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

Article type: Research Article

Authors: Lai, Michelle M.Y.^{a; b; c; *} | Sharman, Matthew J.^d | Ames, David J.^a | Ellis, Kathryn A.^{a; k} | Cox, Kay L.^e | Hepworth, Graham^f | Desmond, Patricia^g | Cyarto, Elizabeth V.^{a; h} | Martins, Ralph N.^{i; j} | Masters, Colin L.^k | Lautenschlager, Nicola T.^{a; l; m}

Affiliations: [a] Academic Unit for Psychiatry of Old Age, Department of Psychiatry, The University of Melbourne, Melbourne, Australia | [b] South Metropolitan Health Service, Perth, Australia | [c] Curtin Medical School, Curtin University, Perth, Australia | [d] School of Health Sciences, University of Tasmania, Launceston, Tasmania, Australia | [e] Medical School, University of Western Australia, Perth, Australia | [f] Statistical Consulting Centre, The University of Melbourne, Melbourne, Australia | [g] Department of Radiology, Royal Melbourne Hospital The University of Melbourne, Australia | [h] Bolton Clarke Research Institute, Melbourne, Australia | [i] School of Medical Sciences, Edith Cowan University, Perth, Australia | [j] Department of Biomedical Sciences, Macquarie University, Sydney, NSW, Australia | [k] The Florey Institute, The University of Melbourne, Melbourne, Australia | [l] WA Centre for Health & Ageing, Medical School, University of Western Australia, Perth, Australia | [m] North Western Mental Health, Melbourne Health, Melbourne, Australia

Correspondence: [*] Correspondence to: Michelle M.Y. Lai, South Metropolitan Health Service, Locked Bag 100 Palmyra DC, WA 6961, Australia. Tel.: +61 08 8152 8205; E-mail: [email protected].

Abstract: 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-α, 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 β= 0.40±0.10 and 0.43±0.09, respectively). Increasing homocysteine levels were weakly associated with poorer global cognition and delayed recall (adjusted β= 0.23±0.10 and –0.20±0.10 respectively). Increasing Framingham cardiovascular scores were related to poorer performance in TMT B (β  = 0.42±0.19). There was early evidence of associations between increasing plasma TNF-α and poorer TMT B (adjusted β  = 0.21±0.10) and between increasing BDNF and better global cognition (β= –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-α, BDNF, and cognitive performance in various domains may offer new insights into potential mechanisms in vascular cognitive impairment.

Keywords: BDNF, biomarkers, cardiovascular disease, cognitive impairment, homocysteine, TNF-α, vascular risk factors

Keywords: Trial Registration: Australia New Zealand Clinical Trials Registry ACTRN126110006129

DOI: 10.3233/JAD-190953

Journal: Journal of Alzheimer's Disease, vol. 74, no. 1, pp. 163-171, 2020