Background: Reports have proposed the retinal choroid as a potential biomarker for dementia and cerebral age‐related disorders. However, the clinical use of the choroid as a surrogate marker remains underexplored. This study investigated the associations among choroidal perfusion, white matter hyperintensity (WMH), and cognitive function. Methods: WMH severity (volume and shape features) and choroidal characteristics, including choroidal vascular volume, choroidal vascularity index, and choriocapillaris flow density, were automatically quantified in aging adults. Partial Spearman correlation was used to examine the relationship between choroidal and WMH metrics. General linear models were used to examine the associations of choroidal metrics and WMH characteristics with cognitive performance, as well as to explore potential interaction effects, whereas generalized estimating equations were applied to account for within‐subject correlations in eye‐specific data. Results: A total of 197 participants were included in the study. Choroidal vascular volume and choroidal vascular index were inversely correlated with total and periventricular WMH volumes. Irregular WMH shape and reduced choroidal vascular volume were both associated with poorer memory performance. A significant interaction was found between choroidal perfusion and periventricular WMH shape on memory, suggesting that the relationship between WMH features and memory function may be more pronounced in individuals with lower choroidal perfusion. Conclusions: The severity of WMH and the status of choroidal perfusion may jointly reflect memory performance, suggesting ischemia as a potential shared mechanism. Future research is warranted to assess the clinical usefulness of WMH and choroidal metrics in predicting cognitive decline.

(1) Introduction: Symptom spectrum can be of great diversity and heterogeneity in mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) patients in clinical practice. Here, we report a case of MELAS presenting asymptomatic refractory hypotension with m.3243 A>G mutation. (2) Case representation: A 51-year-old male patient presented with a headache, vertigo, and difficulty in expression and understanding. The magnetic resonance imaging of the brain revealed an acute stroke-like lesion involving the left temporoparietal lobe. A definitive diagnosis of MELAS was given after the genetic test identified the chrM-3243 A>G mutation. The patient suffered recurrent stroke-like episodes in the 1-year follow-up. Notably, refractory hypotension was observed during hospitalizations, and no significant improvement in blood pressure was found after continuous use of vasopressor drugs and fluid infusion therapy. (3) Conclusions: We report a case of refractory hypotension which was unresponsive to fluid infusion therapy found in a patient with MELAS. Our case suggests that comprehensive management should be paid attention to during treatment. A further study on the pathological mechanism of the multisystem symptoms in MELAS would be beneficial to the treatment of patients.

Background: Biological heterogeneity remains a major challenge in Alzheimer's disease (AD), even among individuals with biomarker‐confirmed disease. The apolipoprotein E (APOE) ε4 allele is associated with greater amyloid burden, neurodegeneration, and vascular dysfunction. We investigated whether retinal microvascular imaging provides complementary information beyond plasma and neuroimaging biomarkers for characterizing APOE ε4‐associated neurovascular heterogeneity in biologically defined AD. Methods: Eighty‐four amyloid‐positive patients with AD underwent color fundus photography, swept‐source optical coherence tomography angiography (OCTA), plasma biomarker assessment, amyloid positron emission tomography, and magnetic resonance imaging. Retinal vascular parameters were compared between APOE ε4 carriers and non‐carriers using generalized estimating equations. Candidate multimodal biomarkers were identified using least absolute shrinkage and selection operator (LASSO) regression, followed by multivariable logistic regression to evaluate the incremental contribution of retinal biomarkers within a multimodal phenotyping model. Results: Compared with non‐carriers, APOE ε4 carriers demonstrated significantly lower retinal superficial vascular complex (SVC) and deep vascular complex densities, reduced retinal vascular fractal dimension, higher amyloid PET standardized uptake value ratios, increased peak width of skeletonized mean diffusivity, and smaller hippocampal volumes (all p < 0.05). Following penalized feature selection, retinal SVC density remained independently associated with APOE ε4 status alongside amyloid burden, hippocampal volume, and white matter microstructural injury. Incorporation of SVC modestly improved discrimination and calibration of the multimodal model compared with neuroimaging biomarkers alone. Conclusions: Retinal microvascular alterations are associated with APOE ε4‐related biological heterogeneity in biomarker‐confirmed AD. Retinal vascular imaging provides complementary information beyond established plasma and neuroimaging biomarkers and may enhance multimodal characterization of neurovascular phenotypes rather than serve as a surrogate for genetic testing.

Secondary cortical degeneration caused by the remote effects of subcortical infarcts has been implicated in long-term outcomes after acute ischemic stroke. However, this process remains insufficiently studied in recent small subcortical infarcts (RSSI). We aimed to verify RSSI-induced cortical damage, determine whether it can be captured by neuroimaging markers, and explore its association with clinical outcomes. RSSI patients with longitudinal Magnetic Resonance Imaging (MRI) were included. Cortical degeneration was assessed using linear mixed-effects models, incorporating a direct approach based on individual diffusion weighted imaging and an indirect approach using the normative connectome from the Human Connectome Project (HCP). Principal component analysis (PCA) was employed to extract features of cortical alterations. The resulting component scores were used in general linear models to assess associations with neuroimaging markers and clinical outcomes. A total of 76 RSSI patients were analyzed. RSSI was found to induce progressive cortical thinning and volume loss in structurally connected regions. PCA identified a component reflecting parenchymal atrophy associated with diffusion-based markers of white matter integrity, as well as the presence of track/cap signs. Moreover, faster cortical degeneration in lesion-connected regions was significantly associated with a greater increase in Hamilton Anxiety Rating Scale (HAMA) scores (β = -2.38, 95% CI = -4.30 - -0.47, p = 0.017). RSSI induces secondary cortical damage through structurally connected fiber tracts, which is detectable by neuroimaging markers of white matter integrity. These regional cortical alterations may be relevant to post-stroke outcomes and require validation in larger longitudinal studies.

Susceptibility alterations in deep gray matter (DGM) across clinical stages of cerebral small vessel disease (CSVD) remain unclear. In this case-control study, we used 7-tesla magnetic resonance imaging quantitative susceptibility mapping (QSM) with source separation (APART-QSM) to characterize stage-related changes in normal controls, preclinical CSVD, and symptomatic CSVD. Compared with controls, CSVD showed increased QSM in the basal ganglia, particularly the putamen and globus pallidus, whereas small-magnitude QSM reductions were observed in selected thalamic and amygdalar subregions (all P < 0.05). Source separation revealed that basal ganglia abnormalities were mainly associated with increased paramagnetic components, whereas some thalamic alterations may involve increased diamagnetic components, suggesting distinct susceptibility contributions. Lower MoCA scores were associated with higher QSM and paramagnetic values in the globus pallidus, as well as higher diamagnetic values across the thalamus, putamen, and nucleus accumbens (all P < 0.05). Notably, right anterior globus pallidus QSM discriminated symptomatic CSVD from controls with the highest accuracy (AUC = 0.818). These findings reveal DGM susceptibility patterns associated with cognitive impairment, suggesting that 7T QSM and susceptibility source separation may provide complementary information for early CSVD characterization and future longitudinal evaluation.