Number Of Cerebral Microbleeds Research Articles

Cerebral Microbleeds in Patients with Parkinson's Disease and Dementia with Lewy Bodies: Comparison Using Magnetic Resonance Imaging and 99mTc-ECD SPECT Subtraction Imaging.

Cerebral microbleeds (CMBs) in patients with Parkinson's disease (PD) or dementia with Lewy bodies (DLB) have not been adequately studied. This study aims to find a difference in the total number, prevalence, and common locations of CMBs between PD and DLB and evaluate 99mTc-ECD SPECT subtraction images of these two diseases. We examined 112 patients with PD (53 males and 59 females; age: 77.4±3.6 years) and 28 age-matched patients with DLB (15 males and 13 females; age: 77.1±6.7 years) using brain magnetic resonance imaging (MRI) and 99mTc-ECD SPECT subtraction imaging. The total number of CMBs was higher in patients with DLB (41.2%) than in those with PD (11.5%), and the prevalence was significantly higher in the former (0.7±1.1) than the latter (0.2±0.5, p < 0.05). The odds ratio was 5.4 (95% confidence interval [CI]: 1.7-17.4). Furthermore, CMBs were commonly located in the basal ganglia of patients with PD (6 out of 87 patients) but in the occipital lobe of patients with DLB (8 out of 17 patients). 99mTc-ECD SPECT subtraction imaging indicated lower cerebral blood flow in the posterior cingulate gyrus among the patients with CMB-positive DLB than among those with CMB-positive PD; additionally, the cerebral blood flow was lower in the bilateral basal ganglia and midbrain among patients with CMB-positive DLB compared to those with CMB-negative DLB. A reduction in occipital glucose metabolism may be related to CMBs in the occipital lobe of patients with DLB.

Relationship between cerebral microbleeds, ventricular enlargement and white matter hyperintensities in Alzheimer’s disease

AbstractBackgroundTo investigate whether the number of cerebral microbleeds (CMB) could be a useful indicator to predict glymphatic system dysfunction in Alzheimer’s disease (AD) patients, by comparing the degree of cerebral spinal fluid (CSF) and interstitial fluid (ISF) stasis.MethodForty probable AD patients were included, with those exhibiting two or more CMB were included in the multiple CMB group (mCMB, n = 21, mean = 11.1), and none or one CMB included in the non‐multiple CMB group (nmCMB, n = 19, mean = 0.84). CMB were defined in axial gradient recalled echo (GRE) T2*‐weighted images. Evans index (EI) was calculated to measure lateral ventricle enlargement, Voxel‐based Specific Regional Analysis System for Alzheimer's Disease (VSRAD) software was used to determine the extent of gray and white matter atrophy, and Fazekas scale (FS) was used to determine white matter hyperintensities (WMH).ResultEI was significantly larger in mCMB than in nmCMB, while the gray and white matter volume was not different between groups. Thus, the difference in lateral ventricle enlargement between AD with and without multiple CMB reflects a combination of the degree of brain atrophy and the extent of CSF stasis. FS was higher in mCMB than in the nmCMB, suggesting the failure of ISF elimination was more severe in mCMB cases.ConclusionThe difference in lateral ventricle enlargement and WMH between AD with or without multiple CMB may reflect a difference in the degree of CSF/ISF stagnation.

The clinical risk factors of cerebral microbleeds and its relationship with cognitive dysfunction

