The neurobiological effects of physical exercise are numerous and
involve a wide range of interrelated effects on brain structure, brain
function, and cognition. A large body of research in
humans has demonstrated that consistent aerobic exercise (e.g.,
30 minutes every day) induces persistent improvements in certain
cognitive functions, healthy alterations in gene expression in the
brain, and beneficial forms of neuroplasticity and behavioral
plasticity; some of these long-term effects include: increased neuron
growth, increased neurological activity (e.g., c-Fos and BDNF
signaling), improved stress coping, enhanced cognitive control of
behavior, improved declarative, spatial, and working memory, and
structural and functional improvements in brain structures and
pathways associated with cognitive control and
memory. The effects of exercise on
cognition have important implications for improving academic
performance in children and college students, improving adult
productivity, preserving cognitive function in old age, preventing or
treating certain neurological disorders, and improving overall quality
In healthy adults, aerobic exercise has been shown to induce transient
effects on cognition after a single exercise session and persistent
effects on cognition following regular exercise over the course of
several months. People who regularly perform aerobic
exercise (e.g., running, jogging, brisk walking, swimming, and
cycling) have greater scores on neuropsychological function and
performance tests that measure certain cognitive functions, such as
attentional control, inhibitory control, cognitive flexibility,
working memory updating and capacity, declarative memory, spatial
memory, and information processing speed. The
transient effects of exercise on cognition include improvements in
most executive functions (e.g., attention, working memory, cognitive
flexibility, inhibitory control, problem solving, and decision making)
and information processing speed for a period of up to 2 hours
Aerobic exercise induces short- and long-term effects on mood and
emotional states by promoting positive affect, inhibiting negative
affect, and decreasing the biological response to acute psychological
stress. Over the short-term, aerobic exercise functions as both an
antidepressant and euphoriant, whereas consistent
exercise produces general improvements in mood and
Regular aerobic exercise improves symptoms associated with a variety
of central nervous system disorders and may be used as an adjunct
therapy for these disorders. There is clear evidence of exercise
treatment efficacy for major depressive disorder and attention deficit
hyperactivity disorder. The American Academy
of Neurology's clinical practice guideline for mild cognitive
impairment indicates that clinicians should recommend regular exercise
(two times per week) to individuals who have been diagnosed with this
condition. Reviews of clinical evidence also support the use of
exercise as an adjunct therapy for certain neurodegenerative
Alzheimer’s disease and Parkinson's
disease. Regular exercise is also associated
with a lower risk of developing neurodegenerative disorders. A
large body of preclinical evidence and emerging clinical evidence
supports the use of exercise therapy for treating and preventing the
development of drug addictions. Regular exercise
has also been proposed as an adjunct therapy for brain cancers.
1 Long-term effects
1.1.2 IGF-1 signaling
1.1.3 VEGF signaling
1.2 Structural growth
1.3 Long-term effects on cognition
2 Short-term effects
2.1 Short-term effects on cognition
Psychological stress and cortisol
2.4 Effects on neurochemicals
2.4.4 Monoamine neurotransmitters
Glutamate and GABA
3 Effects in children
4 Effects on central nervous system disorders
Attention deficit hyperactivity disorder
4.3 Major depressive disorder
4.4 Brain cancers
4.5 Mild cognitive impairment
4.6 Neurodegenerative disorders
4.6.1 Alzheimer's disease
4.6.2 Parkinson's disease
5 See also
Neuroplasticity is the process by which neurons adapt to a disturbance
over time, and most often occurs in response to repeated exposure to
Aerobic exercise increases the production of neurotrophic
factors[note 1] (e.g., BDNF, IGF-1, VEGF) which mediate improvements
in cognitive functions and various forms of memory by promoting blood
vessel formation in the brain, adult neurogenesis,[note 2] and other
forms of neuroplasticity. Consistent aerobic
exercise over a period of several months induces clinically
significant improvements in executive functions and increased gray
matter volume in nearly all regions of the brain, with the most
marked increases occurring in brain regions that give rise to
executive functions. The brain structures that show the
greatest improvements in gray matter volume in response to aerobic
exercise are the prefrontal cortex, caudate nucleus, and
hippocampus; less significant increases in gray matter
volume occur in the anterior cingulate cortex, parietal cortex,
cerebellum, and nucleus accumbens. The prefrontal cortex,
caudate nucleus, and anterior cingulate cortex are among the most
significant brain structures in the dopamine and norepinephrine
systems that give rise to cognitive control. Exercise-induced
neurogenesis (i.e., the increases in gray matter volume) in the
hippocampus is associated with measurable improvements in spatial
memory. Higher physical fitness scores, as measured by
VO2 max, are associated with better executive function, faster
information processing speed, and greater gray matter volume of the
hippocampus, caudate nucleus, and nucleus accumbens. Long-term
aerobic exercise is also associated with persistent beneficial
epigenetic changes that result in improved stress coping, improved
cognitive function, and increased neuronal activity (c-Fos and BDNF
See also: Brain-derived neurotrophic factor
One of the most significant effects of exercise on the brain is the
increased synthesis and expression of BDNF, a neuropeptide hormone, in
the brain and periphery, resulting in increased signaling through its
receptor tyrosine kinase, tropomyosin receptor kinase B
BDNF is capable of crossing the blood–brain
barrier, higher peripheral
BDNF synthesis also increases BDNF
signaling in the brain. Exercise-induced increases in brain BDNF
signaling are associated with beneficial epigenetic changes, improved
cognitive function, improved mood, and improved memory.
Furthermore, research has provided a great deal of support for the
BDNF in hippocampal neurogenesis, synaptic plasticity, and
neural repair. Engaging in moderate-high intensity aerobic
exercise such as running, swimming, and cycling increases BDNF
biosynthesis through myokine signaling, resulting in up to a threefold
increase in blood plasma and brain
BDNF levels; exercise
intensity is positively correlated with the magnitude of increased
BDNF biosynthesis and expression. A meta-analysis of
studies involving the effect of exercise on
BDNF levels found that
consistent exercise modestly increases resting
BDNF levels as
See also: Insulin-like growth factor 1
IGF-1 is a peptide and neurotrophic factor that mediates some of the
effects of growth hormone; IGF-1 elicits its physiological effects
by binding to a specific receptor tyrosine kinase, the IGF-1 receptor,
to control tissue growth and remodeling. In the brain, IGF-1
functions as a neurotrophic factor that, like BDNF, plays a
significant role in cognition, neurogenesis, and neuronal
survival. Physical activity is associated with increased
levels of IGF-1 in blood serum, which is known to contribute to
neuroplasticity in the brain due to its capacity to cross the
blood–brain barrier and blood–cerebrospinal fluid
barrier; consequently, one review noted that IGF-1 is a
key mediator of exercise-induced adult neurogenesis, while a second
review characterized it as a factor which links "body fitness" with
"brain fitness". The amount of IGF-1 released into blood
plasma during exercise is positively correlated with exercise
intensity and duration.
See also: Vascular endothelial growth factor
VEGF is a neurotrophic and angiogenic (i.e., blood vessel
growth-promoting) signaling protein that binds to two receptor
VEGFR1 and VEGFR2, which are expressed in neurons
and glial cells in the brain. Hypoxia, or inadequate cellular
oxygen supply, strongly upregulates VEGF expression and VEGF exerts a
neuroprotective effect in hypoxic neurons. Like
BDNF and IGF-1,
aerobic exercise has been shown to increase VEGF biosynthesis in
peripheral tissue which subsequently crosses the blood–brain barrier
and promotes neurogenesis and blood vessel formation in the central
nervous system. Exercise-induced increases in VEGF
signaling have been shown to improve cerebral blood volume and
contribute to exercise-induced neurogenesis in the
Reviews of neuroimaging studies indicate that consistent aerobic
exercise increases gray matter volume in nearly all regions of the
brain, with more pronounced increases occurring in brain regions
associated with memory processing, cognitive control, motor function,
and reward; the most prominent gains in gray matter
volume are seen in the prefrontal cortex, caudate nucleus, and
hippocampus, which support cognitive control and memory processing,
among other cognitive functions. Moreover, the left and
right halves of the prefrontal cortex, the hippocampus, and the
cingulate cortex appear to become more functionally interconnected in
response to consistent aerobic exercise. Three reviews indicate
that marked improvements in prefrontal and hippocampal gray matter
volume occur in healthy adults that regularly engage in medium
intensity exercise for several months. Other regions of the
brain that demonstrate moderate or less significant gains in gray
matter volume during neuroimaging include the anterior cingulate
cortex, parietal cortex, cerebellum, and nucleus
Regular exercise has been shown to counter the shrinking of the
hippocampus and memory impairment that naturally occurs in late
adulthood. Sedentary adults over age 55 show a
1–2% decline in hippocampal volume annually. A
neuroimaging study with a sample of 120 adults revealed that
participating in regular aerobic exercise increased the volume of the
left hippocampus by 2.12% and the right hippocampus by 1.97% over a
one-year period. Subjects in the low intensity stretching group
who had higher fitness levels at baseline showed less hippocampal
volume loss, providing evidence for exercise being protective against
age-related cognitive decline. In general, individuals that
exercise more over a given period have greater hippocampal volumes and
better memory function.
Aerobic exercise has also been shown to
induce growth in the white matter tracts in the anterior corpus
callosum, which normally shrink with age.
The various functions of the brain structures that show
exercise-induced increases in gray matter volume include:
Prefrontal and anterior cingulate cortices – required for the
cognitive control of behavior, particularly: working memory,
attentional control, decision-making, cognitive flexibility, social
cognition, and inhibitory control of behavior; implicated in
attention deficit hyperactivity disorder (ADHD) and addiction
Nucleus accumbens – responsible for incentive salience
("wanting" or desire, the form of motivation associated with reward)
and positive reinforcement; implicated in addiction
Hippocampus – responsible for storage and consolidation of
declarative memory and spatial memory; implicated in
Cerebellum – responsible for motor coordination and motor
Caudate nucleus – responsible for stimulus-response learning
and inhibitory control; implicated in Parkinson's disease,
Huntington's disease and ADHD
Parietal cortex – responsible for sensory perception, working
memory, and attention
Long-term effects on cognition 
See also: Executive functions
Concordant with the functional roles of the brain structures that
exhibit increased gray matter volumes, regular exercise over a period
of several months has been shown to persistently improve numerous
executive functions and several forms of memory.
In particular, consistent aerobic exercise has been shown to improve
attentional control,[note 3] information processing speed, cognitive
flexibility (e.g., task switching), inhibitory control,[note 4]
working memory updating and capacity,[note 5] declarative memory,[note
6] and spatial memory. In healthy young and
middle-aged adults, the effect sizes of improvements in cognitive
function are largest for indices of executive functions and small to
moderate for aspects of memory and information processing
speed. It may be that in older adults, individuals benefit
cognitively by taking part in both aerobic and resistance type
exercise of at least moderate intensity. Individuals who have a
sedentary lifestyle tend to have impaired executive functions relative
to other more physically active non-exercisers. A reciprocal
relationship between exercise and executive functions has also been
noted: improvements in executive control processes, such as
attentional control and inhibitory control, increase an individual's
tendency to exercise.
