Prevalence Of Cerebral Microbleeds Research Articles

Cerebral Microbleeds in Different Brain Regions and Their Associations With the Digital Clock-Drawing Test: Secondary Analysis of the Framingham Heart Study.

Cerebral microbleeds (CMB) increase the risk for Alzheimer disease. Current neuroimaging methods that are used to detect CMB are costly and not always accessible. This study aimed to explore whether the digital clock-drawing test (DCT) may provide a behavioral indicator of CMB. In this study, we analyzed data from participants in the Framingham Heart Study offspring cohort who underwent both brain magnetic resonance imaging scans (Siemens 1.5T, Siemens Healthcare Private Limited; T2*-GRE weighted sequences) for CMB diagnosis and the DCT as a predictor. Additionally, paper-based clock-drawing tests were also collected during the DCT. Individuals with a history of dementia or stroke were excluded. Robust multivariable linear regression models were used to examine the association between DCT facet scores with CMB prevalence, adjusting for relevant covariates. Receiver operating characteristic (ROC) curve analyses were used to evaluate DCT facet scores as predictors of CMB prevalence. Sensitivity analyses were conducted by further including participants with stroke and dementia. The study sample consisted of 1020 (n=585, 57.35% female) individuals aged 45 years and older (mean 72, SD 7.9 years). Among them, 64 (6.27%) participants exhibited CMB, comprising 46 with lobar-only, 11 with deep-only, and 7 with mixed (lobar+deep) CMB. Individuals with CMB tended to be older and had a higher prevalence of mild cognitive impairment and higher white matter hyperintensities compared to those without CMB (P<.05). While CMB were not associated with the paper-based clock-drawing test, participants with CMB had a lower overall DCT score (CMB: mean 68, SD 23 vs non-CMB: mean 76, SD 20; P=.009) in the univariate comparison. In the robust multiple regression model adjusted for covariates, deep CMB were significantly associated with lower scores on the drawing efficiency (β=-0.65, 95% CI -1.15 to -0.15; P=.01) and simple motor (β=-0.86, 95% CI -1.43 to -0.30; P=.003) domains of the command DCT. In the ROC curve analysis, DCT facets discriminated between no CMB and the CMB subtypes. The area under the ROC curve was 0.76 (95% CI 0.69-0.83) for lobar CMB, 0.88 (95% CI 0.78-0.98) for deep CMB, and 0.98 (95% CI 0.96-1.00) for mixed CMB, where the area under the ROC curve value nearing 1 indicated an accurate model. The study indicates a significant association between CMB, especially deep and mixed types, and reduced performance in drawing efficiency and motor skills as assessed by the DCT. This highlights the potential of the DCT for early detection of CMB and their subtypes, providing a reliable alternative for cognitive assessment and making it a valuable tool for primary care screening before neuroimaging referral.

Elevated Pulse Pressure Is a Risk Factor for Cerebral Microbleeds. A Single Center Case-Control Study

Recent developments in brain magnetic resonance imaging using advanced Susceptibility Weighted Imaging (SWI) have significantly increased the detection and prevalence of Cerebral Microbleeds (CMBs). Here, we aimed to explore the association between Pulse Pressure (PP) and CMBs. Having been implicated in various arteriopathies, we hypothesized that elevated PP could also be a risk for CMBs. A retrospective case-control study was conducted from August 2021 to September 2022 at Zhongnan Hospital of Wuhan University China. Extracted data were analyzed in SPSS. Chi-square test, binary logistic regression, and Spearman’s correlation analysis were conducted.104 patients were analyzed. Univariate analysis showed no significant association between PP and CMBs, OR 1.65 (95% CI: 0.737 - 3.694; p > 0.05), while DBP and alcohol consumption were significant, ORs 2.956 (95% CI: 1.249 - 6.997, p < 0.05) and 2.525 (95% CI: 1.062 - 6.002, p < 0.05) respectively. Multivariate analysis, showed that PP was significantly associated with CMBs, OR 3.194 (95% CI: 1.024 - 9.964, p < 0.05) in combination with SBP, DBP, gender, age, smoking and alcohol consumption. Taken together, the study showed that elevated PP is associated with CMB, but is not an independent risk factor for CMBs.

The global burden of cerebral small vessel disease in low- and middle-income countries: A systematic review and meta-analysis.

