Different implications of daytime and nighttime heart rate variability on total burden of cerebral small vascular disease in patients with nondisabling ischemic cerebrovascular events.

Objective: This study aimed to explore the relationship between total burden of cerebral small vessel disease (CSVD) and daytime and nighttime heart rate variability (HRV) parameters. Method: Consecutive patients with nondisabling ischemic cerebrovascular events were recruited from the cerebrovascular disease clinic of Changzhou Second People's Hospital between January 2022 and June 2023. A total of 144 enrolled participants were divided into a mild CSVD group (74 patients) and a moderate-to-severe CSVD group (70 patients) based on total burden of CSVD. Various HRV parameters measured during 24-h, 4-h daytime, and 4-h nighttime periods (including natural log-transformed [ln] root mean square of successive RR interval differences [RMSSD], ln absolute power of the high-frequency band [0.15-0.4 Hz] [HF], ln absolute power of the low-frequency band [0.04-0.15 Hz][LF], and LF-to-HF ratio [LF/HF]) were then assessed in the 2 groups. Spearman correlation analysis was used to assess the correlation between total burden of CSVD and HRV parameters. HRV parameters with P-value < 0.05 in correlation analysis were included in the multivariable logistic regression analysis, and restricted cubic spline analysis was performed to assess dose-response relationships. Results: Daytime 4-h lnRMSSD (r = -0.221; P = 0.008) and 4-h lnHF (r = -0.232; P = 0.005) were negatively correlated with total burden of CSVD, and daytime 4-h lnLF/HF (r = 0.187; P = 0.025) was positively correlated with total burden of CSVD. There was no correlation between nighttime HRV parameters and total burden of CSVD. After adjustments were made for potential confounders, daytime 4-h lnRMSSD (OR = 0.34; 95% CI: 0.16-0.76), 4-h lnHF (OR = 0.57; 95% CI: 0.39-0.84), and 4-h lnLF/HF (OR = 2.12; 95% CI: 1.18-3.82) were independent predictors of total burden of CSVD (all P < 0.05). S-shaped linear associations with moderate-to-severe total burden of CSVD were seen for daytime 4h-lnRMSSD (P for nonlinearity = 0.543), 4-h lnHF (P for nonlinearity = 0.31), and 4-h lnLF/HF (P for nonlinearity = 0.502). Conclusion: Daytime parasympathetic HRV parameters are independent influencing factors of total burden of CSVD and may serve as potential therapeutic observation indicators for CSVD.

Cognitive impairment and amygdala subregion volumes in elderly with cerebral small vessel disease: A large prospective cohort study.

Although the amygdala is associated with cognitive impairment resulting from cerebral small vessel disease, the relationship between alterations in amygdala structure and cerebral small vessel disease (CSVD) remains controversial. Given that the amygdala comprises several subregions, detecting subtle regional changes through total amygdala volume measurement is challenging. This study aimed to identify the patterns of amygdala subregion atrophy in cerebral small vessel disease patients and their relationship with cognitive impairment. A total of 114 participants diagnosed with cerebral small vessel disease and 129 healthy participants, aged 40 to 70, underwent 3 T magnetic resonance imaging scans. The amygdala subregions were automatically segmented using FreeSurfer. In the Propensity Score Matching (PSM)-matched cohort, Lasso regression was employed to identify subregions associated with cerebral small vessel disease, and restricted cubic splines (RCS) were used to explore their nonlinear relationship with cognitive abilities. Subsequently, multivariate linear regression models were used to investigate the impact of amygdala subregion volumes on various cognitive abilities. Compared to healthy controls (HC), the volume of the left cortical nucleus was significantly reduced in cerebral small vessel disease patients. The volume of the left cortical nucleus was significantly negatively correlated with cerebral small vessel disease progression, and atrophy in this region was also identified as an independent risk factor for decreased cognitive control and processing ability. Our findings suggest that patients with cerebral small vessel disease exhibit atrophy in specific amygdala subregions compared to healthy controls, which correlates with poorer cognitive control and processing abilities. These insights may advance our understanding of the pathogenesis of cerebral small vessel disease.