Short-term effects on cognition
See also: Executive functions
In addition to the persistent effects of regular exercise over the
course of several months on cognitive functions, acute exercise (i.e.,
a single bout of exercise) has been shown to transiently improve a
number of cognitive functions. Reviews and meta-analyses
of research on the effects of acute exercise in healthy young and
middle-aged adults on cognition have concluded that information
processing speed and a number of executive functions – including
attention, working memory, problem solving, cognitive flexibility,
verbal fluency, decision making, and inhibitory control – all
improve for a period of up to 2 hours post-exercise.
A systematic review of studies conducted on children also suggested
that some of the exercise-induced improvements in executive function
are apparent after single bouts of exercise, while other aspects
(e.g., attentional control) only improve following consistent exercise
on a regular basis.
Psychological stress and cortisol
Diagram of the hypothalamic–pituitary–adrenal axis
See also: Effects of stress on memory
The "stress hormone", cortisol, is a glucocorticoid that binds to
Psychological stress induces the
release of cortisol from the adrenal gland by activating the
hypothalamic–pituitary–adrenal axis (HPA axis).
Short-term increases in cortisol levels are associated with adaptive
cognitive improvements, such as enhanced inhibitory
control; however, excessively high exposure or prolonged
exposure to high levels of cortisol causes impairments in cognitive
control and has neurotoxic effects in the human brain. For
example, chronic psychological stress decreases
BDNF expression which
has detrimental effects on hippocampal volume and can lead to
As a physical stressor, aerobic exercise stimulates cortisol secretion
in an intensity-dependent manner; however, it does not result in
long-term increases in cortisol production since this exercise-induced
effect on cortisol is a response to transient negative energy
balance.[note 7] Individuals who have recently exercised exhibit
improvements in stress coping behaviors. Aerobic exercise
increases physical fitness and lowers neuroendocrine (i.e., HPA axis)
reactivity and therefore reduces the biological response to
psychological stress in humans (e.g., reduced cortisol release and
attenuated heart rate response). Exercise also reverses
stress-induced decreases in
BDNF expression and signaling in the
brain, thereby acting as a buffer against stress-related diseases like
Continuous exercise can produce short-term euphoria, an affective
state associated with feelings of profound contentment, elation, and
well-being, which is colloquially known as a "runner's high" in
distance running or a "rower's high" in rowing.
Current medical reviews indicate that several endogenous euphoriants
are responsible for producing exercise-related euphoria, specifically
phenethylamine (an endogenous psychostimulant), β-endorphin (an
endogenous opioid), and anandamide (an
Effects on neurochemicals
β-Phenylethylamine, commonly referred to as phenethylamine, is a
potent human trace amine and neuromodulator which functions as
endogenous amphetamine.[note 8] Thirty minutes of moderate to
high intensity physical exercise has been shown to induce an enormous
increase in urinary β-phenylacetic acid, the primary metabolite of
phenethylamine. Two reviews noted a study where the mean
24 hour urinary β-phenylacetic acid acid concentration following
just 30 minutes of intense exercise rose 77% above its base
level; the reviews suggest that phenethylamine synthesis
sharply increases during physical exercise during which it is rapidly
metabolized due to its short half-life of roughly
30 seconds. In a resting state, phenethylamine is
synthesized in catecholamine neurons from L-phenylalanine by aromatic
amino acid decarboxylase at approximately the same rate at which
dopamine is produced.
In light of this observation, the original paper and both reviews
suggest that phenethylamine plays a prominent role in mediating the
mood-enhancing euphoric effects of a runner's high, as both
phenethylamine and amphetamine are potent euphoriants.
β-Endorphin (contracted from "endogenous morphine") is an endogenous
opioid neuropeptide that binds to μ-opioid receptors, in turn
producing euphoria and pain relief. A meta-analytic review found
that exercise significantly increases the secretion of β-endorphin
and that this secretion is correlated with improved mood states.
Moderate intensity exercise produces the greatest increase in
β-endorphin synthesis, while higher and lower intensity forms of
exercise are associated with smaller increases in β-endorphin
A review on β-endorphin and exercise noted that an individual's mood
improves for the remainder of the day following physical exercise and
that one's mood is positively correlated with overall daily physical
activity level. Exercise-induced improvements in mood occur in
sedentary individuals, recreational exercisers, and marathon runners,
but recreational athletes and marathon runners experience more
pronounced mood-lifting effects from exercising.
Anandamide is an endogenous cannabinoid neurotransmitter that binds to
cannabinoid receptors. It has been shown that aerobic exercise
causes an increase in plasma anandamide levels, where the magnitude of
this increase is highest at moderate exercise intensity (i.e.,
exercising at ~70–80% maximum heart rate). Increases in
plasma anandamide levels are associated with psychoactive effects
because anandamide is able to cross the blood–brain barrier and act
within the central nervous system. Thus, because anandamide is a
euphoriant and aerobic exercise is associated with euphoric effects,
it has been proposed that anandamide partly mediates the short-term
mood-lifting effects of exercise (e.g., the euphoria of a runner's
high) via exercise-induced increases in its synthesis.
In mice it was demonstrated that certain features of a runner's high
depend on cannabinoid receptors. Pharmacological or genetic disruption
of cannabinoid signaling via cannabinoid receptors prevents the
analgesic and anxiety-reducing effects of running.[non-primary
Central nervous system
Central nervous system fatigue
This section needs expansion with: . You can help by adding to it.
Glutamate and GABA
This section needs expansion with: . You can help by adding to it.
Glutamate, one of the most common neurochemicals in the brain, is an
excitatory neurotransmitter involved in many aspects of brain
function, including learning and memory. Based upon animal models,
exercise appears to normalize the excessive levels of glutamate
neurotransmission into the nucleus accumbens that occurs in drug
addiction. A review of the effects of exercise on neurocardiac
function in preclinical models noted that exercise-induced
neuroplasticity of the rostral ventrolateral medulla (RVLM) has an
inhibitory effect on glutamatergic neurotransmission in this region,
in turn reducing sympathetic activity; the review hypothesized
that this neuroplasticity in the RVLM is a mechanism by which regular
exercise prevents inactivity-related cardiovascular disease.
This section needs expansion with: . You can help by adding to it.
Effects in children
This section needs more medical references for verification or relies
too heavily on primary sources. Please review the contents of the
section and add the appropriate references if you can. Unsourced or
poorly sourced material may be challenged and removed. (February 2015)
Sibley and Etnier (2003) performed a meta-analysis that looked at the
relationship between physical activity and cognitive performance in
children. They reported a beneficial relationship in the
categories of perceptual skills, intelligence quotient, achievement,
verbal tests, mathematic tests, developmental level/academic readiness
and other, with the exception of memory, that was found to be
unrelated to physical activity. The correlation was strongest for
the age ranges of 4–7 and 11–13 years. On the other hand,
Chaddock and colleagues (2011) found results that contrasted Sibley
and Etnier's meta-analysis. In their study, the hypothesis was that
lower-fit children would perform poorly in executive control of memory
and have smaller hippocampal volumes compared to higher-fit
children. Instead of physical activity being unrelated to memory
in children between 4 and 18 years of age, it may be that
preadolescents of higher fitness have larger hippocampal volumes, than
preadolescents of lower fitness. According to a previous study done by
Chaddock and colleagues (Chaddock et al. 2010), a larger hippocampal
volume would result in better executive control of memory. They
concluded that hippocampal volume was positively associated with
performance on relational memory tasks. Their findings are the
first to indicate that aerobic fitness may relate to the structure and
function of the preadolescent human brain. In Best’s (2010)
meta-analysis of the effect of activity on children’s executive
function, there are two distinct experimental designs used to assess
aerobic exercise on cognition. The first is chronic exercise, in which
children are randomly assigned to a schedule of aerobic exercise over
several weeks and later assessed at the end. The second is acute
exercise, which examines the immediate changes in cognitive
functioning after each session. The results of both suggest that
aerobic exercise may briefly aid children’s executive function and
also influence more lasting improvements to executive function.
Other studies have suggested that exercise is unrelated to academic
performance, perhaps due to the parameters used to determine exactly
what academic achievement is. This area of study has been a focus
for education boards that make decisions on whether physical education
should be implemented in the school curriculum, how much time should
be dedicated to physical education, and its impact on other academic
Another study found that sixth-graders who participated in vigorous
physical activity at least three times a week had the highest scores
compared to those who participated in moderate or no physical activity
at all. The kids who participated in vigorous physical activity scored
three points higher, on average, on their academic test, which
consisted of math, science, English, and world studies.
Animal studies have also shown that exercise can impact brain
development early on in life. Mice that had access to running wheels
and other such exercise equipment had better neuronal growth in the
neural systems involved in learning and memory. Neuroimaging of
the human brain has yielded similar results, where exercise leads to
changes in brain structure and function. Some investigations have
linked low levels of aerobic fitness in children with impaired
executive function in older adults, but there is mounting evidence it
may also be associated with a lack of selective attention, response
inhibition, and interference control.
Effects on central nervous system disorders
Central nervous system
Central nervous system disorders
Clinical and preclinical evidence indicate that consistent aerobic
exercise, especially endurance exercise (e.g., marathon running),
actually prevents the development of certain drug addictions and is an
effective adjunct treatment for drug addiction, psychostimulant
addiction in particular. Consistent aerobic
exercise magnitude-dependently (i.e., by duration and intensity)
reduces drug addiction risk, which appears to occur through the
reversal of drug-induced, addiction-related neuroplasticity.
One review noted that exercise may prevent the development of drug
addiction by altering
ΔFosB or c-Fos immunoreactivity in the striatum
or other parts of the reward system. Moreover, aerobic exercise
decreases psychostimulant self-administration, reduces the
reinstatement (i.e., relapse) of drug-seeking, and induces opposite
effects on striatal dopamine receptor D2 (DRD2) signaling (increased
DRD2 density) to those induced by pathological stimulant use
DRD2 density). Consequently, consistent aerobic
exercise may lead to better treatment outcomes when used as an adjunct
treatment for drug addiction. As of 2016[update], more
clinical research is still needed to understand the mechanisms and
confirm the efficacy of exercise in drug addiction treatment and
Summary of addiction-related plasticity
Form of neuroplasticity
or behavioral plasticity
Type of reinforcer
High fat or sugar food
ΔFosB expression in
Escalation of intake
conditioned place preference
Reinstatement of drug-seeking behavior
in the nucleus accumbens
Sensitized dopamine response
in the nucleus accumbens
Altered striatal dopamine signaling
↑DRD1, ↓DRD2, ↑DRD3
↑DRD1, ↓DRD2, ↑DRD3
Altered striatal opioid signaling
No change or
Changes in striatal opioid peptides
No change: enkephalin
Mesocorticolimbic synaptic plasticity
Number of dendrites in the nucleus accumbens
Dendritic spine density in
the nucleus accumbens
Attention deficit hyperactivity disorder
Regular physical exercise, particularly aerobic exercise, is an
effective add-on treatment for ADHD in children and adults,
particularly when combined with stimulant medication (i.e.,
amphetamine or methylphenidate), although the best intensity and type
of aerobic exercise for improving symptoms are not currently
known. In particular, the long-term effects of regular
aerobic exercise in ADHD individuals include better behavior and motor
abilities, improved executive functions (including attention,
inhibitory control, and planning, among other cognitive domains),
faster information processing speed, and better memory.