Cerebral small vessel disease (cSVD) is a major cause of stroke and dementia. Previous studies on the prevalence of cSVD are mostly based on single geographically defined cohorts in high-income countries. Studies investigating the prevalence of cSVD in low- and middle-income countries (LMICs) are expanding but have not been systematically assessed. This study aims to systematically review the prevalence of cSVD in LMICs. Articles were searched from the Ovid MEDLINE and EMBASE databases from 1 January 2000 to 31 March 2022, without language restrictions. Title/abstract screening, full-text review, and data extraction were performed by two to seven independent reviewers. The prevalence of cSVD and study sample size were extracted by pre-defined world regions and health status. The Risk of Bias for Non-randomized Studies tool was used. The protocol was registered on PROSPERO (CRD42022311133). A meta-analysis of proportion was performed to assess the prevalence of different magnetic resonance imaging markers of cSVD, and a meta-regression was performed to investigate associations between cSVD prevalence and type of study, age, and male: female ratio. Of 2743 studies identified, 42 studies spanning 12 global regions were included in the systematic review. Most of the identified studies were from China (n = 23). The median prevalence of moderate-to-severe white matter hyperintensities (WMHs) was 20.5%, 40.5%, and 58.4% in the community, stroke, and dementia groups, respectively. The median prevalence of lacunes was 0.8% and 33.5% in the community and stroke groups. The median prevalence of cerebral microbleeds (CMBs) was 10.7% and 22.4% in the community and stroke groups. The median prevalence of moderate-to-severe perivascular spaces was 25.0% in the community. Meta-regression analyses showed that the weighted median age (51.4 ± 0.0 years old; range: 36.3-80.2) was a significant predictor of the prevalence of moderate-to-severe WMH and lacunes, while the type of study was a significant predictor of the prevalence of CMB. The heterogeneity of studies was high (>95%). Male participants were overrepresented. This systematic review and meta-analysis provide data on cSVD prevalence in LMICs and demonstrated the high prevalence of the condition. cSVD research in LMICs is being published at an increasing rate, especially between 2010 and 2022. More data are particularly needed from Sub-Saharan Africa and Central Europe, Eastern Europe, and Central Asia.

Presence of cerebral microbleeds is associated with cognitive decline in acromegaly.

Cognitive decline in acromegaly has gained increasing attention. Cerebral microbleeds (CMBs) as radiographic markers for microvascular injury have been linked to various types of cognitive decline. However, the association between CMB formation and acromegaly has not yet been quantified. This study is designed to investigate the prevalence and the radiographic patterns of CMBs and the association between cognitive function and acromegaly-related CMBs in growth hormone (GH)-secreting pituitary adenoma, which is characterized by acromegaly. In a cohort of 55 patients with GH-secreting pituitary adenoma (acromegaly) and 70 healthy control (HC) patients, we determined the presence of CMBs using a 3.0-T MRI scanner. The numbers, locations, and grades of CMBs were determined via susceptibility-weighted imaging (SWI) and the Microbleed Anatomical Rating Scale. Obstructive sleep apnea (OSA) was assessed using the criteria of the American Academy of Sleep Medicine (AASM) Scoring Manual Version 2.2. The Montreal Cognitive Assessment (MoCA) was used to assess cognitive performance within 3days of admission. The association between CMBs and cognitive function as well as clinical characteristics was explored. The incidence of CMBs was 29.1%, whereas that of OSA was 65.5% in acromegaly. There was a statistically significant difference in the prevalence of CMBs between subjects with and without acromegaly (29.1% and 5.3%, respectively) (p<0.01). The age of acromegaly patients with CMBs was much younger compared with HCs with CMBs. Compared with HCs, a significant cognitive decline and the occurrence of OSA were demonstrated in patients with acromegaly (p<0.01). Binary logistic regression analysis adjusted for age, education, and body mass index (BMI) revealed that CMB was an independent risk factor for cognitive impairment in patients with acromegaly (OR=3.19, 95% CI 1.51-6.76, p=0.002). Furthermore, in the logistic regression models adjusted for age, BMI, diabetes, and hypertension, OSA was independently associated with the occurrence of CMBs in patients with acromegaly (OR=13.34, 95% CI 3.09-57.51, p=0.001). A significant increase of CMBs was demonstrated in patients with acromegaly, which may be a result of OSA in acromegaly. The present study indicated that increasing CMBs are responsible for cognitive decline in patients with acromegaly.

Total Body Irradiation Is Associated with Higher Prevalence of Cerebral Microbleeds in Haematopoietic Stem Cell Transplant Survivors

