Abstract
A growing body of evidence clearly indicates the beneficial effects of physical activity (PA) on cognition. The importance of PA is now being reevaluated due to the increase in sedentary behavior in older adults during the COVID-19 pandemic. Although many studies in humans have revealed that PA helps to preserve brain health, the underlying mechanisms have not yet been fully elucidated. In this review, which mainly focuses on studies in humans, we comprehensively summarize the mechanisms underlying the beneficial effects of PA or exercise on brain health, particularly cognition. The most intensively studied mechanisms of the beneficial effects of PA involve an increase in brain-derived neurotrophic factor (BDNF) and preservation of brain volume, especially that of the hippocampus. Nonetheless, the mutual associations between these two factors remain unclear. For example, although BDNF presumably affects brain volume by inhibiting neuronal death and/or increasing neurogenesis, human data on this issue are scarce. It also remains to be determined whether PA modulates amyloid and tau metabolism. However, recent advances in blood-based biomarkers are expected to help elucidate the beneficial effects of PA on the brain. Clinical data suggest that PA functionally modulates cognition independently of neurodegeneration, and the mechanisms involved include modulation of functional connectivity, neuronal compensation, neuronal resource allocation, and neuronal efficiency. However, these mechanisms are as yet not fully understood. A clear understanding of the mechanisms involved could help motivate inactive persons to change their behavior. More accumulation of evidence in this field is awaited.
Highlights
Cognitive decline and dementia are major health concerns worldwide
Cumulative research results clearly indicate the beneficial effects of physical activity (PA) on brain health, and some reports have suggested that physical inactivity in older adults caused by COVID-19 pandemic-related lockdowns have had a negative impact on brain health (Fiorenzato et al, 2021; Ismail et al, 2021; Tondo et al, 2021; Znazen et al, 2021)
PA may prevent the development of brain pathologies, including Alzheimer’s disease (AD)-related and cerebrovascular pathologies, some evidence indicates that the cognitive benefits of PA are independent of pathological changes in the brain (Buchman et al, 2019)
Summary
Cognitive decline and dementia are major health concerns worldwide. A major cause of dementia is Alzheimer’s disease (AD) and very recently pharmacological treatment with aducanumab was approved in the United States for AD. A systematic review of the effects of exercise intervention on the hippocampus concluded that aerobic exercise helped to preserve hippocampal volume by preventing its decrease, while some of the included studies even showed an increased volume (Firth et al, 2018). The precise mechanisms remain to be elucidated, the neuroprotective effects of PA may be exerted through increased brain-derived neurotrophic factor (BDNF) and blood flow or reduced oxidative stress and amyloid accumulation (as discussed below). Several interventional studies have found evidence of improved white matter integrity (Voss et al, 2013; Burzynska et al, 2017; Clark et al, 2019; Colmenares et al, 2021), but another study failed to show an effect (Venkatraman et al, 2020)
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