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Background: 10-year atherosclerotic cardiovascular disease (ASCVD) risk scores were useful for predicting large vessel disease, but the relationships between them and cerebral small vessel disease (CSVD) were unclear. Our study aimed to evaluate associations of 10-year ASCVD risk scores with CSVD and its magnetic resonance imaging (MRI) markers., Methods: Community-dwelling residents from the PolyvasculaR Evaluation for Cognitive Impairment and vaScular Events study were included in this cross-sectional study. At baseline, we collected data related to the Framingham Risk Score (FRS), pooled cohort equation (PCE), prediction for ASCVD risk in China (China-PAR) and Systematic COronary Risk Evaluation model 2 (SCORE2), and classified participants into low, moderate and high groups. Participants underwent brain MRI scans. We evaluated white matter hyperintensity (WMH), lacunes, cerebral microbleeds (CMBs) and enlarged perivascular spaces in basal ganglia (BG-EPVS) according to criteria of Wardlaw and Rothwell, and calculated total CSVD score and modified total CSVD score., Results: A total of 3063 participants were included, and 53.5% of them were female. A higher FRS was associated with higher total CSVD score (moderate vs. low: cOR 1.89, 95% CI 1.53-2.34; high vs. low: cOR 3.23, 95%CI 2.62-3.97), and the PCE, China-PAR or SCORE2 score was positively related to total CSVD score (P < 0.05). Moreover, higher 10-year ASCVD scores were associated with higher odds of WMH (P < 0.05), lacunes (P < 0.05), CMBs (P < 0.05) and BG-EPVS (P < 0.05)., Conclusions: The 10-year ASCVD scores were positively associated with CSVD and its MRI markers. These scores provided a method of risk stratification in the population with CSVD., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Insulin resistance as a significant vascular risk factor has been studied in relation to cerebral small vessel disease (SVD). Evidence suggests that insulin resistance might trigger high blood pressure (BP). Therefore, we aimed to investigate whether insulin resistance impacts SVD with a mediating effect of BP in nondiabetic subjects., Methods and Results: PRECISE (Polyvascular Evaluation for Cognitive Impairment and Vascular Events) study participants underwent brain and vascular imaging techniques and metabolomic risk factors measurements. Insulin resistance was evaluated by the insulin sensitivity index and the Homeostatic Model Assessment for Insulin Resistance based on the standard oral glucose tolerance test. On average, 2752 nondiabetic subjects (47.1% men) aged 60.9 years were included. The multivariable logistic regression model and linear regression model tested the association of insulin resistance with BP components (including systolic BP [SBP], diastolic BP (DBP), and pulse pressure [PP]) and SVD, and of BP components with SVD. In the mediation analysis, SBP, DBP, and PP were found to partially mediate the detrimental effect of insulin resistance (assessed by the insulin sensitivity index) on lacunes (mediation percentage: SBP, 31.15%; DBP, 34.21%; PP, 10.43%), white matter hyperintensity (mediation percentage: SBP, 37.34%; DBP, 44.15%; PP, 9.80%), and SVD total burden (mediation percentage: SBP, 42.07%; DBP, 49.29%; PP, 11.71%) (all P <0.05). The mediation analysis results were not significant when using the Homeostatic Model Assessment for Insulin Resistance to assess insulin resistance., Conclusions: Higher insulin resistance was associated with SVD in this community-dwelling population. The association of insulin resistance with lacunes, white matter hyperintensity, and SVD total burden was explained in part by BP., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03178448.