Immune system activation and cognitive impairment in arterial hypertension.

Chronic arterial hypertension disrupts the integrity of the cerebral microvasculature, doubling the risk of age-related dementia. Despite sufficient antihypertensive therapy, in still a significant proportion of individuals blood pressure lowering alone does not preserve cognitive health. Accumulating evidence highlights the role of inflammatory mechanisms in the pathogenesis of hypertension. In this review, we introduce a temporal framework to explore how early immune system activation and interactions at neurovascular-immune interfaces pave the way to cognitive impairment. The overall paradigm suggests that pro-hypertensive stimuli induce mechanical stress and systemic inflammatory responses that shift peripheral and meningeal immune effector mechanisms towards a pro-inflammatory state. Neurovascular-immune interfaces in the brain include a dysfunctional blood-brain barrier, crossed by peripheral immune cells; the perivascular space, in which macrophages respond to cerebrospinal fluid- and blood-derived immune regulators; and the meningeal immune reservoir, particularly T cells. Immune responses at these interfaces bridge peripheral and neurovascular unit inflammation, directly contributing to impaired brain perfusion, clearance of toxic metabolites and synaptic function. We propose that deep immunophenotyping in biofluids together with advanced neuroimaging could aid in the translational determination of sequential immune and brain endotypes specific to arterial hypertension. This could close knowledge gaps on how and when immune system activation transits into neurovascular dysfunction and cognitive impairment. In the future, targeting specific immune mechanisms could prevent and halt hypertension disease progression before clinical symptoms arise, addressing the need for new interventions against one of the leading threats to cognitive health.

Mendelian Randomization Analysis to Assess Whether Magnetic Resonance Imaging Signs of Cerebral Small Vessel Disease Can Cause Cognitive Decline and Dementia.

OBJECTIVE: Cognitive decline and dementia have been linked to cerebral small vessel disease, so we explored using Mendelian randomization whether cerebral small vessel disease visible as 10 neuroimaging signs may cause cognitive decline and dementia. METHODS: We analyzed publicly available data from genome-wide association studies using two-sample Mendelian randomization involving inverse variance weighting, weighted median, MR-Egger, and MR-PRESSO approaches. RESULTS: Mendelian randomization suggested that cognitive decline can be caused by lacunar stroke (inverse variance weighting, ß = -0.012, 95% CI -0.024 to -0.001, P = 0.033). Furthermore, an elevated burden of white matter hyperintensities was associated with an increased risk of Dementia due to Parkinson's disease (inverse variance weighting, OR 2.035, 95% CI 1.105 to 3.745, P = 0.023). Notably, no significant associations were observed between neuroimaging markers of Cerebral Small Vessel Disease and other types of dementia. CONCLUSION: This Mendelian randomization study provides evidence that lacunar stroke and white matter lesions can cause cognitive decline, and that white matter hyperintensity may increase risk of dementia due to Parkinson's disease. These results underscore the need for further investigations into the neurocognitive effects of cerebral small vessel disease.

Association between pulse wave velocity and cerebral microbleeds: a systematic review and meta-analysis.

