Joint effects of leukocyte-albumin ratio and hypertension are associated with multidimensional cognitive decline and Alzheimer’s disease risk in older adults: evidence from NHANES and a clinical AD validation cohort
Background Alzheimer’s disease (AD) pathogenesis involves complex interactions between neuroinflammation and vascular dysfunction. While leukocyte-albumin ratio (LAR) and hypertension are independently linked to cognitive decline, their joint associations with multidimensional cognitive impairment and AD risk remain understudied. Methods We analyzed two cohorts: 1,300 adults (≥ 60 years) from NHANES 2011–2014, and a clinical cohort (50 AD patients + 125 age-/gender-matched controls). LAR was calculated, hypertension was defined as per JNC7 criteria, and cognitive function was assessed via AD-sensitive tests standardized to z-scores. Restricted cubic spline (RCS) regression, multivariable linear regression, subgroup analysis, and Cox regression were used to examine LAR, hypertension, and their combined associations with cognitive outcomes. Results In the NHANES cohort, LAR was significantly correlated with DSST performance; participants with co-occurring high LAR + hypertension had lower scores across three cognitive domains, with age- (65–74 years) and sex-specific patterns and a 2.17-fold higher all-cause mortality risk. In the validation cohort, AD patients had higher LAR, with the highest LAR quartile linked to a 3.92-fold increased AD risk (p = 0.015). Conclusion Our findings support an association between LAR, hypertension, and cognitive decline. Elevated LAR in conjunction with hypertension is associated with poorer cognitive performance across multiple domains in older adults, as observed in both the NHANES and a clinical AD cohort. As a low-cost, easily measurable biomarker, LAR may hold promise for early AD risk stratification in primary care, highlighting a potential target for combined anti-inflammatory and antihypertensive interventions. However, its modest discriminative ability (AUC = 0.61) indicates that LAR should not be used as a standalone diagnostic tool. Prospective longitudinal studies are warranted to validate these associations.