Cardiorespiratory Fitness Reduces Dementia, Depression, and Psychosis Risk

Improving cardiorespiratory fitness may significantly reduce the risk of developing dementia, depression, and psychosis later in life, according to a large-scale study published in the journal BMC Medicine. The research, which followed over 60,000 adults in the United Kingdom for more than a decade, found that individuals with higher levels of cardiorespiratory fitness had a substantially lower likelihood of being diagnosed with these serious mental health conditions, even after accounting for genetic predisposition and other confounding factors.

The study, led by researchers at Johns Hopkins University and the Karolinska Institutet, analyzed data from the UK Biobank, a long-term biomedical database containing genetic and health information from half a million participants. Participants’ cardiorespiratory fitness was estimated using a six-minute submaximal exercise test on a stationary bike, a validated method for measuring aerobic capacity without requiring maximal exertion. Over a median follow-up period of 11.5 years, researchers tracked incident cases of dementia, depression, and psychosis through linked hospital records and death registries.

Results showed that individuals in the highest third of cardiorespiratory fitness had a 40% lower risk of developing dementia, a 35% lower risk of depression, and a 20% lower risk of psychosis compared to those in the lowest third. These associations remained significant after adjusting for age, sex, socioeconomic status, smoking, alcohol use, body mass index, and genetic risk scores for each condition. The protective effect was particularly strong for dementia, where higher fitness levels were linked to reduced risk regardless of APOE-ε4 status, a major genetic risk factor for Alzheimer’s disease.

“Cardiorespiratory fitness is a powerful marker of overall brain and body health,” said Dr. Qing Zhe Teo, lead author of the study and a researcher at the Johns Hopkins Bloomberg School of Public Health. “Our findings suggest that maintaining good aerobic fitness through regular physical activity may help protect against some of the most debilitating mental health conditions affecting older adults.”

The researchers emphasized that cardiorespiratory fitness reflects the integrated function of the heart, lungs, blood vessels, and muscles during sustained physical activity. It is influenced by both genetics and lifestyle, with regular aerobic exercise—such as brisk walking, cycling, swimming, or jogging—being the most effective way to improve it. Unlike muscle strength or flexibility, cardiorespiratory fitness specifically measures how efficiently the body delivers and uses oxygen during physical exertion, a process closely tied to cerebral blood flow and neurovascular health.

Potential biological mechanisms behind the observed associations include improved cerebral perfusion, reduced inflammation, enhanced neuroplasticity, and better regulation of the hypothalamic-pituitary-adrenal (HPA) axis, which governs stress response. Animal and human studies have shown that aerobic exercise increases brain-derived neurotrophic factor (BDNF), a protein that supports neuron survival and growth, particularly in the hippocampus—a brain region critical for memory and often affected in depression, and dementia.

While the study is observational and cannot prove causation, its large size, long follow-up, adjustment for genetic risk, and use of objective fitness measurements strengthen confidence in the findings. The researchers noted that reverse causation—where early, undiagnosed brain changes lead to lower fitness—is unlikely to fully explain the results, given the long latency period and exclusion of participants with pre-existing neurological or psychiatric conditions at baseline.

Public health experts say the findings reinforce the importance of promoting aerobic fitness as a preventive strategy for mental health. “We often think of exercise as beneficial for mood or heart health, but this study shows it may also serve as a buffer against neurodegenerative and psychotic disorders,” said Dr. Priya Rajagopalan, a neurologist at Massachusetts General Hospital not involved in the research. “Encouraging midlife and older adults to engage in regular aerobic activity could be a low-cost, high-impact intervention for reducing the burden of these conditions.”

The study authors recommend that clinicians consider assessing cardiorespiratory fitness as part of routine health evaluations, particularly for patients with a family history of dementia, depression, or psychosis. Simple tools like the six-minute bike test or estimated VO₂ max from submaximal treadmill tests could help identify individuals who might benefit from targeted exercise interventions.

Future research will need to explore whether improving cardiorespiratory fitness in midlife or later life can directly reduce incidence rates of these conditions in randomized controlled trials. Nonetheless, the current evidence supports incorporating aerobic fitness into broader brain health recommendations alongside cognitive engagement, social connection, and management of vascular risk factors like hypertension and diabetes.