Reduced forced vital capacity is associated with cerebral small vessel disease burden in cognitively normal individuals

Background: Pulmonary dysfunction is associated with elevated risk of cognitive decline. However, the mechanism underlying this relationship has not been fully investigated. In this study, we investigate the relationships between pulmonary function, cerebral small vessel disease (CSVD) markers, cortical thickness, and the Mini-Mental Status Examination (MMSE) scores in cognitively normal individuals. Methods: We used a cross-sectional study design. We identified 1924 patients who underwent pulmonary function testing, three-dimensional brain magnetic resonance imaging (MRI), and the MMSE. Pulmonary function was analyzed according to the quintiles of percentage predicted values (% pred) for forced vital capacity (FVC) or forced expiratory volume in 1 s (FEV₁). Regarding CSVD markers, we visually rated white matter hyperintensities (WMH) and manually counted lacunes and microbleeds. Cortical thickness was measured by surface-based methods. Results: Compared with the highest quintile of FVC, the lowest quintile of FVC (% pred) showed a higher risk of WMH (OR 1.98, 95% CI: 1.21–3.24) and lacunes (OR 1.86, 95% CI: 1.12–3.08). There were no associations between FVC or FEV₁ and cortical thickness. Low FVC, but not FEV₁, was associated with low MMSE scores. Path analyses showed that WMH partially mediated the positive relationship between FVC (% pred) and MMSE score. Conclusions: Our findings suggested that decreased pulmonary function was associated with increased CSVD burdens, which in turn wass associated with decreased cognition, even in cognitively normal subjects.