Total Small Vessel Disease Research Articles

A new nomogram including total cerebral small vessel disease burden for individualized prediction of early-onset depression in patients with acute ischemic stroke.

ObjectivesThe present study was designed to evaluate the effects of total cerebral small vessel disease (CSVD) on early-onset depression after acute ischemic stroke (AIS), and to develop a new nomogram including total CSVD burden to predict early-onset post-stroke depression (PSD).MethodsWe continuously enrolled patients with AIS who were hospitalized at the First Affiliated Hospital of Soochow University between October 2017 and June 2019. All patients were assessed for depressive symptoms using the 17-item Hamilton Depression Scale (HAMD-17) at 14 ± 2 days after the onset of AIS. The diagnosis for depression was made according to the American Diagnostic and Statistical Manual of Mental Disorders Version 5 (DSM-5). The demographic and clinical data were collected including total CSVD burden. On the basis of a multivariate logistic model, the independent factors of early-onset PSD were identified and the predictive nomogram was generated. The performance of the nomogram was evaluated by Harrell's concordance index (C-index) and calibration plot.ResultsA total of 346 patients were enrolled. When contrasted to a 0 score of total CSVD burden, the score ≥2 (moderate to severe total CSVD burden) was an independent risk factor for early-onset PSD. Besides, gender, cognitive impairments, baseline Barthel Index (BI), and plasma fibrinogen were independently associated with early-onset PSD. The nomogram based on all these five independent risk factors was developed and validated with an Area Under Curve (AUC) of 0.780. In addition, the calibration plot revealed an adequate fit of the nomogram in predicting the risk of early-onset depression in patients with AIS.ConclusionsOur study found the total CSVD burden score of 2–4 points was an independent risk factor of early-onset PSD. The proposed nomogram based on total CSVD burden, gender, cognitive impairments, baseline BI, and plasma fibrinogen concentration gave rise to a more accurate and more comprehensive prediction for early-onset PSD.

Risk factors and predictive scoring system for twice or more strokes in patients with cerebral small vessel disease

Objectives To explore the independent risk factors of twice or more strokes in patients with cerebral small vessel disease, and to construct a predictive scoring system. Methods A retrospective study was carried out in Tangshan, Hebei Province, China. Patients with cerebral small vessel disease suffered from acute stroke and admitted to Neurology Department of Tangshan Gongren Hospital from January 2020 to June 2021 were collected and grouped according to whether they had a previous stroke history. Binary logistic regression models were used to investigate the independent risks for the occurrence of twice or more strokes in patients with cerebral small vessel disease, assigned scores to each factor, then established and evaluated the predictive efficacy of the predictive scoring system. Results A total of 531 patients were included. Regression analysis showed that age, hypertension, diabetes, intracranial arterial stenosis, and total cerebral small vessel disease burden were independent risk factors. On the basis of each regression coefficient, a 10-point predictive scoring system selected the highest Jordon index as the cut-off value, which was 4 points. And the area under the receiver operating characteristic curve was 0.842 (95 %CI: 0.796~0.893, P＜0.001). Conclusions The predictive scoring system based on age, hypertension, diabetes, intracranial arterial stenosis, and total cerebral small vessel disease burden can effectively predict whether patients with cerebral small vessel disease are tend to be onset with twice or more strokes.

The Correlation Between Modified Total Cerebral Small Vessel Disease Score and Gait and Balance Disorder in Middle-aged to Older Adults.

The aim of this study is to investigate the relationships between the original and modified total cerebral Small Vessel Disease (CSVD) score and gait and balance impairment using quantitative and semi-quantitative tests. In our study, patients aged 45 to 85 consecutively recruited. CSVD manifestations were identified with brain Magnetic Resonance Imaging (MRI), and the original and modified CSVD scores were calculated based on the results. Gait and balance function were assessed using both gait parameters and clinical rating scales. The correlation between the original and modified total scores of the CSVD and gait and balance dysfunction was demonstrated. 224 patients were enrolled in the study. Gait and balance disorders were associated with both the original and modified CSVD scores. A significant association remained after adjusting for gender, height, age, hypertension, and other relevant risk factors. The binary logistic regression and chi-squared trend tests revealed that impairment of movement function significantly correlated with the modified CSVD score and that the dysfunction was significantly higher for patients with modified CSVD scores of 5-6 than those with scores of 1-2. In Receiver Operating Characteristic (ROC) analysis, modified CSVD scores were more accurate in predicting gait impairment than original CSVD scores. We found both original and modified total CSVD scores to be related to gait and balance disorder, and the modified CSVD score was more accurate in identifying movement impairment and should be used as an effective tool in investigating CSVD and motor dysfunction.

