AbstractBackgroundCerebrovascular dysfunction occurs with advancing age and is known to contribute to cognitive decline and dementia. Cerebrovascular reactivity is a marker of cerebrovascular function and represents the ability of cerebral blood vessels to regulate cerebral blood flow (CBF) in response to vasodilatory or vasoconstrictive stimuli. Deficits in CVR may contribute to vascular injury and cognitive impairment, however the mechanisms underlying this pathophysiology remain unknown. To explore whether inflammation and endothelial dysfunction may be involved in CVR deficits, we examined whether plasma levels of vascular injury markers indicative of such processes are associated with CVR deficits in older adults.MethodTwenty‐five independently living older adults (mean age = 69.9 years; SD = 8.5; age range 55‐87 years; 24.0% male) free of dementia or clinical stroke were recruited from the community and underwent venipuncture and brain MRI. Plasma was assayed for vascular injury markers (Serum amyloid A (SAA), C‐reactive protein (CRP), intercellular adhesion molecule 1 (ICAM‐1), vascular cell adhesion molecule 1 (VCAM‐1)). Visually guided breath control exercises during pseudo‐continuous arterial spin labeling MRI were utilized to determine global (whole brain) CVR to hypocapnia (0.1Hz paced breathing; vasoconstriction) and hypercapnia (15s breath holds, vasodilation). Pearson correlation and multiple linear regression examined the relationship between circulating vascular injury markers and CVR to hypocapnia and hypercapnia.ResultA significant negative association was observed between circulating levels of SAA and global CVR to hypocapnia (r = ‐.526, p = .017) as well as VCAM‐1 and CVR to hypocapnia (r = ‐.593, p = 0.007). These associations remained significant even after accounting for age and sex in multiple regression analyses.ConclusionBoth SAA and VCAM‐1 are vascular injury markers known to be involved in inflammation and were found to be elevated in older adults with lower global CVR to hypocapnia. Inflammation is associated with atherosclerosis and can lead to endothelial dysfunction, which may ultimately contribute to cognitive decline. Our findings suggest that these biological processes may be related to CVR deficits. Whether higher levels of vascular injury markers represent a protective mechanism or indicate pathological processes remains unknown.