive science, human cognition is broadly defined as a component of brain function that includes information processing, memory, attention, perception, language, and executive function related to decision making (DM) and the initiation or inhibition of behavior. In the context of sport and exercise psychology, researchers have been interested in the possible benefits of increased leisure-time physical activity (PA) and the performance of acute and chronic exercise on various aspects of cognitive function, from infants to older adults. The focus of this entry is human older adult cognitive function. The effects of exercise training and leisure-time PA on magnetic resonance imaging (MRI) derived measures of brain structure and function related to cognitive performance among healthy older adults and those who are at increased risk for cognitive decline and dementia are also discussed.

Acute and Chronic Exercise in Healthy Adults

The performance of a single session of exercise results in improved cognitive performance in healthy younger adults. However, the type, duration, and intensity of the exercise are important, as well as the timing of the cognitive performance during the exercise and after the exercise has ended. In addition, some types of cognitive function improve more than others. During exercise, impairments in cognitive function can occur for complex cognitive tasks, especially during exercise that also may be more cognitively demanding, for example, running compared to stationary cycling. However, evidence for cognitive improvement during exercise may occur for simple tasks that involve rapid DM or require a fast reaction time (RT), and in tasks that are very well learned and, thus, can be performed without much thought or planning. After exercise has ended, improvements in cognitive performance, especially tasks that involve information processing, memory encoding, and memory retrieval, occur over the first 15 minutes and then dissipate thereafter. It is presumed that the heightened physiological arousal during the recovery period contributes to these effects. It is unknown if these effects of acute exercise also occur in healthy older adults or those with cognitive impairments.

Exercise, Physical Activity, and Older Adult Cognition

Among healthy older adults, greater levels of cardiorespiratory fitness and periods of exercise training (other than acute bouts) are associated with better cognitive function. These effects are largest for cognitive tasks that involve information processing and executive control, such as attention and performance during a dual task, efficient switching between different types of tasks, DM, and response inhibition.

There is some evidence that beneficial effects of exercise on cognitive function are stronger in those who are at genetic risk for Alzheimer’s disease, the most common cause of dementia. Apolipoprotein E (APOE) allele status is related to risk for Alzheimer’s disease (as well as cardiovascular disease) through its handling of cholesterol. Possession of one or two copies of the apolipoprotein-epsilon4 (APOE-e4) allele increases the risk of future cognitive decline up to 10 times compared to noncarriers of the APOE-e4 allele. However, engaging in moderate levels of leisure time PA substantially reduces the risk of future cognitive decline in APOE-e4 allele carriers, equal to the risk for noncarriers (the other variants being the most common e3 allele, and the protective and less common e2 allele).

Very little information exists regarding whether these beneficial effects extend to those with existing cognitive impairment. Individuals diagnosed with a very early stage of Alzheimer’s disease, termed mild cognitive impairment, may benefit from exercise training in their ability to perform a semantic fluency task on a day they did not exercise (e.g., naming as many animals or fruits as possible in 30 seconds) but not in tasks that involve episodic memory (e.g., learning a list of words and then being able to later, after doing other tasks, recall that list without any reminders). However, these effects have not been replicated or shown in large samples.

Magnetic Resonance Imaging to Measure Brain Function and Brain Structure

MRI is a tool that can be used in research to assess brain function and brain structure. There are multiple modalities of MRI that can be used (termed multimodal MR imaging) to assess differences between groups of individuals or the effects of interventions, such as exercise, on brain function. Functional magnetic resonance imaging (fMRI) is the most commonly used modality and depends on the blood-oxygen-level-dependent (BOLD) signal—derived from differences in oxygenated and deoxygenated hemoglobin presumed to reflect oxidative metabolism in nerve cells. The BOLD signal is an indirect, but validated, estimate of relative neuronal activation. The absolute rate of cerebral blood flow can be measured using a MRI technique called arterial spin labeling, and using radioactive contrast agents (e.g., gadolinium) cerebral blood volume can be estimated. Structural information about the brain, such as the volume of gray matter, white matter, and cerebrospinal fluid compartments of the cerebrum, can also be obtained using MRI. The structural integrity of brain white matter fiber tracts can be measured using a MRI technique called diffusion tensor imaging (also diffusion-weighted imaging), which assesses the diffusion characteristics of water molecules, which in a healthy person are constrained to diffuse along the boundaries of the intact myelinated white matter fiber bundle. Finally, MR spectroscopy can be used to measure the concentrations of certain metabolites or markers of neurotransmitter function in a single voxel (small three-dimensional cubes of brain tissue). The use of MRI in the context of sport and exercise psychology is appealing; however, caution is warranted as very little is known about the physiological effects of exercise on fundamental MRI signals that may occur independently from, but could appear as, alterations in neuronal firing or cerebral blood flow.

Effects of Physical Activity and Exercise on Multimodal Magnetic Resonance Imaging Outcomes

After robust growth in synaptic connections and brain volume during maturational development, the volume of the brain gradually decreases from roughly the age of 30 years until death. This decline in brain volume contributes to normal age-related cognitive decline, but brain atrophy is accelerated in neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease. There is accumulating evidence that modifiable lifestyle behaviors, such as PA, may help to preserve brain tissue and promote a neural or cognitive reserve, and perhaps the maintenance of cognitive abilities, into old age.