Relationship Between Plasma Lipopolysaccharides, Gut Microbiota, and Dementia: A Cross-Sectional Study

Previous studies have demonstrated associations between gut microbiota, microbial metabolites, and cognitive decline. However, relationships between these factors and lipopolysaccharides (LPS; molecules of the outer membrane of gram-negative bacteria) remain controversial. To evaluate associations between plasma LPS, gut microbiota, and cognitive function. We performed a cross-sectional sub-analysis of data of 127 participants (women: 58%, mean age: 76 years) from our prospective cohort study regarding the relationship between gut microbiota and cognitive function. We enrolled patients who visited our memory clinic and assessed demographics, dementia-related risk factors, cognitive function, brain imaging, gut microbiomes, and microbial metabolites. We evaluated relationships between cognitive decline and plasma LPS using multivariable logistic regression analyses. Plasma LPS concentration increased with increasing degree of cognitive decline and total cerebral small vessel disease (SVD) score (Kruskal-Wallis test; p = 0.016 and 0.007, respectively). Participants with high plasma LPS concentrations tended to have lower concentrations of gut microbial metabolites, such as lactic acid and acetic acid, and were less likely to consume fish and shellfish (44.7% versus 69.6%, p = 0.027) than those with low plasma LPS concentrations. Multivariable analyses revealed that plasma LPS concentration was independently associated with the presence of mild cognitive impairment in participants without dementia (odds ratio: 2.09, 95% confidence interval: 1.14-3.84, p = 0.007). In this preliminary study, plasma LPS concentration was associated with both cognitive decline and cerebral SVD and significantly correlated with beneficial gut microbial metabolites. Plasma LPS may be a risk factor for cognitive decline.

Total Cerebral Small Vessel Disease Score and Cerebral Bleeding Risk in Patients With Acute Stroke Treated With Intravenous Thrombolysis.

ObjectiveThe aim of this study was to investigate the association of total cerebral small vessel disease (cSVD) score with the risk of intracerebral hemorrhage (ICH) in patients with acute ischemic stroke who received intravenous thrombolysis (IVT) using recombinant tissue-plasminogen activator (rt-PA).MethodsWe retrospectively reviewed clinical data from two stroke registries of patients with acute ischemic stroke treated with IVT. We assessed the baseline magnetic resonance (MR) visible cSVD markers and total cSVD score (ranging from 0 to 4) between patients with and without ICH after IVT. Logistic regression analysis was used to determine the association of total cSVD score with the risk of ICH after IVT, adjusted for cofounders selected by least absolute shrinkage and selection operator (LASSO). We additionally performed an E-value analysis to fully explain away a specific exposure-outcome association. Receiver operating characteristic (ROC) curve analysis was used to quantify the predictive potential of the total cSVD score for any ICH after IVT.ResultsAmong 271 eligible patients, 55 (20.3%) patients experienced any ICH, 16 (5.9%) patients experienced a symptomatic ICH (sICH), and 5 (1.85%) patients had remote intracranial parenchymal hemorrhage (rPH). Logistic regression analysis showed that the risk of any ICH increased with increasing cSVD score [per unit increase, adjusted odds ratio (OR) 2.03, 95% CI 1.22–3.41, P = 0.007]. Sensitivity analyses using E-value revealed that it would need moderately robust unobserved confounding to render the exposure-outcome (cSVD-any ICH) association null. ROC analysis showed that compared with the National Institutes of Health Stroke Scale (NIHSS) score alone, a combination of cSVD and NIHSS score had a larger area under the curve for any ICH (0.811, 95% CI 0.756–0.866 vs. 0.784, 95% CI 0.723–0.846, P = 0.0004).ConclusionThe total cSVD score is associated with an increased risk of any ICH after IVT and improves prediction for any ICH compared with NIHSS alone.

White Matter Free Water Outperforms Cerebral Small Vessel Disease Total Score in Predicting Cognitive Decline in Persons with Mild Cognitive Impairment.

