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.


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