AbstractBackgroundTo explore the risk factors of cerebral microbleeds (CMBs) and the relationship between CMBs and cognitive impairment, and to provide more theoretical basis for the prevention and treatment of CMBs and vascular cognitive impairment.MethodThe CMBs group was classified according to the number and location. The basic clinical data were collected and the subjects all received the cognitive tests using Mini‐Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA) and the Neuropsychological Assessment Scales.ResultA total of 138 subjects [71 participants in CMBs group and 67 as control] were enrolled, with an average age of 64.36±10.14 years. Ordered logistic regression analysis showed diastolic blood pressure (OR=1.05, 95% CI: 1.01‐1.09), history of ischemic stroke and transient ischemic attack (TIA) (OR=7.74, 95% CI: 2.74) ‐21.88), white matter hyperintensities (OR = 2.01, 95% CI: 1.46‐2.78) are independently associated with CMBs (P&lt;0.05). Spearman correlation analysis showed that MMSE, MoCA, memory and executive function were correlated with CMBs (MMSE r=‐0.24, P=0.005; MoCA r=‐0.32, P&lt;0.001; memory r=‐0.28, P=0.001; execution function r = ‐0.33, P&lt;0.001). Multivariate linear regression analysis showed that MoCA score, memory and executive function were negatively correlated with CMBs number after adjusting for gender, age, years of education, other imaging biomarkers of cerebral small vessel disease and vascular risk factors (MoCA β=‐0.88, P=0.012; memory β = ‐0.22, P = 0.002; executive function β = ‐0.13, P = 0.001). As for the location, the results showed that the executive function of patients with strict lobe CMBs was lower than that of control group (P=0.046). In terms of speed and motion control, the differences between deep group and control group (P=0.037), deep group and infratentorial group (P=0.005) were statistically significant.ConclusionDiastolic blood pressure, history of ischemic stroke / TIA, white matter hyperintensities were independent risk factors for CMBs. CMBs are associated with cognitive dysfunction. CMBs in the strict lobe area are associated with the decline of executive function, and CMBs in the deep area are associated with the decline of speed and motor control ability.

Relevance of cerebral small vessel disease load scores in first-ever lacunar infarction

AimTo reveal the correlation between total cerebrovascular disease load and primary lacunar infarction. BackgroundCerebral small vessel disease (CSVD) is the lack of specific clinical manifestations, whose clinical diagnoses are highly dependent on neuroimaging results. Total CSVD load scores may be more suitable for the assessment of overall brain function damage caused by CSVD. Little is known about whether the association between imaging markers of CSVD and CSVD total load scores at the time of first-ever lacunar infarction (LI). Methodsclinical data of 396 patients hospitalised from September 2016 to May 2018 due to a first-ever LI (case group), along with patients diagnosed with CSVD based on imaging alone and those with no abnormalities (control group) based on magnetic resonance imaging (MRI). Binary logistic regression and multiple ordered logistic regression were used to analyse the characteristics of imaging markers of CSVD in patients with first-ever LI, including different total score burden and distribution, and the relationship between different markers. ResultsIn 396 patients, smoking, cholesterol level and total small vessel disease (SVD) score were all significantly associated with the first-ever LI. There were more LI, cerebral microbleeds (CMB), white matter hyperintensities (WMH), and moderate to severe enlarged perivascular spaces (EPVS) in the first-ever LI group, relative to controls (p < 0.01). The Fazekas scores for periventricular WMH, deep WMH, and total Fazekas score were all significantly higher in patients with first-ever LI relative to those with no cerebral abnormalities (p < 0.01). An analysis of various imaging markers of CSVD revealed a significant correlation between the presence and degree of any marker and the severity of other markers, even after adjusting for the presence of other markers (p < 0.05). ConclusionsThe first-ever LI group exhibited higher total CSVD score loads, a greater number of lacunae, CMB, severe WMH and moderate to severe EPVS. Smoking is an independent risk factor in patients with first-ever LI.

Oral Carriage of Streptococcus mutans Harboring the cnm Gene Relates to an Increased Incidence of Cerebral Microbleeds.

