The Association of Retinal Microvasculature With Gray Matter Changes and Structural Covariance Network: A Voxel-Based Morphometry Study.

Purpose: Increasing evidence suggests that retinal microvasculature may reflect global cerebral atrophy. However, little is known about the relation of retinal microvasculature with specific brain regions and brain networks. Therefore, we aimed to unravel the association of retinal microvasculature with gray matter changes and structural covariance network using a voxel-based morphometry (VBM) analysis. Methods: One hundred and forty-four volunteers without previously known neurological diseases were recruited from West China Hospital, Sichuan University between April 1, 2021, and December 31, 2021. Retinal microvasculature of superficial vascular plexus (SVP), intermediate capillary plexus (ICP), and deep capillary plexus (DCP) were measured by optical coherence tomography angiography using an automatic segmentation. The VBM and structural covariance network analyses were applied to process brain magnetic resonance imaging (MRI) images. The associations of retinal microvasculature with voxel-wise gray matter volumes and structural covariance network were assessed by linear regression models. Results: In the study, 137 participants (mean age = 59.72 years, 37.2% men) were included for the final analysis. Reduced perfusion in SVP was significantly associated with reduced voxel-wise gray matter volumes of the brain regions including the insula, putamen, occipital, frontal, and temporal lobes, all of which were located in the anterior part of the brain supplied by internal carotid artery, except the occipital lobe. In addition, these regions were also involved in visual processing and cognitive impairment (such as left inferior occipital gyrus, left lingual gyrus, and right parahippocampal gyrus). In regard to the structural covariance, the perfusions in SVP were positively related to the structural covariance of the left lingual gyrus seed with the left middle occipital gyrus, the right middle occipital gyrus, and the left middle frontal gyrus. Conclusions: Poor perfusion in SVP was correlated with reduced voxel-wise gray matter volumes and structural covariance networks in regions related to visual processing and cognitive impairment. It suggests that retinal microvasculature may offer a window to identify aging related cerebral alterations.

Retinal ganglion cell-inner plexiform layer, white matter hyperintensities, and their interaction with cognition in older adults.

Purpose: We explored the interaction of optical coherence tomography (OCT) parameters and white matter hyperintensities with cognitive measures in our older adult cohort. Methods: This observational study enrolled participants who underwent a comprehensive neuropsychological battery, structural 3-T brain magnetic resonance imaging (MRI), visual acuity examination, and OCT imaging. Cerebral small vessel disease (CSVD) markers were read on MR images; lacune, cerebral microbleeds (CMB), white matter hyperintensities (WMH), and enlarged perivascular spaces (EPVS), were defined according to the STRIVE standards. Retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer (GCIPL) thicknesses (µm) were measured on the OCT tool. Results: Older adults with cognitive impairment (CI) showed lower RNFL (p = 0.001), GCIPL (p = 0.009) thicknesses, and lower hippocampal volume (p = 0.004) when compared to non-cognitively impaired (NCI). RNFL (p = 0.006) and GCIPL thicknesses (p = 0.032) correlated with MoCA scores. GCIPL thickness (p = 0.037), total WMH (p = 0.003), PWMH (p = 0.041), and DWMH (p = 0.001) correlated with hippocampal volume in our older adults after adjusting for covariates. With hippocampal volume as the outcome, a significant interaction (p < 0.05) between GCIPL and PWMH and total WMH was observed in our older adults. Conclusion: Both GCIPL thinning and higher WMH burden (especially PWMH) are associated with hippocampal volume and older adults with both pathologies are more susceptible to subclinical cognitive decline.

Increased Serum EphrinA1 Is Associated with Parenchymal Hematoma after Ischemic Stroke.

INTRODUCTION: Previous preclinical studies reported that the level of serum EphrinA1 was associated with blood-brain barrier disruption; however, its role in predicting parenchymal hematoma (PH) after ischemic stroke is underexplored. We aimed to explore the association between the level of serum EphrinA1 and PH in patients with ischemic stroke. METHODS: Patients with ischemic stroke after onset from West China Hospital, Sichuan University, were prospectively enrolled between January 2017 and December 2019. The level of serum EphrinA1 at baseline was measured after admission. PH was diagnosed as hematoma within the infarct territory detected on the brain CT/MRI scans within 7 days after onset but not on the initial scan according to European Cooperative Acute Stroke Study (ECASS) III criteria. The association between the level of serum EphrinA1 and PH after ischemic stroke was assessed by multiple logistic regression analysis. RESULTS: A total of 667 patients were included in the final analysis. The mean age was 67.20 ± 14.31 years, and 57.87% (368/667) were males. Of the 667 patients, 65 (9.75%) patients had PH. The median of EphrinA1 on admission was 82.83 ng/mL (IQR, 70.11-93.75 ng/mL). Compared with patients without PH, those with PH had a higher level of serum EphrinA1 (p = 0.024). Patients were divided into 3 categories based on EphrinA1 tertiles (T1, <79.11 ng/mL, n = 223; T2, 79.11-93.75 ng/mL, n = 222; and T3, >93.75 ng/mL, n = 222). After adjusting for age, sex, atrial fibrillation, smoking, statins, antiplatelets, Trail of Org 10172 in Acute Stroke Treatment (TOAST) classification and National Institutes of Health Stroke Scale (NIHSS) score ≥15, patients in the second and third EphrinA1 tertiles showed a significant increase in PH compared with those in the lowest tertile (OR 2.44, 95% CI: 1.10-5.40, p = 0.028; OR 2.61, 95% CI: 1.19-5.74, p = 0.017, respectively). Additionally, adjusting for reperfusion therapy (thrombolysis and/or endovascular therapy), only patients in the highest group (tertile 3) had a significantly higher risk of PH compared to the lowest group (OR 2.30, 95% CI: 1.03-5.13, p = 0.042). CONCLUSION: Higher serum EphrinA1 is independently associated with a higher risk of PH after ischemic stroke. Future studies with larger sample sizes are needed to validate our findings and elucidate the potential role of EphrinA1 in PH.