Parent-teacher ratings of behavioral and socio-emotional outcomes in
response to regular aerobic exercise include: better overall function,
reduced ADHD symptoms, better self-esteem, reduced levels of anxiety
and depression, fewer somatic complaints, better academic and
classroom behavior, and improved social behavior. Exercising while
on stimulant medication augments the effect of stimulant medication on
executive function. It is believed that these short-term effects
of exercise are mediated by an increased abundance of synaptic
dopamine and norepinephrine in the brain.
Major depressive disorder
A number of medical reviews have indicated that exercise has a marked
and persistent antidepressant effect in humans,
an effect believed to be mediated through enhanced
BDNF signaling in
the brain. Several systematic reviews have analyzed the
potential for physical exercise in the treatment of depressive
disorders. The 2013
Cochrane Collaboration review on physical exercise
for depression noted that, based upon limited evidence, it is more
effective than a control intervention and comparable to psychological
or antidepressant drug therapies. Three subsequent 2014 systematic
reviews that included the Cochrane review in their analysis concluded
with similar findings: one indicated that physical exercise is
effective as an adjunct treatment (i.e., treatments that are used
together) with antidepressant medication; the other two indicated
that physical exercise has marked antidepressant effects and
recommended the inclusion of physical activity as an adjunct treatment
for mild–moderate depression and mental illness in general.
One systematic review noted that yoga may be effective in alleviating
symptoms of prenatal depression. Another review asserted that
evidence from clinical trials supports the efficacy of physical
exercise as a treatment for depression over a 2–4 month
A 2015 review of clinical evidence which included a medical guideline
for the treatment of depression with exercise noted that the available
evidence on the effectiveness of exercise therapy for depression
suffers from some limitations; nonetheless, it stated that there
is clear evidence of efficacy for reducing symptoms of depression.
The review also noted that patient characteristics, the type of
depressive disorder, and the nature of the exercise program all affect
the antidepressant properties of exercise therapy. A meta-analysis
from July 2016 concluded that physical exercise improves overall
quality of life in individuals with depression relative to
This section needs expansion with: . You can help by adding to it.
Mild cognitive impairment
This section needs expansion. You can help by adding to it. (December
The American Academy of Neurology's January 2018 update of their
clinical practice guideline for mild cognitive impairment states that
clinicians should recommend regular exercise (two times per week) to
individuals who have been diagnosed with this condition. This
guidance is based upon a moderate amount of high-quality evidence
which supports the efficacy of regular physical exercise (twice weekly
over a 6 month period) for improving cognitive symptoms in individuals
with mild cognitive impairment.
Alzheimer's Disease is a cortical neurodegenerative disorder and the
most prevalent form of dementia, representing approximately 65% of all
cases of dementia; it is characterized by impaired cognitive function,
behavioral abnormalities, and a reduced capacity to perform basic
activities of daily life. Two meta-analytic systematic reviews
of randomized controlled trials with durations of 3–12 months
have examined the effects of physical exercise on the aforementioned
characteristics of Alzheimer's disease. The reviews found
beneficial effects of physical exercise on cognitive function, the
rate of cognitive decline, and the ability to perform activities of
daily living in individuals with Alzheimer's disease. One
review suggested that, based upon transgenic mouse models, the
cognitive effects of exercise on Alzheimer's disease may result from a
reduction in the quantity of amyloid plaque.
Caerphilly Prospective study
Caerphilly Prospective study followed 2,375 male subjects
over 30 years and examined the association between healthy
lifestyles and dementia, among other factors. Analyses of the
Caerphilly study data have found that exercise is associated with a
lower incidence of dementia and a reduction in cognitive
impairment. A subsequent systematic review of longitudinal
studies also found higher levels of physical activity to be associated
with a reduction in the risk of dementia and cognitive decline;
this review further asserted that increased physical activity appears
to be causally related with these reduced risks.
This section needs expansion with: . You can help by
adding to it. (February 2016)
Parkinson's disease (PD) is a movement disorder that produces symptoms
such as bradykinesia, rigidity, shaking, and impaired gait.
A review by Kramer and colleagues (2006) found that some
neurotransmitter systems are affected by exercise in a positive
way. A few studies reported seeing an improvement in brain health
and cognitive function due to exercise. One particular study by
Kramer and colleagues (1999) found that aerobic training improved
executive control processes supported by frontal and prefrontal
regions of the brain. These regions are responsible for the
cognitive deficits in PD patients, however there was speculation that
the difference in the neurochemical environment in the frontal lobes
of PD patients may inhibit the benefit of aerobic exercise.
Nocera and colleagues (2010) performed a case study based on this
literature where they gave participants with early-to mid-staged PD,
and the control group cognitive/language assessments with exercise
regimens. Individuals performed 20 minutes of aerobic exercise three
times a week for 8 weeks on a stationary exercise cycle. It was found
that aerobic exercise improved several measures of cognitive
function, providing evidence that such exercise regimens may be
beneficial to patients with PD.
Exercise is Medicine
Neurotrophic factors are peptides or other small proteins that
promote the growth, survival, and differentiation of neurons by
binding to and activating their associated tyrosine kinases.
Adult neurogenesis is the postnatal (after-birth) growth of new
neurons, a beneficial form of neuroplasticity.
Attentional control allows an individual to focus their attention on
a specific source and ignore other stimuli that compete for one's
attention, such as in the cocktail party effect.
Inhibitory control is the process of altering one's learned
behavioral responses, sometimes called "prepotent responses", in a way
that makes it easier to complete a particular goal. Inhibitory
control allows individuals to control their impulses and habits when
necessary or desired, e.g., to overcome procrastination.
Working memory is the form of memory used by an individual at any
given moment for active information processing, such as when
reading or writing an encyclopedia article.
Working memory has a
limited capacity and functions as an information buffer, analogous to
a computer's data buffer, that permits the manipulation of information
for comprehension, decision-making, and guidance of behavior.
^ Declarative memory, also known as explicit memory, is the form of
memory that pertains to facts and events.
^ In healthy individuals, this energy deficit resolves simply from
eating and drinking a sufficient amount of food and beverage after
^ In other words, phenethylamine and amphetamine have roughly
identical effects on the central nervous system.
^ a b c d e f g h i j k l m Erickson KI, Hillman CH, Kramer AF (August
2015). "Physical activity, brain, and cognition". Current Opinion in
Behavioral Sciences. 4: 27–32.
^ a b c Paillard T, Rolland Y, de Souto Barreto P (July 2015).
"Protective Effects of Physical Exercise in
Alzheimer's Disease and
Parkinson's Disease: A Narrative Review". J Clin Neurol. 11 (3):
212–219. doi:10.3988/jcn.2015.11.3.212. PMC 4507374 .
PMID 26174783. Aerobic physical exercise (PE) activates the
release of neurotrophic factors and promotes angiogenesis, thereby
facilitating neurogenesis and synaptogenesis, which in turn improve
memory and cognitive functions. ... Exercise limits the
alteration in dopaminergic neurons in the substantia nigra and
contributes to optimal functioning of the basal ganglia involved in
motor commands and control by adaptive mechanisms involving dopamine
and glutamate neurotransmission.
^ a b McKee AC, Daneshvar DH, Alvarez VE, Stein TD (January 2014).
"The neuropathology of sport". Acta Neuropathol. 127 (1): 29–51.
doi:10.1007/s00401-013-1230-6. PMC 4255282 .
PMID 24366527. The benefits of regular exercise, physical fitness
and sports participation on cardiovascular and brain health are
undeniable ... Exercise also enhances psychological health,
reduces age-related loss of brain volume, improves cognition, reduces
the risk of developing dementia, and impedes neurodegeneration.
^ a b c d e f g h Denham J, Marques FZ, O'Brien BJ, Charchar FJ
(February 2014). "Exercise: putting action into our epigenome". Sports
Med. 44 (2): 189–209. doi:10.1007/s40279-013-0114-1.
PMID 24163284. Aerobic physical exercise produces numerous health
benefits in the brain. Regular engagement in physical exercise
enhances cognitive functioning, increases brain neurotrophic proteins,
such as brain-derived neurotrophic factor (BDNF), and prevents
cognitive diseases [76–78]. Recent findings highlight a role for
aerobic exercise in modulating chromatin remodelers [21,
79–82]. ... These results were the first to demonstrate that
acute and relatively short aerobic exercise modulates epigenetic
modifications. The transient epigenetic modifications observed due to
chronic running training have also been associated with improved
learning and stress-coping strategies, epigenetic changes and
increased c-Fos-positive neurons ... Nonetheless, these studies
demonstrate the existence of epigenetic changes after acute and
chronic exercise and show they are associated with improved cognitive
function and elevated markers of neurotrophic factors and neuronal
BDNF and c-Fos). ... The aerobic exercise
training-induced changes to miRNA profile in the brain seem to be
intensity-dependent . These few studies provide a basis for
further exploration into potential miRNAs involved in brain and
neuronal development and recovery via aerobic exercise.
^ a b c d e f g h i j k l m n o p q r Gomez-Pinilla F, Hillman C
(January 2013). "The influence of exercise on cognitive abilities".
Compr. Physiol. 3 (1): 403–428. doi:10.1002/cphy.c110063.
PMC 3951958 . PMID 23720292.
^ a b c d e f g h i j k l m n Erickson KI, Leckie RL, Weinstein AM
(September 2014). "Physical activity, fitness, and gray matter
volume". Neurobiol. Aging. 35 Suppl 2: S20–528.
doi:10.1016/j.neurobiolaging.2014.03.034. PMC 4094356 .
PMID 24952993. Retrieved 9 December 2014.
^ a b c d e f Guiney H, Machado L (February 2013). "Benefits of
regular aerobic exercise for executive functioning in healthy
populations". Psychon Bull Rev. 20 (1): 73–86.
doi:10.3758/s13423-012-0345-4. PMID 23229442.
^ a b c d e f g h i j k l m n Erickson KI, Miller DL, Roecklein KA
(2012). "The aging hippocampus: interactions between exercise,
depression, and BDNF". Neuroscientist. 18 (1): 82–97.
doi:10.1177/1073858410397054. PMC 3575139 .