Cerebral microbleeds (CMB) are associated with stroke and cognitive impairment. We previously reported a high prevalence of CMB in people with Streptococcus mutans expressing Cnm, a collagen-binding protein in the oral cavity. S.mutans is a major pathogen responsible for dental caries. Repeated challenge with S.mutans harboring the cnm gene encoding Cnm induced cerebral bleeding in stroke-prone spontaneously hypertensive rats. The purpose of this longitudinal study is to examine the relationship of cnm-positive S.mutans to the development of CMB. We retrospectively investigated patients with stroke receiving oral microbiological examination and head 3T magnetic resonance imaging evaluations twice in the period 2014 to 2019, allowing >180-day interval. Patients with cnm-positive S.mutans were compared with those without. Quasi-Poisson regression models were used to explore associations between cnm-positive S.mutans and the increase in number of CMB between the 2 magnetic resonance imaging scans. A total of 111 patients were identified; 21 (19%) with cnm-positive S.mutans and 90 (81%) without. Clinical history, including blood pressure and the use of antithrombotic agents, were comparable between the 2 groups. New CMB were more commonly observed in patients with cnm-positive S.mutans (52% versus 23%; P=0.008). The incidence of CMB was significantly higher in the group with cnm-positive S.mutans, especially in deep areas, (incidence rate ratios [95% CI], 5.1 [1.9-13.6] for CMB in any brain region; 15.0 [5.4-42.0] for deep CMB), which persisted after adjusting for age, sex, hypertension, and renal impairment (4.7 [1.8-11.9] for CMB in any brain region; 13.9 [4.3-44.5] for deep CMB). This study demonstrates that cnm-positive S.mutans is associated with an increased incidence of CMB. Treatment for cnm-positive S.mutans infection may be a novel microbiota-based therapeutic approach for stroke and cognitive impairment.

Prediction of amyloid \u03b2 PET positivity using machine learning in patients with suspected cerebral amyloid angiopathy markers

Amyloid-β(Aβ) PET positivity in patients with suspected cerebral amyloid angiopathy (CAA) MRI markers is predictive of a worse cognitive trajectory, and it provides insights into the underlying vascular pathology (CAA vs. hypertensive angiopathy) to facilitate prognostic prediction and appropriate treatment decisions. In this study, we applied two interpretable machine learning algorithms, gradient boosting machine (GBM) and random forest (RF), to predict Aβ PET positivity in patients with CAA MRI markers. In the GBM algorithm, the number of lobar cerebral microbleeds (CMBs), deep CMBs, lacunes, CMBs in dentate nuclei, and age were ranked as the most influential to predict Aβ positivity. In the RF algorithm, the absence of diabetes was additionally chosen. Cut-off values of the above variables predictive of Aβ positivity were as follows: (1) the number of lobar CMBs > 16.4(GBM)/14.3(RF), (2) no deep CMBs(GBM/RF), (3) the number of lacunes > 7.4(GBM/RF), (4) age > 74.3(GBM)/64(RF), (5) no CMBs in dentate nucleus(GBM/RF). The classification performances based on the area under the receiver operating characteristic curve were 0.83 in GBM and 0.80 in RF. Our study demonstrates the utility of interpretable machine learning in the clinical setting by quantifying the relative importance and cutoff values of predictive variables for Aβ positivity in patients with suspected CAA markers.

Cerebrospinal Fluid Metals and the Association with Cerebral Small Vessel Disease.

Brain metal homeostasis is essential for brain health, and deregulation can result in oxidative stress on the brain parenchyma. Our objective in this study was to focus on two hemorrhagic MRI manifestations of small vessel disease [cerebral microbleeds (CMBs) and cortical superficial siderosis (cSS)] and associations with cerebrospinal fluid (CSF) iron levels. In addition, we aimed to analyze CSF biomarkers for dementia and associations with CSF metal levels. This is a cross-sectional study of 196 patients who underwent memory clinic investigation, including brain MRI. CSF was collected and analyzed for metals, amyloid-β (Aβ) 42, total tau (T-tau), and phosphorylated tau (P-tau), and CSF/serum albumin ratios. Statistical analyses were performed using generalized linear models. No significant difference was found between CSF metal levels across diagnostic groups. Higher iron and copper levels were associated with higher CSF levels of Aβ42, T-tau, P-tau, and CSF/serum albumin ratios (p < 0.05). Zinc was associated with higher CSF/serum albumin ratios. There was no significant association between CMBs or cSS and CSF iron levels. An increase in CSF iron with the number of CMBs was seen in APOEɛ4 carriers. CSF iron levels are elevated with cerebral microbleeds in APOEɛ4 carriers, with no other association seen with hemorrhagic markers of small vessel disease. The association of elevated CSF iron and copper with tau could represent findings of increased neurodegeneration in these patients.

