Relationship of Established Cardiovascular Risk Factors and Peripheral Biomarkers on Cognitive Function in Adults at Risk of Cognitive Deterioration

Background: There is a paucity of information on the role of microvascular and inflammatory biomarkers in cognitive dysfunction. Objective: This study sought to evaluate the relationships between established and a number of peripheral biomarkers on cognitive patterns in 108 older adults with memory complaints. Methods: Participants in the AIBL Active study aged 60 years and older with at least one vascular risk factor and memory complaints completed a neuropsychological test battery and provided cross-sectional health data. Linear regression models adjusted for covariates examined associations between cognitive performance and a panel of vascular risk factors (Framingham cardiovascular scores, hs-CRP, homocysteine, fasting glucose, LDL-cholesterol) and peripheral biomarkers (TNF-alpha, BDNF, VCAM-1, ICAM-1, PAI-1, CD40L). Results: Higher fasting glucose and homocysteine levels were independent factors associated with poorer performance in Trail Making Test (TMT) B (adjusted beta = 0.40 +/- 0.10 and 0.43 +/- 0.09, respectively). Increasing homocysteine levels were weakly associated with poorer global cognition and delayed recall (adjusted beta = 0.23 +/- 0.10 and -0.20 +/- 0.10 respectively). Increasing Framingham cardiovascular scores were related to poorer performance in TMT B (beta = 0.42 +/- 0.19). There was early evidence of associations between increasing plasma TNF-alpha and poorer TMT B (adjusted beta = 0.21 +/- 0.10) and between increasing BDNF and better global cognition (beta =-0.20 +/- 0.09). Conclusion: This study provides evidence to support the associations between vascular risk factors (Framingham scores, fasting glucose, and homocysteine) and poorer cognitive functions. Additionally, we measured several peripheral biomarkers to further investigate their associations with cognition. The relationship between TNF-alpha, BDNF, and cognitive performance in various domains may offer new insights into potential mechanisms in vascular cognitive impairment.