1 Physics Department, Concordia University, SP Building, Room 367.067141 Sherbrooke St. W, Montreal, QC, H4B 1R6, Canada.
2 Centre EPIC and Research Center, Montreal Heart Institute, Montreal, QC, H1T 1N6, Canada.
3 School of Health, Concordia University, Montreal, QC, H4B 1R6, Canada.
4 Department of Biomedical Science, Faculty of Medicine, Université de Montreal, Montreal, QC, H2V 0B3, Canada.
5 Kinesiology & Health Science, Faculty of Health, York University, Toronto, ON, M3J 1P3, Canada.
6 Dr Sandra Black Centre for Brain Resilience and Recovery, Sunnybrook Research Institute, Toronto, ON, M4N 3M5, Canada.
7 Department of Psychology, Concordia University, Montreal, QC, H4B 1R6, Canada.
8 Department of Medicine, Université de Montreal, Montreal, QC, H2V 0B3, Canada.
9 Department of Nutrition, Université de Montréal, Montreal, QC, H2V 0B3, Canada.
10 Research Center, Institut Universitaire de Gériatrie de Montréal, Montréal, QC, H3W 1W5, Canada.
11 Physics Department, Concordia University, SP Building, Room 367.067141 Sherbrooke St. W, Montreal, QC, H4B 1R6, Canada. claudine.gauthier@concordia.ca.
12 Centre EPIC and Research Center, Montreal Heart Institute, Montreal, QC, H1T 1N6, Canada. claudine.gauthier@concordia.ca.
13 School of Health, Concordia University, Montreal, QC, H4B 1R6, Canada. claudine.gauthier@concordia.ca.

This study investigated whether higher cardiorespiratory fitness (VO2peak) is associated with better cerebral vascular and metabolic health-specifically cerebral blood flow (CBF), cerebrovascular reactivity (CVR), cerebral metabolic rate of oxygen (CMRO2), and oxygen extraction fraction (OEF) across healthy older adults and patients with coronary artery disease (CAD). Thirty-seven healthy adults (65.3 ± 8.3 years old) and 35 CAD patients (66.4 ± 9.3 years old) underwent calibrated fMRI using hypercapnic and hyperoxic gas challenges (including carbogen) to quantify gray matter CBF, CVR, CMRO2, and OEF. VO2peak was obtained from a maximal cycle ergometer cardiopulmonary exercise test. Associations between VO2peak and brain biomarkers were evaluated with group terms to test CAD-specific effects. Across all participants, VO2peak was positively associated with CBF (ß = 0.32, p = 0.02) and CVR (ß = 0.002, p = 0.04) in gray matter, indicating an association between aerobic fitness and vascular health. Metabolic effects differed by group: in CAD patients, VO2peak correlated positively with CMRO2 (ß = 0.08, p = 0.02), suggesting higher fitness may be associated with preserved oxidative metabolism, while in healthy controls, VO2peak was negatively associated with OEF (ß = -3.6, p = 0.02), consistent with aging-related adaptations driven by improved CBF without CMRO2 changes. VO2peak is positively associated with cerebral vascular function in older adults and shows group-specific metabolic benefits: in CAD, higher VO2peak relates to preserved CMRO2, whereas in healthy individuals it is linked primarily to enhanced perfusion and reduced extraction. These findings support aerobic exercise as a promising strategy to mitigate CAD-related brain alterations and highlight VO2peak as a potentially modifiable target for prevention and rehabilitation.