Macular vessel density is associated with cognitive function in preclinical p.R544C NOTCH3 mutation carriers
Chien-Chih Chou1,2,3,4, Chiao-Ying Liang2, Chen-Yu Lin2
1Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan, ROC.
Journal of the Chinese Medical Association : JCMA
|July 3, 2025
Summary
In asymptomatic NOTCH3 mutation carriers, increased retinal vessel density in the superficial retinal plexus may indicate early cognitive decline, even before symptoms appear. This finding highlights potential early detection markers for cerebral autosomal dominant arteriopathy.
Area of Science:
- Neurology
- Ophthalmology
- Genetics
Background:
- Investigating preclinical markers for cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL).
- Focusing on asymptomatic NOTCH3 mutation carriers to identify early signs of disease.
- Exploring the link between cerebrovascular changes and cognitive function.
Purpose of the Study:
- To determine the relationship between retinal microcirculation, brain white matter hyperintensities (WMH), and cognitive decline.
- To assess if retinal vessel density predicts cognitive decline in preclinical CADASIL.
- To understand early pathological changes in NOTCH3 mutation carriers.
Main Methods:
- Studied 49 asymptomatic NOTCH3 mutation carriers without prior stroke or cognitive complaints.
- Measured retinal vessel density using optical coherence tomography angiography.
- Quantified white matter hyperintensities (WMH) via MRI and assessed cognitive function with standard tests.
Main Results:
- Higher parafoveal vessel density in the superficial retinal plexus (SRP) significantly predicted lower scores on the Montreal Cognitive Assessment (MoCA).
- Similar associations were found for Color Trails Tests (CTT)-1 and CTT-2 scores.
- Parafoveal vessel density of the SRP was a significant predictor of cognitive performance, independent of WMH volume.
Conclusions:
- Increased parafoveal vessel density of the SRP may indicate early cognitive decline in asymptomatic NOTCH3 mutation carriers.
- This finding suggests potential autoregulatory compensatory mechanisms in response to capillary dysfunction.
- Retinal microcirculation assessment could serve as a non-invasive biomarker for preclinical CADASIL.