Cerebral microbleeds are associated with events that are among the highest mortality and disability events combined worldwide, as well as with hypertensive vasculopathy. The aim of the present study was to investigate the relationship between a marker of hypertensive vasculopathy, arterial stiffness assessed by pulse wave velocity, and cerebral microbleeds. A systematic review and meta-analysis was performed using PubMed, Scopus, and Web of Science, according to the Meta-analysis of Observational Studies in Epidemiology (MOOSE) and Cochrane Collaboration Handbook statements. Data extraction, quality assessment and statistical analyses were performed following pre-established criteria. Twenty-one studies involving 18,436 participants were included. Higher levels of pulse wave velocity were associated with a higher presence of cerebral microbleeds p-OR = 1.26 (95% CI; 1.09-1.45), with considerable heterogeneity; even adjusting for potential confounding variables p-OR = 1.12 (95% CI, 1.05-1.20), with substantial heterogeneity. Only the percentage of women was related to p-OR in the adjusted model. Sensitivity analyses confirmed the robustness of our results. Adjusted models showed publication bias. Higher levels of arterial stiffness are associated with greater presence of cerebral microbleeds. This phenomenon may be caused by damage to the brain under higher blood flow loads, in turn due to age-induced reversal of the stiffness gradient between large and small vessels. As the world's population is undergoing demographic ageing, our results underline the importance of establishing pulse wave velocity as a cardiovascular marker for early screening and delaying the onset of the characteristic signs of both diseases.

Baseline Blood Pressure Was Associated with Hemispheric Cerebral Blood Flow in Acute Small Subcortical Infarcts.

INTRODUCTION: While increased baseline blood pressure (BP) is a prevalent comorbidity in the acute phase of ischemic stroke, the association between baseline BP and the state of hemispheric perfusion in patients with acute small subcortical infarcts (SSIs) has not been studied in detail. The aim of this study was to investigate the relationship between baseline BP and hemispheric cerebral blood flow (CBF) in acute SSIs. METHODS: This retrospective study included 101 patients with acute SSIs. Baseline hemispheric CBF was assessed through co-registration of baseline CT perfusion imaging and follow-up diffusion-weighted imaging. The association between baseline BP, CBF, and different cerebral small vessel disease (CSVD) biomarkers was assessed. RESULTS: Baseline systolic BP (SBP) and diastolic BP (DBP) were negatively associated with contralateral hemispheric CBF after multivariate-adjusted linear analysis (SBP: ß = -0.001, 95% CI: -0.002 to 0.000, p = 0.030; DBP: ß = -0.002, 95% CI: -0.003∼0.001, p = 0.006). Among other CSVD biomarkers, the presence of any cerebral microbleeds showed a significant association with lower CBF in the contralateral hemisphere of the infarct lesion (r = -0.270, p = 0.035). CONCLUSION: In patients with acute SSIs, increased baseline BP was associated with reduced CBF in the contralateral hemisphere of the infarct lesion, which probably could be interpreted by the exacerbation of the CSVD burden, suggesting a potential mechanistic link between BP autoregulation dysfunction and the aggravation of neurovascular impairment in SSIs.

Cerebral salt wasting syndrome in an elderly patient with cerebral small vessel disease.

Hyponatremia is a common electrolyte disturbance seen among the acute geriatric admissions with two common diagnostic entities; the syndrome of inappropriate antidiuretic hormone (SIADH) and cerebral salt wasting syndrome (CSWS) that have different clinical and biochemical presentations, different pathogenesis and therapeutic approaches. Hyponatremia caused by CSWS in patients with cerebral small vessel disease (cSVD) a prevalent condition among the elderly, can be masked in geriatric patients with concomitant fluctuating neurological deficits. Correct diagnosis is crucial to appropriate management. In this case report we describe an association between hyponatremia caused by CSWS in a patient with cSVD.

Cognition mediates the relationship between white matter hyperintensity and motor function in patients with cerebral small vessel disease: a cross-sectional study.

