Le Cao

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.

Background: Severe carotid artery stenosis or occlusion (CASO) is associated with white matter injury and cognitive impairment, but markers of accompanying microvascular dysfunction remain incompletely characterized. We investigated the relationships among retinal microvascular abnormalities on optical coherence tomography angiography, white matter hyperintensities (WMH), and cognitive impairment in severe unilateral CASO. Methods: In this multicenter cross‐sectional study, 860 participants were included: 566 patients with severe unilateral CASO without acute cerebral infarction and 294 control participants with similar age and sex distributions. All participants underwent multimodal imaging, including automated WMH segmentation on brain magnetic resonance imaging and macular optical coherence tomography angiography. Cognitive function was assessed using the Montreal Cognitive Assessment. Results: Compared with controls, patients with CASO showed lower vessel length density across retinal layers and greater WMH burden. Within the group with CASO , the retina ipsilateral to the stenosis showed lower vessel length density and greater vessel dilation, paralleling the greater burden of deep WMH in the ipsilateral hemisphere (all adjusted P <0.05). Retinal microvascular abnormalities and greater WMH burden were both associated with worse concurrent cognitive performance. Adding optical coherence tomography angiography metrics to clinical and WMH ‐based models provided modest additional discrimination for identifying concurrent cognitive impairment in internal cross‐validation, increasing the area under the curve from 0.652 to 0.695 ( Δarea under the curve , 0.043 [95% CI , 0.021–0.064]). Conclusions: In severe unilateral CASO, retinal microvascular abnormalities were associated with ipsilateral white matter injury and lower cognitive performance. Optical coherence tomography angiographymetrics provided modest complementary discriminatory information beyond conventional clinical variables and WMH for identifying concurrent cognitive impairment, although external validation is required. Registration: URL: https://www.chictr.org.cn/ . Unique identifier: ChiCTR2300074640.

Background: Hemodynamic depression is common after carotid artery stenting (CAS), but whether its two phenotypes, persistent hypotension and bradycardia, reflect shared or distinct autonomic responses remains unclear. We aimed to characterize perioperative autonomic changes associated with these outcomes via continuous Holter monitoring. Methods: In this prospective, single-center cohort, consecutive CAS patients were enrolled, and a prospective subcohort underwent Holter monitoring from 24 hours before to 24 hours after stenting. Sympathetic activity index (SAI) and parasympathetic activity index (PAI) were derived from heartbeat series to reflect autonomic modulation. Persistent hypotension was defined as systolic blood pressure<90 mmHg or vasopressor requirement for ≥6 hours, and persistent bradycardia as heart rate<60 beats/min for ≥6 hours within 24 hours after CAS. Exploratory mediation-style analysis examined the extent to which autonomic changes accounted for each outcome. Results: Among 735 enrolled patients, 301 had valid recordings for autonomic analysis. In this monitored subcohort, CAS was associated with a reciprocal autonomic shift, with decreased SAI and increased PAI (both p<0.001). Reduced SAI statistically explained a larger proportion of the modeled association with bradycardia (88.9%; residual association p=0.570), whereas autonomic indices explained only a modest proportion of the modeled association with hypotension (SAI 20.0%; PAI 16.1%; both mediation p<0.001), with a significant residual association remaining (p<0.001). Conclusions: CAS was associated with sympathetic withdrawal and parasympathetic activation. These exploratory findings suggest that bradycardia was more tightly associated with heart rate-derived autonomic changes than hypotension, which was less fully captured by SAI/PAI and may involve additional factors.

