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Objectives: Cerebral small vessel disease (SVD) is commonly observed among elderly individuals with cognitive impairment and has been recognized as a vascular contributor to dementia and behavioral and psychological symptoms (BPS), however, the relationship between BPS and SVD burden remains unclear., Methods: We prospectively recruited 42 patients with mild cognitive impairment (MCI) or mild dementia from the memory clinic in our hospital, who were assigned to either a clinical dementia rating (CDR) of 0.5 or 1.0, respectively. The presence of BPS was determined through interviews with caregivers. The patients underwent brain MRI and three types of SVD scores, total, cerebral amyloid angiopathy (CAA), and modified CAA, were assigned. Patients were also evaluated through various neuropsychological assessments., Results: The CDR was significantly higher in patients with BPS ( p  = 0.001). The use of antihypertensive agents was significantly higher in patients without BPS ( p  = 0.038). The time taken to complete trail making test set-A was also significantly longer in patients with BPS ( p  = 0.037). There was no significant difference in total SVD and CAA-SVD score ( p  = 0.745, and 0.096) and the modified CAA-SVD score was significantly higher in patients with BPS ( p  = 0.046). In addition, the number of total CMBs and lobar CMBs was significantly higher in patients with BPS ( p  = 0.001 and 0.001). Receiver operating characteristic curves for BPS showed that for modified CAA-SVD, a cutoff score of 3.5 showed 46.7% sensitivity and 81.5% specificity. Meanwhile, for the total number of cerebral microbleeds (CMBs), a cut-off score of 2.5 showed 80.0% sensitivity and 77.8% specificity and for the number of lobar CMBs, a cut-off score of 2.5 showed 73.3% sensitivity and 77.8% specificity., Conclusion: Overall, patients with BPS showed worse CDRs, reduced psychomotor speed, higher modified CAA-SVD scores, larger numbers of total and lobar CMBs. We propose that severe modified CAA scores and higher numbers of total and lobar CMBs are potential risk factors for BPS in patients with mild dementia or MCI. Therefore, by preventing these MRI lesions, the risk of BPS may be mitigated., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as potential conflicts of interest., (Copyright © 2023 Shinohara, Matsuda, Ii, Tabei, Nakamura, Hirata, Ishikawa, Matsuyama, Matsuura, Maeda, Tomimoto and Shindo.)

Background: To further our understanding of the pathophysiology of spontaneous intracerebral hemorrhage (ICH) and related injury, we provided a postmortem neuropathological examination of acute microvascular lesions (microbleeds and microinfarcts) within the perihematomal area., Methods: We included all consecutive cases (2005-2019) from the Lille University Hospital brain bank of ICH patients who died within the first month. Paraffin-embedded tissue sections from the perihematomal area were processed for several stainings and immunolabelings to investigate the presence of acute microbleeds and microinfarcts in the perihematomal area and to characterize surrounding neuronal and systemic inflammatory reaction (macrophages and neutrophils)., Results: We included 14 ICH cases (median age, 78 years; 10 females). Acute microbleeds were observed in the perihematomal area in 12/14 patients (86%, ranging from 1 through >10) and microinfarcts in 5/14 (36%, ranging from 1 through 4). Microbleeds were observed whatever the delay from ICH onset to death was, while most cases with acute microinfarcts were observed between day 3 and day 7 (n=3/5). Both lesions were characterized by an abundant accumulation of systemic inflammatory cells and necrotic areas., Conclusions: Acute microbleeds and microinfarcts might contribute to the propagation of secondary brain tissue damages after ICH. Our examinations also question the potential role of massive systemic inflammatory cells recruitment in the genesis of these microvascular injuries.

Cerebral amyloid angiopathy (CAA) is characterized by the accumulation of the amyloid β (Aβ) protein in blood vessels and leads to hemorrhages, strokes, and dementia in elderly individuals. Recent reports have shown elevated copper levels colocalized with vascular amyloid in human CAA and Alzheimer's disease patients, which have been suggested to contribute to cytotoxicity through the formation of reactive oxygen species. Here, we treated a transgenic rat model of CAA (rTg-DI) with the copper-specific chelator, tetrathiomolybdate (TTM), via intraperitoneal (IP) administration for 6 months to determine if it could lower copper content in vascular amyloid deposits and modify CAA pathology. Results showed that TTM treatment led to elevated Aβ load in the hippocampus of the rTg-DI rats and increased microbleeds in the wild type (WT) animals. X-ray fluorescence microscopy was performed to image the distribution of copper and revealed a surprising increase in copper colocalized with Aβ aggregates in TTM-treated rTg-DI rats. Unexpectedly, we also found an increase in the copper content in unaffected vessels of both rTg-DI and WT animals. These results show that IP administration of TTM was ineffective in removing copper from vascular Aβ aggregates in vivo and increased the development of disease pathology in CAA.

