Effect of Cerebral Blood Flow on Cognition across Healthy Adulthood

Abstract

Both cognitive function and cerebral blood flow (CBF) decline across the lifespan. However, the relation between them remains unclear, particularly in the context of aging. Furthermore, fitness improves both cognition and CBF, and may be associated with preserved cognitive and cerebrovascular function in an older population.PurposeThe aims of this study were to 1) clarify the effect of CBF on cognition across healthy adulthood, and the extent to which age‐related reductions are modulated by the usually‐observed impairment in cerebrovascular function, and 2) examine the association of aerobic fitness on baseline CBF and cognitive performance in healthy young and older adults.MethodUsing a placebo‐controlled, single‐blinded, randomized cross‐over design, we tested the hypothesis that an acute reduction in CBF (using indomethacin [1.2 mg/kg oral dose]) would impair cognition in both young (n = 13; 25 ± 4y) and older (n = 12; 58 ± 6y) adults. Cerebrovascular function was assessed using blood velocity in the middle cerebral artery (MCAv; Transcranial Doppler Ultrasound). Cerebrovascular CO2 reactivity (CVRCO2) was calculated as the change in MCAv for a given change in end‐tidal CO2 (mm Hg). Cognitive function was measured using visuomotor, inhibitory, and mental switching response time tasks. Aerobic fitness was predicted using a submaximal exercise test (i.e., V̇O2peak). Linear and rank‐based mixed models were used to assess the individual and interactive effects of cerebrovascular function and cognition, while accounting for age, sex, and aerobic fitness.ResultsOlder adults had 11% lower MCAv and 15% worse response time overall (all p ≤ 0.049), but not reliably lower CVRCO2 (p ≥ 0.16). Indomethacin decreased MCAv by 26 ± 11% and CVRCO2 by 69 ± 25% (all p < 0.01), regardless of age. The degree of indomethacin‐induced reductions in CVRCO2 was strongly associated with baseline CVRCO2 (r = 0.87, p < 0.01). Visuomotor response time was 6 ± 13% slower after indomethacin (p = 0.04), but this impairment was not linearly associated with decreases of MCAv (r = −0.26). Finally, aerobic fitness was not associated with baseline CBF in either group (r ≤ 0.14), and was only weakly associated with response time performance in young (r ≤ −0.34), but not older (r ≤ 0.21) adults.ConclusionThe impairments in cognitive function from indomethacin were not evidently associated with the 26% reduction in cerebral perfusion, even in older adults. Compared to young, older adults had worse cognitive performance and decreased CBF but did not have impaired cerebrovascular function. Aerobic fitness was only weakly associated with resting CBF and cognition in both young and older adults. Therefore, cognitive performance may not be influenced by a ≤26% reduction in CBF per se in healthy young and older adults.Support or Funding InformationFunding support from the School of Physical Education, Sport and Exercise Sciences, and Department of Medicine.