Hemorrhagic risk after intravenous thrombolysis for ischemic stroke in patients with cerebral microbleeds and white matter disease

ObjectivesAim of this study was to evaluate the association between cerebral microbleeds (CMBs) and white matter disease (WMD) with intracerebral hemorrhage (ICH) after intravenous thrombolysis (IVT) with rt-PA. We also evaluated whether CMBs characteristics and WMD burden correlate with symptomatic ICH and outcome.MethodsWe included acute ischemic stroke (AIS) patients treated with IVT. The number and location of CMBs as well as severity of WMD were rated analyzing pre- or post-treatment MRI. Multivariable regression analysis was used to determine the impact of CMB and WMD on ICH subgroups and outcome measures.Results434 patients were included. CMBs were detected in 23.3% of them. ICH occurred in 34.7% of patients with CMBs. Independent predictors of parenchymal hemorrhage were the presence of CMBs (OR 2.724, 95% CI 1.360–5.464, p = 0.005) as well as cortical-subcortical stroke (OR 3.629, 95% CI 1.841–7.151, p < 0.001) and atherothrombotic stroke subtype (OR 3.381, 95% CI 1.335–8.566, p = 0.010). Either the presence, or number, and location of CMBs, as well as WMD, was not independently associated with the development of SICH. No independent association between the presence, number, or location of CMBs or WMD and outcome measures was observed.ConclusionsThe results of our study suggest that the exclusion of eligible candidates to administration of IV rt-PA only on the basis of CMBs presence is not justified. The clinical decision should be weighed with a case-by-case approach. Additional data are needed to evaluate the benefit-risk profile of rt-PA in patients carrying numerous microbleeds.

Homocysteinemia is Associated with the Presence of Microbleeds in Cognitively Impaired Patients

Background & ObjectiveHomocysteine is possibly associated with cerebral small vessel diseases such as leukoaraiosis, silent brain infarction and cerebral microbleeds, which are in turn associated with cognitive dysfunction. We aimed to examine the relationships between cerebral microbleeds (CMBs) and plasma total homocysteine (tHcy) level, methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and cognitive function. MethodsA total of 819 patients with memory disturbance who visited a dementia clinic consecutively were included in this study. We retrospectively collected demographic, clinical and laboratory data including tHcy level, MTHFR C677T polymorphism and Mini-Mental State Examination (MMSE). All patients underwent brain MRI including fluid attenuated inversion recovery (FLAIR) image and T2*-weighed gradient-echo (GRE) image. Logistic regression analysis was performed to test the association between risk factors and the presence of microbleeds. ResultsOne hundred and sixty-one (19.7%) patients had CMBs, of whom 88 (54.7%) had CMBs in the lobar region. CMBs were more common in older hypertensive male patients with hyperhomocysteinemia. In multivariable analysis, plasma tHcy remained an independent predictor of the presence of CMBs after adjusting other confounders (OR: 1.035, 95% CI: 1.009-1.062, p = 0.009). Higher plasma tHcy level was also associated with number of CMBs, TT MTHFR genotype, and lower MMSE scores. ConclusionsElevated plasma tHcy level is related to high prevalence of CMBs and cognitive dysfunction. Lowering plasma tHcy could be helpful in cognitively impaired patients who have CMBs or the MTHFR TT genotype.

Oral anticoagulant use and the development of new cerebral microbleeds in cardioembolic stroke patients with atrial fibrillation.