Introduction Myeloablative conditioning (MAC) for haematopoietic stem cell transplant (HSCT) is associated with a wide range of toxicities. Cognitive impairment (CI) is a common late effect occurring in over 50% of HSCT survivors. We previously reported an increased incidence of cerebral microbleeds (CMBs) - haemosiderin deposits, appearing as hypointense lesions on magnetic resonance imaging (MRI) - in patients with ITP. No healthy controls in this cohort had CMBs (Cooper, 2020). CMBs can be caused by a range of factors, including cranial irradiation with 18 Gy or higher. Studies in patients receiving cranial irradiation for cerebral tumours have correlated CMBs with cognitive impairment. The presence of multiple CMBs has also been independently linked to an increased risk of dementia, stroke and intracerebral haemorrhage. TBI doses used in HSCT rarely exceed 15 Gy. Although this dose is smaller than reported in previous studies linking irradiation to CMBs, it is delivered at a time of considerable physiological stress. To date, there are no studies investigating the effect of TBI on the prevalence of CMBs. Aims Given the established association of CMBs with cranial radiotherapy, this study aims to assess the impact of TBI-based MAC on the prevalence of CMBs, as well as their association with cognitive impairment. Method We recruited HSCT survivors, at least 3 years post-HSCT. Patients who received TBI as part of their MAC (TBI group) and those who received purely chemotherapeutic MAC (control group) were included. We excluded patients with a known history of cranial irradiation, uncontrolled hypertension or insulin-dependent diabetes. All participants underwent a Susceptibility Weighted Imaging (SWI) MRI and CANTAB Insight cognitive testing. The number of CMBs was reported by a neuro-radiologist blinded to the patient data. Mann-Whitney U test was used to assess the location shift in CMB numbers between groups and Fisher's exact test was used to compare the prevalence of at least one or at least three CMBs. We used Spearman's rank correlation to assess the association between CMB number and CI. Results A total of 15 patients were recruited: 9 in the TBI group and 6 in control. The median patient age was 42 years: 41 years in the TBI group (range: 32-59 years) and 43.5 years in control (range: 27-62 years) with the median time since transplant being 66 months: 81 months in TBI group (range: 41-149 years) and 43.5 years in control (range: 40-72 years). All patients had a primary diagnosis of either AML (TBI: 5, control: 4), ALL (TBI: 2, control: 1) or CML (TBI: 2, control: 1). 8 patients received conditioning with cyclophosphamide-TBI and 1 with etoposide-TBI (median TBI dose 13.2 Gy; range: 12-14.4 Gy). 4 patients in the control group received thiotepa-busulfan-fludarabine and 2 received busulfan-cyclophosphamide. The median time to platelet engraftment was 18 days: 18 days in the TBI group (range: 13-73 days) and 21.5 days in control (range: 16-44 days). 5 patients in the TBI group and 4 in the control group had a history of chronic GVHD. None had disease relapse or more than one transplant. 9 of 15 patients had at least one CMB; 7 in TBI group (78%) compared to 2 in control (33%) (p=0.119). Although this was not significantly different, patients following TBI were more likely to have a higher number of CMBs: 4 patients (44%) in the TBI group had 3 or more CMBs, compared to none in the control (p=0.092). Median number of CMBs was 2 in TBI group (range: 0-9) and 0 in control (range: 0-2) (p=0.05) (Fig.1). Older age at HSCT was positively correlated with CMB number (ρ=0.5, p=0.06) with the correlation reaching statistical significance in an analysis of the TBI group only (ρ=0.78, p=0.01) (Fig.2). 7 patients (47%) showed impairment in processing speed and 6 (40%) in executive function. However, CMB number was not significantly correlated with the number of cognitively impaired domains on CANTAB insight testing (p=0.535). Conclusions The study provides the first evidence that low radiation doses, delivered through TBI, may increase CMB burden in HSCT survivors. The clinical significance of CMBs in this population remains unclear and our study did not demonstrate an association with impaired cognitive function. Given the complexity of peri-transplant physiology, further studies with larger cohorts would benefit from robust case-control matching and a longer follow-up with baseline cognitive assessment. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Genotype and Phenotype Differences in CADASIL from an Asian Perspective.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary cerebral small-vessel disease caused by mutations in the NOTCH3 gene. Classical pathogenic mechanisms are associated with cysteine gain or loss, but recent studies suggest that cysteine-sparing mutations might have a potential role as a pathogen. In comparison with CADASIL patients in Western countries, there are several differences in Asian patients: (1) prevalent locus of NOTCH3 mutations (exons 2–6 [particularly exon 4] vs. exon 11), (2) age at symptom onset, (3) prevalence of cerebral microbleeds and hemorrhagic stroke, (4) clinical symptoms, and (5) severity of white matter hyperintensities and typical involvement of the anterior temporal pole in magnetic resonance imaging. Both ethnicity and founder effects contribute to these differences in the clinical NOTCH3 spectrum in different cohorts. More functional investigations from diverse races are needed to clarify unknown but novel variants of NOTCH3 mutations. This review may broaden the spectrum of NOTCH3 variants from an Asian perspective and draw attention to the hidden pathogenic roles of NOTCH3 variants.

High Prevalence of Cerebral Microbleeds in Young Ischemic Stroke Patients.