^ a b c d e f g h Buckley J, Cohen JD, Kramer AF, McAuley E, Mullen SP
(2014). "Cognitive control in the self-regulation of physical activity
and sedentary behavior". Front Hum Neurosci. 8: 747.
doi:10.3389/fnhum.2014.00747. PMC 4179677 .
^ a b c d e Cox EP, O'Dwyer N, Cook R, Vetter M, Cheng HL, Rooney K,
O'Connor H (August 2016). "Relationship between physical activity and
cognitive function in apparently healthy young to middle-aged adults:
A systematic review". J. Sci. Med. Sport. 19 (8): 616–628.
doi:10.1016/j.jsams.2015.09.003. PMID 26552574. A range of
validated platforms assessed CF across three domains: executive
function (12 studies), memory (four studies) and processing speed
(seven studies). ... In studies of executive function, five found
a significant ES in favour of higher PA, ranging from small to large.
Although three of four studies in the memory domain reported a
significant benefit of higher PA, there was only one significant ES,
which favoured low PA. Only one study examining processing speed had a
significant ES, favouring higher PA.
CONCLUSIONS: A limited body of evidence supports a positive effect of
PA on CF in young to middle-aged adults. Further research into this
relationship at this age stage is warranted. ...
Significant positive effects of PA on cognitive function were found in
12 of the 14 included manuscripts, the relationship being most
consistent for executive function, intermediate for memory and weak
for processing speed.
^ a b c Schuch FB, Vancampfort D, Rosenbaum S, Richards J, Ward PB,
Stubbs B (July 2016). "Exercise improves physical and psychological
quality of life in people with depression: A meta-analysis including
the evaluation of control group response". Psychiatry Res. 241:
47–54. doi:10.1016/j.psychres.2016.04.054. PMID 27155287.
Exercise has established efficacy as an antidepressant in people with
depression. ... Exercise significantly improved physical and
psychological domains and overall QoL. ... The lack of
improvement among control groups reinforces the role of exercise as a
treatment for depression with benefits to QoL.
^ Pratali L, Mastorci F, Vitiello N, Sironi A, Gastaldelli A,
Gemignani A (November 2014). "Motor Activity in Aging: An Integrated
Approach for Better Quality of Life". Int. Sch. Res. Notices. 2014:
257248. doi:10.1155/2014/257248. PMC 4897547 .
PMID 27351018. Research investigating the effects of exercise on
older adults has primarily focused on brain structural and functional
changes with relation to cognitive improvement. In particular, several
cross-sectional and intervention studies have shown a positive
association between physical activity and cognition in older persons
 and an inverse correlation with cognitive decline and dementia
. Older adults enrolled in a 6-month aerobic fitness intervention
increased brain volume in both gray matter (anterior cingulate cortex,
supplementary motor area, posterior middle frontal gyrus, and left
superior temporal lobe) and white matter (anterior third of corpus
callosum) . In addition, Colcombe and colleagues showed that older
adults with higher cardiovascular fitness levels are better at
activating attentional resources, including decreased activation of
the anterior cingulated cortex. One of the possible mechanisms by
which physical activity may benefit cognition is that physical
activity maintains brain plasticity, increases brain volume,
stimulates neurogenesis and synaptogenesis, and increases neurotrophic
factors in different areas of the brain, possibly providing reserve
against later cognitive decline and dementia [89, 90].
^ a b c d e f g h i j Basso JC, Suzuki WA (March 2017). "The Effects
of Acute Exercise on Mood, Cognition, Neurophysiology, and
Neurochemical Pathways: A Review". Brain Plasticity. 2 (2): 127–152.
doi:10.3233/BPL-160040 . Lay summary – Can A Single Exercise
Session Benefit Your Brain? (12 June 2017). A large collection of
research in humans has shown that a single bout of exercise alters
behavior at the level of affective state and cognitive functioning in
several key ways. In terms of affective state, acute exercise
decreases negative affect, increases positive affect, and decreases
the psychological and physiological response to acute stress .
These effects have been reported to persist for up to 24 hours after
exercise cessation [28, 29, 53]. In terms of cognitive functioning,
acute exercise primarily enhances executive functions dependent on the
prefrontal cortex including attention, working memory, problem
solving, cognitive flexibility, verbal fluency, decision making, and
inhibitory control . These positive changes have been demonstrated
to occur with very low to very high exercise intensities , with
effects lasting for up to two hours after the end of the exercise bout
(Fig. 1A) . Moreover, many of these neuropsychological assessments
measure several aspects of behavior including both accuracy of
performance and speed of processing. McMorris and Hale performed a
meta-analysis examining the effects of acute exercise on both accuracy
and speed of processing, revealing that speed significantly improved
post-exercise, with minimal or no effect on accuracy . These
authors concluded that increasing task difficulty or complexity may
help to augment the effect of acute exercise on accuracy. ...
However, in a comprehensive meta-analysis, Chang and colleagues found
that exercise intensities ranging from very light (<50% MHR) to
very hard (>93% MHR) have all been reported to improve cognitive
^ a b Cunha GS, Ribeiro JL, Oliveira AR (June 2008). "[Levels of
beta-endorphin in response to exercise and overtraining]". Arq Bras
Endocrinol Metabol (in Portuguese). 52 (4): 589–598.
PMID 18604371. Interestingly, some symptoms of OT are related to
beta-endorphin (beta-end(1-31)) effects. Some of its effects, such as
analgesia, increasing lactate tolerance, and exercise-induced
euphoria, are important for training.
^ a b Boecker H, Sprenger T, Spilker ME, Henriksen G, Koppenhoefer M,
Wagner KJ, Valet M, Berthele A, Tolle TR (2008). "The runner's high:
opioidergic mechanisms in the human brain". Cereb. Cortex. 18 (11):
2523–2531. doi:10.1093/cercor/bhn013. PMID 18296435. The
runner's high describes a euphoric state resulting from long-distance
^ a b c d Josefsson T, Lindwall M, Archer T (2014). "Physical exercise
intervention in depressive disorders: meta-analysis and systematic
review". Scand J Med Sci Sports. 24 (2): 259–272.
doi:10.1111/sms.12050. PMID 23362828.
^ a b c Rosenbaum S, Tiedemann A, Sherrington C, Curtis J, Ward PB
(2014). "Physical activity interventions for people with mental
illness: a systematic review and meta-analysis". J Clin Psychiatry. 75
(9): 964–974. doi:10.4088/JCP.13r08765. PMID 24813261. This
systematic review and meta-analysis found that physical activity
reduced depressive symptoms among people with a psychiatric illness.
The current meta-analysis differs from previous studies, as it
included participants with depressive symptoms with a variety of
psychiatric diagnoses (except dysthymia and eating
disorders). ... This review provides strong evidence for the
antidepressant effect of physical activity; however, the optimal
exercise modality, volume, and intensity remain to be
Few interventions exist whereby patients can hope to achieve
improvements in both psychiatric symptoms and physical health
simultaneously without significant risks of adverse effects. Physical
activity offers substantial promise for improving outcomes for people
living with mental illness, and the inclusion of physical activity and
exercise programs within treatment facilities is warranted given the
results of this review.
^ a b c d Szuhany KL, Bugatti M, Otto MW (October 2014). "A
meta-analytic review of the effects of exercise on brain-derived
neurotrophic factor". J Psychiatr Res. 60C: 56–64.
doi:10.1016/j.jpsychires.2014.10.003. PMC 4314337 .
PMID 25455510. Consistent evidence indicates that exercise
improves cognition and mood, with preliminary evidence suggesting that
brain-derived neurotrophic factor (BDNF) may mediate these effects.
The aim of the current meta-analysis was to provide an estimate of the
strength of the association between exercise and increased
in humans across multiple exercise paradigms. We conducted a
meta-analysis of 29 studies (N = 1111 participants) examining the
effect of exercise on
BDNF levels in three exercise paradigms: (1) a
single session of exercise, (2) a session of exercise following a
program of regular exercise, and (3) resting
BDNF levels following a
program of regular exercise. Moderators of this effect were also
examined. Results demonstrated a moderate effect size for increases in
BDNF following a single session of exercise
(Hedges' g = 0.46, p < 0.001). Further,
regular exercise intensified the effect of a session of exercise on
BDNF levels (Hedges' g = 0.59, p = 0.02).
Finally, results indicated a small effect of regular exercise on
BDNF levels (Hedges' g = 0.27,
p = 0.005). ...
Effect size analysis supports the role
of exercise as a strategy for enhancing
BDNF activity in humans.
^ a b Lees C, Hopkins J (2013). "Effect of aerobic exercise on
cognition, academic achievement, and psychosocial function in
children: a systematic review of randomized control trials". Prev
Chronic Dis. 10: E174. doi:10.5888/pcd10.130010. PMC 3809922 .
PMID 24157077. This omission is relevant, given the evidence that
aerobic-based physical activity generates structural changes in the
brain, such as neurogenesis, angiogenesis, increased hippocampal
volume, and connectivity (12,13). In children, a positive relationship
between aerobic fitness, hippocampal volume, and memory has been found
(12,13). ... Mental health outcomes included reduced depression
and increased self-esteem, although no change was found in anxiety
levels (18). ... This systematic review of the literature found
that [aerobic physical activity (APA)] is positively associated with
cognition, academic achievement, behavior, and psychosocial
functioning outcomes. Importantly, Shephard also showed that
curriculum time reassigned to APA still results in a measurable,
albeit small, improvement in academic performance (24). ... The
actual aerobic-based activity does not appear to be a major factor;
interventions used many different types of APA and found similar
associations. In positive association studies, intensity of the
aerobic activity was moderate to vigorous. The amount of time spent in
APA varied significantly between studies; however, even as little as
45 minutes per week appeared to have a benefit.
^ a b c d Mura G, Moro MF, Patten SB, Carta MG (2014). "Exercise as an
add-on strategy for the treatment of major depressive disorder: a
systematic review". CNS Spectr. 19 (6): 496–508.
doi:10.1017/S1092852913000953. PMID 24589012. Considered overall,
the studies included in the present review showed a strong
effectiveness of exercise combined with antidepressants. ...
This is the first review to have focused on exercise as an add-on
strategy in the treatment of MDD. Our findings corroborate some
previous observations that were based on few studies and which were
difficult to generalize.41,51,73,92,93 Given the results of the
present article, it seems that exercise might be an effective strategy
to enhance the antidepressant effect of medication treatments.
Moreover, we hypothesize that the main role of exercise on
treatment-resistant depression is in inducing neurogenesis by
BDNF expression, as was demonstrated by several recent
^ a b c d Ranjbar E, Memari AH, Hafizi S, Shayestehfar M, Mirfazeli
FS, Eshghi MA (June 2015). "Depression and Exercise: A Clinical Review
and Management Guideline". Asian J. Sports Med. 6 (2): e24055.
doi:10.5812/asjsm.6(2)2015.24055. PMC 4592762 .
