Abstract 4146369: Association of Midlife Systemic Inflammatory Markers and Interval Change with Cognition: Insights from the HeartSCORE Study

Introduction: Systemic inflammation may be associated with risk for neuroinflammation and cognitive decline. We investigated the association of midlife inflammatory markers and their 1-year change with Montreal Cognitive Evaluation (MoCA) score in a longitudinal cohort. Methods: In the Heart Strategies Concentrating on Risk Evaluation (HeartSCORE) study, baseline serum levels of high-sensitivity c-reactive protein (hs-CRP|), interleukin-6 (IL-6), CD40L, and intercellular adhesion molecule-1 (ICAM-1) were measured, along with their one-year changes (delta). Using linear regression, association of inflammatory biomarkers and interval change with MoCA scores taken 10-12 years later, were examined in models adjusted for traditional risk factors (age, sex, race, smoking, smoking, triglycerides, high density lipoprotein and total cholesterol, systolic and diastolic blood pressure, hypertension, diabetes, metabolic syndrome, antihypertensive use, statin use, and aspirin use). Model 2 added the one-year change in each biomarker. Results: Among 673 participants (mean age [SD]: 59 [6.8] years), 63.9% were women and 31.6% were self-reported Black. While univariate modelling showed an inverse association of IL-6 with MoCA; this was not significant when adjusted for covariates. Baseline ICAM levels had a significant inverse association with MoCA scores [β: -0.47 (-0.93 --0.02) p<0.05] in fully adjusted models (Table). One year change in these markers did not show any statistically significant association with MoCA scores. Conclusion: Midlife ICAM, known to initiate neuro and systemic inflammatory responses, may be an early risk marker for cognitive impairment. Future studies can examine the mechanisms of ICAM and its role in inflammatory cascade and neurocognitive decline.