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Maintaining cognition and brain fitness is a priority for many patients. And exercise is one of the strategies that has been shown to optimize both mitochondrial and cognitive function, potentially decelerating cognitive decline and attenuating neurodegeneration. Our understanding of how exercise and other factors such as nutrition, sleep, and social activities impact cognition and brain structure continues to evolve. Early interventions focused on modifiable lifestyle factors may slow neurodegeneration and improve brain health, which continues to be backed by emerging research.

In the following video, IFM educator Robert Rountree, MD, talks about the growing concern about brain health and its flipside, cognitive decline, among his patients.

Exercise, Mitochondrial Health, and Brain Fitness

Studies have suggested that physical activity may delay brain aging and degenerative pathologies, improve cognitive processes and memory, and even promote a sense of well-being.¹ A 2019 meta-analysis assessed 48 studies that compared the effects of exercise on both physical function and cognitive function in older adults (60 years of age or older) and suggested that exercise training has a significant benefit, improving both functions in this population.² Other recent meta-analyses and controlled trials have found that several different types of physical activity, including the following, may improve attention, executive function, and memory:

• Both low to moderate and high intensity exercise^3,4
• Short-term interval training and aerobic exercise^5,6
• Social dancing⁷
• Multimodal physical exercise⁸
• Mind-body exercises such as tai chi, yoga, and qigong⁹

One component of exercise benefits on brain health is the optimization of mitochondrial function. Aging has been associated with a decrease in specific mitochondrial functions, such as biogenesis and mitophagy.¹⁰ In addition, neuroinflammation, oxidative stress, and mitochondrial dysfunction have all been noted in the progression of neurodegenerative disorders such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and multiple sclerosis (MS).^11,12 Research suggests that physical activity may have an anti-aging impact through the improvement of mitochondrial functions and by contributing an anti-inflammatory effect.^10,13

• Exercise may protect neurons against dysfunction and degeneration as the neurons respond to activity by activating signaling pathways, including those that stimulate mitochondrial biogenesis such as transcription factor coactivator PGC-1a and those that upregulate autophagy and mitophagy.^1,14
• Both endurance activity and resistance exercise may induce an increase of circulating neurotrophins such as brain-derived neurotrophic factor (BDNF), which in turn stimulates mitochondrial biogenesis.¹
• Exercise may also impact the regulation of neuroinflammation and glial activation, which both play active roles in neurodegenerative diseases. A 2019 review found that while the mechanisms have not been clearly determined, exercise may regulate microglial activation through an increase in anti-inflammatory factors.¹³

BRAIN VOLUME

Research has suggested that exercise improves neuroplasticity by altering synaptic structure and function in various brain regions.^13,15 In addition, movement and specific types of exercise may even impact the quality and physical amount of brain matter.^16,17 A 2020 report with synthesized data from two independent population-based cohorts indicated that cardiorespiratory fitness is positively associated with total brain volume as well as grey matter volume in adults.¹⁷ Study conclusions suggested that cardiorespiratory fitness may not only contribute to improved brain health, but also potentially decelerate any grey matter decrease associated with disease pathologies.¹⁷

Cognitive Impairment & Neurodegenerative Disorders

Exercise can be an effective strategy to improve plasticity, preserve neuronal function, and reduce the risk of cognitive decline and dementia later in life.^15,18 In addition, application of exercise intervention strategies in the early stages of neurocognitive disorders may improve executive functions.

• Aerobic training has been suggested to potentially delay the progression of vascular cognitive impairment (VCI), and a small randomized controlled trial found that moderate-intensity aerobic training improved executive functions and neural efficiency for those older patients with mild subcortical ischemic VCI.⁶
• A small randomized controlled trial investigated the impact of exercise on mild cognitive impairment (MCI) and AD. After following a 12-week multimodal physical exercise program, those elderly patients with MCI showed improvements in both mobility and executive functions. Those patients with AD did not show those same improvements.⁸

Appropriate exercise interventions for the treatment of neurodegenerative disorders potentially improves cognitive functions, slows degeneration, and may also enhance quality of life for patients. A 2020 review suggested that exercise training as an adjunctive therapy for PD improves both motor disorders, including balance and risk of falls, and non-motor disorders, such as cognitive function and quality of life.¹⁹ Recent research also suggests that for patients with MS, in addition to improving quality of life, exercise may enhance aerobic fitness, strength, and cognition.^4,20

Clinical Takeaways: Brain Health Strategies

Personalizing a comprehensive treatment strategy that includes an appropriate exercise program is part of a Functional Medicine approach to optimizing brain health. From improving neuroplasticity and preserving neuronal function to enhancing quality of life, exercise is an important part of a patient’s personalized clinical intervention for boosting cognitive function and slowing neurodegeneration.

Within the Functional Medicine framework, practitioners collaborate with patients to develop personalized therapeutic strategies that are most beneficial to their current conditions and concerns. Treatments for patients with cognitive issues and those concerned about brain-aging may include support of mitochondrial health and concurrent consideration of multiple lifestyle factors, including exercise, nutrition, sleep, and relationships. Learn more about tools and strategies to help patients achieve sustainable lifestyle change and improve their well-being through IFM’s new course Lifestyle: The Foundations of Functional Medicine.