PMID 26448838. Keeping in mind that exercise shows no medication
side effects such as withdrawal symptoms (20), weight gain, dry mouth
or insomnia (21), but shows potential health benefits such as weight
reduction, it is highly recommended to use exercise as an adjunctive
treatment for depression (22). New findings confirm that exercise can
be recommended as a first-line treatment for mild to moderate
depression; as an adjunct to medications (23); as an alternative to
cognitive behavioral therapy (11); and in preventing depression in
clinical as well as healthy populations (24–26). ... Although
recent findings have shown that exercise can decrease depressive
symptoms, there are still many questions and limitations to wider
application of exercise in depression. For instance, there are
deficiencies in methodological planning such as uncontrolled
nonrandomized trials, small sample sizes, inadequate allocation
concealment, lack of intention-to-treat analyses, non-blinded outcome
assessments, and inclusion of subjects without clinical diagnosis that
limit the interpretability of research outcomes (53).
Box 1: Patients with Depression Who May Particularly Benefit From
Box 2: Depressive Disorders Other Than Major Depression That May
Benefit From Exercise Programs
Box 3: The Characteristics of an Exercise Program that will Maximize
the Anti-depressive Properties
^ a b c d e f Den Heijer AE, Groen Y, Tucha L, Fuermaier AB, Koerts J,
Lange KW, Thome J, Tucha O (July 2016). "Sweat it out? The effects of
physical exercise on cognition and behavior in children and adults
with ADHD: a systematic literature review". J. Neural. Transm.
(Vienna). doi:10.1007/s00702-016-1593-7. PMID 27400928.
^ a b c Kamp CF, Sperlich B, Holmberg HC (July 2014). "Exercise
reduces the symptoms of attention-deficit/hyperactivity disorder and
improves social behaviour, motor skills, strength and
neuropsychological parameters". Acta Paediatr. 103 (7): 709–14.
doi:10.1111/apa.12628. PMID 24612421. The present review
summarises the impact of exercise interventions (1–10 weeks in
duration with at least two sessions each week) on parameters related
to ADHD in 7-to 13-year-old children. We may conclude that all
different types of exercise (here yoga, active games with and without
the involvement of balls, walking and athletic training) attenuate the
characteristic symptoms of ADHD and improve social behaviour, motor
skills, strength and neuropsychological parameters without any
undesirable side effects. Available reports do not reveal which type,
intensity, duration and frequency of exercise is most effective in
this respect and future research focusing on this question with
randomised and controlled long-term interventions is warranted.
^ a b c Petersen RC, Lopez O, Armstrong MJ, Getchius T, Ganguli M,
Gloss D, Gronseth GS, Marson D, Pringsheim T, Day GS, Sager M, Stevens
J, Rae-Grant A (January 2018). "Practice guideline update summary:
Mild cognitive impairment – Report of the Guideline
Development, Dissemination, and Implementation Subcommittee of the
American Academy of Neurology". Neurology.
Special article. 90 (3):
1–10. doi:10.1212/WNL.0000000000004826. PMID 29282327. Lay
summary – Exercise may improve thinking ability and memory (27
December 2017). In patients with MCI, exercise training (6 months) is
likely to improve cognitive measures and cognitive training may
improve cognitive measures. ... Clinicians should recommend
regular exercise (Level B). ... Recommendation
For patients diagnosed with MCI, clinicians should recommend regular
exercise (twice/week) as part of an overall approach to management
^ a b c d e Farina N, Rusted J, Tabet N (January 2014). "The effect of
exercise interventions on cognitive outcome in Alzheimer's disease: a
systematic review". Int Psychogeriatr. 26 (1): 9–18.
doi:10.1017/S1041610213001385. PMID 23962667. Six RCTs were
identified that exclusively considered the effect of exercise in AD
patients. Exercise generally had a positive effect on rate of
cognitive decline in AD. A meta-analysis found that exercise
interventions have a positive effect on global cognitive function,
0.75 (95% CI = 0.32–1.17). ... The most prevalent
subtype of dementia is
Alzheimer’s disease (AD), accounting for up
to 65.0% of all dementia cases ... Cognitive decline in AD is
attributable at least in part to the buildup of amyloid and tau
proteins, which promote neuronal dysfunction and death (Hardy and
Selkoe, 2002; Karran et al., 2011). Evidence in transgenic mouse
models of AD, in which the mice have artificially elevated amyloid
load, suggests that exercise programs are able to improve cognitive
function (Adlard et al., 2005; Nichol et al., 2007). Adlard and
colleagues also determined that the improvement in cognitive
performance occurred in conjunction with a reduced amyloid load.
Research that includes direct indices of change in such biomarkers
will help to determine the mechanisms by which exercise may act on
cognition in AD.
^ a b c d Rao AK, Chou A, Bursley B, Smulofsky J, Jezequel J (January
2014). "Systematic review of the effects of exercise on activities of
daily living in people with Alzheimer's disease". Am J Occup Ther. 68
(1): 50–56. doi:10.5014/ajot.2014.009035. PMID 24367955.
Alzheimer’s disease (AD) is a progressive neurological disorder
characterized by loss in cognitive function, abnormal behavior, and
decreased ability to perform basic activities of daily living
[(ADLs)] ... All studies included people with AD who completed an
exercise program consisting of aerobic, strength, or balance training
or any combination of the three. The length of the exercise programs
varied from 12 weeks to 12 months. ... Six studies involving 446
participants tested the effect of exercise on ADL performance ...
exercise had a large and significant effect on ADL performance
(z = 4.07, p < .0001; average effect
size = 0.80). ... These positive effects were apparent
with programs ranging in length from 12 wk (Santana-Sosa et al., 2008;
Teri et al., 2003) and intermediate length of 16 wk (Roach et al.,
2011; Vreugdenhil et al., 2012) to 6 mo (Venturelli et al., 2011) and
12 mo (Rolland et al., 2007). Furthermore, the positive effects of a
3-mo intervention lasted 24 mo (Teri et al., 2003). ... No
adverse effects of exercise on ADL performance were noted. ...
The study with the largest effect size implemented a walking and
aerobic program of only 30 min four times a week (Venturelli et al.,
^ a b Mattson MP (2014). "Interventions that improve body and brain
Parkinson's disease risk reduction and therapy". J
Parkinsons Dis. 4 (1): 1–13. doi:10.3233/JPD-130335.
^ a b c Grazina R, Massano J (2013). "
Physical exercise and
Parkinson's disease: influence on symptoms, disease course and
prevention". Rev Neurosci. 24 (2): 139–152.
doi:10.1515/revneuro-2012-0087. PMID 23492553.
^ a b van der Kolk NM, King LA (September 2013). "Effects of exercise
on mobility in people with Parkinson's disease". Mov. Disord. 28 (11):
1587–1596. doi:10.1002/mds.25658. PMID 24132847.
^ a b Tomlinson CL, Patel S, Meek C, Herd CP, Clarke CE, Stowe R, et
al. (September 2013). "Physiotherapy versus placebo or no intervention
in Parkinson's disease". Cochrane Database Syst Rev. 9: CD002817.
doi:10.1002/14651858.CD002817.pub4. PMID 24018704.
^ a b c Blondell SJ, Hammersley-Mather R, Veerman JL (May 2014). "Does
physical activity prevent cognitive decline and dementia?: A
systematic review and meta-analysis of longitudinal studies". BMC
Public Health. 14: 510. doi:10.1186/1471-2458-14-510.
PMC 4064273 . PMID 24885250. Longitudinal observational
studies show an association between higher levels of physical activity
and a reduced risk of cognitive decline and dementia. A case can be
made for a causal interpretation. Future research should use objective
measures of physical activity, adjust for the full range of
confounders and have adequate follow-up length. Ideally, randomised
controlled trials will be conducted. ... On the whole the results
do, however, lend support to the notion of a causal relationship
between physical activity, cognitive decline and dementia, according
to the established criteria for causal inference.
^ a b c Carroll ME, Smethells JR (February 2016). "Sex Differences in
Behavioral Dyscontrol: Role in Drug
Addiction and Novel Treatments".
Front. Psychiatry. 6: 175. doi:10.3389/fpsyt.2015.00175.
PMC 4745113 . PMID 26903885. There is accelerating
evidence that physical exercise is a useful treatment for preventing
and reducing drug addiction ... In some individuals, exercise has
its own rewarding effects, and a behavioral economic interaction may
occur, such that physical and social rewards of exercise can
substitute for the rewarding effects of drug abuse. ... The value
of this form of treatment for drug addiction in laboratory animals and
humans is that exercise, if it can substitute for the rewarding
effects of drugs, could be self-maintained over an extended period of
time. Work to date in [laboratory animals and humans] regarding
exercise as a treatment for drug addiction supports this
hypothesis. ... However, a RTC study was recently reported by
Rawson et al. (226), whereby they used 8 weeks of exercise as a
post-residential treatment for METH addiction, showed a significant
reduction in use (confirmed by urine screens) in participants who had
been using meth 18 days or less a month. ... Animal and human
research on physical exercise as a treatment for stimulant addiction
indicates that this is one of the most promising treatments on the
horizon. [emphasis added]
^ a b c d e f Lynch WJ, Peterson AB, Sanchez V, Abel J, Smith MA
(September 2013). "Exercise as a novel treatment for drug addiction: a
neurobiological and stage-dependent hypothesis". Neurosci Biobehav
Rev. 37 (8): 1622–1644. doi:10.1016/j.neubiorev.2013.06.011.
PMC 3788047 . PMID 23806439.
^ a b c d e f g h i j k l m n o p q Olsen CM (December 2011). "Natural
rewards, neuroplasticity, and non-drug addictions". Neuropharmacology.
61 (7): 1109–1122. doi:10.1016/j.neuropharm.2011.03.010.
PMC 3139704 . PMID 21459101. Similar to environmental
enrichment, studies have found that exercise reduces
self-administration and relapse to drugs of abuse (Cosgrove et al.,
2002; Zlebnik et al., 2010). There is also some evidence that these
preclinical findings translate to human populations, as exercise
reduces withdrawal symptoms and relapse in abstinent smokers (Daniel
et al., 2006; Prochaska et al., 2008), and one drug recovery program
has seen success in participants that train for and compete in a
marathon as part of the program (Butler, 2005). ... In humans,
the role of dopamine signaling in incentive-sensitization processes
has recently been highlighted by the observation of a dopamine
dysregulation syndrome in some patients taking dopaminergic drugs.
This syndrome is characterized by a medication-induced increase in (or
compulsive) engagement in non-drug rewards such as gambling, shopping,
or sex (Evans et al., 2006; Aiken, 2007; Lader, 2008).