Objective: This study aims to investigate the associations of glymphatic system with the presence, severity and neuroimaging phenotypes of cerebral small vessel disease (CSVD) in a community-based population., Method: This report included 2219 community-dwelling people aged 50-75 years who participated in the PolyvasculaR Evaluation for Cognitive Impairment and vaScular Events cohort. The diffusivity along perivascular spaces based on diffusion tensor imaging (DTI-ALPS index) was measured to assess glymphatic pathway. The presence and severity of CSVD were estimated using a CSVD score (points from 0 to 4) and a modified CSVD score (points from 0 to 4), which were driven by 4 neuroimaging features of CSVD, including white matter hyperintensity (WMH), enlarged perivascular spaces (EPVS), lacunes, cerebral microbleeds. Brain atrophy (BA) was also evaluated. Binary or ordinal logistic regression analyses were carried out to investigate the relationships of DTI-ALPS index with CSVD., Result: The mean age was 61.3 (SD 6.6) years, and 1019 (45.9%) participants were men. The average DTI-ALPS index was 1.67±0.14. Individuals in the first quartile (Q1) of the DTI-ALPS index had higher risks of the presence of CSVD (OR 1.77, 95% CI 1.33 to 2.35, p<0.001), modified presence of CSVD (odds ratio (OR) 1.80, 95% CI 1.38 to 2.34, p<0.001), total burden of CSVD (common OR (cOR) 1.89, 95% CI 1.43 to 2.49, p<0.001) and modified total burden of CSVD (cOR 1.95, 95% CI 1.51 to 2.50, p<0.001) compared with those in the fourth quartile (Q4). Additionally, individuals in Q1 of the DTI-ALPS index had increased risks of WMH burden, modified WMH burden, lacunes, basal ganglia-EPVS and BA (all p<0.05)., Conclusion: A lower DTI-ALPS index underlay the presence, severity and typical neuroimaging markers of CSVD, implying that glymphatic impairment may interact with CSVD-related pathology in the general ageing population., Trial Registration Number: NCT03178448., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Deep medullary veins (DMVs) were not considered a typical marker of cerebral small vessel disease (CSVD) due to limited understanding of their involvement in pathology of CSVD. This study aimsto investigate potential vascular risk factors for DMVs and their associations with CSVD., Methods: In total, 1909 community-dwelling participants were included in this analysis. Demographic, clinical, laboratory, and imaging data were collected. DMV scores (0-18) werecalculated as the sum of bilateral frontal, parietal, and occipital regional scores using a semiquantitative visual scale (0-3). The presence, total burden, and imaging markers of CSVD were assessed. Linear regression analyses were conducted to explore potential vascular factors for DMV scores. Binary and ordinal logistic regression analyses were performed to investigate the associations of DMV scores with CSVD and its markers., Results: Mean age was 61.8 (SD 6.5) years, and 1027 (53.8%) of participants were men. The median DMV scores were14 (IQR 12-16). DMV scores wererelated to age, male sex, body mass index, diastolic blood pressure, hypercholesterolaemia, atrial fibrillation, current drinking, total cholesterol, triglycerides, low-density lipoprotein, hemoglobin A1c, leukocytes, lymphocytes, hemoglobin, and platelets (p < .05). DMV scores wereassociated with the presence and total burden of CSVD (Rothwell's scale), modified white matter hyperintensity burden, and enlarged perivascular spaces in centrum semiovale (p < .05). However, these associations between DMV scores and CSVD disappeared after adjusting for potential confounders., Conclusion: Several conventional vascular factors were associated with DMVs. The relationship between DMVs and CSVD was vulnerable, suggesting decreased visible and discontinuous DMVs may differ mechanistically from traditional markers of CSVD., (© 2023 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

Introduction: Cerebral small vessel disease (CSVD) is a significant burden of morbidity and mortality among elderly people around the world. Epidemiological data with complete CSVD evaluations and a large sample size in the general population are still limited., Methods: Community-dwelling residents in Lishui city in China from the cross-sectional survey of the Polyvascular Evaluation for Cognitive Impairment and Vascular Events (PRECISE) study were included in this study from 2017 to 2019. All participants underwent 3 Tesla brain magnetic resonance images to assess CSVD imaging markers. Demographic and risk factor data were collected. The general and age-specific prevalence of lacune, confluent white matter hyperintensity (WMH), moderate-severe enlarged perivascular spaces (EPVS), cerebral microbleed (CMB), and total CSVD score (an ordinal scale from 0 to 4, counting the presence of four imaging markers of CSVD) was evaluated. Associations between vascular risk factors and these markers were analyzed by multivariable logistic regression., Results: A total of 3,063 participants were enrolled. The mean age was 61.2 years and 46.5% were men. The most prevalent CSVD marker was confluent WMH (16.7%), followed by CMB (10.2%), moderate-severe EPVS in the basal ganglia (BG-EPVS) (9.8%), and lacune (5.6%). 30.5% of the participants have at least one of the four markers (total CSVD score ≥1 points). The prevalence of CSVD markers increases as age increases. Age and hypertension were independent risk factors for four CSVD markers and the total CSVD score., Conclusions: In this Chinese cohort with community-based adults aged 50-75 years, our findings showed a prevalence of 30.5% for CSVD. The most prevalent CSVD marker was confluent WMH, followed by CMB, moderate-severe BG-EPVS, and lacune. The risk factors for CSVD must be strictly screened and controlled in adults living in the community., (© 2023 S. Karger AG, Basel.)

