[9][16][17][18] 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 these conditions.

[1] 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.

[37] 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.

[5] Aerobic exercise has also been shown to induce growth in the white matter tracts in the anterior corpus callosum, which normally shrink with age.

[29][50] Furthermore, research has provided a great deal of support for the role of BDNF in hippocampal neurogenesis, synaptic plasticity, and neural repair.

[50][54][55] 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;[5][50][53][54] 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".

[56] VEGF is a neurotrophic and angiogenic (i.e., blood vessel growth-promoting) signaling protein that binds to two receptor tyrosine kinases, VEGFR1 and VEGFR2, which are expressed in neurons and glial cells in the brain.

[55] 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.

[12][62][63] Reviews and meta-analyses of research on the effects of acute exercise on cognition in healthy young and middle-aged adults 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.

[44] Other research has suggested immediate performative enhancements during exercise, such as exercise-concurrent improvements in processing speed and accuracy during both visual attention and working memory tasks.

[74] 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.

[75][76][77] Two reviews noted a study where the average 24 hour urinary β-phenylacetic acid concentration among participants following just 30 minutes of intense exercise increased by 77% relative to baseline concentrations in resting control subjects;[75][76][77] the reviews suggest that phenethylamine synthesis sharply increases while an individual is exercising, during which time it is rapidly metabolized due to its short half-life of roughly 30 seconds.

[75][76][77][78] In a resting state, phenethylamine is synthesized in catecholamine neurons from L-phenylalanine by aromatic amino acid decarboxylase (AADC) at approximately the same rate at which dopamine is produced.

[12][85] Exercise also reverses stress-induced decreases in BDNF expression and signaling in the brain, thereby acting as a buffer against stress-related diseases like depression.

[86] Based upon animal models, exercise appears to normalize the excessive levels of glutamate neurotransmission into the nucleus accumbens that occurs in drug addiction.

[21] 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;[87] the review hypothesized that this neuroplasticity in the RVLM is a mechanism by which regular exercise prevents inactivity-related cardiovascular disease.

[87] Exerkines are putative "signalling moieties released in response to acute and/or chronic exercise, which exert their effects through endocrine, paracrine and/or autocrine pathways".

[88] Engaging in active physical pursuits has demonstrated positive effects on the mental health of children and adolescents,[89] enhances their academic performance,[90] boosts cognitive function,[91] and diminishes the likelihood of obesity and cardiovascular diseases among this demographic.

Children 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.

[98] Some investigations have linked low levels of aerobic fitness in children with impaired executive function when older as adults, but lack of selective attention, response inhibition, and interference control may also explain this outcome.

[20][21][22][23] Consistent aerobic exercise magnitude-dependently (i.e., by duration and intensity) may reduce drug addiction risk, which appears to occur through the reversal of drug-induced, addiction-related neuroplasticity.

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.

[5] These benefits have also been noted in old age, with a review conducted in 2019 finding that exercise is an effective treatment for clinically diagnosed depression in older adults.

[106] A 2024 systematic review and network meta-analysis of 218 randomized controlled trials involving over 14,000 participants found that various forms of exercise, including walking or jogging, yoga, resistance training, and mixed aerobic activities, were associated with reductions in depressive symptoms.

While confidence in the findings was limited by methodological concerns in the included studies, the review noted that exercise produced significant improvements in symptoms across a wide range of participants and treatment contexts.

[114][115][116] The increase in NO production may lead to improved post-stroke cerebral blood flow, ensuring a sufficient oxygen and nutrient supply to the brain.

These effects collectively contribute to the reduction of brain infarction and edema, leading to potential improvements in neurological and functional outcomes.

[127][128][129] 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.

[26] Parkinson's disease symptoms reflect various functional impairments and limitations, such as postural instability, gait disturbance, immobility, and frequent falls.

[130] A 2017 study found that strength and endurance training in people with Parkinson's disease had positive effects lasting for several weeks.