Vascular pathology is an important partner of Alzheimer's disease (AD). Both total cerebral small vessel disease (CSVD) score and white matter free water (FW) are useful markers that could reflect cerebral vascular injury. We aim to investigate the efficacy of these two metrics in predicting cognitive declines in patients with mild cognitive impairment (MCI). We enrolled 126 MCI subjects with 3D T1-weighted images, fluid-attenuated inversion recovery images, T2* images, diffusion tensor imaging images, cerebrospinal fluid biomarkers and neuropsychological tests from the Alzheimer's Disease Neuroimaging Initiative database. The total CSVD score and FW values were calculated. Simple and multiple linear regression analyses were applied to explore the association between vascular and cognitive impairments. Linear mixed effect models were constructed to investigate the efficacy of total CSVD score and FW on predicting cognitive decline. FW was associated with baseline cognition and could predict the decline of executive and language functions in MCI subjects, while no association was found between total CSVD score and cognitive declines. FW is a promising imaging marker for investigating the effect of CSVD on AD progression.

Association between periodic limb movements during sleep and neuroimaging features of cerebral small vessel disease: A preliminary cross-sectional study.

Evidence on the relationship between periodic limb movements during sleep (PLMS) and cerebral small vessel disease is lacking. This study aimed to assess the association between the PLMS index and the neuroimaging features of cerebral small vessel disease on magnetic resonance imaging. Consecutive patients diagnosed with cerebral small vessel disease were enrolled. Data on the clinical characteristics, polysomnography, and brain magnetic resonance imaging were collected. The Accubrain software was used to calculate automatically the volume of white matter hyperintensities, the number of lacunar infarctions, and cerebral microbleeds. The severity of white matter hyperintensities, enlarged basal ganglia perivascular spaces, and the total cerebral small vessel disease scores were also rated visually using semiquantitative scales. The severity of PLMS was measured using the PLMS index, and the patients were divided into two groups using an established cut-off value of ≥15 per hour. Logistic regression was used to examine the association between PLMS and the neuroimaging features of cerebral small vessel disease. In total, 37 patients were included in the final analyses. The mean age was 66.49±11.31years, and 73.0% were males. The mean PLMS index was 19.30±10.18. In univariate analyses, it was found that patients with cerebral small vessel disease with a PLMS index ≥15had increased enlarged basal ganglia perivascular spaces (OR 6.136, 95%CI 1.101-34.214) and increased total cerebral small vessel disease scores (OR 6.0, 95%CI 1.253-28.742). Only the association between the PLMS index and the total cerebral small vessel disease burden score remained statistically significant after adjusting for age, sex, and the presence of moderate to severe obstructive sleep apnea syndrome. In conclusion, an elevated PLMS index is likely to be associated with a greater cerebral small vessel disease burden. PLMS might be a novel potential marker of cerebral small vessel disease.

Predictive Value of Total Small-Vessel Disease Score for Recurrent Stroke in Patients Undergoing Maintenance Hemodialysis

ObjectivesWe sought to examine the validity of the total small-vessel disease (SVD) score in patients receiving maintenance hemodialysis by investigating its predictive value for recurrent stroke. MethodsWe identified 159 patients who showed acute ischemic stroke while receiving maintenance hemodialysis at our institute between January 1, 2008, and December 31, 2020; retrospectively calculated the total SVD score for each patient; and extracted data on demographic factors and comorbidities that could potentially affect recurrent stroke. Death was thought to be a potential competing risk for recurrent stroke because the perceived risk of death was considerably higher than the risk of recurrent stroke in these patients. Thus, we investigated the association between the total SVD score and recurrent stroke by analyzing the competing risk of non-stroke death. ResultsThe median (interquartile range) age was 72 (62-80) years. A total of 38 (23.9%) recurrent strokes occurred, and 69 (43.4%) patients died during the 505 patient-year follow-up study. The estimated cumulative incidence of recurrent stroke at five years was 13.3%, 13.4%, 24.1%, 50%, and 60% for scores of 0 to 4, respectively, and the hazard ratio (HR), adjusted for variables that had been reported to be risk factors of stroke in dialysis patients, per unit increase in the score was 1.72 (95% CI, 1.34-2.21; p<0.001). ConclusionA higher total SVD score was associated with an increased risk of recurrent stroke in patients undergoing maintenance hemodialysis.