Background: White matter hyperintensity (WMH) is a common neuroimaging marker of cerebral small vessel disease (SVD) and a critical independent predictor of motor dysfunction, which increases the risk of disability, morbidity, and mortality. However, the mechanism underlying the relationship between WMH and motor function has not yet been fully clarified. It was hypothesized that cognitive impairment mediates the relationship between WMH and motor dysfunction in patients with SVD, which were considered predictor and outcome variables, respectively. Methods: A total of 221 patients with SVD were enrolled in this study, and their magnetic resonance imaging (MRI), neuropsychological, and motor function data were collected. The MRI data were visually assessed to determine the WMH burden using the Fazekas scale. Cognition was evaluated using the Montreal Cognitive Assessment (MoCA). Motor function was assessed using the Tinetti Gait and Balance Scale and the Short Physical Performance Battery (SPPB). Finally, a bootstrap analysis was performed to determine whether cognition mediated the relationship between WMH and motor function. Results: Of all the patients, 30.3% had mild WMH, 37.6% had moderate WMH, and 32.1% had severe WMH. Patients' cognition and motor function decreased as the WMH burden increased (P<0.01). The MoCA scores were associated with the Tinetti scale (r=0.545, P<0.01) and SPPB scores (r=0.365, P<0.01). Finally, multi-categorical mediation models confirmed our research hypothesis; the coefficients for the indirect effects had 95% confidence intervals (CIs) that excluded zero, indicating statistically significant mediation effects. Conclusions: WMH is associated with motor dysfunction, and this association is mediated by cognition in patients with SVD. This finding highlights the importance of early interventions targeting cognitive function to reduce the risk of motor dysfunction.

Quantitative comparison of CSVD imaging markers between patients with possible amyloid small vessel disease and with non-amyloid small vessel disease.

The spatial distribution patterns of cerebral microbleeds are associated with different types of cerebral small vessel disease (CSVD). This study aims to examine the disparities in brain imaging markers of CSVD among patients diagnosed with possible amyloid and non-amyloid small vessel disease. The head MR scans including susceptibility-weighted imaging (SWI) sequences from 351 patients at our institute were collected for analysis. CSVD imaging markers were quantified or graded across various CSVD dimensions in the patient images. Patients were categorized into the cerebral amyloid angiopathy group (CAA), hypertensive arteriopathy group (HA), or mixed small vessel disease group (Mixed), based on the spatial distribution of microbleeds. White matter lesions (WML) were segmented using an artificial neural network and assessed via a voxel-wise approach. Significant differences were observed among the three groups in several indices: microbleed count, lacune count at the centrum semiovale and basal ganglia levels, grade of enlarged perivascular space (EPVS) at the basal ganglia, and white matter lesion volume. These indices were substantially higher in the Mixed group compared to the other groups. Additionally, the incidences of cerebral hemorrhages (χ2 = 7.659, P = 0.006) and recent small subcortical infarcts (χ2 = 4.660, P = 0.031) were significantly more frequent in the HA group than in the CAA group. These results indicate that mixed spatial distribution patterns of microbleeds demonstrated the highest burden of cerebral small vessel disease. Microbleeds located in the deep brain regions were associated with a higher incidence of recent small subcortical infarcts and cerebral hemorrhages compared to those in the cortical areas.

Artificial intelligence-assisted oculo-gait measurements for cognitive impairment in cerebral small vessel disease.

INTRODUCTION: Oculomotor and gait dysfunctions are closely associated with cognition. However, oculo-gait patterns and their correlation with cognition in cerebral small vessel disease (CSVD) remain unclear. METHODS: Patients with CSVD from a hospital-based cohort (n = 194) and individuals with presumed early CSVD from a community-based cohort (n = 319) were included. Oculo-gait patterns were measured using the artificial intelligence (AI) -assisted 'EyeKnow' eye-tracking and 'ReadyGo' motor evaluation systems. Multivariable linear and logistic regression models were employed to investigate the association between the oculo-gait parameters and cognition. RESULTS: Anti-saccade accuracy, stride velocity, and swing velocity were significantly associated with cognition in both patients and community dwellers with CSVD, and could identify cognitive impairment in CSVD with moderate accuracy (area under the curve [AUC]: hospital cohort, 0.787; community cohort, 0.810) after adjusting for age and education. DISCUSSION: The evaluation of oculo-gait features (anti-saccade accuracy, stride velocity, and swing velocity) may help screen cognitive impairment in CSVD. HIGHLIGHTS: Oculo-gait features (lower anti-saccade accuracy, stride velocity, and swing velocity) were associated with cognitive impairment in cerebral small vessel disease (CSVD). Logistic model integrating the oculo-gait features, age, and education level moderately distinguished cognitive status in CSVD. Artificial intelligence-assisted oculomotor and gait measurements provide quick and accurate evaluation in hospital and community settings.