Background: To contrast retinal and choroidal vascular alterations between carotid artery dissection (CAD) and carotid artery stenosis (CAS), and analyze their associations with cerebral infarction patterns and stenosis severity. Methods: This observational study included stenotic‐degree‐matched patients with CAD and patients with CAS. Retinal ischemic signs—cotton wool spots, retinal artery occlusion, and paracentral acute middle maculopathy—were evaluated using fovea‐centered optical coherence tomography/angiography. Retinal vascular density and choroidal metrics (choriocapillaris density, thickness, vascular volume, and index) were analyzed. Results: The final analysis included 863 eyes from 467 participants (85 with CAD, 274 with CAS, 108 controls). Patients with CAD showed a significantly higher prevalence of paracentral acute middle maculopathy than Patients with CAS (6.4% versus 0.61%, P P P P =0.022) and severe stenosis/occlusion ( P =0.008). Notably, retinal signs correlated with cerebral infarction topography: subcortical infarctions were predominantly associated with paracentral acute middle maculopathy, whereas cortical infarctions were linked to cotton wool spots and retinal artery occlusion ( P =0.004). Conclusions: Compared with atherosclerotic stenosis, CAD exhibits a distinct oculovascular phenotype characterized by a higher burden of acute retinal ischemia but compensatory choroidal hyperperfusion. Retinal imaging serves as a noninvasive window into CAD pathophysiology, offering biomarkers for assessing hemodynamic stability and thromboembolic risk. Registration: URL: www.chictr.org.cn ; Unique identifier: ChiCTR2300074640.

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.

Background and Objectives: Thalamic infarction (TI) can lead to gait disturbances (GDs), even in the absence of significant motor impairments. Understanding the characteristics of GDs in TI patients is crucial for developing targeted rehabilitation strategies. Nonetheless, very little is known about the detailed gait changes in TI patients. This study aimed to investigate and characterize these parameters in TI patients.Methods: Ninety participants, including 45 subacute TI patients and 45 age‐sex‐matched healthy controls, were cross‐sectionally and consecutively included from West China Hospital, Sichuan University. A detailed set of spatiotemporal gait analyses was performed with forty‐one parameters as output, evaluated using the “ReadyGo” three‐dimensional motion balance testing system. Additionally, we analyzed the correlation between cerebral small vessel disease (CSVD) and gait parameters in TI and healthy controls (HC) and performed a Fisher z‐test to determine whether there was a significant difference.Results: Variability, stride length, stride speed, and swing velocity significantly differed in the affected and unaffected sides of TI patients. TI patients exhibited differences in thirty‐eight gait parameters compared to controls. Coordination analysis revealed impairments in the timed up and go test, with longer total time, turn time, stand‐up time, and reduced stride speed. Additionally, deficits were noted in the Heel‐Knee‐Shin test and Finger‐Nose test. However, no differences were found in Romberg's test. Balance assessment showed variations in sit time, torso rocking degree, torso forward roll degree, and walking speed. The correlation between gait parameters and CSVD in TI and HC is presented. Additionally, it was found that total burden leads to a decrease in step width in TI patients and increases trunk sway degree in the tandem stance test in TI.Conclusion: This study demonstrates distinct spatiotemporal gait impairment patterns, coordination, and balance deficits in TI patients. Additionally, our findings suggest that the mechanisms underlying GDs may differ between TI patients and HC in relation to CSVD. These findings emphasize the need for personalized rehabilitation strategies to target these specific GDs in TI patients.

Background: The association between baseline cerebral perfusion status and perilesional white matter degeneration in recent single subcortical infarcts (RSSIs) is still not well understood. We aimed to investigate the clinical relevance and possible predictors of long‐term morphological changes of RSSIs. Methods: Patients with RSSI who had baseline computed tomography perfusion and at least 1 follow‐up magnetic resonance imaging were retrospectively enrolled from the stroke registry databases. Computed tomography perfusion measurements, infarct size and location, small vessel disease burden, and clinical and radiological outcomes were evaluated. We assessed the association between perfusion status and neuroimaging evolution. Results: Among the eligible 104 patients with RSSI, the majority (80.8%) had cavitated lesion evolution, and nearly half (46.2%) developed white matter tract degeneration. Patients with secondary white matter injury showed worse functional outcomes. The computed tomography perfusion parameter ratios were defined as the measurements in the regions of interest (infarct lesion or mirrored region) divided by those in the hemisphere of the same side with regions of interest. Lower cerebral blood flow ratio and cerebral blood volume ratio on either lesion side and opposite side were independently associated with white matter tract degeneration after adjusting for hypertension, National Institutes of Health Stroke Scale score, lesion volume, corticospinal tract infarction and follow‐up time. We also found a mediation effect of the contralateral cerebral blood flow ratio between corticospinal tract infarction and white matter injury. Conclusions: White matter tract degeneration has potential clinical value for indicating worse functional outcomes in RSSIs. Baseline regional hypoperfusion, especially with a lower contralateral cerebral blood flow ratio, independently predicts secondary white matter injury.