ObjectiveCerebral microbleeds (CMBs) are a magnetic resonance imaging (MRI) marker for cerebral small vessel disease. Existing CMBs and those that newly develop are associated with the risks of stroke incidence and recurrence. The purpose of the present study was to investigate the association of oral anticoagulant (OAC) use and the development of new CMBs in cardioembolic stroke patients with atrial fibrillation.Subjects and methodsWe prospectively followed cardioembolic stroke patients with atrial fibrillation who had been hospitalized in the stroke center of our hospital, had been prescribed anticoagulants at discharge, and underwent repeated brain MRI with an interval of at least one year from the baseline MRI. Assessing the presence, number and location of CMBs using T2*-weighted gradient-recalled echo MRI, we used logistic regression models to investigate the associations between OAC use and the incidence of new CMBs. We also examined associations of subsequent stroke with OACs and CMBs during the follow-up.ResultsA total of 81 patients, consisting of 45 patients receiving direct oral anticoagulants (DOACs) and 36 patients receiving warfarin (WF), were analyzed in the present study. Baseline CMBs were observed in 19/81 patients (23.5%) and new CMBs in 18/81 patients (22.2%) on follow-up MRI (median interval, 34 months). Of the 31 new CMBs, 25 (80.6%) developed in the lobar location and 6 (19.4%) in the deep or infratentorial location. New CMBs occurred in 4 patients (10.0%) taking DOACs alone, in 10 patients (35.7%) taking WF alone, in 3 patients (37.5%) taking WF plus antiplatelet agents and in 1 patient (20.0%) taking DOAC plus antiplatelet agent. Regarding location, the new CMBs were the lobar type in 7 of the 10 patients taking WF alone, as well as in 3 of the 4 patients taking DOACs alone. In multivariate analysis, the presence of CMBs at baseline and WF use (vs. DOAC use) were associated with new CMBs (CMB presence at baseline: OR 4.16, 95% CI 1.19–14.44; WF use: OR 3.38, 95% CI 1.02–11.42). The presence of ≥ 2 CMBs at baseline was related to a higher risk of subsequent stroke (OR 7.25, 95% CI 1.01–52.35, P = 0.048).ConclusionOur findings suggest that DOAC compared with WF use at discharge is associated with a lower incidence of new CMBs in cardioembolic stroke patients with atrial fibrillation. Further prospective studies in the clinical setting are needed to confirm our exploratory data.

Antiplatelet therapy may be safe in ischemic stroke patients with cerebral microbleed.

ObjectiveWe examined whether antiplatelet therapy is safe for ischemic stroke patients with cerebral microbleed.MethodsWe retrospectively analyzed ischemic stroke patients admitted to our hospital from 2015 to 2018. Baseline information was extracted from the computerized database. Adverse events, including symptomatic cerebral hemorrhage, recurrent cerebral infarction, and death, were collected by phone.ResultsA total of 184 ischemic stroke patients were examined, including 106 with and 78 without cerebral microbleed. No patient experienced symptomatic cerebral hemorrhage after discharge. Patients with cerebral microbleed had a higher prevalence of hypertension (92% vs 74%) and suffered from more serious leukoaraiosis (3.0 ± 1.7 vs 1.3 ± 1.4 points on the Fazekas scale). Leukoaraiosis scores were correlated with the number of cerebral microbleeds (r = 0.42).ConclusionsAntiplatelet therapy may be safe for ischemic stroke patients with cerebral microbleed. The risk-benefit ratio should be carefully evaluated before withholding antiplatelet therapy.

Role of magnetic susceptibility-weighted imaging in characterization of cerebral microbleeds in acute ischemic stroke Egyptian obese patients

ObjectiveThe study was done to investigate the role of susceptibility-weighted imaging (SWI) in characterization of cerebral microbleeds (CMBs) and incidence of CMBs in acute ischemic stroke obese patients.Materials and methodsWe recruited 120 acute ischemic stroke obese patients. All participants or their relatives gave written informed consent. MRI of the brain with SWI sequences was done for all patients.ResultsSWI showed 30% of the patients have CMBs. The total numbers of CMBs were statistically significant higher in small vessel diseases (SVDs) than large vessel diseases (LVDs) (P = 0.008). According to the severity scale, CMBs were more prominent in patients with grade 0 (70%) followed by grade III (25.8%) then grade II (4.2%). BMI was independent risk factors for developing CMBs as shown in simple regression analysis (х2 = 6.008, P = 0.002). SVDs and hypertension were statistically significant independent predictors and had higher odds to exhibit CMBs. Patients with SVDs had 5.3 times higher odds to exhibit CMBs (P = 0.002) while patients with hypertension had 3.9 times higher odds to exhibit CMBs (P = 0.032).ConclusionSWI is a gold standard MR imaging technique in diagnosis and characterization of CMBs with more prevalence especially in obese patients suffering from acute ischemia stroke due to SVDs. Hypertension was an independent risk factor for development of CMBs but IHD, use of antiplatelet medications, increased BMI, and dyslipidemia must be taken into consideration.