Association of novel lipid indices with the white matter hyperintensities in cerebral small vessel disease: a cross-sectional study.

BACKGROUND: Lipids are associated with atherosclerosis, and novel lipid indices have been recently identified to be closely linked to cardiovascular diseases. This study explored the association between four novel lipid indices and the white matter hyperintensities (WMHs) in patients diagnosed with cerebral small vessel disease (CSVD). METHODS: Between January 2023 and February 2024, 219 patients were recruited, including 165 patients with CSVD WMHs and 54 healthy controls. Based on WMHs severity, patients with CSVD were categorised into mild and moderate-to-severe cohorts using the Fazekas rating scale. The plasma levels of four novel lipid indices (low-density lipoprotein cholesterol/high-density lipoprotein cholesterol ratio [LDL-C/HDL-C], triglyceride/high-density lipoprotein cholesterol ratio [TG/HDL-C], total cholesterol/high-density lipoprotein cholesterol ratio [TC/HDL-C], and non-high-density lipoprotein cholesterol [Non-HDL-C]), were rigorously monitored in the enrolled patients. RESULTS: A total of 165 patients with CSVD WMHs were enrolled, including 94 with mild WMHs and 71 with moderate-to-severe WMHs. Multivariable logistic regression analysis revealed that LDL-C/HDL-C, TG/HDL-C, TC/HDL-C, and Non-HDL-C levels were significantly associated with WMHs (all P ≤ 0.001). Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic performance of plasma lipid levels for WMHs in patients with CSVD. The novel lipid indicators outperformed traditional lipid indicators in assessing the diagnostic capability of WMHs. The combined index of the four blood lipid indices had an optimal cutoff point (OCP) of 0.489, with 88.3% sensitivity and 60.6% specificity. The area under the curve (AUC) is 0.800 (95% confidence interval [CI], 0.731-0.869; P < 0.001). Compared with males (OR = 1.126, 95% CI = 0.779-1.628), females (OR = 2.484, 95% CI = 1.398-4.414; P for interaction = 0.023) had a higher risk of developing WMHs. CONCLUSION: This study demonstrates a significant association between four novel lipid indices and the cerebral WMHs in CSVD, highlighting the potential of these markers as novel plasma biomarkers and predictive indicators for assessing CSVD progression and guiding clinical management.

Intracranial Aneurysms and Cerebral Small Vessel Disease: Is There an Association between Large- and Small-Artery Diseases?

Background/Objectives: Intracranial aneurysms (IAs) may be connected to interactions between large and small intracranial vessels. We aimed to investigate the association between IAs and cerebral small-vessel disease (CSVD) and assess CSVD impact on IA patient management. Methods: This retrospective study analyzed clinical data and MRI features of CSVD in 192 subarachnoid hemorrhage (SAH) patients: 136 with incidental IA, 147 with severe CSVD without SAH/IA, and 50 controls without SAH, IA, or severe CSVD. MRI assessments followed the Standards for Reporting Vascular Changes on Neuroimaging (STRIVE), with a total burden of small-vessel disease (TBSVD) score calculated. Statistical analyses included forward selection and binary logistic regression. Results: TBSVD differed significantly across groups (p < 0.001), except between SAH and IA groups (p = 0.8). Controls had the lowest TBSVD (1.00; 1.22 ± 0.996), followed by SAH (2.00; 2.08 ± 1.013) and IA groups (2.00; 2.04 ± 1.141), with the highest in the CSVD group (1.00; 1.22 ± 0.996). White-matter hyperintensity (WMH) patterns varied with IA rupture status (p = 0.044); type A was prevalent in SAH patients and type D in the IA group. Incorporating MRI CSVD features and TBSVD into risk assessments did not enhance IA prediction or outcome models. Conclusions: IA patients exhibit a higher CSVD burden than controls, suggesting a link between small and large intracranial vessels. WMH patterns distinguish between ruptured and unruptured IA patients, offering potential markers for IA rupture risk assessment and signaling a paradigm shift in understanding IAs and CSVD.

