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opencc-zeroDec 2020View details →

Genetic overlap and causal inferences between kidney function and cerebrovascular disease

Objective: Leveraging large-scale genetic data, we aimed to identify shared pathogenic mechanisms and causal relationships between impaired kidney function and cerebrovascular disease phenotypes. Methods: We used summary statistics from genome-wide association studies (GWAS) of kidney function traits (<a name="_Hlk536087805">chronic kidney disease (CKD) diagnosis, estimated glomerular filtration rate (eGFR), and Urinary Albumin-to-Creatinine Ratio (UACR)</a>), and of cerebrovascular disease phenotypes: ischemic stroke and its subtypes, intracerebral hemorrhage (ICH), white matter hyperintensities (WMH) on brain MRI. We (i) tested the genetic overlap between them with polygenic risk scores (PRS), (ii) searched for common pleiotropic loci with pairwise GWAS analyses, and (iii) explored causal associations by employing two-sample Mendelian Randomization (MR). Results: A PRS for lower eGFR was associated with higher large-artery stroke (LAS) risk (p=1x10-4). Multiple pleiotropic loci were identified between kidney function traits and cerebrovascular disease phenotypes, with 12q24 associated with eGFR and both LAS and small-vessel stroke (SVS), and 2q33 associated with UACR and both SVS and WMH. MR revealed associations of both lower eGFR (OR per 1-log decrement=2.10, 95%CI=1.38-3.21) and higher UACR (OR per 1-log increment=2.35, 95%CI=1.12-4.94) with a higher risk of LAS, as well as between higher UACR and higher risk of ICH. Conclusions: Impaired kidney function, as assessed by decreased eGFR and increased UACR, may be causally involved in the pathogenesis of LAS. Increased UACR, previously proposed as a marker of systemic small vessel disease, is involved in ICH risk and shares a genetic risk factor at 2q33 with manifestations of cerebral small vessel disease.

opencc-zeroOct 2021View details →

Supplementary data from: Fish intake and MRI burden of cerebrovascular disease in older adults

Background and Objective: Fish intake may prevent cerebrovascular disease (CVD), yet the mechanisms are unclear, especially regarding its impact on subclinical damage. Assuming that fish may have pleiotropic effect on cerebrovascular health, we investigated the association of fish intake with global CVD burden based on brain MRI markers. Methods: This cross-sectional analysis included participants from the Three-City Dijon population-based cohort study (aged ≥65 years) without dementia, stroke, or history of hospitalized cardiovascular disease, who underwent brain MRI with an automated assessment of white matter hyperintensities, visual detection of covert infarcts, and grading of dilated perivascular spaces. Fish intake was assessed through a frequency questionnaire and the primary outcome measure of CVD burden was defined as the first component of a factorial analysis of mixed data applied to MRI markers. The association of fish intake with the CVD burden indicator was studied using linear regressions. Results: In total, 1,623 participants (mean age, 72.3 years; 63% women) were included. The first component of factorial analysis (32.4% of explained variance) was associated with higher levels of all three MRI markers. Higher fish intake was associated with lower CVD burden. In a model adjusted for total intracranial volume, compared to participants consuming fish less than once a week, those consuming fish 2 to 3 times per week and ≥4 times per week had a β = -0.19 units (95% CI, -0.37; -0.01) and β = -0.30 (-0.57; -0.03) lower indicator of global CVD burden, respectively (P for trend <0.001). We found evidence of effect modification by age, so that the association of fish to CVD was stronger in younger participants (65-69 years) and not significant in the older age group (≥75 years). For comparison, in the younger age group, consuming fish 2-3 times a week was roughly equivalent (in the opposite direction) to the effect of hypertension, and consuming fish ≥4 times had double that effect. Discussion: In this large population-based study, higher frequency of fish intake was associated with lower CVD burden, especially among participants younger than 75 years, suggesting a beneficial effect on brain vascular health before manifestation of overt brain disease.

opencc-zeroMar 2022View details →

Data from: Diabetes mellitus, glycemic traits, and cerebrovascular disease: A Mendelian randomization study