The relation between APOE genotype and cerebral microbleeds in cognitively unimpaired middle- and old-aged individuals

Positive associations between cerebral microbleeds (CMBs) and APOE-ε4 (apolipoprotein E) genotype have been reported in Alzheimer’s disease, but show conflicting results. We investigated the effect of APOE genotype on CMBs in a cohort of cognitively unimpaired middle- and old-aged individuals enriched for APOE-ε4 genotype. Participants from ALFA (Alzheimer and Families) cohort were included and their magnetic resonance scans assessed (n = 564, 50% APOE-ε4 carriers). Quantitative magnetic resonance analyses included visual ratings, atrophy measures, and white matter hyperintensity (WMH) segmentations. The prevalence of CMBs was 17%, increased with age (p < 0.05), and followed an increasing trend paralleling APOE-ε4 dose. The number of CMBs was significantly higher in APOE-ε4 homozygotes compared to heterozygotes and non-carriers (p < 0.05). This association was driven by lobar CMBs (p < 0.05). CMBs co-localized with WMH (p < 0.05). No associations between CMBs and APOE-ε2, gray matter volumes, and cognitive performance were found. Our results suggest that cerebral vessels of APOE-ε4 homozygous are more fragile, especially in lobar locations. Co-occurrence of CMBs and WMH suggests that such changes localize in areas with increased vascular vulnerability.

Association of Cerebral Microbleeds with Cognitive Decline: A Longitudinal Study.

The role of cerebral microbleeds (CMBs) in cognitive impairment remains controversial. To investigate the possible links between the presence, progression, number, and location of CMBs and cognition. We assessed 792 subjects from the Alzheimer's Disease Neuroimaging Initiative who underwent both brain 3 Tesla MRI scans and cognitive testing. The association between CMBs and cognitive change was explored using linear mixed-effects models (LME). Presence and number of CMBs were associated with memory (β= -0.03, p = 0.015; β= -0.01, p = 0.003), executive function (β= -0.04, p = 0.010; β= -0.01, p = 0.014), and global cognitive function (β= -0.06, p = 0.025; β= -0.03, p < 0.001). Progression of CMBs showed significant negative associations with executive function (β= -0.05, p = 0.025) and global cognitive function (β= -0.12, p = 0.015). The relations with cognitive performance (memory, executive function and global cognitive function) were mainly driven by lobar CMBs (β= -0.03, p = 0.041; β= -0.04, p = 0.010; β= -0.07, p = 0.029, respectively), especially those located in temporal lobe (β= -0.08, p = 0.027; β= -0.13, p = 0.001; β= -0.26, p < 0.001, respectively). Furthermore, white matter hyperintensities may mediate the association between CMBs and cognition. The presence, progression, number, and location of CMBs, especially those located in temporal lobe, are associated with cognitive decline. These findings suggest CMBs play a role in cognitive impairment.

Cerebral Microbleeds Are Associated with Cerebral Hypoperfusion in Patients with Alzheimer's Disease.

