Slowing Neurodegeneration With Exercise

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