Abstract TP185: Cardiac Gadolinium Enhancement And Cerebral Small Vessel Disease

Background: Accumulation of cerebral small vessel disease (CSVD) leads to various well described detrimental clinical consequences. Similar to CSVD, the development of coronary microvascular disease (CMD) yields end-organ dysfunction, namely myocardial ischemia and chamber dilation. We aimed to investigate the relationship between cardiac gadolinium enhancements (CGE), a marker for CMD, on CSVD burden on brain MRI. Methods: We performed a retrospective cross-sectional analysis of adults between January 2014 and December 2019 who completed a cardiac and brain MRI within one year of each other. The ordinal total small vessel disease score (tSVD) was used to quantify CSVD with two cohorts being created: tSVD 0 to 1 (low CSVD) and tSVD 2 to 4 (high CSVD). Cardiac MRI data was obtained under the guidance of an experienced cardiologist with advanced cardiac imaging training. Chi-squared or Fisher’s, Wilcoxon rank-sum analyses were performed for binary and ordinal variables, respectively. Adjusted multivariate logistic regression models were used to calculate odds ratios. Statistical significance was defined as &lt; 0.05. Results: A total of 259 individuals were included with 140 and 119 in the low and high CSVD groups, respectively. Those with low CSVD were significantly lower in age, predominately female and had lower rates of hypertension, hyperlipidemia, diabetes mellitus and congestive heart failure. CGE was more common in those with higher burdens of CSVD (23.2% vs 47.2%, p&lt;0.001). CGE increased the odds of being within the high CSVD group despite adjustment for significant clinical and demographic factors (OR 2.1, 95% CI 1.1 - 4.0). Discussion: In those with CMD as identified by CGE, there was a 2 fold increase in being within the high burden of CSVD cohort likely as a result of similar intrinsic pathological processes. Further studies are needed to determine whether CGE predates development of CSVD, its association with development of acute cerebrovascular diseases and its influence on specific subtypes of CSVD.

Macular Microvasculature Is Associated With Total Cerebral Small Vessel Disease Burden in Recent Single Subcortical Infarction.

PurposeTo assess the retinal microvasculature, choriocapillaris, and choroidal thickness in recent single subcortical infarction (RSSI) patients compared with healthy controls. We also assessed the correlation between the macular microvascular changes and choroidal changes with their clinical implications in RSSI patients.MethodsForty-six RSSI patients and 39 healthy controls (HC) were enrolled in our study. Magnetic resonance imaging (MRI) was done for all RSSI patients, and a total cerebral small vessel disease (CSVD) score was assessed for all patients. Swept-source optical coherence tomography (SS-OCT) was used to image and assess the choroidal thickness and SS-OCT angiography (SS-OCTA) was used to image and assess the macular microvasculature and choriocapillaris in all participants. Clinical information was collected for all participants.ResultsRSSI patients showed significantly sparser inner retinal microvasculature (P = 0.003) when compared with healthy controls. RSSI patients showed significantly thinner choroidal thickness (P < 0.001) when compared with HC. No significant difference (P = 0.247) was seen when the choriocapillaris was compared between the two groups. CSVD burden (P = 0.014) and NIHSS score (P = 0.010) showed significant correlation with the inner retinal microvasculature of RSSI patients. The inner retinal microvasculature (P = 0.016) and choroidal thickness (P = 0.018) showed a significant correlation with the MoCA scores in RSSI patients.ConclusionsOur report suggests that retinal and choroidal imaging may serve as useful indicators to expand our understanding of RSSI and its clinical validity.

Automated grading of enlarged perivascular spaces in clinical imaging data of an acute stroke cohort using an interpretable, 3D deep learning framework