Using MRI to examine the structural volume of the brain, several studies have demonstrated the benefits of PA and cardiorespiratory fitness as a method to preserve brain volume. The greatest effects of exercise on brain volume have been shown in the hippocampus, a medial temporal lobe brain region critical to all learning and memory processes; a region that is an early first target of Alzheimer’s disease neuropathology. People who self-report being more physically active, as well as people who possess greater cardiorespiratory fitness, tend to have greater brain volume in several additional brain regions, including the parietal, frontal, prefrontal, and subgenual cortices. Importantly, exercise training may result in an increase in the volume of the hippocampus in healthy older adults. This exercise training effect appears to be stronger in the anterior portion of the hippocampus, which is known to show more severe atrophy in Alzheimer’s disease. Among healthy, cognitively intact, older adults who are at increased genetic risk for Alzheimer’s disease, greater levels of self-reported PA reduces the risk of future cognitive decline and helps to preserve (but not increase) hippocampal volume over 18 months. However, it is not known if leisure time PA will lead to reduced rates of Alzheimer’s disease diagnosis. In patients previously diagnosed with early stage Alzheimer’s disease, greater cardiorespiratory fitness is associated with greater brain volume. However, it is currently unknown if exercise training will help preserve brain tissue volume over time in older adults diagnosed with Alzheimer’s disease, or if these effects translate into a slowing of disease progression.

Evidence from fMRI experiments suggests that PA and cardiorespiratory fitness are associated with enhanced patterns of neural activation during executive control and semantic memory tasks. For example, in one study, healthy older adults completed a flanker task during the scan, which consisted of indicating the direction a central target arrow was pointed among flanking arrows that were congruent (>>>>>) or incongruent (>><>>) with the direction of the target. This task involves attention and visual information processing as well as inhibition of motor responses during the more difficult incongruent condition. Older adults who had greater cardiorespiratory fitness and others who had completed a 6-month walking exercise intervention (compared to the less fit and the stretching exercise controls groups, respectively) showed greater activation in areas involved in executive control, including the right middle frontal gyrus and superior parietal lobule, and lesser activation in the anterior cingulate cortex, a region activated in response to unexpected conflict and adaptations to attentional control processes. In another study, older adults completed a famous name discrimination task. In this task, the participant makes a right index finger button press to indicate the name is famous (e.g., Frank Sinatra) and a right middle finger button press to indicate the name is not famous (e.g., Rebecca Hall). Older adults, even those with cognitive impairment, perform the task very well with about 90% accuracy. Only correct trials are included in the analysis in order to remove activation related to errors in memory performance. In the analysis of the brain activation response, a “famous” minus “unfamiliar” metric is calculated in order to remove brain activation related to the common sensory and motor aspects of the two name conditions, thus providing a measure of activation related to semantic memory retrieval. Greater levels of self-reported PA were associated with a greater spatial extent and a greater intensity of neural activation in several brain regions involved in semantic memory. Furthermore, these effects were much greater in the more physically active participants who possessed a genetic risk for Alzheimer’s disease with the APOE-e4 allele. Larger effects of PA on brain amyloid levels, measured using positron emission tomography, have also been reported in APOE-e4 allele carriers. Accumulation of amyloid plaque in the brain is a hallmark feature of Alzheimer’s disease, and the early accumulation of brain amyloid is greater in APOE-e4 allele carriers, even prior to any symptoms of memory loss. Physically active APOE-e4 allele carriers showed substantially lower brain amyloid than those who were less physically active, levels that were similar to those who did not possess the genetic risk factor. Thus, exercise and PA may help preserve brain volume in regions involved in memory and executive function and may help preserve the ability to activate these regions to perform cognitive tasks. These effects are hypothesized to provide a cognitive or neural reserve that may provide protection against potential neural insults or neuropathological processes. Despite a genetic disposition to develop Alzheimer’s disease in APOE-e4 allele carriers, PA may promote cognitive resilience and the ability to maintain intact cognitive function and functional independence with age.

Exercise-Induced Angiogenesis and Neurogenesis

The possible neurophysiological mechanism(s) for the effects of PA on brain function have been well characterized using animal models. The most well-known finding is that exercise induces neurogenesis, the birth and growth of new nerve cells, in the hippocampus. Exercise in rodents produces increases in brain-derived neurotrophic factor (BDNF) and BDNF messenger RNA in the hippocampus and dentate gyrus. These exercise-induced neurotrophic effects in the hippocampus are hypothesized to contribute to the mnemonic benefits of exercise on memory. An important concomitant of neurogenesis is angiogenesis, the birth and growth of new blood vessels or capillaries, and exercise has been shown to induce angiogenesis in rodent motor cortex. The neurogenic and angiogenic effects of exercise are coupled and likely combine to affect cognitive function. In younger healthy adults, exercise training led increased cerebral blood volume in the dentate gyrus, an effect also observed in mice along with markers of hippocampal neurogenesis. Importantly, these effects are related to improved memory performance.

References:

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