Serum Albumin as a Biomarker of Brain and Microvascular Health in Older Adults: Implications for Community-Based Aging Research

Background: Identifying circulating biomarkers that reflect cerebrovascular health may help clarify underlying mechanisms associated with brain damage. Serum albumin, a multifunctional protein with antioxidant, anti-inflammatory, and endothelial-stabilizing properties, could serve as a marker of cerebral integrity. We examined the association between albumin levels and neuroimaging markers of cerebral small vessel disease (cSVD) in a rural population of older adults. Methods: We conducted a cross-sectional study among community-dwelling individuals aged ≥ 60 years in rural Ecuador. Participants were invited to undergo brain MRI and laboratory testing as part of the study protocol. Inclusion was based on completion of these procedures and serum albumin levels within the physiological range of 3.0–5.0 g/dL. Logistic regression models were fitted to assess the association between serum albumin and cSVD markers, adjusting for demographics and cardiovascular health metrics. Results: Among 409 participants (mean age: 66.2 ± 6.1 years; 60% women), moderate-to-severe white matter hyperintensities (WMH) were present in 34% of participants. Serum albumin showed a non-linear inverse association with WMH. Only participants in the highest albumin quartile (4.42-5.0 g/dL) showed significantly lower odds of moderate-to-severe WMH (adjusted OR: 0.48; 95% CI: 0.25-0.93). No significant associations emerged with other cSVD markers. Conclusion: Higher physiological albumin levels were associated with a lower burden of WMH, consistent with a threshold-dependent protective effect on the cerebral microvasculature. These findings support serum albumin as a candidate biomarker of brain health in aging populations. Albumin may capture systemic processes – such as endothelial integrity and vascular inflammation – that contribute to cSVD. Its accessibility and affordability underscore its potential utility in community-based aging research and population-level screening.