Cerebral small vessel injury in mice with damage to ACE2-expressing cerebral vascular endothelial cells and post COVID-19 patients.

INTRODUCTION: The angiotensin-converting enzyme 2 (ACE2), which is expressed in cerebral vascular endothelial cells (CVECs), has been currently identified as a functional receptor for SARS-CoV-2. METHODS: We specifically induced injury to ACE2-expressing CVECs in mice and evaluated the effects of such targeted damage through magnetic resonance imaging (MRI) and cognitive behavioral tests. In parallel, we recruited a single-center cohort of COVID-19 survivors and further assessed their brain microvascular injury based on cognition and emotional scales, cranial MRI scans, and blood proteomic measurements. RESULTS: Here, we show an array of pathological and behavioral alterations characteristic of cerebral small vessel disease (CSVD) in mice that targeted damage to ACE2-expressing CVECs, and COVID-19 survivors. These CSVD-like manifestations persist for at least 7 months post-recovery from COVID-19. DISCUSSION: Our findings suggest that SARS-CoV-2 may induce cerebral small vessel damage with persistent sequelae, underscoring the imperative for heightened clinical vigilance in mitigating or treating SARS-CoV-2-mediated cerebral endothelial injury throughout infection and convalescence. HIGHLIGHTS: Cerebral small vessel disease-associated changes were observed after targeted damage to angiotensin-converting enzyme 2-expressing cerebral vascular endothelial cells. SARS-CoV-2 may induce cerebral small vessel damage with persistent sequelae. Clinical vigilance is needed in preventing SARS-CoV-2-induced cerebral endothelial damage during infection and recovery.

Hippocampal fimbria atrophy and its mediating effect between cerebral small vessel disease and cognitive impairment.

We aimed to investigate the relationship between the volume reduction in hippocampal (HP) subregions and cognitive impairment in patients with cerebral small vessel disease (CSVD). Clinical, cognitive, and magnetic resonance imaging data were obtained for 315 participants. The CSVD group included 146 participants with a total CSVD score of 1-4. 169 participants with a total CSVD score of zero were used as control group (CSVD-0). The volume differences of 19 HP subregions between CSVD and CSVD-0 groups were analyzed, and we investigated the hazard factors that might cause subregional volume reduction in HP. Mediation analysis was performed to detect the relationship among HP subregional volumes, CSVD burden, and cognitive function. In our results, significant differences can be found in the volumes of CA4 body, presubiculum-head, presubiculum-body, subiculum-body, GC-ML-DG-head, GC-ML-DG-body, fimbria, and HP tail between CSVD group and control group. Regression analysis showed that fimbria was the most impacted HP subregion by CSVD. And mediation analysis revealed fimbria volume was a mediator variable between total CSVD score and MoCA/SCWT score. These results suggest that the volumes of HP subregions, especially the fimbria, may be effective potential biomarkers for early detecting cognitive impairment in CSVD.

Cognition in (pre)symptomatic Dutch-type hereditary and sporadic cerebral amyloid angiopathy.