^ a b c Linke SE, Ussher M (2015). "Exercise-based treatments for
substance use disorders: evidence, theory, and practicality". Am J
Drug Alcohol Abuse. 41 (1): 7–15. doi:10.3109/00952990.2014.976708.
PMC 4831948 . PMID 25397661. The limited research
conducted suggests that exercise may be an effective adjunctive
treatment for SUDs. In contrast to the scarce intervention trials to
date, a relative abundance of literature on the theoretical and
practical reasons supporting the investigation of this topic has been
published. ... numerous theoretical and practical reasons support
exercise-based treatments for SUDs, including psychological,
behavioral, neurobiological, nearly universal safety profile, and
overall positive health effects.
^ a b c d Zhou Y, Zhao M, Zhou C, Li R (July 2015). "Sex differences
in drug addiction and response to exercise intervention: From human to
animal studies". Front. Neuroendocrinol. 40: 24–41.
doi:10.1016/j.yfrne.2015.07.001. PMC 4712120 .
PMID 26182835. Collectively, these findings demonstrate that
exercise may serve as a substitute or competition for drug abuse by
ΔFosB or cFos immunoreactivity in the reward system to
protect against later or previous drug use. ... As briefly
reviewed above, a large number of human and rodent studies clearly
show that there are sex differences in drug addiction and exercise.
The sex differences are also found in the effectiveness of exercise on
drug addiction prevention and treatment, as well as underlying
neurobiological mechanisms. The postulate that exercise serves as an
ideal intervention for drug addiction has been widely recognized and
used in human and animal rehabilitation. ... In particular, more
studies on the neurobiological mechanism of exercise and its roles in
preventing and treating drug addiction are needed.
^ a b Cormie P, Nowak AK, Chambers SK, Galvão DA, Newton RU (April
2015). "The potential role of exercise in neuro-oncology". Front.
Oncol. 5: 85. doi:10.3389/fonc.2015.00085. PMC 4389372 .
^ a b Malenka RC, Nestler EJ, Hyman SE (2009). Sydor A, Brown RY, eds.
Molecular Neuropharmacology: A Foundation for Clinical Neuroscience
(2nd ed.). New York: McGraw-Hill Medical. pp. 5, 351.
ISBN 9780071481274. The clinical actions of fluoxetine, like
those of many neuropharmacologic agents, reflect drug-induced neural
plasticity, which is the process by which neurons adapt over time in
response to chronic disturbance. ... For example, evidence
indicates that prolonged increases in cortisol may be damaging to
hippocampal neurons and can suppress hippocampal neurogenesis (the
generation of new neurons postnatally).
^ Malenka RC, Nestler EJ, Hyman SE (2009). "Chapter 8:Atypical
Neurotransmitters". In Sydor A, Brown RY. Molecular Neuropharmacology:
A Foundation for Clinical Neuroscience (2nd ed.). New York:
McGraw-Hill Medical. pp. 199, 215. ISBN 9780071481274.
Neurotrophic factors are polypeptides or small proteins that support
the growth, differentiation, and survival of neurons. They produce
their effects by activation of tyrosine kinases.
^ a b c Tarumi T, Zhang R (January 2014). "Cerebral hemodynamics of
the aging brain: risk of Alzheimer disease and benefit of aerobic
exercise". Front Physiol. 5: 6. doi:10.3389/fphys.2014.00006.
PMC 3896879 . PMID 24478719. Exercise-related improvements
in brain function and structure may be conferred by the concurrent
adaptations in vascular function and structure. Aerobic exercise
increases the peripheral levels of growth factors (e.g., BDNF, IFG-1,
and VEGF) which cross the blood-brain barrier (BBB) and stimulate
neurogenesis and angiogenesis (Trejo et al., 2001; Lee et al., 2002;
Fabel et al., 2003; Lopez-Lopez et al., 2004).
^ a b c d e f g h i Silverman MN, Deuster PA (October 2014).
"Biological mechanisms underlying the role of physical fitness in
health and resilience". Interface Focus. 4 (5): 20140040.
doi:10.1098/rsfs.2014.0040. PMC 4142018 .
^ a b c Batouli SH, Saba V (June 2017). "At least eighty percent of
brain grey matter is modifiable by physical activity: A review study".
Behavioural Brain Research. 332: 204–217.
doi:10.1016/j.bbr.2017.06.002. PMID 28600001. The results of this
study showed that a large network of brain areas, equal to 82% of the
total grey matter volume, were associated with PA. This finding has
important implications in utilizing PA as a mediator factor for
educational purposes in children, rehabilitation applications in
patients, improving the cognitive abilities of the human brain such as
in learning or memory, and preventing age-related brain
deteriorations. ... There is a significant association between
the volume of the brain areas and their corresponding functions.
Examples include the association of total and regional brain volumes
(BV) with executive function and speed of processing, intelligence,
working, verbal and spatial memory, and skill acquisition performance
[27–29]. The connections between brain function and structure is due
to the neural information processing being dependent on the size,
arrangement, and configuration of the neurons, the number and type of
the synaptic connections of the neurons, on the quality of their
connection with distant neurons, and on the properties of non-neuronal
cells such as glia . ... This study showed that PA is
positively associating with nearly all brain regions.
^ a b c Malenka RC, Nestler EJ, Hyman SE (2009). "Chapter 6: Widely
Projecting Systems: Monoamines, Acetylcholine, and Orexin". In Sydor
A, Brown RY. Molecular Neuropharmacology: A Foundation for Clinical
Neuroscience (2nd ed.). New York: McGraw-Hill Medical.
pp. 147–148, 154–157. ISBN 9780071481274.
^ Carvalho A, Rea IM, Parimon T, Cusack BJ (2014). "Physical activity
and cognitive function in individuals over 60 years of age: a
systematic review". Clin Interv Aging. 9: 661–682.
doi:10.2147/CIA.S55520. PMC 3990369 . PMID 24748784.
^ a b Ehlert T, Simon P, Moser DA (February 2013). "Epigenetics in
sports". Sports Med. 43 (2): 93–110. doi:10.1007/s40279-012-0012-y.
PMID 23329609. Alterations in epigenetic modification patterns
have been demonstrated to be dependent on exercise and growth hormone
(GH), insulin-like growth factor 1 (IGF-1), and steroid
administration. ... the authors observed improved stress coping
in exercised subjects. Investigating the dentate gyrus, a brain region
which is involved in learning and coping with stressful and traumatic
events, they could show that this effect is mediated by increased
phosphorylation of serine 10 combined with H3K14 acetylation, which is
associated with local opening of condensed chromatin. Consequently,
they found increased immediate early gene expression as shown for
c-FOS (FBJ murine osteosarcoma viral oncogene homologue).
^ a b c d e f g Phillips C, Baktir MA, Srivatsan M, Salehi A (2014).
"Neuroprotective effects of physical activity on the brain: a closer
look at trophic factor signaling". Front Cell Neurosci. 8: 170.
doi:10.3389/fncel.2014.00170. PMC 4064707 .
^ a b c Heinonen I, Kalliokoski KK, Hannukainen JC, Duncker DJ,
Nuutila P, Knuuti J (November 2014). "Organ-Specific Physiological
Responses to Acute Physical Exercise and Long-Term Training in
Humans". Physiology. 29 (6): 421–436.
doi:10.1152/physiol.00067.2013. PMID 25362636.
^ a b c d Torres-Aleman I (2010). "Toward a comprehensive neurobiology
of IGF-I". Dev Neurobiol. 70 (5): 384–96. doi:10.1002/dneu.20778.
^ a b c Aberg D (2010). "Role of the growth hormone/insulin-like
growth factor 1 axis in neurogenesis". Endocr Dev. 17: 63–76.
doi:10.1159/000262529. PMID 19955757.
^ a b c Malenka RC, Nestler EJ, Hyman SE (2009). Sydor A, Brown RY,
eds. Molecular Neuropharmacology: A Foundation for Clinical
Neuroscience (2nd ed.). New York: McGraw-Hill Medical. pp. 221,
412. ISBN 9780071481274.
^ Gatti R, De Palo EF, Antonelli G, Spinella P (July 2012).
"IGF-I/IGFBP system: metabolism outline and physical exercise". J.
Endocrinol. Invest. 35 (7): 699–707. doi:10.3275/8456.
PMID 22714057. Copeland et al. (90) studied the effect of a
moderate-intensity exercise and a high-intensity equal duration
intervalled exercise in healthy males. IGF-I and IGFBP-3 increased
during both exercise trials, but only the IGFBP-3 area under curve was
significantly greater during high-intensity exercise than resting
control session. ... Decreased IGF-I and increased IGFBP-1
levels, observed by Rarick et al. (100) after mild aerobic training,
might be an adaptive physiological response to prevent hypoglycemia
following insulin-sensitizing training. In fact the decrease of
circulating IGF-I during short-term training seems to be reflective of
favorable neuromuscular anabolic adaptation and is a normal adaptive
response to increased physical activity. The potential for
exercise-induced increases in circulating IGF-I seems to require
longer training duration (100).
^ a b Bouchard J, Villeda SA (2015). "Aging and brain rejuvenation as
systemic events". J. Neurochem. 132 (1): 5–19.
doi:10.1111/jnc.12969. PMC 4301186 . PMID 25327899.
^ a b Valkanova V, Eguia Rodriguez R, Ebmeier KP (June 2014). "Mind
over matter—what do we know about neuroplasticity in adults?". Int
Psychogeriatr. 26 (6): 891–909. doi:10.1017/S1041610213002482.
PMID 24382194. Control group: Active
Intervention: Aerobic exercise
[Increased GMV in:] Lobes (dorsal anterior cingulate cortex,
supplementary motor area, middle frontal gyrus bilaterally); R
inferior frontal gyrus, middle frontal gyrus and L superior temporal
lobe; increase in the volume of anterior white matter tracts ...
↑GMV anterior hippocampus
^ Ruscheweyh R, Willemer C, Krüger K, Duning T, Warnecke T, Sommer J,
Völker K, Ho HV, Mooren F, Knecht S, Flöel A (July 2011). "Physical
activity and memory functions: an interventional study". Neurobiol.
Aging. 32 (7): 1304–19. doi:10.1016/j.neurobiolaging.2009.08.001.
^ a b c Erickson KI, Voss MW, Prakash RS, Basak 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 (February 2011).
"Exercise training increases size of hippocampus and improves memory".
Proc. Natl. Acad. Sci. U.S.A. 108 (7): 3017–3022.
doi:10.1073/pnas.1015950108. PMC 3041121 .
^ a b c d e f g Malenka RC, Nestler EJ, Hyman SE (2009). "Chapter 13:
Higher Cognitive Function and Behavioral Control". In Sydor A, Brown
RY. Molecular Neuropharmacology: A Foundation for Clinical
Neuroscience (2nd ed.). New York: McGraw-Hill Medical.
pp. 313–321. ISBN 9780071481274.