BACKGROUND Although cerebral microbleeds (CMBs) are commonly observed in patients with Alzheimer's disease (AD), their clinical relevance for AD remains unclear. OBJECTIVE We investigated the significance of CMBs in AD by examining the relationship between CMBs and cerebral blood flow (CBF) in patients with AD. METHODS Thirty-four patients (aged 77.9±7.6 years; 17 men) with probable AD and multiple (≥8) CMBs were selected from 394 consecutive patients. For each lobe of the brain, the correlation between the number of CMBs observed on susceptibility-weighted images and the decrease in CBF observed on single-photon emission computed tomography was assessed. RESULTS The number of microbleeds was significantly correlated with the severity of decrease in the occipital lobe (Spearman's r = 0.531, p < 0.001) and temporal lobe (r = 0.437, p < 0.001) but not in the frontal lobe (r = 0.201, p = 0.101) and parietal lobe (r = 0.178, p = 0.146). These results were unchanged in the partial correlational analysis after controlling the effect of other small vessel disease such as lacunars and white matter hyperintensities. CONCLUSION Multiple CMBs are associated with cerebral hypoperfusion in AD. The effects of CMBs on CBF differed according to brain location, possibly reflecting different distributions of the underlying cerebral amyloid angiopathy and AD-related histopathology, such as neurofibrillary tangles.

Plasma neurofilament light chain and glial fibrillary acidic protein predict stroke in CADASIL

BackgroundStroke remains the most cumbersome disease burden in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). This study aimed to investigate whether plasma biomarkers can reflect disease severity and predict stroke recurrence in CADASIL patients.MethodsSixty-three CADASIL patients (mean age 58.9 ± 9.3 years old, male 63%) from a multicenter registry and 17 controls were recruited. Plasma biomarkers, namely neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), tau, and ubiquitin carboxy-terminal hydrolase L1 (UCHL1), were measured using an ultra-sensitive single molecule array at baseline. Neuroimaging markers assessed included the Fazekas scale of white matter hyperintensity, numbers of lacunes, and cerebral microbleeds (CMBs). Cox proportional hazards regression models were applied to calculate the hazard ratio (HR) of plasma biomarkers at baseline for predicting incident stroke during follow-up.ResultsPlasma NfL, GFAP, and UCHL1 levels were significantly elevated in the CADASIL patients than in the controls. Among the CADASIL patients, both plasma NfL and GFAP levels positively correlated with the numbers of CMBs (r = 0.32 and r = 0.37, respectively; both p < 0.05). Higher plasma levels of NfL and GFAP were associated with any stroke (odds ratio 2.02, 95% confidence interval [CI] 1.06–3.87) and ICH (odds ratio 2.06, 95% CI 1.26–3.35) at baseline, respectively. Within a mean follow-up period of 3.1 ± 2.1 years, 10 patients (16%) had incident stroke and 6 of them were ICH. Higher baseline NfL (HR 1.93, 95% CI 1.19–3.13) predicted any incident stroke, whereas higher GFAP (HR 2.80, 95% CI 1.21–6.53) predicted incident ICH.ConclusionsIn CADASIL patients, plasma NfL can be a promising biomarker for monitoring incident stroke, whereas GFAP may have a role in cerebral hemorrhage.

Lower Coated-Platelet Levels, RANTES and Fibrinogen Correlate with the Number of Cerebral Microbleeds in Carotid Stenosis (2335)

Lower Coated-Platelet Levels, RANTES and Fibrinogen Correlate with the Number of Cerebral Microbleeds in Carotid Stenosis (2335)

Cerebral Microbleeds and Chronic Kidney Disease in Acute Ischemic Stroke Patients with Atrial Fibrillation