Background: The aim of this study was to investigate the relationship between serum cystatin C levels and the presence and severity of cerebral small vessel disease (CSVD)., Methods: Community-dwelling residents in the Lishui city in China from the cross-sectional survey of the PRECISE (Poly-Vascular Evaluation for Cognitive Impairment and Vascular Events) cohort study were included in present study from 2017 to 2019. Total CSVD burden and modified total CSVD burden score, as well as the markers of CSVD on magnetic resonance imaging, including white matter hyperintensity, lacunes, cerebral microbleeds, and perivascular spaces, were assessed at baseline survey. Participants were divided into 4 groups according to the quartiles of cystatin C. The association of serum cystatin C with total CSVD burden and imaging markers was analyzed using ordinal or binary logistic regression models. Furthermore, 2-sample Mendelian randomization analysis was performed to investigate the genetically predicted effect of cystatin C on CSVD., Results: A total of 3061 participants were included in this study. The mean age of the participants was 61.2±6.7 years, and 1637 (53.5%) were women. Higher level of cystatin C was associated with an increased total CSVD burden and modified total CSVD burden (Q4 versus Q1: common odds ratio [OR], 1.30 [95% CI, 1.03-1.64] and 1.32 [95% CI, 1.01-1.73]) after adjustment for covariates. Further, compared with the first quartile of cystatin C, subjects in the last quartile had higher risk of lacunes (OR, 1.99 [95% CI, 1.05-3.76]), modified white matter hyperintensity burden (common OR, 1.42 [95% CI, 1.07-1.90]), and moderate-to-severe perivascular spaces (OR, 2.15 [95% CI, 1.29-3.59]) but not cerebral microbleeds. The Mendelian randomization analysis showed that a genetically predicted higher cystatin C level was associated with increased risk of lacunar stroke (OR, 1.16 [95% CI, 1.06-1.27])., Conclusions: In this community-based study, we found a possible association between cystatin C and CSVD, especially for lacunes, that was independent of estimated glomerular filtration rate.

Introduction: Cerebral small vessel disease (cSVD) is highly prevalent and results in irreversible cognitive impairment and reduced quality of life. Previous studies reported controversial associations between insulin resistance and cSVD. Here, we estimated the association between insulin resistance and cSVD in non-diabetic communities in southeastern China., Research Design and Methods: The Polyvascular Evaluation for Cognitive Impairment and Vascular Events study (NCT03178448) recruited 3670 community-dwelling adults. We estimated the association of insulin resistance, assessed by the insulin sensitivity index (ISI 0,120 ) and the homeostatic model assessment for insulin resistance (HOMA-IR) based on the standard oral glucose tolerance test, with cSVD in those without a history of diabetes mellitus. cSVD was measured for both main neuroimaging manifestations of cSVD and total SVD burden scores., Results: A total of 2752 subjects were enrolled. In the multivariable logistic regression analysis, the first quartile of ISI 0,120 was found to be potentially associated with an increased risk of lacunes (OR 1.96, 95% CI 1.15 to 3.36), severe age-related white matter changes (OR 1.97, 95% CI 1.15 to 3.38), and higher total SVD burden (4-point scale: common OR (cOR) 1.34, 95% CI 1.04 to 1.72; 6-point scale: cOR 1.43, 95% CI 1.14 to 1.79). The associations between HOMA-IR and lacunes (OR 1.90, 95% CI 1.11 to 3.25) and the 4-point scale of total SVD burden (cOR 1.33, 95% CI 1.04 to 1.70) were also significant after adjustment for age, gender, medical history, and medications. However, the associations were not statistically significant after further adjustment for blood pressure/hypertension and body mass index (BMI)., Conclusions: A potential association was found between insulin resistance and cSVD, and the ISI 0,120 index presented a greater association with increased risk of cSVD as compared with the HOMA-IR. However, these associations were greatly influenced by blood pressure and BMI., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The purpose of this study is to examine the associations of Life's Simple 7 (LS7) with risks of cerebral small vessel disease (CSVD) and its magnetic resonance imaging markers., Methods: Community-dwelling residents in Lishui city in China from the cross-sectional survey of the PRECISE study (Polyvascular Evaluation for Cognitive Impairment and Vascular Events) were included in this study from 2017 to 2019. LS7 was analyzed as the total score, medical score (derived from the 3 metrics based on medical history and testing), and behavioral score (based on 4 metrics based on behaviors), and categorized as poor, intermediate, or ideal. A CSVD score or a modified CSVD score was derived from 4 magnetic resonance imaging markers (lacunes, microbleeds, perivascular spaces, and white matter hyperintensity) at baseline. Binary logistic regression or ordinal logistic regression model was used to estimate the relationship of LS7 scores with CSVD and magnetic resonance imaging markers., Results: A total of 3061 participants were included in this study. Compared with poor total LS7 score, ideal LS7 total score was associated with reduced adjusted odds of higher CSVD score (common odds ratio [cOR], 0.73 [95% CI, 0.58-0.90]) and higher modified CSVD score (cOR, 0.78 [95% CI, 0.64-0.95]). Compared with poor LS7 medical score, ideal LS7 medical score was associated with reduced adjusted odds of higher CSVD score (cOR, 0.65 [95% CI, 0.53-0.80]) and higher modified CSVD score (cOR, 0.67 [95% CI, 0.56-0.81]). Higher total LS7 score and LS7 medical score were associated with a lower risk of white matter hyperintensities and lacunes. Higher LS7 behavioral score was associated with lower risk of lacunes., Conclusions: Ideal LS7 score, indicating excellent cardiovascular health, was associated with lower total CSVD burden. Optimizing the risk factors captured by LS7 may reduce the progression of CSVD.