Objective: We employed Mendelian randomization (MR) to explore the effects of genetic predisposition to type 2 diabetes (T2D), hyperglycemia, insulin resistance, and β-cell dysfunction on risk of stroke subtypes and related cerebrovascular phenotypes. <a name="_Hlk49339275">Methods: </a>We selected instruments for genetic predisposition to T2D (74,124 cases, 824,006 controls), HbA1c levels (n=421,923), fasting glucose levels (n=133,010), insulin resistance (n=108,557), and β-cell dysfunction (n=16,378) based on published genome-wide association studies. Applying two-sample MR, we examined associations with ischemic stroke (60,341 cases, 454,450 controls), intracerebral hemorrhage (1,545 cases, 1,481 controls), and ischemic stroke subtypes (large artery, cardioembolic, small vessel stroke), as well as with related phenotypes (carotid atherosclerosis, imaging markers of cerebral white matter integrity, and brain atrophy). Results: Genetic predisposition to T2D and higher HbA1c levels were associated with higher risk of any ischemic stroke, large artery stroke, and small vessel stroke. Similar associations were also noted for carotid atherosclerotic plaque, fractional anisotropy, a white matter disease marker, and markers of brain atrophy. We further found associations of genetic predisposition to insulin resistance with large artery and small vessel stroke, whereas predisposition to β-cell dysfunction was associated with small vessel stroke, intracerebral hemorrhage, lower grey matter volume, and total brain volume. Conclusions: This study supports causal effects of T2D and hyperglycemia on large artery and small vessel stroke. <a name="_Hlk52240657">We show associations of genetically predicted insulin resistance and β-cell dysfunction with large artery and small vessel stroke that might have implications for anti-diabetic treatments targeting these mechanisms.</a> Classification of Evidence: This study provides Class II evidence that genetic predisposition to T2D and higher HbA1c levels are associated with a higher risk of large artery and small vessel ischemic stroke.

Cerebrovascular Dysregulation in Chronic Kidney Disease

ClinicalTrials.gov study NCT05571605. IPD Sharing: NO. Countries: 1. Publications: 0.

a Cohort Study of Ischemic Cerebrovascular Disease

ClinicalTrials.gov study NCT05922540. IPD Sharing: NO. Countries: 1. Publications: 0.

Quantifying Collateral Perfusion in Cerebrovascular Disease-Moyamoya Disease and Stroke Patients

ClinicalTrials.gov study NCT01419275. IPD Sharing: Not stated. Countries: 1. Publications: 0.

The Effectiveness and Cost Effectiveness of Intelligent Assessment of Gait Disorder in Silent Cerebrovascular Disease

ClinicalTrials.gov study NCT04457908. IPD Sharing: NO. Countries: 0. Publications: 19.

A Study of Donepezil Hydrochloride in Patients With Dementia Associated With Cerebrovascular Disease

ClinicalTrials.gov study NCT02660983. IPD Sharing: Not stated. Countries: 1. Publications: 0.

Optimal Regimen in Endovascular Therapy in Ischemic Cerebrovascular Disease Based on Clopidogrel Resistance

ClinicalTrials.gov study NCT01925872. IPD Sharing: Not stated. Countries: 0. Publications: 2.

Association Between Gait Assessed by Intelligent System and Cognitive Function in Silent Cerebrovascular Disease

ClinicalTrials.gov study NCT04456348. IPD Sharing: NO. Countries: 0. Publications: 20.

publicMay 2019View details →

Data from: CSF biomarkers of neuroinflammation and cerebrovascular dysfunction in early Alzheimer's disease

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publicMar 2022View details →

Data from: Diabetes mellitus, glycemic traits, and cerebrovascular disease: A Mendelian randomization study

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publicOct 2021View details →

Supplementary data from: Fish intake and MRI burden of cerebrovascular disease in older adults

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publicDec 2020View details →

Genetic overlap and causal inferences between kidney function and cerebrovascular disease

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geo24/100

Cerebrovascular p16INK4A expression induces cerebral small vessel disease-related phenotypes

GEO Series GSE304696. Mus musculus. 12 samples. Type: Expression profiling by high throughput sequencing.

openGEO-OpenAug 2025View details →

ClinicalTrials.gov24/100

Safety of Donepezil in Patients With Dementia Associated With Cerebrovascular Disease

ClinicalTrials.gov study NCT00188812. IPD Sharing: Not stated. Countries: 1. Publications: 0.

ClinicalTrials.gov24/100

Efficacy and Cost-Effectiveness of Cost-free Pharmacotherapy for Smoking Cessation for High-risk Smokers With Cerebrovascular Disease

ClinicalTrials.gov study NCT00962988. IPD Sharing: Not stated. Countries: 1. Publications: 0.