Abstract P2092: The Association of Change in Circulating Biomarkers of Brain Injury with Cognitive Change and MRI Findings in the Cardiovascular Health Study

Background: Understanding how circulating biomarkers of brain injury correlate with cognitive function and magnetic resonance imaging. (MRI) findings of vascular brain injury is critical for developing early interventions. We aimed to elucidate the associations of change in circulating blood-based biomarkers of brain injury with change in cognitive measures and MRI findings in a cohort of older adults from the Cardiovascular Health Study. Methods: Four biomarkers (glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), total tau, and ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1)) were measured twice over 4 years in up to 780 participants. Biomarkers were log-transformed, and multiple linear regression was applied, adjusting for age and eGFR. Changes in residuals from year 5 to year 9 were the primary exposure variable. Cognitive changes (DSST and 3MSE) were calculated over the same period. MRI at the second biomarker measurement assessed cerebrovascular markers (WMH, lacunar/non-lacunar infarcts). Multivariable regression, adjusting for key covariates, examined associations between biomarker changes, cognitive outcomes, and MRI findings. Results: Rising NfL levels were associated with a decline in processing speed and executive function (DSST change: β = -0.63 points per standard deviation (SD) increase, 95% CI [-1.24, -0.02]). Changes in GFAP, total tau, and UCH-L1 were not significantly associated with cognitive change. A direct association was observed between change in total tau and WMH grade (β = 0.17 points per SD increase, 95% CI [0.00, 0.35]). In logistic regression models, NfL change was marginally associated with lacunar infarcts (OR = 0.82, 95% CI [0.68, 1.00]), but not with non-lacunar infarcts. Conclusion: Our findings suggest that changes in circulating NfL may serve as a biomarker for predicting decline in processing speed and executive function, whereas NfL and total tau appears to be linked to the burden cerebrovascular disease. Further research should investigate how these biomarkers can inform early risk stratification and personalized interventions to maximize brain health and cognition in older adults.