INTRODUCTION: Cerebral amyloid angiopathy (CAA) is a main cause of cognitive dysfunction in the elderly. We investigated specific cognitive profiles, cognitive function in the stage before intracerebral hemorrhage (ICH), and the association between magnetic resonance imaging (MRI) based cerebral small vessel disease (cSVD) burden in CAA because data on these topics are limited. METHODS: We included Dutch-type hereditary CAA (D-CAA) mutation carriers with and without ICH, patients with sporadic CAA (sCAA), and age-matched controls. Cognition was measured with a standardized test battery. Linear regression was performed to assess the association between MRI-cSVD burden and cognition. RESULTS: D-CAA ICH- mutation carriers exhibited poorer global cognition and executive function compared to age-matched controls. Patients with sCAA performed worse across all cognitive domains compared to D-CAA ICH+ mutation carriers and age-matched controls. MRI-cSVD burden is associated with decreased processing speed. DISCUSSION: CAA is associated with dysfunction in multiple cognitive domains, even before ICH, with increased MRI-cSVD burden being associated with slower processing speed. HIGHLIGHTS: Cognitive dysfunction is present in early disease stages of cerebral amyloid angiopathy (CAA) before the occurrence of symptomatic intracerebral hemorrhage (sICH). Presymptomatic Dutch-type CAA (D-CAA) mutation carriers show worse cognition than age-matched controls. More early awareness of cognitive dysfunction in CAA before first sICH is needed. Increased cerebral small vessel disease CAA-burden on magnetic resonance imaging is linked to a decrease in processing speed.

Risk factors and clinical significance of post-stroke incident ischemic lesions.

INTRODUCTION: While incident ischemic lesions (IILs) are not unusual on follow-up magnetic resonance imaging (MRI) following stroke, their risk factors and prognostic significance remain unknown. METHODS: In a prospective multicenter study of 503 acute stroke patients, we assessed IILs on registered MRI images at baseline and 6 months, analyzing risk factors and clinical outcomes across 36 months. RESULTS: At 6 months, 78 patients (15.5%) had IILs, mostly diffusion-weighted imaging-positive (72%) and clinically covert (91%). Older age and small vessel disease (SVD) lesions were baseline risk factors for IILs. IILs were associated with worse cognitive (beta for global cognition: -0.31, 95% confidence interval [CI]: -0.48 to -0.14) and functional outcomes (beta for modified Rankin scale [mRS]: 0.36, 95% CI: 0.14 to 0.58), and higher recurrent stroke risk (hazard ratio: 3.81, 95% CI: 1.35 to 10.69). IILs partially explained the relationship between SVD and poor cognition. DISCUSSION: IILs are common and are associated with worse cognitive and functional outcomes and stroke recurrence risk. Assessing IILs following stroke might aid prognostication. HIGHLIGHTS: Incident ischemic lesions (IILs) were assessed with registered baseline and 6-month magnetic resonance imaging (MRI) scans in a stroke cohort. IILs 6 months after stroke are present in one-sixth of patients and are mostly clinically silent. Small vessel disease burden is the main baseline risk factor for IILs. IILs are associated with cognitive and functional impairment and stroke recurrence. Assessing IILs by follow-up MRI aids long-term prognostication for stroke patients.

More severe cerebral small vessel disease associated with poor leptomeningeal collaterals in symptomatic intracranial atherosclerotic stenosis.

We investigated the association between cerebral small vessel disease (CSVD) and ipsilateral leptomeningeal collateral (LMC) status in patients with symptomatic intracranial atherosclerotic stenosis (sICAS). In 108 patients with 50-99% symptomatic intracranial internal carotid artery or M1 middle cerebral artery stenosis, 4 CSVD imaging markers (lacunes, cerebral microbleeds, enlarged perivascular spaces [EPVSs], and white matter hyperintensities [WMHs]) were assessed in MRI. Score of 0 or 1 was assigned to each marker and added up as a summary CSVD score (ranging 0-4) to reflect an overall CSVD burden. Ipsilateral LMC status was assessed by determining the laterality of distal vessels in anterior and posterior cerebral artery territories on CT angiography. Moderate-to-severe EPVSs (adjusted odds ratio [aOR] = 4.15; p = 0.031) and WMHs (aOR = 5.90; p = 0.010), and higher summary CSVD score (aOR = 1.66; p = 0.030) were independently associated with poor LMCs. There was significant interaction between stenosis percentage in sICAS and summary CSVD score on poor LMCs (p = 0.022 for interaction), when higher CSVD score was significantly associated with poor LMCs in patients with severe sICAS (aOR = 2.84; p = 0.011) but not in those with moderate sICAS. The findings indicated possibly adverse effect of CSVD on the recruitment or development of LMCs in sICAS patients, especially in patients with severe sICAS.

