Elevated Soluble Vascular Cell Adhesion Molecule-1 Is Associated With Cerebrovascular Resistance and Cognitive Function

Background: Elevated plasma soluble vascular cell adhesion molecule-1 (sVCAM-1) is a presumed marker of endothelial dysfunction, both in the brain and systemic circulation. Impairments in memory and cognition have been associated with cardiovascular diseases, but little is known about their relationships to abnormal cerebral endothelial function. Methods: We studied the cross-sectional association between sVCAM-1 and markers of cerebrovascular hemodynamics and cognitive function in 680 community-dwelling participants in the MOBILIZE Boston Study, aged 65 years and older. Cognitive function was assessed using the Hopkins Verbal Learning Memory Test and Trail Making Tests (TMTs) A and B. Global cognitive impairment was defined as MiniMental State Examination (MMSE) score less than 24. sVCAM-1 was measured by ELISA assay. Beat-to-beat blood flow velocity (BFV) and cerebrovascular resistance (CVR = mean arterial pressure /BFV) in the middle cerebral artery were assessed at rest by transcranial Doppler ultrasound. Results: sVCAM-1 concentrations were higher among participants with an MMSE score < 24 versus = 24 (1,201 +/- 417 vs 1,122 +/- 494 ng/mL). In regression models adjusted for sociodemographic characteristics and health conditions, increasing levels of sVCAM-1 were linearly associated with higher resting CVR (p =.006) and lower performance on the Hopkins Verbal Learning Memory (immediate recall and delayed recall) and adjusted TMT B tests (p <.05). Higher levels of sVCAM-1 were also associated with global cognitive impairment on the MMSE (odds ratio = 3.9; 95% confidence interval: 1.4-10.9; p =.011). Conclusions: In this cohort of elderly participants, we observed a cross-sectional association between elevated sVCAM-1 levels and both cognitive impairment and increased cerebrovascular resistance. Longitudinal studies are needed to determine whether elevated sVCAM-1 is a cause or consequence of cerebrovascular damage.