Most studies of cerebral microbleeds place more emphasis on the elderly, which made it difficult to obtain data on youth, particularly young ischemic stroke patients. Our study sought to investigate the incidence and related risk factors of cerebral microbleeds in young ischemic stroke patients. Young ischemic stroke patients who sought medical advice at Beijing Chaoyang Hospital between June 2016 and September 2020 were included in our study. The clinical and imaging data of these patients were collected and assessed. These patients were grouped by cerebral microbleed presence, count, and location. Univariate and multivariate logistic regression analyses were performed to investigate the association between these groups and screen the influencing factors of cerebral microbleeds in young patients with ischemic stroke. Among the 187 young ischemic stroke patients, the prevalence of microbleeds was 16%. The presence of cerebral microbleeds was associated with hypertension (odds ratio [OR] 8.787, 95% confidence interval [CI] 1.016-76.006, P=0.048), lower estimated glomerular filtration rate (OR 0.976, 95%CI 0.957-0.995, P=0.014) and moderate/severe white matter hyperintensity (OR 10.681, 95%CI 3.611-31.595, P<0.001) in young ischemic stroke patients. Cerebral microbleeds were common in young ischemic stroke patients and were associated with hypertension, lower estimated glomerular filtration rate, and moderate/severe white matter hyperintensity.

Epidemiology of cerebral microbleeds and risk of adverse outcomes in atrial fibrillation: a systematic review and meta-analysis.

The aim of this study is to perform a systematic review and meta-analysis on the epidemiology of cerebral microbleeds (CMBs) and the risk of intracranial haemorrhage (ICH) and ischaemic stroke (IS) in patients with atrial fibrillation (AF). PubMed and EMBASE databases were systematically searched from inception to 6 March 2021. All studies reporting the prevalence of CMBs and incidence of ICH and IS in AF patients with and without CMBs were included. Meta-analysis was conducted using random-effect models; odds ratios (ORs), 95% confidence intervals (CIs), and prediction intervals (PIs) were calculated for each outcome. Subgroup analyses were performed according to the number and localization of CMBs. A total of 562 studies were retrieved, with 17 studies finally included in the meta-analysis. Prevalence of CMBs in AF population was estimated at 28.3% (95% CI: 23.8-33.4%). Individuals with CMBs showed a higher risk of ICH (OR: 3.04, 95% CI: 1.83-5.06, 95% PI 1.23-7.49) and IS (OR: 1.78, 95% CI: 1.26-2.49, 95% PI 1.10-2.87). Patients with ≥5 CMBs showed a higher risk of ICH. Metaregression showed how higher of prevalence of diabetes mellitus in AF cohort is associated with higher prevalence of CMBs. Cerebral microbleeds are common in patients with AF, found in almost one out of four subjects. Cerebral microbleeds were associated with both haemorrhagic and thromboembolic events in AF patients. Moreover, the risk of ICH increased consistently with the burden of CMBs. Cerebral microbleeds may represent an important overlooked risk factor for both ICH and IS in adults with AF.

Cerebral Microbleeds With Atrial Fibrillation After Ablation Therapy.

BackgroundThe prevalence of cerebral microbleeds (CMBs) is significantly higher in patients with atrial fibrillation (AF) than in those without AF. CMBs in patients with AF have been reported to be primarily of the lobar type, but the exact cause of this remains unknown. We investigated the possibility that hemorrhagic transformation of embolic microinfarction can account for de novo lobar CMBs.MethodsA total of 101 patients who underwent ablation therapy for AF were prospectively registered, and 72 patients completed the assessment with MRI 6 months after catheter ablation. Brain MRI, including diffusion-weighted imaging (DWI) and susceptibility-weighted imaging (SWI), were examined at 1–3 days (baseline) and 6 months after catheter ablation. We quantitatively evaluated the spatial and temporal distribution of embolic microinfarctions and de novo CMBs.ResultsOf the 101 patients, 68 were enrolled in this study. Fifty-nine patients (86.8%) showed embolic microinfarctions on baseline DWI immediately after catheter ablation. There were 137 CMBs in SWI, and 96 CMBs were of the lobar type. Six months later, there were 208 CMBs, including 71 de novo CMBs, and 60 of 71 (84.5%) were of the lobar type. Of the 71 de novo CMBs, 56 (78.9%) corresponded to the location of previous embolic microinfarctions found on baseline DWI. The platelet count was significantly lower and hematocrit/hemoglobin and Fazekas score were higher in the group with de novo CMBs than in the group without de novo CMBs.ConclusionDe novo CMBs frequently appeared after catheter ablation therapy. Our results suggest that embolic microinfarction can cause lobar CMBs.

Abstract WP216: Breast Cancer Susceptibility Genes And Cerebral Small Vessel Disease

