Insulin resistance, vascular dysfunction and inflammation biomarkers associations with an increased CAIDE risk score in APOE‐ε4 carriers with subjective cognitive decline from the PENSA study

Abstract

AbstractBackgroundThe CAIDE (Cardiovascular Risk Factors –CVRF‐, Aging, and Incidence of Dementia) Dementia Risk Score is a validated tool to predict late‐life dementia risk based on midlife CVRF. Sex differences in metabolic pathways related to cognitive decline have been described. The aim of this study was to explore associations between measures of insulin resistance, biomarkers of endothelial activation and peripheral inflammation and an increased CAIDE risk score (CAIDE‐rs) in individuals at higher risk of Alzheimer’s disease (AD). Sex differences in these associations were explored.MethodA total of 129 participants of the PENSA study were recruited. Participants were categorized into high (≥ 9 points) or low CAIDE‐rs groups (HR and LR respectively). Homeostatic model assessment was calculated (HOMA IR = fasting insulin (μIU/ml) × fasting glucose (mmol/ml)/22.5). The following biomarkers were analyzed: soluble intercellular adhesion molecule‐1 (ICAM‐1, ng/ml), vascular cell activation molecule‐1 (VCAM‐1, ng/ml), C‐reactive protein (CRP, mg/dl) and fibrinogen (mg/dl), using ELISA and Clauss method assays.ResultParticipants were 67.2 ±4.8 years, 65.1% were women and 32.6% were classified into the HR group. The HR group was older (68.5 vs. 66.5 years, P = 0.026) and presented higher levels of CRP (median of 0.08 vs. 0.06 mg/dL; P = 0.037) and HOMA‐IR (2.1 vs. 1.6; P = <.001). No differences were found for ICAM‐1, VCAM‐1 or fibrinogen.Comparisons between sex groups showed higher fibrinogen median values in women both among the HR group and in the global sample (HR 372 vs. 327mg/dl; P = 0.011; GS 350.5 vs. 340.5mg/dl; P = 0.032). Higher HOMA‐IR and VCAM‐1 median values in men were found in the global sample (2.13 vs. 1.65; P = 0.006 and 495.8 vs. 434.5 ng/ml; P = 0.028). The HR female group showed higher HOMA‐IR and fibrinogen median values than the LR female group (2.06 vs. 1.58; p = <.001 and 372 vs. 343 mg/dl; P = 0.029 respectively). HR male group showed higher CRP values compared to LR male group (0.03 vs. 0.12 mg/dl; p = 0.026).ConclusionAssociations of metabolic alterations and an increased CAIDE‐rs were found in individuals at higher risk of AD. Moreover, sex differences in metabolic alterations were also found. These results highlight the necessity of personalizing preventive interventions for AD taking into account sex‐related profiles.