Plasma Homocysteine Levels Are Associated with Cognitive Impairment: A Population-Based Cross-Sectional Study in a Rural Area of Xi’an, China

Introduction: High plasma homocysteine (Hcy) is a well-established risk factor for cardiovascular disease and stroke, but its role in cognitive impairment (CogI) remains unclear. This study investigated the relationship between plasma Hcy levels and CogI in middle-aged and elderly Chinese adults. Methods: This community-based cross-sectional study included 1,805 participants (≥40 years) from a village in Xi’an, China. CogI was diagnosed using a three-step protocol. Plasma Hcy was measured via chemiluminometric assay and categorized into tertiles: low-level group (<12.50 μmol/L), moderate-level group (12.5–16.10 μmol/L), and high-level group (>16.10 μmol/L). Multivariable logistic regression and subgroup analyses were performed to assess the relationship between Hcy and CogI. Nonlinear relationships were explored using restricted cubic splines (RCSs). Results: Among 1,805 subjects, 145 (8.0%) met the criteria for CogI. The prevalence of CogI increased across Hcy tertiles (low-level group: 4.9%; moderate-level group: 7.0%; high-level group: 12.2%). Multivariable logistic regression analysis showed that each 1 μmol/L increase in Hcy was associated with a 3.1% higher risk of CogI (OR = 1.031, 95% CI: 1.013–1.049, p < 0.001). Participants in the high-level Hcy group had a significantly higher risk than the low-level group (OR = 1.894, 95% CI: 1.162–3.055, p = 0.010). RCS analysis indicated no significant nonlinear relationship (pnonlinear = 0.317). Interaction analyses showed sex, age, stroke history, diabetes, BMI, and SBP did not modify this association. Conclusion: Elevated plasma Hcy is independently associated with increased risk of CogI in middle-aged and elderly adults. Further cohort and interventional studies are needed to confirm these findings.