Introduction: Aside from being implicated in breast and ovarian cancer, breast cancer susceptibility genes (BRCA) growing evidence suggests an additional intersection between BRCA mutations and hypercholesterolemia, endothelial damage, hyperglycemia and an increased non-neoplastic mortality. With the influence of BRCA on typical cerebrovascular risk factors, we aimed to identify if BRCA mutations increased the prevalence of cerebral small vessel disease (CSVD). Methods: We performed a retrospective cross-sectional chart review of adults with confirmed BRCA1 or BRCA2 mutations compared against BRCA wild-type individuals with breast and/or ovarian cancer. Demographic and medical history were recorded. Brain MRI was interpreted for markers of CSVD. Statistical significance (p &lt; 0.05) was tested via the Chi-squared or Fisher’s, Wilcoxon rank-sum and the Student’s t-test analyses for binary, ordinal or interval variables, respectively. Adjusted logistic regression models were fit to calculate odds ratio. All models were tested for multicollinearity by variance inflation factor calculation and for goodness-of-fit (GOF) via the Hosmer-Lemeshow GOF test. Results: One hundred forty individuals were included, with 47% (66/140) being BRCA mutant. Demographic and cerebrovascular risk factors were similar amongst the cohort. Estrogen antagonist therapy was more common in the BRCA wild-type group [25% (16/64) vs 44.6% (33/74), p = 0.016]. Lacunar infarcts, Fazekas grading and perivascular spaces were not significantly different across the cohort. Cerebral microbleeds (CMBs) were more prevalent in those with BRCA mutation: [36.4% (24/66) vs 18.9% (14/74), p = 0.021]. This finding persisted despite adjustment for cerebrovascular risk factors (OR 2.71, 95%CI 1.20 - 6.14, p = 0.017) yielding a predicted probability of 18.2% (95%CI 3.7 - 32.8). Conclusion: For those with BRCA mutation, we identified a nearly 3 fold increase in CMB prevalence despite adjustment for cerebrovascular risk factors. The mechanism underlying is presently unknown, though likely related to endothelial dysregulation. Further studies are needed to confirm our findings on a larger scale and investigate intraparenchymal hemorrhage risk amongst those with BRCA mutations.

Abstract TP138: Prevalence And Risk Factors Associated With Cerebral Microbleeds In Patients With Acute Respiratory Distress Syndrome

Introduction: Acute respiratory distress syndrome (ARDS) is associated with pulmonary vascular endothelial injury. Cerebral microbleeds (CMB) have been reported in patients with critical illness such as ARDS, particularly involving the splenium of the corpus callosum and immediate subcortical white matter. We aimed to examine the prevalence and risk factors of CMB in ARDS. Methods: We reviewed patient data from an ARDS registry at a tertiary medical center from January 2010 to October 2018. Patients were excluded if MRI imaging was motion degraded or did not include susceptibility weighted imaging (SWI) or T2*weighted gradient echo sequences. CMB were defined as hypointense SWI or T2* lesions &lt;5 mm. Microbleeds were labeled as diffuse if there were ≥10 present in a region. ARDS rescue therapies included extracorporeal membrane oxygenation, inhaled vasodilators, recruitment maneuvers, high frequency oscillatory ventilation, neuromuscular blockade, and proning. Univariate analysis was performed to examine association with CMB. Results: Of the 678 patients with ARDS, 61 had MRI’s meeting inclusion criteria. CMB were present in 12 patients, with median age 62.5 years. Ten patients had lobar CMB, of which 4 were diffuse and also involved the cerebellum. There were 3 patients with CMB in the corpus callosum, all involving the splenium, of which 2 were diffuse among patients who had diffuse lobar involvement. Acute Physiology and Chronic Health Evaluation III and Sequential Organ Failure Assessment scores did not differ between those with and without CMB, but ARDS rescue therapies were more commonly used in patients with CMB (66.7% vs 22.4%, p=.003). CMB was associated with acute cerebral ischemia on MRI (41.7% with CMB vs 10.2% without CMB, p=.008). Conclusions: CMB are common in ARDS, mostly involving the cerebral lobes and cerebellum. CMB might be associated with ARDS rescue therapies and higher risk for ischemic infarcts.

Abstract TMP20: Cerebrovascular Injury Associated With COVID-19 And Non-COVID-19 Acute Respiratory Distress Syndrome

Background: Neurologic complications of Coronavirus Disease 2019 (COVID-19) may be associated with neurotropism of the virus or secondary brain injury from systemic inflammation. Acute respiratory distress syndrome (ARDS) is associated with cerebrovascular injury, including both ischemia and hemorrhage. We aimed to compare brain MRI findings of COVID-19 associated ARDS with non-COVID-19 ARDS. Methods: A registry of patients with COVID-19 from March 2020 through July 2021 from a hospital network was reviewed. Patients who met criteria for ARDS by Berlin definition and underwent MRI during their hospitalization were included. These patients were matched 1:1 by age and sex with patients who underwent MRI from another registry of patients of ARDS in the same hospital between 2010 and 2018. Cerebrovascular injury was classified as either acute cerebral ischemia (ischemic infarct or hypoxic ischemic brain injury) or intracranial hemorrhage (ICH) including intraparenchymal hemorrhage, subarachnoid hemorrhage, subdural hematoma, and cerebral microbleeds (CMBs). Results: Of 13,319 patients with COVID-19 infection, 26 patients had ARDS and MRI. Sixty-six of 678 non-COVID-19 ARDS patients had an MRI and were matched 1:1 by age and sex resulting in 23 matched pairs. The median age was 66 and 59% of patients were male. Patients with COVID-19 ARDS were more likely to have hypertension and chronic kidney disease but otherwise baseline medical characteristics were similar. ARDS severity as determined by PaO2/FiO2 ratio at ICU admission was similar between both groups. No difference was seen in the prevalence of cerebrovascular injury (52% vs 61%, p=0.8), cerebral ischemia (35% vs 43%, p=0.8), ICH (43% vs 48%, p=1.0), or CMBs (43% vs 39% p=1.0) on MRI between the COVID-19 and non-COVID-19 cohorts. However, two unique patterns of injury were seen only among COVID-19 patients: hemorrhagic leukoencephalitis (3 patients, 12%) and bilateral cerebral peduncular ischemia with microhemorrhage (2 patients, 8%). Conclusion: Cerebrovascular injury was common in both COVID-19 and non-COVID-19 ARDS without significant frequency difference. However, COVID-19 ARDS had unique neuroimaging patterns that may indicate distinct patterns of brain injury of COVID-19.

