The association of retinal vessel calibre, white matter hyperintensities and cognitive decline in community-dwelling older adults

Abstract

Background Retinal vessel calibres (RVCs) are non-invasive markers of microvascular health and may serve as accessible indicators of cerebral small vessel disease (CSVD) and future cognitive impairment. This study examines whether RVCs are associated with cognitive decline, and how these associations compare with those observed for white matter hyperintensities (WMH), a known marker of CSVD. Methods Data were analysed from community-dwelling participants aged 70+ in the ASPREE trial and sub-studies, free of dementia and cardiovascular disease at baseline. RVCs were measured from fundus photography and WMH volumes from 3 T magnetic resonance imaging. Covariate-adjusted linear mixed-effects models assessed cognitive trajectories relative to baseline RVCs and WMH volumes. Cross-sectional associations between baseline RVCs and WMHs were examined via linear regression. Results This study included 3540 participants with RVC data and 489 with WMH data (median [IQR] age: 73.2 [71.4-76.3] and 72.5 [71.2-75.4] years; female: 52.9% and 47.6%) over a median follow-up of 7.4 [IQR 5.5-8.5] and 3.8 [IQR 2.9-5.3] years, respectively. Baseline RVCs were not significantly associated with cognitive trajectories nor with baseline WMHs. Larger baseline WMH volumes were associated with greater global (Modified Mini-Mental State Examination) decline (mean 0.40 points/year; 95% CI 0.57, 0.22) and declines in delayed memory (HVLT-r) (-0.13 [-0.22, -0.04]), psychomotor function (Symbol Digit Modalities Test) (-0.29 [-0.52, -0.07]) and to a lesser extent, executive function (Controlled Oral Word Association Test) (-0.09 [95% CI -0.22, 0.03]). Conclusion In contrast to WMH volumes, RVCs were not associated with cognitive decline. Exploring longitudinal changes in a broader range of retinal and brain biomarkers may provide deeper insights into the relationship between ocular and cerebral biomarkers in CSVD and clinical outcomes.