Schmidt, John E.

Reduced cerebral blood flow and reactivity may explain age‐related changes in cognitive function. We examined cerebrovascular reactivity, and the potential role of prostaglandins, in young and old healthy humans. Middle cerebral artery velocity (MCAv) responses to stepped hypercapnia were measured in young (26±2y; 6M/5F) and old (66±2y, 3M/4F) adults before (PRE) and 90 min after (POST) oral indomethacin (1.2mg/kg). To account for any changes in blood pressure, cerebrovascular conductance index (CVCi) was calculated as the MCAv divided by mean arterial pressure. Cerebrovascular reactivity slopes were calculated using linear regression between either MCA velocity or CVCi and end‐tidal CO 2 . There were no differences between young and old adults in height, weight, BMI, or brachial blood pressures. Young adults demonstrated greater MCAv (53.7±6.7 vs. 32.0±3.3), MCAv reactivity (1.62±0.21 vs. 0.94±0.10), and CVCi (0.66±0.08 vs. 0.39±0.04) compared with old adults at PRE (P<0.05 for all). In both young and old adults, MCAv, MCAv reactivity, CVCi, and CVCi reactivity decreased between PRE and POST measurements. Furthermore, any age‐related differences in these cerebrovascular variables were abolished by indomethacin. These results suggest that cerebral blood flow and cerebrovascular reactivity is attenuated in aging adults and that this reduction may be mediated by prostaglandins. NIH: AG16574‐11PP2

Blood flow and vasodilatory responses are altered by age in a number of vascular beds, including the cerebral circulation. To test the role of prostaglandins as regulators of cerebral vascular function, we examined cerebral vasodilator responses to CO2 (cerebrovascular reactivity) in young (26 ± 5 yr; 6 males/6 females) and older (65 ± 6 yr, 5 males/5 females) healthy humans before and after cyclooxygenase inhibition (using indomethacin). Middle cerebral artery velocity (MCAv) responses to stepped hypercapnia were measured before and 90 min after indomethacin. Changes in MCAv during the recovery from hypercapnia (vasoconstrictor responses) were also evaluated before and after indomethacin. Cerebrovascular reactivity was calculated using linear regression between MCAv and end-tidal CO2. Young adults demonstrated greater MCAv (55 ± 6 vs. 39 ± 5 cm/s: P < 0.05) and MCAv reactivity (1.67 ± 0.20 vs. 1.09 ± 0.19 cm·s−1·mmHg−1; P < 0.05) to hypercapnia compared with older adults ( P < 0.05). In both groups MCAv and MCAv reactivity decreased between control and indomethacin. Furthermore, the age-related differences in these cerebrovascular variables were abolished by indomethacin. During the recovery from hypercapnia, there were no age-related differences in MCAv reactivity; however, indomethacin significantly reduced the MCAv reactivity in both groups. Taken together, these results suggest that cerebral blood flow velocity and cerebrovascular reactivity are attenuated in aging humans, and may be due to a loss of prostaglandin-mediated vasodilation.