Enlarged perivascular spaces (EPVS), specifically in stroke patients, has been shown to strongly correlate with other measures of small vessel disease and cognitive impairment at 1 year follow-up. Typical grading of EPVS is often challenging and time consuming and is usually based on a subjective visual rating scale. The purpose of the current study was to develop an interpretable, 3D neural network for grading enlarged perivascular spaces (EPVS) severity at the level of the basal ganglia using clinical-grade imaging in a heterogenous acute stroke cohort, in the context of total cerebral small vessel disease (CSVD) burden. T2-weighted images from a retrospective cohort of 262 acute stroke patients, collected in 2015 from 5 regional medical centers, were used for analyses. Patients were given a label of 0 for none-to-mild EPVS (< 10) and 1 for moderate-to-severe EPVS (≥ 10). A three-dimensional residual network of 152 layers (3D-ResNet-152) was created to predict EPVS severity and 3D gradient class activation mapping (3DGradCAM) was used for visual interpretation of results. Our model achieved an accuracy 0.897 and area-under-the-curve of 0.879 on a hold-out test set of 15% of the total cohort (n = 39). 3DGradCAM showed areas of focus that were in physiologically valid locations, including other prevalent areas for EPVS. These maps also suggested that distribution of class activation values is indicative of the confidence in the model’s decision. Potential clinical implications of our results include: (1) support for feasibility of automated of EPVS scoring using clinical-grade neuroimaging data, potentially alleviating rater subjectivity and improving confidence of visual rating scales, and (2) demonstration that explainable models are critical for clinical translation.

Total magnetic resonance imaging of cerebral small vessel disease burden predicts dysphagia in patients with a single recent small subcortical infarct

BackgroundThis study was performed to identify the association between the total magnetic resonance imaging burden of small vessel disease and the occurrence of post-stroke dysphagia in patients with a single recent small subcortical infarct (RSSI).MethodsWe retrospectively identified all patients with a magnetic resonance imaging-confirmed single RSSI. The water-swallowing test and volume-viscosity swallow test were performed within the first 24 h following admission to assess swallowing. Demographic and clinical data were extracted from our stroke database. Based on brain magnetic resonance imaging, we independently rated the presence of cerebral microbleeds, lacunes, white matter hyperintensities and enlarged perivascular spaces. The presence of each small vessel disease feature was summed to determine the total small vessel disease burden, ranging from 0 to 4.ResultsIn total, 308 patients with a single RSSI were enrolled. Overall, 54 (17.5%) were diagnosed with post-stroke dysphagia. The risk factors related to post-stroke dysphagia included the following: older age, higher National Institute of Health Stroke Scale scores, higher C-reactive protein level and higher fibrinogen level. Based on multiple logistic regression, National Institute of Health Stroke Scale scores and total small vessel disease burden were independent risk factors of post-stroke dysphagia in patients with a single RSSI, after adjusting for age, gender, history of hypertension, C-reactive protein level and fibrinogen level.ConclusionsDysphagia in patients with a single RSSI was associated with a more severe total small vessel disease burden as reflected by MRI. Total MRI of cerebral small vessel disease burden may predict dysphagia in these patients. Furthermore, more severe total small vessel disease burden was associated with systemic inflammation.

Association of total cerebral small vessel disease burden with the cavitation of recent small subcortical infarcts.

Recent small subcortical infarcts (RSSIs) could evolve into cavitation (lacunes) or non-cavitation (white matter hyperintensities or disappearance) during the chronic period, but the factors involved remain unclear. To explore the association between total cerebral small vessel disease (CSVD) burden and lesion cavitation. We retrospectively selected 202 inpatients with an isolated RSSI who underwent baseline and follow-up magnetic resonance imaging (median interval = 16.6 months; interquartile range [IQR]=8.2-30.1). Inpatients were divided into cavitation and non-cavitation groups depending on whether a fluid-filled cavity formed. Data including demographic, clinical, and radiological features were collected and analyzed. To determine total CSVD burden, four imaging markers, including lacunes, microbleeds, white matter hyperintensities, and enlarged perivascular spaces, were rated and summed as a final practical score between 0 and 4. Overall, 137 (67.8%) patients progressed to cavitation and 65 (32.2%) to non-cavitation. Binary multivariable regression analysis showed that the baseline total CSVD burden (P = 0.005) and infarct diameter (P = 0.002) were independent risk factors for cavitation. A severe total burden (scores of 3-4) at baseline was independently related to cavitation (P = 0.001). Moreover, the total CSVD burden score varied from 2 (IQR=1-3) at baseline to 3 (IQR=2-4) at follow-up. The extent of the increase in total burden was correlated with cavitation (r = 0.201; P = 0.004). Total CSVD burden, both the baseline value and extent of increase, was positively associated with cavitation. RSSIs with severe total CSVD burden at baseline have a greater potential to become cavitated.

