Retinal parameters, cortical cerebral microinfarcts, and their interaction with cognitive impairment

Abstract

Background: Quantitative changes in retinal vessels and thinning of optic nerves have been associated with subclinical (atherosclerosis, inflammation) and clinical age-related brain pathologies (stroke and neurodegeneration). However, data on the association between both retinal vascular and neuronal parameters with cortical cerebral microinfarcts (CMIs) and how these factors jointly influence cognition is lacking. Aim: We investigated the association of retinal vascular and neuronal changes with CMIs on 3T MRI and explored their interaction with cognitive impairment in a memory-clinic population. Methods: A total of 538 participants were included. Retinal vascular parameters (caliber, tortuosity, fractal dimension) were measured from retinal fundus photographs using a semi-automated computer-assisted program. Retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer (GC-IPL) thicknesses were obtained from optical coherence tomography. Cortical CMIs were defined as hypointense on T1-weighted MRI, <5mm in diameter and restricted to the cortex. Cognition was assessed using Clinical Dementia Rating Sum-of-Boxes (CDR-SoB) score and detailed neuropsychological test. Multivariable regression analysis was conducted adjusting for age, sex, hypertension, hyperlipidemia, diabetes mellitus, smoking, diagnosis, white matter hyperintensities volume, lacunes and cerebral microbleeds. Results: Larger venular caliber (Rate ratios (RR):1.15, 95%CI:1.01-1.38, p=0.014), increased venular fractal dimension (RR:1.58, 95%CI:1.31-1.91, p=<0.001), increased venular tortuosity (RR:1.54, 95%CI:1.35-1.75, p=<0.001) and thinner GC-IPL (RR:1.24, 95%CI:1.13-1.36, p=<0.001) were associated with CMI counts. Among individuals in highest tertile of retinal parameters, a significant interaction was observed between venular tortuosity (RR:1.12, 95%CI:1.02-1.22, p-interaction=0.014), and GC-IPL (RR:1.05, 95%CI:1.01-1.11, p-interaction<0.001) with CMIs on CDR-SoB. Conclusions: Retinal vascular and neuronal parameters are associated with cortical CMIs and persons with both pathologies are likely to have cognitive impairment. Further studies may be warranted to evaluate the clinical utility of retinal parameters and CMI in risk prediction for cognitive dysfunction. Data access statement: The data that support the findings of this study is available from the corresponding author upon request.

Distinct alterations of retinal structure between thalamic and extra‐thalamic subcortical infarction patients: A cross‐sectional and longitudinal study

“…The retina is highly susceptible to ischemic stress because it is a metabolically demanding tissue. Previous reports showed GCIPL thinning is more sensitive to neurodegeneration in stroke patients compared with the RNFL thickness 15 . Correspondingly, we showed GCIPL thinning was more severe in thalamic infarction patients compared with extra‐thalamic infarction patients, suggesting that GCIPL may be more informative and sensitive to post‐stroke secondary neurodegeneration, particularly in subjects with strategic lesion locations.…”

“…It is suggested that structural changes in the retinal structural thicknesses may reflect neurodegeneration in the brain of individuals with stroke. Past studies showed individuals with ischemic stroke had thinner RNFL 10–13 and GCIPL 15,16 thicknesses compared with the control group. Baseline analysis in our study showed thalamic stroke patients had thinner RNFL and GCIPL thicknesses compared with extra‐thalamic stroke patients.…”

Cerebral small vessel disease: Recent advances and future directions

“…Initially visualized on high-field strength 7T MRI, these have now been shown to be detectable on 3T MRI as shown in Figure 3 33 and have been associated with cognitive impairment. 34 Less data are available on CAA, but recent studies suggest that similar mechanisms may be responsible. A paper by Durrani in this month issue reports that altered white matter diffusivity, cerebrovascular reactivity, and atrophy, taken together, accounted for about half the effect of CAA on cognition.…”

Retinal Thickness Associates with Cognition Dysfunction in Young Adult with Type 1 Diabetes in Taiwan

“…In our study, the average values of CRT had significant correlations with the attention domain of CANTAB tests even adjusted off multiple variables, which suggested that the more thinning of the retinal fiber, the worse response latency in attention test. Hilal et al had demonstrated that in general population, the retinal vascular and neuronal parameters were associated with cortical microinfarct, and persons with both pathologies were likely to have cognitive impairment [ 49 ]. From UK biobank study, the retinal thickness had a significant association with total brain volume, gray matter, and white matter volumes [ 22 ].…”