Enhancing cognitive performance prediction by white matter hyperintensity connectivity assessment.

White matter hyperintensities of presumed vascular origin (WMH) are associated with cognitive impairment and are a key imaging marker in evaluating brain health. However, WMH volume alone does not fully account for the extent of cognitive deficits and the mechanisms linking WMH to these deficits remain unclear. Lesion network mapping (LNM) enables to infer if brain networks are connected to lesions and could be a promising technique for enhancing our understanding of the role of WMH in cognitive disorders. Our study employed LNM to test the following hypotheses: (1) LNM-informed markers surpass WMH volumes in predicting cognitive performance, and (2) WMH contributing to cognitive impairment map to specific brain networks. We analyzed cross-sectional data of 3,485 patients from 10 memory clinic cohorts within the Meta VCI Map Consortium, using harmonized test results in 4 cognitive domains and WMH segmentations. WMH segmentations were registered to a standard space and mapped onto existing normative structural and functional brain connectome data. We employed LNM to quantify WMH connectivity to 480 atlas-based gray and white matter regions of interest (ROI), resulting in ROI-level structural and functional LNM scores. We compared the capacity of total and regional WMH volumes and LNM scores in predicting cognitive function using ridge regression models in a nested cross-validation. LNM scores predicted performance in three cognitive domains (attention/executive function, information processing speed, and verbal memory) significantly better than WMH volumes. LNM scores did not improve prediction for language functions. ROI-level analysis revealed that higher LNM scores, representing greater connectivity to WMH, in gray and white matter regions of the dorsal and ventral attention networks were associated with lower cognitive performance. Measures of WMH-related brain network connectivity significantly improve the prediction of current cognitive performance in memory clinic patients compared to WMH volume as a traditional imaging marker of cerebrovascular disease. This highlights the crucial role of network integrity, particularly in attention-related brain regions, improving our understanding of vascular contributions to cognitive impairment. Moving forward, refining WMH information with connectivity data could contribute to patient-tailored therapeutic interventions and facilitate the identification of subgroups at risk of cognitive disorders.

Automatic segmentation and diameter measurement of deep medullary veins.

PURPOSE: As one of the pathogenic factors of cerebral small vessel disease, venous collagenosis may result in the occlusion or stenosis of deep medullary veins (DMVs). Although numerous DMVs can be observed in susceptibility-weighted MRI images, their diameters are usually smaller than the MRI resolution, making it difficult to segment them and quantify their sizes. We aim to automatically segment DMVs and measure their diameters from gradient-echo images. METHODS: A neural network model was trained for DMV segmentation based on the gradient-echo magnitude and phase images of 20 subjects at 7 T. The diameters of DMVs were obtained by fitting measured complex images with model images that accounted for the DMV-induced magnetic field and point spread function. A phantom study with graphite rods of different diameters was conducted to validate the proposed method. Simulation was carried out to evaluate the voxel-size dependence of measurement accuracy for a typical DMV size. RESULTS: The automatically segmented DMV masks had Dice similarity coefficients of 0.68 ± 0.03 (voxel level) and 0.83 ± 0.04 (cluster level). The fitted graphite-rod diameters closely matched their true values. In simulation, the fitted diameters closely matched the true value when voxel size was ≤ 0.45 mm, and 92.2% of DMVs had diameters between 90 µm and 200 µm with a peak at about 120 µm, which agreed well with an earlier ex vivo report. CONCLUSION: The proposed methods enabled efficient and quantitative study of DMVs, which may help illuminate the role of DMVs in the etiopathogenesis of cerebral small vessel disease.