Dumitrașcu, Oana

ABSTRACT Background The brain–heart axis is central to vascular health, yet no imaging biomarkers capture integrated dysfunction across neural and coronary microvascular networks. Although coronary microvascular dysfunction links to cognitive decline, neural correlates connecting cerebral efficiency with coronary physiology remain unclear. Objectives To determine whether the Unified Structural and Functional Connectivity (USFC)—a multimodal magnetic resonance imaging (MRI) “traffic map” of brain network efficiency—predicts coronary endothelial function and cognition in women with ischemia and no obstructive coronary artery disease (INOCA). Methods Thirty‐three women with suspected INOCA from the Women's Ischemia Syndrome Evaluation (WISE) study (NCT03876223) underwent invasive coronary function testing, cardiac MRI, cognitive evaluation, and multimodal brain MRI. USFC, structural connectivity (SC), and functional connectivity (FC) were computed for predefined 10 backbone pathways. Support vector regression and logistic classification assessed predictive performance. Results USFC explained 16%–20% more variance in coronary endothelial function, myocardial perfusion reserve, and cognition than SC or FC alone ( p < 0.05). Connectivity between the left caudate–superior medial orbital gyrus and right calcarine–inferior occipital gyrus emerged as robust predictors of crystallized cognition ( r = –0.78, p FDR < 0.05) and coronary endothelial function ( r = 0.70, p FDR < 0.05), respectively. USFC also best discriminated low versus high coronary blood flow (area under the ROC curve [AUC]: USFC 0.622 vs. SC 0.349 and FC 0.425; p < 0.05). Conclusions USFC identifies neuro–cardiac pathways linking cerebral efficiency with coronary endothelial function. These results introduce a sensitive biomarker of systemic vulnerability, highlighting occipital and frontostriatal pathways as shared substrates of dysfunction. USFC offers a mechanistic framework for detecting vascular risk across metabolically demanding tissues. Trial Registration ClinicalTrials.gov identifier: NCT03876223

Background Retinal vascular imaging offers a non‐invasive window into the central nervous system health and has shown promise in the study of neurodegenerative diseases. Emerging evidence highlights that Parkinson's disease (PD) exhibits structural and functional changes in the retina, including vascular alterations. This pilot study evaluated whether retinal vascular morphological features, quantified using the deep learning tool Automorph, discriminate PD from non‐PD subjects in the UK Biobank cohort. Methods We analyzed color fundus photographs (CFPs) from 303 PD participants (mean age 62.6 ± 5.4 years, hypertension (HTN) = 67%, diabetes mellitus (DM) = 13%) and 516 non‐PD controls (age = 55.9±8.1, HTN = 22.8%, DM = 3%) enrolled in the UK Biobank. Six retinal vascular morphology features were quantified: fractal dimension, vessel density, average width, distance tortuosity, squared curvature tortuosity, and tortuosity density. General linear models were used to assess group differences while adjusting for age, hypertension, and diabetes. We also evaluated the association between retinal features and age, and the left‐right eye retinal fractal measures correlations using Pearson correlation and Fisher Z‐test. Results Compared to non‐PD individuals, PD patients showed significantly altered retinal vessel average width, both without (p = 0.001) and with (p = 0.002) vascular covariate adjustment. Group‐by‐age interaction effects were also significant for fractal dimension (p = 0.010) and vessel density (p = 0.023). Furthermore, inter‐eye correlation of vessel density differed significantly between groups (p = 0.034), suggesting altered bilateral vascular symmetry in PD. Conclusion Measurable alterations in retinal vascular morphology in PD support the potential of retina vascular imaging for non‐invasive neurodegenerative disease research. These results warrant further validation in larger cohorts, with improved analytic robustness and automated retinal vascular grading.

