Understanding age-related changes in cerebral perfusion and regulation of cerebral blood flow is crucial for determining neurological pathology. Previous studies have shown that total cerebral blood flow (CBF) is inversely associated with ageing in men and women (1); however, not all studies demonstrate an age-related reduction in CBF, specifically when comparing young and middle-aged adults (2). In addition, sex differences in both CBF and cerebrovascular resistance (CVR) have been reported with women having greater total CBF and lower CVR (1). Our aim was to evaluate age-related changes in CBF and CVR in healthy young and middle-aged adults. We evaluated 11 young women (age=29±4 yr), 10 young men (age=28±4 yr), 13 middle-aged women (age=57±7 yr), and 8 middle-aged men (age=53±7 yr). Mean arterial pressure (MAP) was measured using automated sphygmomanometry during magnetic resonance imaging (MRI). CBF was assessed using phase-contrast MRI at 3T. Blood flow was measured in the left and right internal carotid arteries (ICA) and basilar artery (BA) 1cm above the convergence of the vertebral arteries. Total CBF was calculated as the sum of blood flow in the ICAs and BA. Blood flow was normalized for tissue volume (grey and white matter, measured from T1 weighted fast spoiled gradient echo imaging). CVR was calculated as MAP/CBF. Middle-aged adults had significantly higher CVR compared with young adults (1.53±0.04 vs. 1.37±0.04 mL/100mL tissue/mmHg/min; p<0.05). Furthermore, CVR was significantly and positively associated with age (r=0.30; p<0.05). MAP was also greater in middle-aged adults compared with young adults (94±2 vs. 85±2 mmHg; p<0.001) and positively correlated with age (r=0.46; p<0.01). In contrast, CBF was not different between young and middle-aged adults (63±2 vs. 62±2 mL/100mL tissue/min; p=0.68) and not associated with age (r=-0.01; p=0.94). Finally, we evaluated potential interactions between sex and age. There were no significant interactions for CBF; however, CVR was higher in middle-aged women compared with young women (1.50±0.05 vs. 1.32±0.07 mL/100mL tissue/mmHg/min; p<0.05), and the age-related difference in men did not reach significance (1.42±0.04 vs. 1.57±0.09 mL/100mL tissue/mmHg/min, in young compared with middle-age; p=0.13). MAP was greater in young men compared with young women (90±1 mmHg vs. 80±2 mmHg; p<0.001). MAP was also higher in middle-aged women compared with young women (92±2 mmHg vs. 80±2 mmHg; p<0.001). Our results demonstrated higher CVR in middle-aged adults compared with young adults, despite no age-related differences in CBF. This suggests that elevated CVR in normotensive middle-aged adults may be linked to age-related increases in blood pressure typically seen in older adults. Furthermore, it is possible that the higher CVR is driving an increase in arterial pressure to maintain adequate cerebral perfusion. Funding-BHF