The influence of cerebrovascular disease in dementia with Lewy bodies and Parkinson's disease dementia.

Lewy body dementia (LBD), including dementia with Lewy bodies (DLB) and Parkinson's disease dementia, is a common form of neurodegenerative dementia. The frequency and influence of comorbid cerebrovascular disease is not understood but has potentially important clinical management implications. A systematic literature search was conducted (MEDLINE and Embase) for studies including participants with DLB and/or Parkinson's disease dementia assessing cerebrovascular lesions (imaging and pathological studies). They included white matter changes, cerebral amyloid angiopathy, cerebral microbleeds (CMB), macroscopic infarcts, microinfarcts and intracerebral haemorrhage. Of 4411 articles, 63 studies were included. Cerebrovascular lesions commonly studied included white matter changes (41 studies) and CMB (18 studies). There was an increased severity of white matter changes on magnetic resonance imaging (visualized as white matter hyperintensities), but not neuropathology, in LBD compared to Parkinson's disease without dementia and age-matched controls. CMB prevalence in DLB was highly variable but broadly similar to Alzheimer's disease (0%-48%), with a lobar predominance. No relationship was found between large cortical or small subcortical infarcts or intracerebral haemorrhage and the presence of LBD. The underlying mechanisms of white matter hyperintensities in LBD require further exploration, as their increased severity in LBD was not supported by neuropathological examination of white matter. CMB in LBD had a similar prevalence to Alzheimer's disease. There is a need for larger studies assessing the influence of cerebrovascular lesions on clinical symptoms, disease progression and outcomes.

Multi-organ assessment in mainly non-hospitalized individuals after SARS-CoV-2 infection: The Hamburg City Health Study COVID programme.

AimsLong-term sequelae may occur after SARS-CoV-2 infection. We comprehensively assessed organ-specific functions in individuals after mild to moderate SARS-CoV-2 infection compared with controls from the general population.Methods and resultsFour hundred and forty-three mainly non-hospitalized individuals were examined in median 9.6 months after the first positive SARS-CoV-2 test and matched for age, sex, and education with 1328 controls from a population-based German cohort. We assessed pulmonary, cardiac, vascular, renal, and neurological status, as well as patient-related outcomes. Bodyplethysmography documented mildly lower total lung volume (regression coefficient −3.24, adjusted P = 0.014) and higher specific airway resistance (regression coefficient 8.11, adjusted P = 0.001) after SARS-CoV-2 infection. Cardiac assessment revealed slightly lower measures of left (regression coefficient for left ventricular ejection fraction on transthoracic echocardiography −0.93, adjusted P = 0.015) and right ventricular function and higher concentrations of cardiac biomarkers (factor 1.14 for high-sensitivity troponin, 1.41 for N-terminal pro-B-type natriuretic peptide, adjusted P ≤ 0.01) in post-SARS-CoV-2 patients compared with matched controls, but no significant differences in cardiac magnetic resonance imaging findings. Sonographically non-compressible femoral veins, suggesting deep vein thrombosis, were substantially more frequent after SARS-CoV-2 infection (odds ratio 2.68, adjusted P < 0.001). Glomerular filtration rate (regression coefficient −2.35, adjusted P = 0.019) was lower in post-SARS-CoV-2 cases. Relative brain volume, prevalence of cerebral microbleeds, and infarct residuals were similar, while the mean cortical thickness was higher in post-SARS-CoV-2 cases. Cognitive function was not impaired. Similarly, patient-related outcomes did not differ.ConclusionSubjects who apparently recovered from mild to moderate SARS-CoV-2 infection show signs of subclinical multi-organ affection related to pulmonary, cardiac, thrombotic, and renal function without signs of structural brain damage, neurocognitive, or quality-of-life impairment. Respective screening may guide further patient management.

Heme as an inducer of cerebral damage in hemorrhagic stroke: potential therapeutic implications.

Heme as an inducer of cerebral damage in hemorrhagic stroke: potential therapeutic implications.