Purpose White matter hyperintensity (WMH) is associated with heterogeneous pathologies. In neurodegeneration, the prevailing hypothesis is that WMH primarily reflects vascular pathology, exerting an additive effect in AD. Alternatively, a subset of WMH may arise secondary to AD‐related pathophysiology. APOE4 genotype, the greatest genetic risk factor for late‐onset AD, impacts the blood‐brain barrier and WMH burden. Herein, we investigate the association between regional WMH burden and APOE4 allelic dosage in cognitively normal individuals. Methods We used deep learning to automatically segment WMH from T2‐FLAIR MRI from 154 cognitively intact individuals older than 50. We mapped WMH to 4 specific brain regions (lobar, periventricular, basal ganglia and infratentorial, further parcellated into sub‐regions, Table 1) using atlas‐based registration and FastSurfer. WMH volumes were adjusted for total intracranial volume and normalized using log transformation. The APOE4 groups were compared for WMH burden using linear regression, controlling for age and vascular risk factors (hypertension, diabetes, hypercholesterolemia, cigarette smoking). For brain regions where more than 20% of participants had no WMH, a two‐part hurdle model was applied. Results We included 13 APOE4 homozygotes, 50 heterozygotes (ε4/ ε3) and 91 non‐carriers. Compared to non‐carriers, APOEε4 homozygotes exhibited significantly greater WMH burden in the whole brain, periventricular (posterior) and lobar regions (Figure 1a). Homozygotes exhibited a significantly greater WMH burden in the whole brain and posterior periventricular region, when compared to heterozygotes (Figure 1b). No significant whole‐brain or region‐specific differences were observed between heterozygotes and non‐carriers (Figure 1c). Conclusion In cognitively intact individuals at risk for AD, APOE4 homozygosity is associated with significantly greater WMH burden, particularly in the posterior periventricular space, after controlling for age and vascular risk factors. The relationship between regional‐specific WMH burden and neurodegeneration warrants further investigation. image image

Background: In younger patients (<60 years) with cryptogenic stroke (CS) presumed to be patent foramen ovale (PFO)-related, the standard approach involves transcatheter PFO closure combined with antithrombotic therapy. However, due to their exclusion from randomized clinical trials (RCTs), no formal recommendations exist for patients ⩾60 years. This study had two objectives (1) to compare the efficacy and safety of PFO closure versus antithrombotic therapy alone (ATA) exclusively in older patients (⩾60 years) and (2) to assess the outcomes of PFO closure in patients ⩾ 60 years versus < 60 years. Methods: We searched PubMed, Embase, Web of Science, and ScienceDirect databases to obtain articles in all languages from January 2004 until July 2025. The primary outcome was risk of recurrent stroke during follow-up. Secondary outcomes were risk of new-onset atrial fibrillation (AF), all-cause mortality, and in-hospital complications. PROSPERO registration ID: CRD420250652870. Results: Only one RCT (post hoc evaluation of the DEFENSE-PFO trial) and 11 observational studies were included. In patients aged ⩾ 60 years, risk of recurrent stroke was lower when PFO was closed compared with ATA (5.48% vs 10.05%, respectively, hazard ratio (HR) = 0.56, 95% confidence interval (CI) = 0.45–0.80, p < 0.001, I 2 = 45.6%). All-cause mortality was also lower for PFO closure versus ATA (1.73% vs 7.59%, respectively, HR = 0.41; 95% CI = 0.19–0.90, p = 0.02; I 2 = 43.8%). There was no difference between PFO closure and ATA in risk of new-onset AF (HR = 1.13, 95% CI = 0.53–2.44, p = 0.74). Compared with patients < 60 years, individuals ⩾ 60 years who underwent PFO closure had a higher risk of recurrent stroke (2.94% vs 1.04%, respectively, HR = 3.47; 95% CI = 1.61–7.48; p = 0.001), new-onset AF (4.86% vs 1.01%, respectively, HR = 4.12; 95% CI = 1.90–8.95; p < 0.001), and all-cause mortality during follow-up (8.32% vs 0.39%, respectively, HR = 8.24; 95% CI = 3.49–19.46; p < 0.0001). In-hospital complications after PFO closure were comparable between two age groups. Due to insufficient data, we were not able to perform a subgroup analysis based on anatomic features of PFO, antithrombotic regimen, or occluder devices. Conclusion: Based on available data, which is predominantly derived from observational studies, PFO closure is associated with a reduced risk of recurrent stroke compared to ATA in patients over 60 years. However, these findings are subjected to limitations, including the potential for selection bias, unmeasured confounding, and insufficient long-term follow-up. Furthermore, long-term randomized trials are essential to definitively confirm efficacy and establish clinical guidelines for PFO closure in this older population.