Total Cerebral Small Vessel Disease Burden on MRI Correlates With Cognitive Impairment in Outpatients With Amnestic Disorders.

Objectives: The main markers of cerebral small vessel disease (cSVD) on MRI may be entered into a scoring system, with the total score representing the overall burden of cSVD. An association between total cSVD score and cognitive dysfunction has been reported in several cohorts. The present study aimed to investigate this association in outpatients with amnestic disorders.Materials and Methods: Outpatients with amnestic complaints in a memory clinic (n = 289) were recruited retrospectively. All the patients had undergone clinical and cognitive evaluation at first presentation. Cognitive function was assessed by Montreal Cognitive Assessment (MoCA) scale. The total cSVD score was based on the following markers on MRI: lacune; white matter hyperintensities, microbleed, and enlarged perivascular spaces. The association between total cSVD score and MoCA score was tested via Spearman's analysis and a linear regression model.Results: Among the 289 patients, rates for 0–4 cSVD markers respectively ranged from 30.4 to 2.8%. A multiple linear regression model revealed an inverse correlation between the total cSVD score and MoCA score. The association remained significant after adjusting for gender, age, education, levels of medial temporal lobe atrophy, and classical vascular risk factors [β = −0.729, 95% CI (−1.244, −0.213); P = 0.006]. When individual markers were individually analyzed after adjusting for the same factors, only microbleed associated with MoCA score [β = −3.007, 95% CI (−4.533, −1.480), P < 0.001].Conclusions: A significant association was demonstrated between total cSVD score and cognitive performance in the outpatients with amnestic disorders.

The Relationship Between Renal Function and Imaging Markers and Total Burden of Cerebral Small Vessel Disease.

Previous studies demonstrating the association between renal functions and cerebral small vessel diseases have usually focused on white matter hyperintensity in the general population or lacunar stroke patients. This study aimed to investigate the effects of renal function on imaging markers of cerebral small vessel disease and etiologic subtypes of stroke in patients with acute ischemic stroke or transient ischemic attack. A total of 356 consecutive patients with acute ischemic stroke or transient ischemic attack who were admitted to the Stroke Unit and underwent brain magnetic resonance imaging were evaluated. Demographic data, vascular risk factors, stroke etiology, estimated glomerular filtration rate and severity of cerebral small vessel disease markers, and total cerebral small vessel disease burden were evaluated. There was a significant inverse correlation between estimated glomerular filtration rate and total number of lacunes, periventricular and deep subcortical Fazekas scores, grade of enlarged perivascular spaces in the centrum semiovale, lobar and total cerebral microbleeds, and total cerebral small vessel disease burden. Impaired renal function was an independent risk factor for the presence of lacunes, deep cerebral microbleeds, and increased total burden. Renal function impairment and periventricular white matter hyperintensities were significantly associated with the etiologic subgroup of small vessel occlusion. The results were still significant after the exclusion of patients below 50 years of age. Our results indicate that there is a relationship between renal function impairment and increased total burden, as well as acute ischemic stroke/transient ischemic attack due to small vessel occlusion.

Magnetic Resonance Imaging-Visible Perivascular Spaces in the Basal Ganglia Are Associated With the Diabetic Retinopathy Stage and Cognitive Decline in Patients With Type 2 Diabetes.

Purpose: The aim of this study was to evaluate whether perivascular space (PVS) severity and retinal ganglion cell layer (GCL) thickness differed based on the stage of diabetic retinopathy (DR) and the cognitive status in patients with DR.Methods: A total of 81 patients with DR (51 in the non-proliferative group and 30 in the proliferative group) were included in this retrospective, cross-sectional study. PVS severity was assessed in the basal ganglia (BG) and centrum semiovale using MRI. The total cerebral small vessel disease (SVD) score was determined based on the numbers of lacunes and microbleeds and the severity of white matter hyperintensity. Optical coherence tomography was used to measure foveal and perifoveal GCL thicknesses. Cerebral SVD markers and cognitive function were compared between the groups, and correlations between the BG-PVS severity and the Mini-Mental Status Examination (MMSE) scores and GCL parameters were evaluated.Results: Patients with proliferative DR had higher BG-PVS severity (P = 0.012), higher total cerebral SVD scores (P = 0.035), reduced GCL thicknesses in the inferior (P = 0.027), superior (P = 0.046), and temporal (P = 0.038) subfields compared to patients with non-proliferative DR. In addition, the BG-PVS severity was negatively correlated with the MMSE score (P = 0.007), and the GCL thickness was negatively correlated with the BG-PVS severity (P-values < 0.05 for inferior, superior, and temporal subfields).Conclusion: BG-PVS severity and retinal GCL thickness may represent novel imaging biomarkers reflecting the stage of DR and cognitive decline in diabetic patients. Furthermore, these results suggest a possible link between cerebral and retinal neurodegeneration at the clinical level.