^ Malenka RC, Nestler EJ, Hyman SE (2009). "Chapter 13: Higher
Cognitive Function and Behavioral Control". In Sydor A, Brown RY.
Molecular Neuropharmacology: A Foundation for Clinical Neuroscience
(2nd ed.). New York: McGraw-Hill Medical. p. 315.
ISBN 9780071481274. The anterior cingulate cortex is involved in
processes that require correct decision-making, as seen in conflict
resolution (eg, the Stroop test, see in Chapter 16), or cortical
inhibition (eg, stopping one task and switching to another). The
medial prefrontal cortex is involved in supervisory attentional
functions (eg, action-outcome rules) and behavioral flexibility (the
ability to switch strategies). The dorsolateral prefrontal cortex, the
last brain area to undergo myelination during development in late
adolescence, is implicated in matching sensory inputs with planned
motor responses. The ventromedial prefrontal cortex seems to regulate
social cognition, including empathy. The orbitofrontal cortex is
involved in social decision making and in representing the valuations
assigned to different experiences.
^ Malenka RC, Nestler EJ, Hyman SE (2009). Sydor A, Brown RY, eds.
Molecular Neuropharmacology: A Foundation for Clinical Neuroscience
(2nd ed.). New York: McGraw-Hill Medical. pp. 147, 266, 376.
^ a b c Malenka RC, Nestler EJ, Hyman SE (2009). Sydor A, Brown RY,
eds. Molecular Neuropharmacology: A Foundation for Clinical
Neuroscience (2nd ed.). New York: McGraw-Hill Medical. pp. 148,
324–328, 438. ISBN 9780071481274.
^ Grimaldi G, Argyropoulos GP, Bastian A, Cortes M, Davis NJ, Edwards
DJ, Ferrucci R, Fregni F, Galea JM, Hamada M, Manto M, Miall RC,
Morales-Quezada L, Pope PA, Priori A, Rothwell J, Tomlinson SP, Celnik
P (2014). "Cerebellar Transcranial Direct Current Stimulation (ctDCS):
A Novel Approach to Understanding Cerebellar Function in Health and
Disease". Neuroscientist. 22: 83–97. doi:10.1177/1073858414559409.
PMC 4712385 . PMID 25406224.
^ Sereno MI, Huang RS (2014). "Multisensory maps in parietal cortex".
Curr. Opin. Neurobiol. 24 (1): 39–46.
doi:10.1016/j.conb.2013.08.014. PMC 3969294 .
^ a b c d e Diamond A (2013). "Executive functions". Annu Rev Psychol.
64: 135–168. doi:10.1146/annurev-psych-113011-143750.
PMC 4084861 . PMID 23020641.
^ a b c Janssen M, Toussaint HM, van Mechelen W, Verhagen EA (2014).
"Effects of acute bouts of physical activity on children's attention:
a systematic review of the literature". Springerplus. 3: 410.
doi:10.1186/2193-1801-3-410. PMC 4132441 . PMID 25133092.
There is weak evidence for the effect of acute bouts of physical
activity on attention. ... Fortunately, the literature-base on
the acute effect of PA on the underlying cognitive processes of
academic performance is growing. Hillman et al. (2011) found in their
review a positive effect of acute PA on brain health and cognition in
children, but concluded it was complicated to compare the different
studies due to the different outcome measures (e.g. memory, response
time and accuracy, attention, and comprehension). Therefore, this
review focuses on the sole outcome measure ‘attention’ as a
mediator for cognition and achievement.
^ Moreau D, Kirk IJ, Waldie, KE (2017). "High-intensity training
enhances executive function in children in a randomized,
placebo-controlled trial". eLife. 6:e25062. doi:10.7554/eLife.25062.
PMC 5566451 . PMID 28825973.
^ a b Ilieva IP, Hook CJ, Farah MJ (2015). "Prescription Stimulants'
Effects on Healthy Inhibitory Control, Working Memory, and Episodic
Memory: A Meta-analysis". J Cogn Neurosci. 27: 1–21.
doi:10.1162/jocn_a_00776. PMID 25591060.
^ Northey, Joseph Michael; Cherbuin, Nicolas; Pumpa, Kate Louise;
Smee, Disa Jane; Rattray, Ben (2017-03-30). "Exercise interventions
for cognitive function in adults older than 50: a systematic review
with meta-analysis". Br J Sports Med: bjsports–2016–096587.
doi:10.1136/bjsports-2016-096587. ISSN 0306-3674.
^ a b Basso JC, Shang A, Elman M, Karmouta R, Suzuki WA (November
2015). "Acute Exercise Improves Prefrontal Cortex but not Hippocampal
Function in Healthy Adults". Journal of the International
Neuropsychological Society : JINS. 21 (10): 791–801.
doi:10.1017/S135561771500106X. PMID 26581791.
^ a b McMorris T, Hale BJ (December 2012). "Differential effects of
differing intensities of acute exercise on speed and accuracy of
cognition: a meta-analytical investigation". Brain and Cognition. 80
(3): 338–351. doi:10.1016/j.bandc.2012.09.001.
^ a b c d Malenka RC, Nestler EJ, Hyman SE (2009). "Chapter 14: Mood
and Emotion". In Sydor A, Brown RY. Molecular Neuropharmacology: A
Foundation for Clinical Neuroscience (2nd ed.). New York: McGraw-Hill
Medical. pp. 350–359. ISBN 9780071481274. The excessive
release of stress hormones, such as cortisol, which occurs in many
individuals with mood disorders, may result from hyperfunctioning of
the PVN of the hypothalamus, hyperfunctioning of the amygdala (which
activates the PVN), or hypofunctioning of the hippocampus (which
exerts a potent inhibitory influence on the PVN). ... Chronic
stress decreases the expression of brain-derived neurotrophic factor
(BDNF) in the hippocampus, which in turn may contribute to the atrophy
of CA3 neurons and their increased vulnerability to a variety of
neuronal insults. Chronic elevation of glucocorticoid levels is also
known to decrease the survival of these neurons. Such activity may
increase the dendritic arborizations and survival of the neurons, or
help repair or protect the neurons from further damage. ...
Stress and glucocorticoids inhibit, and a wide variety of
antidepressant drugs, exercise, and enriched environments activate
^ a b c d e Fuqua JS, Rogol AD (July 2013). "Neuroendocrine
alterations in the exercising human: implications for energy
homeostasis". Metab. Clin. Exp. 62 (7): 911–921.
doi:10.1016/j.metabol.2013.01.016. PMID 23415825.
^ a b c d Ebner NC, Kamin H, Diaz V, Cohen RA, MacDonald K (January
2015). "Hormones as "difference makers" in cognitive and
socioemotional aging processes". Front Psychol. 5: 1595.
doi:10.3389/fpsyg.2014.01595. PMC 4302708 .
^ a b Zschucke E, Gaudlitz K, Ströhle A (January 2013). "Exercise and
physical activity in mental disorders: clinical and experimental
evidence". J Prev Med Public Health. 46 Suppl 1: S12–521.
doi:10.3961/jpmph.2013.46.S.S12. PMC 3567313 .
PMID 23412549. In psychiatric patients, different mechanisms of
action for PA and EX have been discussed: On a neurochemical and
physiological level, a number of acute changes occur during and
following bouts of EX, and several long-term adaptations are related
to regular EX training. For instance, EX has been found to normalize
reduced levels of brain-derived neurotrophic factor (BDNF) and
therefore has neuroprotective or even neurotrophic effects [7–9].
Animal studies found EX-induced changes in different neurotransmitters
such as serotonin and endorphins [10,11], which relate to mood, and
positive effects of EX on stress reactivity (e.g., the
hypothalamus-pituitary-adrenal axis [12,13]). Finally, anxiolytic
effects of EX mediated by atrial natriuretic peptide have been
reported . Potential psychological mechanisms of action include
learning and extinction, changes in body scheme and health
attitudes/behaviors, social reinforcement, experience of mastery,
shift of external to more internal locus of control, improved coping
strategies, or simple distraction [15,16].
^ a b Raichlen DA, Foster AD, Gerdeman GL, Seillier A, Giuffrida A
(2012). "Wired to run: exercise-induced endocannabinoid signaling in
humans and cursorial mammals with implications for the 'runner's
high'". J. Exp. Biol. 215 (Pt 8): 1331–1336. doi:10.1242/jeb.063677.
PMID 22442371. Humans report a wide range of neurobiological
rewards following moderate and intense aerobic activity, popularly
referred to as the 'runner's high', which may function to encourage
habitual aerobic exercise. ... Thus, a neurobiological reward for
endurance exercise may explain why humans and other cursorial mammals
habitually engage in aerobic exercise despite the higher associated
energy costs and injury risks
^ Cohen EE, Ejsmond-Frey R, Knight N, Dunbar RI (2010). "Rowers' high:
behavioural synchrony is correlated with elevated pain thresholds".
Biol. Lett. 6 (1): 106–108. doi:10.1098/rsbl.2009.0670.
PMC 2817271 . PMID 19755532.
^ a b c d e Szabo A, Billett E, Turner J (2001). "Phenylethylamine, a
possible link to the antidepressant effects of exercise?". Br J Sports
Med. 35 (5): 342–343. doi:10.1136/bjsm.35.5.342.
PMC 1724404 . PMID 11579070. The 24 hour mean urinary
concentration of phenylacetic acid was increased by 77% after
exercise. ... As phenylacetic acid reflects phenylethylamine
levels3, and the latter has antidepressant effects, the antidepressant
effects of exercise appear to be linked to increased phenylethylamine
concentrations. Furthermore, considering the structural and
pharmacological analogy between amphetamines and phenylethylamine, it
is conceivable that phenylethylamine plays a role in the commonly
reported "runners high" thought to be linked to cerebral β-endorphin
activity. The substantial increase in phenylacetic acid excretion in
this study implies that phenylethylamine levels are affected by
exercise. ... A 30 minute bout of moderate to high intensity
aerobic exercise increases phenylacetic acid levels in healthy
regularly exercising men.
^ a b c d e Lindemann L, Hoener MC (2005). "A renaissance in trace
amines inspired by a novel GPCR family". Trends Pharmacol. Sci. 26
(5): 274–281. doi:10.1016/j.tips.2005.03.007. PMID 15860375.
The pharmacology of TAs might also contribute to a molecular
understanding of the well-recognized antidepressant effect of physical
exercise . In addition to the various beneficial effects for brain
function mainly attributed to an upregulation of peptide growth
factors [52,53], exercise induces a rapidly enhanced excretion of the
main β-PEA metabolite β-phenylacetic acid (b-PAA) by on average 77%,
compared with resting control subjects , which mirrors increased
β-PEA synthesis in view of its limited endogenous pool half-life of
~30 s [18,55].
^ a b c d e Berry MD (2007). "The potential of trace amines and their
receptors for treating neurological and psychiatric diseases". Rev
Recent Clin Trials. 2 (1): 3–19. doi:10.2174/157488707779318107.