Related Articles

Slowing Neurodegeneration With Nutrition

Nutrition: A Key Modulator of Cognitive Health

Protecting the Brain With Exercise

Clinical Application and Treatment for Neurodegenerative Decline

Sleep Deprivation: A Deeper Dive

References

1. Di Liegro CM, Schiera G, Proia P, Di Liegro I. Physical activity and brain health. Genes (Basel). 2019;10(9):720. doi:10.3390/genes10090720
2. Falck RS, Davis JC, Best JR, Crockett RA, Liu-Ambrose T. Impact of exercise training on physical and cognitive function among older adults: a systematic review and meta-analysis. Neurobiol Aging. 2019;79:119-130. doi:10.1016/j.neurobiolaging.2019.03.007
3. Moreau D, Chou E. The acute effect of high-intensity exercise on executive function: a meta-analysis. Perspect Psychol Sci. 2019;14(5):734-764. doi:10.1177/1745691619850568
4. Zaenker P, Favret F, Lonsdorfer E, Muff G, de Seze J, Isner-Horobeti ME. High-intensity interval training combined with resistance training improves physiological capacities, strength and quality of life in multiple sclerosis patients: a pilot study. Eur J Phys Rehabil Med. 2018;54(1):58-67. doi:10.23736/S1973-9087.17.04637-8
5. Bouaziz W, Schmitt E, Vogel T, et al. Effects of a short-term Interval Aerobic Training Programme with active Recovery bouts (IATP-R) on cognitive and mental health, functional performance and quality of life: a randomised controlled trial in sedentary seniors. Int J Clin Pract. 2019;73(1):e13219. doi:10.1111/ijcp.13219
6. Hsu CL, Best JR, Davis JC, et al. Aerobic exercise promotes executive functions and impacts functional neural activity among older adults with vascular cognitive impairment. Br J Sports Med. 2018;52(3):184-191. doi:10.1136/bjsports-2016-096846
7. Vaccaro MG, Izzo G, Ilacqua A, et al. Characterization of the effects of a six-month dancing as approach for successful aging. Int J Endocrinol. 2019;2019:2048391. doi:10.1155/2019/2048391
8. de Oliveira Silva F, Ferreira JV, Plácido J, et al. Three months of multimodal training contributes to mobility and executive function in elderly individuals with mild cognitive impairment, but not in those with Alzheimer’s disease: a randomized controlled trial. Maturitas. 2019;126:28-33. doi:10.1016/j.maturitas.2019.04.217
9. Zou L, Loprinzi PD, Yeung AS, Zeng N, Huang T. The beneficial effects of mind-body exercises for people with mild cognitive impairment: a systematic review with meta-analysis. Arch Phys Med Rehabil. 2019;100(8):1556-1573. doi:10.1016/j.apmr.2019.03.009
10. Moreira OC, Estébanez B, Martínez-Florez S, de Paz JA, Cuevas MJ, González-Gallego J. Mitochondrial function and mitophagy in the elderly: effects of exercise. Oxid Med Cell Longev. 2017;2017:2012798. doi:10.1155/2017/2012798
11. Swerdlow RH. Mitochondria and mitochondrial cascades in Alzheimer’s disease. J Alzheimers Dis. 2018;62(3):1403-1416. doi:10.3233/JAD-170585
12. García S, Martín Giménez VM, Mocayar Marón FJ, Reiter RJ, Manucha W. Melatonin and cannabinoids: mitochondrial-targeted molecules that may reduce inflammaging in neurodegenerative diseases. Histol Histopathol. 2020:18212. doi:10.14670/HH-18-212
13. Mee-Inta O, Zhao ZW, Kuo YM. Physical exercise inhibits inflammation and microglial activation. Cells. 2019;8(7):691. doi:10.3390/cells8070691
14. Raefsky SM, Mattson MP. Adaptive responses of neuronal mitochondria to bioenergetic challenges: roles in neuroplasticity and disease resistance. Free Radic Biol Med. 2017;102:203-216. doi:10.1016/j.freeradbiomed.2016.11.045
15. Lin TW, Tsai SF, Kuo YM. Physical exercise enhances neuroplasticity and delays Alzheimer’s disease. Brain Plast. 2018;4(1):95-110. doi:3233/BPL-180073
16. Valkenborghs SR, Noetel M, Hillman CH, et al. The impact of physical activity on brain structure and function in youth: a systematic review. Pediatrics. 2019;144(4):e20184032. doi:10.1542/peds.2018-4032
17. Wittfeld K, Jochem C, Dörr M, et al. Cardiorespiratory fitness and gray matter volume in the temporal, frontal, and cerebellar regions in the general population. Mayo Clinic Proc. 2020;95(1):44-56. doi:10.1016/j.mayocp.2019.05.030
18. Bernardo TC, Marques-Aleixo I, Beleza J, Oliveira PJ, Ascensão A, Magalhães J. Physical exercise and brain mitochondrial fitness: the possible role against Alzheimer’s disease. Brain Pathol. 2016;26(5):648-663. doi:10.1111/bpa.12403
19. Feng YS, Yang SD, Tan ZX, et al. The benefits and mechanisms of exercise training for Parkinson’s disease. Life Sci. 2020;245:117345. doi:10.1016/j.lfs.2020.117345
20. Halabchi F, Alizadeh Z, Sahraian MA, Abolhasani M. Exercise prescription for patients with multiple sclerosis; potential benefits and practical recommendations. BMC Neurol. 2017;17(1):185. doi:10.1186/s12883-017-0960-9