Cognition, cerebral blood flow (CBF) and its major regulator (i.e., arterial CO₂), increase with submaximal exercise and decline with severe exercise. These responses may depend on fitness. We investigated whether exercise-related changes in cognition are mediated in part by concomitant changes in CBF and CO₂, in ten active (26 ± 3 years) and ten inactive (24 ± 6 years) healthy adults.

Participants completed two randomised sessions; exercise and a resting CO₂-control—wherein end-tidal CO₂ (PETCO₂) was matched between sessions and clamped across conditions at exercise-associated increases (+ 3 mmHg) and hypercapnia (+ 10 mmHg). Exercise comprised inclined walking at submaximal and severe intensities. CBF was indexed using right middle cerebral artery blood velocity (MCAv). Cognition (visuomotor, switching and inhibitory response time) was measured before, during, and after exercise.

MCAv and its inverted-U response to exercise were comparable between groups, whereas visuomotor performance improved during submaximal exercise in the active group only (p = 0.046). Submaximal, but not severe (p = 0.33), exercise increased MCAv (p ≤ 0.03). Hypercapnia increased MCAv during the CO₂-control (27 ± 12%) and during submaximal exercise (39 ± 17%; p < 0.01). Despite the acute increases in MCAv, cognition was impaired during both levels of increased PETCO₂ (3–6%; p ≤ 0.04), regardless of session. Overall, resting or exercise-related changes in PETCO₂ and MCAv did not associate with changes in cognition (r ≤ 0.29 ± 0.34). Fitness (O_2MAX) was associated with baseline cognition (r ≥ 0.50).

Acute increases in PETCO₂ and MCAv were not associated with improved cognition. In fact, cognitive performance was impaired at both levels of increased PETCO₂, regardless of session. Finally, fitter people were found to have better cognition.