Background: This study investigated the relationships of neutrophil count (NC), neutrophil-to-lymphocyte ratio (NLR) and systemic immune-inflammation index (SII) with cerebral small vessel disease (CSVD)., Methods: A total of 3052 community-dwelling residents from the Poly-vasculaR Evaluation for Cognitive Impairment and vaScular Events (PRECISE) study were involved in this cross-sectional study. CSVD burden and imaging markers, including white matter hyperintensity (WMH), lacunes, cerebral microbleeds (CMBs) and enlarged perivascular spaces in basal ganglia (BG-EPVS), were assessed according to total CSVD burden score. The associations of NC, NLR and SII with CSVD and imaging markers were evaluated using logistic regression models. Furthermore, two-sample Mendelian randomization (MR) analysis was performed to investigate the genetically predicted effect of NC on CSVD. The prognostic performances of NC, NLR and SII for the presence of CSVD were assessed., Results: At baseline, the mean age was 61.2 ± 6.7 years, and 53.5% of the participants were female. Higher NC was suggestively associated with increased total CSVD burden and modified total CSVD burden (Q4 vs. Q1: common odds ratio (cOR) 1.33, 95% CI 1.05-1.70; cOR 1.28, 95% CI 1.02-1.60) and marginally correlated with the presence of CSVD (OR 1.29, 95% CI 1.00-1.66). Furthermore, elevated NC was linked to a higher risk of lacune (OR 2.13, 95% CI 1.25-3.62) and moderate-to-severe BG-EPVS (OR 1.67, 95% CI 1.14-2.44). A greater NLR was related to moderate-to-severe BG-EPVS (OR 1.68, 95% CI 1.16-2.45). Individuals with a higher SII had an increased risk of modified WMH burden (OR 1.35, 95% CI 1.08-1.69) and moderate-to-severe BG-EPVS (OR 1.70, 95% CI 1.20-2.41). MR analysis showed that genetically predicted higher NC was associated with an increased risk of lacunar stroke (OR 1.20, 95% CI 1.04-1.39) and small vessel stroke (OR 1.21, 95% CI 1.06-1.38). The addition of NC to the basic model with traditional risk factors improved the predictive ability for the presence of CSVD, as validated by the net reclassification index and integrated discrimination index (all p < 0.05)., Conclusions: This community-based population study found a suggestive association between NC and CSVD, especially for BG-EPVS and lacune, and provided evidence supporting the prognostic significance of NC., (© 2022. The Author(s).)

Background: High plasma levels of trimethylamine N-oxide (TMAO) and its precursor choline have been linked to stroke; however, their association with cerebral small vessel disease remains unclear. Here we evaluated the association of plasma levels of TMAO and choline with imaging markers of cerebral small vessel disease, including white matter hyperintensities, lacunes, and cerebral microbleeds. Methods: We performed a baseline cross-sectional analysis of a multicenter hospital-based cohort study from 2015 to 2018. The data were collected from 30 hospitals in China and included 1,098 patients with ischemic stroke/transient ischemic attack aged ≥18 years. White matter hyperintensities, lacunes, and cerebral microbleeds were evaluated with the patients' demographic, clinical, and laboratory information removed. White matter hyperintensities were rated using the Fazekas visual grading scale, while the degree of severity of the lacunes and cerebral microbleeds was defined by the number of lesions. Results: Increased TMAO levels were associated with severe white matter hyperintensities [adjusted odds ratio (aOR) for the highest vs. lowest quartile, 1.5; 95% confidence interval (CI), 1.0–2.1, p = 0.04]. High TMAO levels were more strongly associated with severe periventricular white matter hyperintensities (aOR for the highest vs. lowest quartile, 1.6; 95% CI, 1.1–2.3, p = 0.009) than deep white matter hyperintensities (aOR for the highest vs. lowest quartile, 1.3; 95% CI, 0.9–1.9, p = 0.16). No significant association was observed between TMAO and lacunes or cerebral microbleeds. Choline showed trends similar to that of TMAO in the association with cerebral small vessel disease. Conclusions: In patients with ischemic stroke or transient ischemic attack, TMAO and choline appear to be associated with white matter hyperintensities, but not with lacunes or cerebral microbleeds; TMAO and choline were associated with increased risk of a greater periventricular, rather than deep, white matter hyperintensities burden. [ABSTRACT FROM AUTHOR]