The cerebrovascular role in cognition during physiological stress
Shoemaker, Leena Noelle
Cognition may depend in part on cerebral blood flow (CBF) and its regulation. All are affected in similar directions by stress acutely (e.g., mental and exercise-related) and chronically (e.g., fitness and age). For example, cognition, CBF and its major regulator (CO2 pressure in the blood; PETCO2) all show inverted-U responses to exercise intensity. Additionally, cognition, CBF and its reactivity to changes in CO2 improve with fitness and decline with age. However, the relation between changes in cognition and changes in CBF or PETCO2 remains unknown, particularly in an exercise-context. Therefore, the primary aim of this thesis was to manipulate CBF (as indexed by middle cerebral artery blood velocity; MCAv) or PETCO2 upward and downward, and examine their effects on cognition (visuomotor speed, inhibitory control, and mental switching). Secondary aims were to examine possible modulating effects of fitness, training-specificity, swimming (as an accessible but understudied mode of aerobic exercise), and age. Study 1 was a validation study to characterise the cerebrovascular and haemodynamic responses during acute mental stress, which may occur during cognitive testing. High mental stress increased MCAv by 7% (p<0.01), driven largely by increased blood pressure (17%; p<0.01). High stress also increased the sensitivity of MCAv to increases in PETCO2 (CVRCO2) by 46% (p=0.03). Therefore, acute mental stress can alter the regulation of CBF. Study 2 demonstrated that the cognitive benefit from acute bouts of exercise is not solely mediated by concomitant changes in PETCO2 and MCAv. Specifically, treadmill walking improved visuomotor performance in active (p=0.046), but not inactive (p=0.15) young adults. However, this improvement was unrelated to exercise-mediated increases in PETCO2 (≥3 mmHg) and MCAv (13%; p<0.01). Hypercapnia increased MCAv (27-39%; p<0.01), but impaired cognition (3-6%; p≤0.04), regardless of session. Overall, increased PETCO2 and MCAv per se were not sole mediators of exercise-related cognitive improvement. Study 3 revealed that swimming increased MCAv mostly due to postural and PETCO2 effects (p≤0.01), with minimal contributions from water immersion (p=0.76) or motor activity (p=0.32). Swimming at a moderate-intensity for 20 min improved visuomotor speed by 4% (p=0.03), unrelated to increases in MCAv. Upright water immersion increased MCAv by 12% (p<0.01) but without measurable cognitive improvements (p≥0.15). Thus, exercise appears to benefit cognition beyond its effects on MCAv, regardless of exercise modality and environment. In Study 4 we used indomethacin to acutely decrease MCAv and CVRCO2, by ≥25% and ≥52%, respectively (p<0.01), in young (25±4 y) and older adults (58±6 y). Mental switching was 6% worse after indomethacin (p=0.04), regardless of age, and not measurably associated with changes in MCAv (r=-0.26). Prior to indomethacin, older compared with younger adults had 15% worse cognition overall and 11% lower MCAv (all p<0.05) but not impaired CVRCO2 (p=0.16). The main finding of this study was that cognitive performance may not be influenced by ≥25% reduction in CBF per se in healthy adults. This thesis experimentally manipulated CBF and PETCO2 while concurrently measuring cognition. Collectively, these studies indicate that: 1) the acute cognitive benefit from exercise is not mediated by increases in CBF per se; 2) In fact, there appears to be no measurable cognitive effect from acute increases or decreases in CBF in healthy adults; 3) age (r≥0.63) and fitness (r≤-0.30) modulate cognitive function, but only age markedly modulates resting MCAv (r=0.35); and 4) CVRCO2 was weakly associated with cognitive performance (r≤-0.14), age (r=-0.23) and fitness (r=-0.16).
Advisor: Cotter, James D.; Wilson, Luke C.; Machado, Liana; Lucas, Samuel J.E.
Degree Name: Doctor of Philosophy
Degree Discipline: School of Physical Education, Sport and Exercise Sciences
Publisher: University of Otago
Keywords: cognition; cerebral blood flow; cerebrovascular reactivity; exercise; reaction time; response time; executive function; middle cerebral artery; cerebral blood velocity; fitness; aging
Research Type: Thesis