Evaluating the relationship between endostatin and cognition in mild cognitive impairment (MCI), coronary artery disease (CAD), and Alzheimer’s disease (AD)

Abstract Background Endostatin is an endogenous angiogenesis inhibitor that can regulate pro‐and anti‐angiogenic factors, notably vascular endothelial growth factor. Research shows that endostatin levels in the brain are associated with amyloid plaque formation in Alzheimer’s disease (AD), and may contribute to AD pathogenesis. Hence, endostatin may be relevant to the broad range of cognitive impairments, namely people with mild cognitive impairment (MCI), AD, and/or coronary artery disease (CAD) who are at risk for cognitive impairment. We examine associations between serum endostatin and global cognition. Methods Participants with MCI, AD, or CAD (with or without MCI) were recruited. Serum endostatin concentrations were measured and analyzed using enzyme‐linked immunosorbent assays. MCI was diagnosed using either the Petersen criteria or the Diagnostic and Statistical Manual of Mental Disorders (DSM‐5) criteria. AD was diagnosed using DSM‐5 criteria. CAD was defined as at least 1 of previous hospitalization for acute myocardial infarction, coronary angiographic evidence of ≥ 50% blockage in ≥ 1 major coronary artery or a prior revascularization procedure. Global cognition was assessed by the Montreal Cognitive Assessment (MoCA). Linear regression analyses were used to assess the association between endostatin levels and global cognition with and without covariates. Endostatin levels were log‐transformed prior to analyses due to significant departure from normality in Shapiro‐Wilk tests. Results In 119 participants, 94 (79.0%) were male, 102 (85.7%) had CAD, and 23 (19.3%) had MCI or AD; the mean(SD) age was 65.6(7.5), years of education were 16.4(3.3), and endostatin levels were 156.3(38.6) ng/mL. Endostatin was associated with global cognition alone [F(1,117) = 11.39, p <.001, R 2 = .089] and also when considering covariates: age, sex, body mass index (BMI), education, MCI/AD diagnosis, and CAD diagnosis [F(7,111) = 11.27, p< .001, R 2 = .415]. All variables except age, sex, BMI, and CAD diagnosis added significantly to the association (p< .05). Controlling for other variables, one log endostatin unit was associated with a total MoCA score 5.08 (SE= 2.52) points lower. Conclusion In this sample, lower serum endostatin concentrations were associated with higher cognitive performance. This relationship may support the involvement of endostatin in cognitive functions and neurodegenerative diseases.