In an evolving health landscape, emerging research continues to highlight concerns that could impact everyday wellbeing. Here’s the key update you should know about:
A year of consistent aerobic activity didn’t just boost fitness; it shifted MRI-based brain age in early to midlife adults, suggesting exercise may help preserve brain health long before old age.
Study: Fitness and exercise effects on brain age: A randomized clinical trial. Image credit: Robert Kneschke/Shutterstock.com
Performing moderate-to-vigorous aerobic exercise for 12 months can reduce a brain-age biomarker, brain-predicted age difference (brain-PAD), in early- to midlife adults, as reported in a new study published in the Journal of Sport and Health Science.
Exercise habits emerge as early determinants of brain aging
Lifestyle habits, including physical activity, play a vital role in modifying midlife risk factors associated with age-related morphological and functional brain deterioration, dementia, and other neurodegenerative diseases. Regular physical activity in midlife has been linked to reduced risk of cognitive decline and Alzheimer’s disease in late adulthood.
Existing evidence indicates that a prolonged neural impact of cardiometabolic health and lifestyle begins years before the clinical manifestation of age-related cognitive decline. Despite the significant impact of midlife cardiovascular and lifestyle risk factors on brain health, most physical exercise interventions designed to improve cardiorespiratory fitness (CRF) have been limited to late adulthood.
This lack of strategic interventions highlights the need for evaluating the impact of early and mid-adulthood physical exercise on biomarkers associated with age-related brain health and estimated brain age.
Mechanistic evidence indicates that exercise improves brain health by increasing CRF. Higher CRF is associated with improved cognitive performance and reduced dementia risk. Exercise-induced reduction in cardiometabolic risk factors, such as blood pressure and body weight, has also been linked to improved brain health.
Given the significant association between exercise and age-related brain health, researchers from AdventHealth Research Institute and the University of Pittsburgh, USA, investigated the effect of a 12-month aerobic exercise intervention on CRF and brain-PAD, a neuroimaging-based surrogate marker of brain aging.
A year-long randomized trial tests aerobic exercise effects
This 12-month randomized clinical trial included 130 participants aged 26 to 58 years who were relatively healthy but physically inactive. They were randomly assigned to a moderate-to-vigorous intensity aerobic exercise group, intervention, or a usual-care control group, control.
The intervention group participants completed two supervised 60-minute sessions per week in a laboratory setting, along with home-based exercise, to achieve 150 minutes of exercise per week.
The impact of exercise on CRF and brain age was assessed at baseline and after 12 months. Brain age was assessed using the brain-predicted age difference, brain-PAD. This neuroimaging biomarker quantifies the gap between chronological age, actual age, and predicted brain age derived from structural magnetic resonance imaging and machine learning algorithms. Cognitive performance and dementia outcomes were not primary endpoints of this trial.
The impact of potential mediators on the effect of exercise on brain age was also analyzed. These mediators were body composition, blood pressure, and brain-derived neurotrophic factor (BDNF).
Exercise lowered MRI-based brain age by nearly one year
The study found a significant association between increased CRF and reduced brain-PAD at baseline. This finding indicates that individuals with improved heart, lung, and blood vessel function in early and mid-adulthood tend to have “younger-appearing” brains on MRI. However, this cross-sectional association does not directly measure the rate of brain aging or predict individual long-term brain aging trajectories.
After 12 months of intervention, the exercise group participants showed a mean reduction of approximately 0.60 years in brain-PAD, whereas the control group showed a non-significant increase of about 0.35 years. The between-group difference corresponded to nearly a 1-year, 0.95-year, lower brain-PAD in the exercise group relative to controls. No such improvement in brain health was observed in the control group after 12 months of standard care.
Regarding CRF, the study found a significant improvement in maximal oxygen uptake, a measure of cardiovascular fitness and aerobic endurance, at 12 months in participants in the exercise group. In contrast, control group participants showed a slight reduction. No significant effect of the exercise intervention on body composition, blood pressure, or circulating brain-derived neurotrophic factor levels was observed. However, BDNF showed a borderline increase in the exercise group compared with controls.
The mediation analysis, conducted to identify possible physiological and biological mediators of the observed associations, revealed that exercise-induced improvement in CRF has no significant influence on the exercise-induced reduction in brain aging, as measured by brain-PAD. Similarly, no mediation effects of body composition, blood pressure, and brain-derived neurotrophic factor were observed on the observed associations.
Early and midlife exercise linked to healthier brain aging markers
The study highlights the importance of a 12-month moderate-to-vigorous-intensity aerobic exercise program for improving cardiorespiratory fitness and reducing a neuroimaging-based marker of brain aging in young and middle-aged adults.
The study finds approximately 1.83 years lower brain-PAD with every standard deviation increase in maximal oxygen uptake, about 7 mL/kg/min. These findings suggest that individuals with higher CRF are less vulnerable to midlife brain aging, as reflected in MRI-based brain-age estimates. Existing evidence linking CRF with gray matter volume and white matter integrity further supports these findings.
Regarding possible mediators of the observed associations, the study found no effect of CRF on the exercise-induced reduction in brain aging. One possible explanation is that exercise-induced changes in CRF, as measured by maximal oxygen uptake, reflect the lifestyle-modifiable component of CRF. In contrast, familial factors, such as shared environment and genetic factors, contribute significantly to CRF variation when measured cross-sectionally.
Another explanation would be that the influence of CRF may be more pronounced in individuals with elevated cardiovascular risk. The current study included largely healthy, early to midlife adults with relatively low cardiovascular risk, which may mask any mediation that only emerges in those with subclinical or overt vascular pathology.
The authors also note several limitations, including that only about 62 percent of participants completed post-intervention brain imaging and that COVID-19–related disruptions affected follow-up assessments.
Overall, the study findings suggest that performing moderate-to-vigorous physical activity in early and mid-adulthood may delay the progression of brain aging as estimated by neuroimaging biomarkers and could potentially reduce the risk of dementia in late adulthood, but longer-term studies are needed to determine whether these brain-PAD changes translate into sustained cognitive or clinical benefits.
