Benefits of exercise training on cerebrovascular and cognitive function in ageing

Abstract

Derangements in cerebrovascular structure and function can impair cognitive performance throughout ageing and in cardiometabolic disease states, thus increasing dementia risk. Modifiable lifestyle factors that cause a decline in cardiometabolic health, such as physical inactivity, exacerbate these changes beyond those that are associated with normal ageing. The purpose of this review was to examine cerebrovascular, cognitive and neuroanatomical adaptations to ageing and the potential benefits of exercise training on these outcomes in adults 50 years or older. We systematically searched for cross-sectional or intervention studies that included exercise (aerobic, resistance or multimodal) and its effect on cerebrovascular function, cognition and neuroanatomical adaptations in this age demographic. The included studies were tabulated and described narratively. Aerobic exercise training was the predominant focus of the studies identified; there were limited studies exploring the effects of resistance exercise training and multimodal training on cerebrovascular function and cognition. Collectively, the evidence indicated that exercise can improve cerebrovascular function, cognition and neuroplasticity through areas of the brain associated with executive function and memory in adults 50 years or older, irrespective of their health status. However, more research is required to ascertain the mechanisms of action.

Keywords: Dementia; ageing; cerebrovascular function; cognition; exercise training.

Figure 1.

Ageing is associated with hormonal imbalances and increased low-grade systemic inflammation. It is also associated with the increased production of reactive oxygen species (ROS), which may be due to diminished nuclear regulation factor 2 and superoxide dismutase expression and increased expression of nicotinamide adenine dinucleotide phosphate oxidase complexes, resulting in increased mitochondrial superoxide production. Uncoupled endothelial nitric oxide (NO) synthase (eNOS) increases superoxide production by catalysing nicotinamide adenine dinucleotide phosphate, instead of synthesising NO. Increased arginase activity reduces l-arginine supply, thus promoting the uncoupling of eNOS.^, This may also be associated with diminished tetrahydrobiopterin availability and increased asymmetrical dimethylarginine concentrations, which subsequently acts as a competitive inhibitor of eNOS, thus reducing NO biosynthesis. These promote and lead to endothelial dysfunction, which subsequently manifests as local ischemia and micro-haemorrhages in the microvasculature, leading to reductions in capillary density and BBB function (i.e. reduced cerebrovascular function).^, It may also be a result of increased conduit artery stiffness, which then diffuses to the cerebral circulation and increases pulsatility of the cerebral microvasculature, reducing CBF and promoting ischaemic-induced leukoaraiosis. Nevertheless, increased inflammation and oxidative stress, hypoperfusion and decreased BBB integrity are potentiated by these events.^,,– This subsequently promotes increased microglial activity, amyloid-β production and decreased amyloid-β clearance, which may act as a trigger for enhanced S100B and glial fibrillary acidic protein secretion to form astrocytes, thus promoting the inflammatory cycle and the continued accumulation of neurotoxic products.^,,– Further, the increase in amyloid-β accumulation in the brain can further compromise cerebrovascular function that manifests into neurodegeneration and further structural and functional changes within the brain.

Figure 2.

A summary of the potential mechanisms that may be elicited by exercise in improving cerebrovascular function and cognition. CBF: cerebral blood flow; eNOS: endothelial nitric oxide synthase, NO: nitric oxide; BHB: beta-hydroxybutyrate; GH: growth hormone; VEGF: vascular endothelial growth factor; BDNF: brain-derived neurotrophic factor; IGF1: insulin-like growth factor-1; PGC-1a: peroxisome proliferator-activated receptor gamma coactivator 1-alpha.