Abstract
INTRODUCTION: The plasma proteome's mediating or moderating roles in the association between poor cardiovascular health (CVH) and brain white matter (WM) microstructural integrity are largely unknown. METHODS: Data from 3953 UK Biobank participants were used (40-70 years, 2006-2010), with a neuroimaging visit between 2014 and 2021. Poor CVH was determined using Life's Essential 8 (LE8) and reversing standardized z-scores (LE8(z) (_rev)). The plasma proteome was examined as a potential mediator or moderator of LE8(z) (_rev)'s effects on quantitative diffusion-weighted magnetic resonance imaging (dMRI) metrics. RESULTS: LE8(z_rev) was significantly associated with deteriorated WM microstructural integrity, as reflected by lower tract-averaged fractional anisotropy (dMRI-FA(mean)), (β ± standared error (SE): -0.00152 ± 0.0003, p < 0.001) and higher tract-averaged orientation dispersion (dMRI-OD(mean)), (β ± SE:+0.00081 ± 0.00017, p < 0.001). Ten strongly mediating plasma proteins of 1463 were identified, with leptin as the principal driver. DISCUSSION: Poor CVH is linked to poor WM microstructural integrity measures (lower FA(mean) and higher OD(mean)), mostly mediated through leptin. HIGHLIGHTS: Up to 3953 UK Biobank participants were selected for this study. Poor cardiovascular health (CVH) was determined using Life's Essential 8. The plasma proteome was examined as a potential mediator or moderator of poor CVH's effect on dMRI metrics. Ten plasma proteins were identified with strong mediating effects, with leptin being the principal driver.