Total cerebral small vessel disease score and all-cause mortality in older adults of Amerindian ancestry: The Atahualpa Project.

Cerebral small vessel disease (SVD) predicts all-cause mortality in Eastern Asian and Caucasian populations. However, little is known about SVD impact in individuals of different races/ethnic groups. In this study, we sought to estimate the mortality risk according to the total SVD (tSVD) score in older adults of Amerindian ancestry. Participants aged ≥60 years from the prospective population-based Atahualpa Project cohort underwent brain MRI between June 2012 and June 2017. The tSVD score was calculated based on the presence of moderate-to-severe white matter hyperintensities, enlarged perivascular spaces, one or more lacune, and one or more cerebral microbleed. We ascertained all-cause mortality during post-MRI follow-up. Poisson regression and Cox-proportional hazards models adjusted for demographics and cardiovascular risk were obtained to estimate mortality risk according to the tSVD score. Analysis included 375 participants with available brain MRI and clinical data (mean age 69.0 ± 8.3 years, 56.3% women). The tSVD score was 0 point in 216 individuals (57.6%), 1 point in 71 (18.9%), 2 points in 53 (14.1%), and 3-4 points in 35 (9.3%). Increasing tSVD score was associated with advancing age, hypertension, low level of education, and physical inactivity. Using tSVD score of 0 as reference, a multivariate Poisson regression model showed an increased mortality for individuals with a tSVD score 3-4 points (IRR: 2.27; 95% CI: 1.20-4.28). Likewise, in the Cox-proportional model adjusted for demographics and cardiovascular risk, participants with a tSVD score 3-4 maintained a greater than two-fold mortality risk when compared to those with tSVD score of 0 points (HR: 2.32; 95% CI: 1.23-4.39). High-burden SVD as determined by the tSVD score predicts mortality in community-dwelling older adults of Amerindian ancestry. Incidental diagnosis of covert SVD should prompt aggressive control of cardiovascular health.

Subclinical Vascular Brain Lesions in Young Adults With Acute Ischemic Stroke.

Subclinical vascular brain lesions are highly prevalent in elderly patients with stroke. Little is known about predisposing factors and their impact on long-term outcome of patients with stroke at a young age. We quantified magnetic resonance-defined subclinical vascular brain lesions, including lacunes and white matter hyperintensities, perivascular spaces and cerebral microbleeds, and assessed total small-vessel disease (SVD) score in patients with first-ever acute ischemic stroke aged 18 to 45 years, and followed them up, as part of the multicentre Italian Project on Stroke in Young Adults. The primary end point was a composite of ischemic stroke, transient ischemic attack, myocardial infarction, or other arterial events. We assessed the predictive accuracy of magnetic resonance features and whether the addition of these markers improves outcome prediction over a validated clinical tool, such as the Italian Project on Stroke in Young Adults score. Among 591 patients (males, 53.8%; mean age, 37.5±6.4 years), 117 (19.8%) had subclinical vascular brain lesions. Family history of stroke was associated with lacunes (odds ratio, 2.24 [95% CI, 1.30-3.84]) and total SVD score (odds ratio, 2.06 [95% CI, 1.20-3.53] for score≥1), hypertension with white matter hyperintensities (odds ratio, 2.29 [95% CI, 1.22-4.32]). After a median follow-up of 36.0 months (25th-75th percentile, 38.0), lacunes and total SVD score were associated with primary end point (hazard ratio, 2.13 [95% CI, 1.17-3.90] for lacunes; hazard ratio, 2.17 [95% CI, 1.20-3.90] for total SVD score ≥1), and the secondary end point brain ischemia (hazard ratio, 2.55 [95% CI, 1.36-4.75] for lacunes; hazard ratio, 2.61 [95% CI, 1.42-4.80] for total SVD score ≥1). The predictive performances of the models, including magnetic resonance features were comparable to those of the random model. Adding individual magnetic resonance features to the Italian Project on Stroke in Young Adults score did not improve model prediction. Subclinical vascular brain lesions affect ≈2 in 10 young adults with ischemic stroke. Although lacunes and total SVD score are associated with thrombotic recurrence, they do not improve accuracy of outcome prediction over validated clinical predictors.

