Retinal and Cerebral Microvasculopathy: Relationships and Their Genetic Contributions

Abstract

PURPOSE. Retinal microvasculopathy may reflect small vessel disease in the brain. Here we test the relationships between retinal vascular parameters and small vessel disease, the influence of cardiovascular risk factors on these relationships, and their common genetic background in a monozygotic twin cohort. METHODS. We selected 134 cognitively healthy individuals (67 monozygotic twin pairs) aged ‡60 years from the Netherlands Twin Register for the EMIF-AD PreclinAD study. We measured seven retinal vascular parameters averaged over both eyes using fundus images analyzed with Singapore I Vessel Assessment. Small vessel disease was assessed on MRI by a volumetric measurement of periventricular and deep white matter hyperintensities. We calculated associations between RVPs and WMH, estimated intratwin pair correlations, and performed twin-specific analyses on relationships of interest. RESULTS. Deep white matter hyperintensities volume was positively associated with retinal tortuosity in veins (P ¼ 0.004) and fractal dimension in arteries (P ¼ 0.001) and veins (P ¼ 0.032), periventricular white matter hyperintensities volume was positively associated with retinal venous width (P ¼ 0.028). Intratwin pair correlations were moderate to high for all small vessel disease/retinal vascular parameter variables (r ¼ 0.49-0.87, P < 0.001). Crosstwin cross-trait analyses showed that retinal venous tortuosity of twin 1 could predict deep white matter hyperintensities volume of the co-twin (r ¼ 0.23, P ¼ 0.030). Within twin-pair differences for retinal venous tortuosity were associated with within twin-pair differences in deep white matter hyperintensities volume (r ¼ 0.39, P ¼ 0.001). CONCLUSIONS. Retinal arterial fractal dimension and venous tortuosity have associations with deep white matter hyperintensities volume. Twin-specific analyses suggest that retinal venous tortuosity and deep white matter hyperintensities volume have a common etiology driven by both shared genetic factors and unique environmental factors, supporting the robustness of this relationship.

Is retinal vasculature a biomarker in amyloid proven Alzheimer's disease?

“…Given the thorough characterization of our participants, we were able to correlate retinal vascular measurements with WMH on MRI, Aβ 1-42 , Tau -181 , and pTau in CSF and MMSE. Venular tortuosity was inversely correlated with WMH scores on MRI in control subjects, while in contrast an earlier study reported a positive correlation between WMH and venular tortuosity in control subjects [32] . Confirming an earlier report, we found an inverse association between macular vessel density and WMH scores in AD, possibly reflecting microvasculature changes in chronic cerebral microinfarction.…”

“…Seven retinal vascular parameters, previously shown to have good reproducibility [32] , showed no group differences between AD patients and control participants ( Fig. 2 A).…”

“…Values from both eyes of every participant were averaged; if only one suitable image was present, only this eye was included (n = 3). We assessed vascular parameters that were earlier found to have high intraobserver intraclass correlation (>0.80) [32] , namely CRAE, CRVE, arteriole-to-venule ratio, fractal dimension of the arteriolar network (FDa), fractal dimension of the venular network, curvature tortuosity of the arterioles (cTORTa), and curvature tortuosity of the venules. We averaged vascular parameters of two raters.…”

Optical coherence tomography angiography in preclinical Alzheimer’s disease

“…In earlier studies, we found higher intratwin pair correlations for other retinal markers such as retinal vascular parameters on fundus photography. 34 The reason for these lower correlations of OCTA markers may lie in lower reproducibility of vessel density measures, as we noticed that vessel density is very much affected by scan quality (lower quality=lower vessel density) as well as clouding of the media (floaters and cataract), making this a less reliable measure. This also explains the high number of participants who were excluded due to insufficient quality scans of both eyes (N=14).…”

The Ion Channel and GPCR Toolkit of Brain Capillary Pericytes

“…K + , PGE 2 , and EETs, for example, have been implicated in control of blood flow in both circulations (Newman, 2013;Longden et al, 2017;Gonzales et al, 2020). Recent studies have also indicated the utility of non-invasive examinations of the retinal vasculature as a marker for detecting cerebrovascular diseases, due to a similar susceptibility of both circulations to vascular risk factors such as hypertension or diabetes (Patton et al, 2005;van de Kreeke et al, 2018;McGrory et al, 2019;Querques et al, 2019). Data on gene expression in vascular cells of the retina are currently lacking, but would provide a useful standpoint for deeper comparisons of the similarities and differences between these vascular beds.…”