Macular vessel density is associated with cognitive function in preclinical p.R544C NOTCH3 mutation carriers.

Background: The study aimed to examine the relationship between retinal microcirculation, brain white matter hyperintensities (WMH) seen on magnetic resonance imaging (MRI), and cognitive decline in asymptomatic carriers of NOTCH3 mutations, a preclinical stage of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy.

Methods: Forty-nine asymptomatic carriers without stroke history or cognitive complaints were studied. Retinal vessel density and WMH volume were measured via optical coherence tomography angiography and MRI, respectively. Cognitive function was assessed using various tests.

Results: In a multivariable regression model which included both, the whole brain WMH volume and parafoveal vessel density of superficial retinal plexus (SRP) as independent variables, parafoveal vessel density of SRP emerged as a significant predictor for Montreal Cognitive Assessment (MoCA) score ( β = -0.31; 95% confidence interval, -0.1516 to -0.0002; p = 0.044) in this cohort, and consistent findings were observed for Color Trails Tests (CTT)-1 and CTT-2 scores.

Conclusion: In asymptomatic NOTCH3 mutation carriers, higher parafoveal vessel density of the SRP may serve as an indicator of cognitive decline, and may also indicate autoregulatory compensatory mechanisms in response to a dysfunctional capillary plexus, potentially signifying early-stage cognitive decline.