Association of cerebral small vessel disease burden with brain structure and cognitive and vascular risk trajectories in mid-to-late life

We characterize the associations of total cerebral small vessel disease (SVD) burden with brain structure, trajectories of vascular risk factors, and cognitive functions in mid-to-late life. Participants were 623 community-dwelling adults from the Whitehall II Imaging Sub-study with multi-modal MRI (mean age 69.96, SD = 5.18, 79% men). We used linear mixed-effects models to investigate associations of SVD burden with up to 25-year retrospective trajectories of vascular risk and cognitive performance. General linear modelling was used to investigate concurrent associations with grey matter (GM) density and white matter (WM) microstructure, and whether these associations were modified by cognitive status (Montreal Cognitive Asessment [MoCA] scores of < 26 vs. ≥ 26). Severe SVD burden in older age was associated with higher mean arterial pressure throughout midlife (β = 3.36, 95% CI [0.42-6.30]), and faster cognitive decline in letter fluency (β = −0.07, 95% CI [−0.13–−0.01]), and verbal reasoning (β = −0.05, 95% CI [−0.11–−0.001]). Moreover, SVD burden was related to lower GM volumes in 9.7% of total GM, and widespread WM microstructural decline (FWE-corrected p < 0.05). The latter association was most pronounced in individuals who demonstrated cognitive impairments on MoCA (MoCA < 26; F3,608 = 2.14, p = 0.007). These findings highlight the importance of managing midlife vascular health to preserve brain structure and cognitive function in old age.

Early life predictors of late life cerebral small vessel disease in four prospective cohort studies.

Development of cerebral small vessel disease, a major cause of stroke and dementia, may be influenced by early life factors. It is unclear whether these relationships are independent of each other, of adult socio-economic status or of vascular risk factor exposures.We examined associations between factors from birth (ponderal index, birth weight), childhood (IQ, education, socio-economic status), adult small vessel disease, and brain volumes, using data from four prospective cohort studies: STratifying Resilience And Depression Longitudinally (STRADL) (n = 1080; mean age = 59 years); the Dutch Famine Birth Cohort (n = 118; mean age = 68 years); the Lothian Birth Cohort 1936 (LBC1936; n = 617; mean age = 73 years), and the Simpson’s cohort (n = 110; mean age = 78 years). We analysed each small vessel disease feature individually and summed to give a total small vessel disease score (range 1–4) in each cohort separately, then in meta-analysis, adjusted for vascular risk factors and adult socio-economic status.Higher birth weight was associated with fewer lacunes [odds ratio (OR) per 100 g = 0.93, 95% confidence interval (CI) = 0.88 to 0.99], fewer infarcts (OR = 0.94, 95% CI = 0.89 to 0.99), and fewer perivascular spaces (OR = 0.95, 95% CI = 0.91 to 0.99). Higher childhood IQ was associated with lower white matter hyperintensity burden (OR per IQ point = 0.99, 95% CI 0.98 to 0.998), fewer infarcts (OR = 0.98, 95% CI = 0.97 to 0.998), fewer lacunes (OR = 0.98, 95% CI = 0.97 to 0.999), and lower total small vessel disease burden (OR = 0.98, 95% CI = 0.96 to 0.999). Low education was associated with more microbleeds (OR = 1.90, 95% CI = 1.33 to 2.72) and lower total brain volume (mean difference = −178.86 cm3, 95% CI = −325.07 to −32.66). Low childhood socio-economic status was associated with fewer lacunes (OR = 0.62, 95% CI = 0.40 to 0.95).Early life factors are associated with worse small vessel disease in later life, independent of each other, vascular risk factors and adult socio-economic status. Risk for small vessel disease may originate in early life and provide a mechanistic link between early life factors and risk of stroke and dementia. Policies investing in early child development may improve lifelong brain health and contribute to the prevention of dementia and stroke in older age.