VO₂ max refers to the maximum rate at which the body can take in, transport, and use oxygen during intense exercise. Dr Glorioso, a neuroscientist and physician, describes it as the body’s engine capacity. Rather than reflecting a single system, VO₂ max captures how well multiple organ systems work together, including the lungs, heart, blood vessels, and muscles. This integrated function is why VO₂ max is considered one of the most robust markers of overall physiological fitness. Its relevance extends beyond physical performance. Evidence from large cohort studies shows that cardiorespiratory fitness is a strong modifiable predictor of long-term brain health. Individuals with higher fitness levels consistently demonstrate a 36–88% lower risk of cognitive decline and dementia, underscoring why VO₂ max is increasingly discussed in the context of both physical and brain health.

Current research shows a strikingly consistent relationship between cardiorespiratory fitness, often measured through VO₂ max, and the risk of cognitive decline or dementia later in life. Large longitudinal studies point to both risk reduction and delayed onset. For example, long-term follow-up of adults over 25 years found that individuals in the highest fitness category had a 36% lower risk of dementia compared with those least fit. Similar findings have emerged from midlife studies in women, where high cardiovascular fitness was associated with an 88% lower dementia risk and an average delay in onset of nearly a decade. Importantly, this relationship follows a clear dose–response pattern. Each 1-MET increase in fitness corresponds to roughly a 16% reduction in dementia incidence, with no clear upper threshold identified. This suggests that incremental improvements in fitness, even later in adulthood, could translate into substantial gains in cognitive resilience. In fact, moving from very low to high fitness levels may delay dementia onset by five to nine years, a magnitude of effect that exceeds what any current pharmaceutical intervention has been shown to achieve.

From a biological standpoint, higher cardiorespiratory fitness appears to influence brain health through several well-characterised mechanisms. Dr Glorioso explains that regular exercise increases levels of brain-derived neurotrophic factor (BDNF), a protein that supports neurogenesis, synaptic plasticity, and neuronal survival. Aerobic training has also been shown to improve cerebral circulation. Studies indicate that a one-year aerobic exercise programme can lead to a 5% increase in global cerebral blood flow, alongside reduced cerebrovascular resistance. At the same time, exercise helps shift the brain’s immune environment from pro-inflammatory to anti-inflammatory states and strengthens the integrity of the blood–brain barrier. Cardiovascular adaptations play a parallel role. Improvements in blood pressure and lipid profiles help protect the brain’s delicate vasculature, while enhanced insulin sensitivity may address mechanisms implicated in what researchers describe as the ‘type 3 diabetes’ hypothesis of Alzheimer’s disease. Perhaps most strikingly, aerobic exercise has been shown to increase anterior hippocampal volume by around 2%, effectively reversing one to two years of age-related atrophy in a region critical for memory.

Evidence suggests that midlife is a particularly strategic period to improve VO₂ max, as cardiorespiratory fitness naturally declines by around 10% per decade after age 30, accelerating to as much as 15% per decade after age 50 in the absence of countermeasures. Building a higher fitness reserve earlier in adulthood provides a greater buffer against this age-related decline. That said, research consistently shows that benefits aren’t limited to those who start early. Large population studies indicate that what matters most isn’t baseline fitness alone, but whether fitness is maintained or improved over time. Individuals who moved from lower to higher fitness categories experienced a 48% reduction in dementia risk, regardless of the age at which improvement occurred. Clinical trials in people with mild cognitive impairment further reinforce this point, showing that structured exercise can help stabilise cognitive function, even in groups where progressive decline is typically expected. Taken together, the evidence suggests that while earlier intervention offers advantages, the trajectory of fitness across adulthood is critical, and improvements in cardiorespiratory fitness can confer meaningful brain health benefits at any age.

For people who aren’t athletes, improving VO₂ max doesn’t require elite-level training. Dr Glorioso points to the Norwegian 4×4 protocol as one of the most well-studied and effective approaches. The protocol involves a 10-minute warm-up, followed by four 4-minute intervals performed at 90–95% of maximum heart rate, with 3-minute periods of active recovery in between. Research shows this approach can produce a 7.2% improvement in VO₂ max within eight weeks. That said, gains aren’t limited to structured interval protocols. Any form of exercise that substantially elevates heart rate, including brisk walking, cycling, swimming, or vigorous yoga that incorporates cardio intervals, can be effective when performed consistently. The key lies in combining regular moderate-intensity activity with some higher-intensity efforts. For a typical 50-year-old, increases of 3–5 ml/kg/min over several months are realistic and clinically relevant. Each 3.5 ml/kg/min increase has been associated with an approximate 20% reduction in dementia risk. From a functional standpoint, a VO₂ max of around 17.5 ml/kg/min is often cited as a threshold for independent living, making it important to maintain fitness well above this level to preserve reserve with ageing.