Background: Cerebral microbleeds (CMBs) are associated with the risk of intracerebral hemorrhage in stroke patients with atrial fibrillation (AF). We investigated the association between CMBs and chronic kidney disease (CKD) in patients with acute ischemic stroke and AF. Methods: We retrospectively examined consecutive patients with acute ischemic stroke and AF who underwent brain gradient-echo T2*-weighted magnetic resonance imaging. The number and distribution (lobar, deep or infratentorial, and mixed) of CMBs were assessed. Kidney function was assessed according to the estimated glomerular filtration rate (eGFR), which was calculated using a modified version of the Modification of Diet in Renal Disease equation. Results: Of the 357 included patients, 105 (29.4%) had CMBs. CKD (eGFR < 60 mL/min/1.73 m2) was found in 131 (36.7%) patients. Patients with CKD showed a higher prevalence of any form of CMB (41.2% versus 22.6%, P < .001), deep or infratentorial CMBs (19.9% versus 9.3%, P < .01), and mixed CMBs (14.5% versus 5.3%, P < .01) than those without CKD. After adjusting for age and other confounding factors, CKD was found to be independently associated with the presence of any form of CMB (odds ratio 1.89, P = .02) and mixed CMBs (odds ratio 3.10, P < .01). Moreover, moderate to severe CKD (eGFR < 45 mL/min/1.73 m2) was independently associated with the presence of multiple CMBs (odds ratio 2.31, P = .04). Conclusions: CMBs and CKD are common in acute ischemic stroke patients with AF, and CKD may be a risk factor for CMBs. Further longitudinal studies are needed to evaluate whether maintaining kidney function can prevent the development of CMBs.

Increased Presence of Cerebral Microbleeds Correlates With Ventricular Enlargement and Increased White Matter Hyperintensities in Alzheimer's Disease.

Objective: To investigate whether the number of cerebral microbleeds (CMB) could be a useful indicator to predict glymphatic system dysfunction in Alzheimer’s disease (AD) patients, by comparing the degree of cerebral spinal fluid (CSF) and interstitial fluid (ISF) stasis.Methods: Forty probable AD patients were included, with those exhibiting two or more CMB were included in the multiple CMB group (mCMB, n = 21, mean = 11.1), and none or one CMB included in the non-multiple CMB group (nmCMB, n = 19, mean = 0.84). CMB was defined in axial gradient recalled echo (GRE) T2*-weighted images. Evans index (EI) was calculated to measure lateral ventricle enlargement, Voxel-based Specific Regional Analysis System for Alzheimer’s Disease (VSRAD) software was used to determine the extent of gray and white matter atrophy, and Fazekas scale (FS) was used to determine white matter hyperintensities (WMH).Results: EI was significantly larger in mCMB than in nmCMB, while the gray and white matter volume was not different between groups. Thus, the difference in lateral ventricle enlargement between AD with and without multiple CMB reflects a combination of the degree of brain atrophy and the extent of CSF stasis. FS was higher in mCMB than in the nmCMB, suggesting the failure of ISF elimination was more severe in mCMB cases.Conclusion: The difference in lateral ventricle enlargement and WMH between AD with or without multiple CMB may reflect a difference in the degree of CSF/ISF stagnation.

Do cerebral microbleeds affect cognition in patients with symptomatic small vessel disease?

BackgroundDementia and cognitive impairment are becoming increasingly a major health problem, pronounced by increased life expectancy. Cerebral small vessel disease (cSVD) is among the major causes of cognitive deterioration, yet cerebral microbleeds (CMBs) which are a common association of cSVD are still not sure to be related to cognition.Aim of the studyThe study aims to determine whether the number and localization of CMBs correlate with cognition in patients with symptomatic small vessel disease (SVD), according to Montreal Cognitive Assessment (MoCA) test.Subjects and methodsThis cross-sectional study included 85 Egyptian patients with symptomatic SVD, from the neuropsychiatry clinic of the Main Suez Hospital in Suez City, in the period between February 2017 and February 2018. Subjects were classified according to CMB presence into CMB-positive and CMB-negative groups. Both groups are assessed using MRI imaging and MoCA test for cognitive function.ResultsIn our study, CMBs recorded a high prevalence rate of SVD patients. Subjects with MBs were mainly males and significantly older, with higher white matter lesion volume and more lacunar infarcts. MoCA test detected significant impairment in visuospatial/executive function, attention, and total scores in CMB-positive group. Both frontal and parietal MBs showed independent association with visuospatial/executive impairment. Deep MBs in the basal ganglia were proved to be independent risk factor for attention affection.ConclusionNumber and localization of MBs proved to be important in determining cognitive consequences. The relations with cognitive performance were mainly driven by frontal, parietal, and deep located MBs in the basal ganglia. Memory affection in frontal MBs was dependent to severe white matter intensities and lacunes.