PMID 18473983. It has also been suggested that the antidepressant
effects of exercise are due to an exercise-induced elevation of PE
^ a b c d e f Dinas PC, Koutedakis Y, Flouris AD (2011). "Effects of
exercise and physical activity on depression". Ir J Med Sci. 180 (2):
319–325. doi:10.1007/s11845-010-0633-9. PMID 21076975.
^ a b c d e Tantimonaco M, Ceci R, Sabatini S, Catani MV, Rossi A,
Gasperi V, Maccarrone M (2014). "Physical activity and the
endocannabinoid system: an overview". Cell. Mol. Life Sci. 71 (14):
2681–2698. doi:10.1007/s00018-014-1575-6. PMID 24526057.
^ "β-phenylethylamine: Biological activity". Guide to Pharmacology.
The International Union of Basic and Clinical Pharmacology. Retrieved
10 February 2015.
^ "Dexamfetamine: Biological activity". Guide to Pharmacology. The
International Union of Basic and Clinical Pharmacology. Retrieved 10
^ a b Broadley KJ (March 2010). "The vascular effects of trace amines
and amphetamines". Pharmacol. Ther. 125 (3): 363–375.
doi:10.1016/j.pharmthera.2009.11.005. PMID 19948186. Trace amines
are metabolized in the mammalian body via monoamine oxidase (MAO; EC
220.127.116.11) (Berry, 2004) (Fig. 2) ... It deaminates primary and
secondary amines that are free in the neuronal cytoplasm but not those
bound in storage vesicles of the sympathetic neurone ...
Similarly, β-PEA would not be deaminated in the gut as it is a
selective substrate for MAO-B which is not found in the gut ...
Brain levels of endogenous trace amines are several hundred-fold below
those for the classical neurotransmitters noradrenaline, dopamine and
serotonin but their rates of synthesis are equivalent to those of
noradrenaline and dopamine and they have a very rapid turnover rate
(Berry, 2004). Endogenous extracellular tissue levels of trace amines
measured in the brain are in the low nanomolar range. These low
concentrations arise because of their very short
^ Fuss J, Steinle J, Bindila L, Auer MK, Kirchherr H, Lutz B, and Gass
P (2015). "A runner's high depends on cannabinoid receptors in mice".
PNAS. 112 (42): 13105–13108. doi:10.1073/pnas.1514996112.
PMC 4620874 . PMID 26438875.
^ Malenka RC, Nestler EJ, Hyman SE (2009). "Chapter 5: Excitatory and
Inhibitory Amino Acids". In Sydor A, Brown RY. Molecular
Neuropharmacology: A Foundation for Clinical Neuroscience (2nd ed.).
New York: McGraw-Hill Medical. pp. 117–130.
ISBN 9780071481274. • The major excitatory
neurotransmitter in the brain is glutamate; the major inhibitory
neurotransmitter is GABA. ...
• The most extensively studied form of synaptic plasticity is
long-term potentiation (LTP) in the hippocampus, which is triggered by
strong activation of NMDA receptors and the consequent large rise in
postsynaptic calcium concentration.
• Long-term depression (LTD), a long-lasting decrease in
synaptic strength, also occurs at most excitatory and some inhibitory
synapses in the brain. ... The bidirectional control of synaptic
strength by LTP and LTD is believed to underlie some forms of learning
and memory in the mammalian brain.
^ a b Mischel NA, Subramanian M, Dombrowski MD, Llewellyn-Smith IJ,
Mueller PJ (May 2015). "(In)activity-related neuroplasticity in
brainstem control of sympathetic outflow: unraveling underlying
molecular, cellular, and anatomical mechanisms". Am. J. Physiol. Heart
Circ. Physiol. 309 (2): H235–43. doi:10.1152/ajpheart.00929.2014.
PMC 4504968 . PMID 25957223.
^ a b c d Sibley BA, Etnier JL (2003). "The Relationship Between
Physical Activity and
Cognition in Children: A Meta-Analysis".
Pediatric Exercise Science. 15 (3): 243–256.
^ a b Chaddock L, Hillman CH, Buck SM, Cohen NJ (2011). "Aerobic
Fitness and Executive Control of Relational
Memory in Preadolescent
Children". Medicine & Science in Sports & Exercise. 43 (2):
^ a b c Chaddock I, Erickson KI, Prakash RS, Kim JS, Voss MA,
VanPatter M, et al. (2010). "A neuroimaging investigation of the
association between aerobic fitness, hippocampal volume, and memory
performance in preadolescent children". Brain Research. 1358:
172–183. doi:10.1016/j.brainres.2010.08.049. PMC 3953557 .
^ a b c Best JR (2010). "Effects of physical activity on children's
executive function: Contributions of experimental research on aerobic
exercise". Developmental Review. 30 (4): 331–351.
^ a b c Hillman CH, Erickson KI, Kramer AF (2008). "Be smart, exercise
your heart: exercise effects on brain and cognition". Nature Reviews
Neuroscience. 9: 58–65. doi:10.1038/nrn2298.
^ COE, DAWN PODULKA; PIVARNIK, JAMES M.; WOMACK, CHRISTOPHER J.;
REEVES, MATHEW J.; MALINA, ROBERT M. (2006-08-01). "Effect of Physical
Education and Activity Levels on Academic Achievement in Children".
Medicine & Science in Sports & Exercise. 38 (8): 1515–1519.
doi:10.1249/01.mss.0000227537.13175.1b. ISSN 0195-9131.
^ a b Rommel AS, Halperin JM, Mill J, Asherson P, Kuntsi J (September
2013). "Protection from genetic diathesis in
attention-deficit/hyperactivity disorder: possible complementary roles
of exercise". J. Am. Acad. Child Adolesc. Psychiatry. 52 (9):
900–910. doi:10.1016/j.jaac.2013.05.018. PMC 4257065 .
PMID 23972692. As exercise has been found to enhance neural
growth and development, and improve cognitive and behavioural
functioning in [healthy] individuals and animal studies, we reviewed
the literature on the effects of exercise in children and adolescents
with ADHD and animal models of ADHD behaviours.
A limited number of undersized non-randomized, retrospective and
cross-sectional studies have investigated the impact of exercise on
ADHD and the emotional, behavioural and neuropsychological problems
associated with the disorder. The findings from these studies provide
some support for the notion that exercise has the potential to act as
a protective factor for ADHD. ... Although it remains unclear
which role, if any,
BDNF plays in the pathophysiology of ADHD,
enhanced neural functioning has been suggested to be associated with
the reduction of remission of ADHD symptoms.49,50,72 As exercise can
elicit gene expression changes mediated by alterations in DNA
methylation38, the possibility emerges that some of the positive
effects of exercise could be caused by epigenetic mechanisms, which
may set off a cascade of processes instigated by altered gene
expression that could ultimately link to a change in brain
^ a b Cooney GM, Dwan K, Greig CA, Lawlor DA, Rimer J, Waugh FR,
McMurdo M, Mead GE (September 2013). "Exercise for depression".
Cochrane Database Syst. Rev. 9 (9): CD004366.
doi:10.1002/14651858.CD004366.pub6. PMID 24026850. Exercise is
moderately more effective than a control intervention for reducing
symptoms of depression, but analysis of methodologically robust trials
only shows a smaller effect in favour of exercise. When compared to
psychological or pharmacological therapies, exercise appears to be no
more effective, though this conclusion is based on a few small
^ Brené S, Bjørnebekk A, Aberg E, Mathé AA, Olson L, Werme M
(2007). "Running is rewarding and antidepressive". Physiol. Behav. 92
(1–2): 136–140. doi:10.1016/j.physbeh.2007.05.015.
PMC 2040025 . PMID 17561174.
^ Gong H, Ni C, Shen X, Wu T, Jiang C (February 2015). "
prenatal depression: a systematic review and meta-analysis". BMC
Psychiatry. 15: 14. doi:10.1186/s12888-015-0393-1.
PMC 4323231 . PMID 25652267.
^ Adlard PA, Perreau VM, Pop V, Cotman CW (2005). "Voluntary exercise
decreases amyloid load in a transgenic model of Alzheimer's disease".
J. Neurosci. 25 (17): 4217–21. doi:10.1523/JNEUROSCI.0496-05.2005.
^ a b Elwood P, Galante J, Pickering J, Palmer S, Bayer A, Ben-Shlomo
Y, Longley M, Gallacher J (December 2013). "Healthy lifestyles reduce
the incidence of chronic diseases and dementia: evidence from the
Caerphilly cohort study". PLoS ONE. 8 (12): e81877.
doi:10.1371/journal.pone.0081877. PMC 3857242 .
^ Morgan GS, Gallacher J, Bayer A, Fish M, Ebrahim S, Ben-Shlomo Y
(2012). "Physical activity in middle-age and dementia in later life:
findings from a prospective cohort of men in Caerphilly, South Wales
and a meta-analysis". J. Alzheimers Dis. 31 (3): 569–80.
doi:10.3233/JAD-2012-112171. PMID 22647258.
^ Baatile J, Langbein WE, Weaver F, Maloney C, Jost MB (2000). "Effect
of exercise on perceived quality of life of individuals with
Parkinson's Disease". Journal of Rehabilitation Research and
Development. 37 (5): 529–534.
^ a b Kramer AF, Erickson KI, Colcombe SJ (2006). "Exercise,
cognition, and the aging brain". Journal of Applied Physiology. 101
(4): 1237–1242. doi:10.1152/japplphysiol.00500.2006.
^ Kramer AF, Hahn S, Cohen NJ, Banich MT, McAuley E, Harrison CR,
Chason J, Vakil E, Bardell L, Boileau RA, Colcombe A (July 1999).
"Ageing, fitness and neurocognitive function". Nature. 400 (6743):
418–419. doi:10.1038/22682. PMID 10440369.
^ a b Nocera JR, Altman LJ, Sapienza C, Okun MS, Hass CJ (2010). "Can
exercise improve language and cognition in Parkinson's disease? A case
report". Neurocase: The Neural Basis of Cognition. 16 (4): 301–306.
Outline of exercise
Neurobiological effects of physical exercise
"The Magical Number Seven, Plus or Minus Two"
Tip of the tongue
List of memory biases
Misattribution of memory
Art of memory
Memory and aging
Indirect tests of memory
Lost in the mall technique
Methods used to study memory
The Seven Sins of Memory
Neurobiological effects of physical exercise
False memory syndrome
Memory and social interactions
Politics of memory
Atkinson–Shiffrin memory model
Effects of alcohol
Emotion and memory
Memory and trauma
Sleep and memory
Robert A. Bjork
Stephen J. Ceci
Judith Lewis Herman
Marcia K. Johnson
Paul R. McHugh
George Armitage Miller
Henry L. Roediger III
Arthur P. Shimamura