Abstract 10763: Atrial Fibrillation and Supraventricular Ectopy in Relation to Brain Morphology and Subclinical Vascular Brain Injury: The Multi-Ethnic Study of Atherosclerosis

Introduction: Atrial fibrillation (AF) increases stroke risk and is associated with accelerated cognitive decline. Information is mixed about the relationship of AF and other supraventricular (SV) arrhythmias with brain changes on magnetic resonance imaging (MRI). Hypothesis: Prevalent AF and SV ectopy are associated with reduced gray matter (GM) volume and subclinical vascular brain injury. Methods: In the Multi-Ethnic Study of Atherosclerosis (MESA), participants completed Zio Patch monitoring and brain MRI. Prevalent AF was estimated from ambulatory monitoring, hospital surveillance, Medicare claims, and MESA electrocardiogram (ECG). For secondary analyses, AF was categorized into continuous - AF during 100% of monitoring - and intermittent - prevalent AF with &lt;100% AF during monitoring. Brain MRI measures included GM volume, white matter (WM) lesion volume, WM fractional anisotropy, and presence of cerebral microbleeds (CMBs). Linear and Poisson regression analyses were adjusted for cardiovascular risk factors and socioeconomic status. Results: In MESA, 967 participants without a history of stroke or transient ischemic attack (TIA) completed &gt;24 hours of ECG monitoring (median, 14.0 days) and completed brain MRI a median 17 months later. Mean (standard deviation) age was 72 (8) years; 53% were women. A total of 116 participants had prevalent AF, of whom 20 had continuous AF. Compared with no AF, prevalent AF was associated with lower WM FA (-0.22 standard deviations, 95% CI: -0.39, -0.04) and higher prevalence of CMBs (prevalence ratio: 1.46, 95% CI: 1.18, 1.80). In secondary analyses, compared with no AF, continuous but not intermittent AF was associated with lower GM volume (-18.6 mL, 95% CI: -31.4, -5.8). Rates of premature atrial contractions and runs of SV tachycardia were not significantly associated with brain MRI measures. Conclusions: In a multi-ethnic sample free of a history of stroke or TIA, prevalent AF was associated with lower WM FA, a measure of WM injury, and presence of CMBs. These results highlight the importance of AF prevention for brain health. Further analysis of subclinical infarcts is needed in this sample, and study in other settings is needed to confirm whether greater AF burden is associated with reduced GM volume.

Cerebral Microbleed Burden in Ischemic Stroke Patients on Aspirin: Prospective Cohort of Intracranial Hemorrhage.

Objective: This investigation aimed at studying the prevalence of cerebral microbleeds (CMBs), including risk factors and the correlation of CMBs to ischemic stroke (IS) patient end results.Methods: Four hundred and fifty-nine acute IS cases were recruited between April 2014 and December 2016. Cerebral microbleeds were analyzed using susceptibility-weighted imaging (SWI) brain MRI scan. The enrolled patients with acute IS were followed up for 12–24 months, with a median follow-up time of 19 months. The follow-up endpoint events including recurrent ischemic stroke (RIS), intracranial hemorrhage (ICH), transient ischemic attack (TIA), mortality, and cardiovascular events. The associations between vascular risk factors and CMBs in IS patients were analyzed using univariate and multivariate logistic regression analysis. Cox regression model was employed for evaluating CMB impact on clinical outcome.Results: Among 459 enrolled patients, 187 (40.7%) had CMBs and 272 (59.2%) had no CMB. In comparison with patients with no CMBs, age was higher and hypertension was more frequent in patients with CMBs. Multivariate logistic regression analyses revealed age and hypertension were independently associated with the presence of CMBs. Among the patient cohort, 450 cases completed the follow-up. During the follow-up period, 22 (4.9%) of patients developed ICH, 12 (2.7%) developed TIA, 68 (15.1%) developed RIS, cardiovascular events occurred in 20 (4.44%), and 13 (2.89%) cases were mortalities. Compared with patients without CMBs, IS patients with CMBs have an increased prevalence of ICH (p < 0.05). However, no statistically valid variations regarding other outcome incidences between both groups was identified (p > 0.05). The incidence of ICH was elevated in tandem with elevations in number of CMBs. Following adjusting for age, multivariate Cox proportional-hazards regression analysis revealed that CMBs ≥10 were independent predictors of ICH in acute IS patients.Conclusion: Age and hypertension are independently associated with the presence of CMBs. Intracranial hemorrhage incidence rate was increased with the number of CMBs, and the number of CMBs ≥10 were independent predictors of ICH in acute stroke patients.

Cerebral microbleeds and risk of adverse outcomes in patients with atrial fibrillation: a systematic review and meta-analysis

Abstract Background Long-term anticoagulation in patients with atrial fibrillation (AF) imposes a careful balance between the thromboembolic and hemorrhagic risks. An association between cerebral microbleeds (CMBs) and an increased risk of intracranial hemorrhage (ICH) has already been described; however, conflicting evidence exist on the association with ischemic stroke (IS). Although CMBs are often observed in AF patients, the actual prevalence and the magnitude of the risk of adverse events in patients with CMBs is unclear. Purpose We aimed to estimate the pooled prevalence of CMBs in patients with AF through a systematic review and meta-analysis of the literature. Additionally, we evaluated the risk of ICH and IS according to the presence and burden of CMBs. Methods We perform a systematic search on PubMed and EMBASE from inception to 6th March 2021. We included all studies reporting the prevalence of CMBs, the incidence of ICH and/or IS in AF by presence of CMBs. Pooled prevalence and odds ratios (OR), along with their 95% Confidence Intervals (CI), were computed using random-effect models; we also calculated 95% Prediction Intervals (PI) for each outcome investigated. Additionally, we performed subgroup analyses according to the number and localization of CMBs. Results We retrieved 562 records from the literature search, and 17 studies were finally included. Pooled prevalence of CMBs in AF population was 28.3% (95% CI: 23.8%-33.4%; 95% PI: 12.2%-52.9%, Figure 1). Individuals with CMBs showed a higher risk of both ICH (OR: 3.04, 95% CI: 1.83–5.06) and IS (OR: 1.78, 95% CI: 1.26–2.49). Moreover, patients with more than 5 CMBs, as well as patients with both lobar and mixed CMBs, showed a higher risk of ICH. Conclusions CMBs were found in 28.3% of AF patients, with 95% PIs indicating a potentially higher prevalence. Moreover, CMBs were associated with an increased risk of both ICH and IS, with the effect potentially modulated by their number and localization. CMBs may represent an important and often overlooked risk factor for adverse outcomes in patients with AF. Funding Acknowledgement Type of funding sources: None. Prevalence of CMBs in patients with AF

Prevalence and Risk Factors of Cerebral Microbleeds: Analysis From the UK Biobank.

To determine the prevalence of and risk factors for cerebral microbleeds (CMBs) at different locations in a large healthy community population. A total of 8,159 participants from the UK Biobank with MRI scans suitable for CMB analysis were included. Brain susceptibility-weighted imaging data were acquired on 2 identical 3.0T scanners. The Microbleed Anatomical Rating Scale was used to identify definite CMBs. Generalized linear models were used to determine independent associations with all CMBs and lobar, deep, and infratentorial CMBs. The mean age at scan was 62.1 ± 7.4 years. One or more definite CMBs were detected in 572 (7.0%) participants. Of those with CMBs, 439 (76.7%) had lobar CMBs, 103 (18.0%) had deep CMBs, and 83 (14.5%) had infratentorial CMBs. Age was an independent risk factor for CMBs in all locations. APOE4 and male sex were positively associated and higher body mass index was negatively associated with lobar CMBs. Hypertension, smoking, and alcohol consumption were associated with deep CMBs, but not with lobar CMBs. Only age was associated with infratentorial CMBs. The associations were unchanged after controlling for white matter hyperintensity lesion volume as a marker of small vessel disease severity. In this large population-based study, CMB prevalence detected using a low sensitivity and high specificity system was 7%. There were distinct risk factor profiles for CMBs in lobar and deep locations consistent with different underlying pathophysiologic processes. Clinical Trial registration number: UK Biobank application number 19463.

Antiplatelet therapy and future intracerebral hemorrhage in hemodialysis patients with cerebral microbleeds

The use of antiplatelet drugs is thought to increase the risk for intracerebral hemorrhage (ICH) in patients with cerebral microbleeds (CMBs). However, hemodialysis (HD) patients have a high prevalence of CMBs and diverse pathologies that require antiplatelet therapy. In this study, we investigated whether the use of antiplatelet drugs increases the risk for ICH in HD patients with CMBs. Brain magnetic resonance imaging (MRI), including T2*-weighted MRI, was performed in 179 HD patients with no history of cerebrovascular events. CMBs were detected and patients were followed prospectively with a median follow-up period of 5.2 [1.4–6.2] years. To investigate whether the influence of antiplatelet therapy on the development of ICH differs in cases with and without CMBs, the inverse probability of treatment weighting method was used, including an interaction term between the presence or absence of CMBs and use of antiplatelet drugs. As a result, CMBs were detected in 45 patients (25.1%), and antiplatelet drugs were used in 66 patients (36.9%). When the effect of antiplatelet therapy on the incidence of ICH was modified by the presence of CMBs at baseline (P for interaction <0.001), the use of antiplatelet drugs was a significant risk factor for ICH in HD patients without CMBs, but not in HD patients with CMBs. Furthermore, the burden of CMBs significantly increased the risk for ICH, but the increase in this risk was slower in antiplatelet drug users as compared to non-antiplatelet drug users (P for interaction = 0.02). The influence of antiplatelet drugs on the development of ICH differed depending on the presence or absence of CMBs. In fact, the use of antiplatelet drugs did not increase the risk for ICH in HD patients with CMBs.