Background and purpose: Cerebral microbleeds (CMBs), cortical superficial siderosis, white matter lesions (WML), and cerebral atrophy may signify greater bleeding risk particularly in patients in whom anticoagulation is to be considered. We investigated their prevalence and associations with stroke type in patients with stroke and atrial fibrillation (AF). Materials and Methods: Cross-sectional sample, Monash Medical Centre (Melbourne, Australia) between 2010 and 2013, with brain MRI. MRI abnormalities were rated using standardized methods. Logistic regression was used to study associations adjusting for age and sex. results: There were 170 patients, mean age 78 years (SD 9.8), 154 (90.6%) with ischemic stroke. Prevalence of MRI markers were any microbleed 49%, multiple (>2) microbleeds 30%, confluent WMLs 18.8%, siderosis 8.9%, severe cerebral atrophy 37.7%. Combinations of the severe manifestations of these markers were much less prevalent (2.9-12.4%). Compared with ischemic stroke, those with hemorrhagic stroke were more likely to have >10 microbleeds (OR 5.50 95% CI 1.46-20.77, p = 0.012) and siderosis (OR 6.24, 95% CI 1.74-22.40, p = 0.005). Siderosis was associated with multiple microbleeds (OR 8.14, 95% CI 2.38-27.86, p = 0.001). Patients admitted with hemorrhagic stroke and multiple microbleeds were more frequently anticoagulated prior to stroke (6/7, 85.7%) than in those with single (1/2, 50%) or no microbleeds (4/7, 57%). conclusion: Multiple CMBs, severe WML, and severe cerebral atrophy were common individually in hospitalized patients with stroke and AF, but less so in combination. A higher burden of CMBs may be associated with intracerebral hemorrhage in stroke patients with AF. [ABSTRACT FROM AUTHOR]

Background: Long-term exposure to ambient air pollution has been associated with impaired cognitive function and vascular disease in older adults, but little is known about these associations among people with concerns about memory loss.Objective: To examine associations between exposures to fine particulate matter and residential proximity to major roads and markers of small vessel disease.Methods: From 2004-2010, 236 participants in the Massachusetts Alzheimer's Disease Research Center Longitudinal Cohort participated in neuroimaging studies. Residential proximity to major roads and estimated 2003 residential annual average of fine particulate air pollution (PM2.5) were linked to measures of brain parenchymal fraction (BPF), white matter hyperintensities (WMH), and cerebral microbleeds. Associations were modeled using linear and logistic regression and adjusted for clinical and lifestyle factors.Results: In this population (median age [interquartile range] = 74 [12], 57% female) living in a region with median 2003 PM2.5 annual average below the current Environmental Protection Agency (EPA) standard, there were no associations between living closer to a major roadway or for a 2μg/m3 increment in PM2.5 and smaller BPF, greater WMH volume, or a higher odds of microbleeds. However, a 2μg/m3 increment in PM2.5 was associated with -0.19 (95% Confidence Interval (CI): -0.37, -0.005) lower natural log-transformed WMH volume. Other associations had wide confidence intervals.Conclusions: In this population, where median 2003 estimated PM2.5 levels were below the current EPA standard, we observed no pattern of association between residential proximity to major roads or 2003 average PM2.5 and greater burden of small vessel disease or neurodegeneration. [ABSTRACT FROM AUTHOR]

Background: Decompressive hemicraniectomy (DhC) is a life-saving surgical procedure being increasingly employed for malignant middle cerebral artery strokes. We examined the incidence of hemorrhagic transformation following DhC.Methods: We retrospectively reviewed the charts and radiological images of patients who underwent DhC for malignant middle cerebral artery strokes. We classified the hemorrhagic events and assessed the short-term 30-day outcome associated with these events.Results: A total of 23 DhCs were performed for supratentorial ischemic strokes in 22 patients. There were 16 males and 6 females with an average age of 47 years (21-69 years). Of the 22 patients, 13 (59%) developed a new hemorrhage following DhC. There were 3 mortalities (14%). Of the survivors, 6 (27%) were discharged home with a modified Rankin Scale (mRS) score of 2. The remaining 13 patients (59%) recovered to a degree wherein they were discharged to a rehabilitation center (mRS score 3-4). No patient persisted in a vegetative or semivegetative state (mRS score 5).Conclusions: In this study, the rate of hemorrhagic transformation following DhC for ischemic stroke was 59%. This is much higher than that reported in the stroke thrombolysis literature. The presence of any type of new hemorrhagic transformation in this patient population does not appear to alter the natural history of their ischemic strokes in terms of Glasgow outcome scores or destination of disposition. [ABSTRACT FROM AUTHOR]

Goal: Cognitive impairment and dementia are common disabilities after stroke and are associated with increased risks of mortality and recurrent stroke. The prevention of dementia and preserving cognitive function are also important in stroke patients, but its strategy is not established yet. This PICASSO-COG (PreventIon of CArdiovascular events in iSchemic Stroke patients with high risk of cerebral hemOrrhage for reducing COGnitive decline) substudy aims to assess the effects of cilostazol and/or probucol on cognitive function.Materials and Methods: The substudy aims to assess the reduction in cognitive decline of patients treated with cilostazol and/or probucol in the PICASSO trial. Patients will be assessed using the Korean version of mini-mental state examination and Montreal Cognitive Assessment at 4, 7, 10, 13, 25, 37, and 49 months after randomization. The primary outcome is the change in mini-mental status examination score, compared between treatment groups, with a modified intention-to-treat population using a restricted maximum likelihood-based mixed effects model repeat measurement. This will allow a within-subject correlation due to repeated cognitive tests as well as a different number of measurements among subjects at baseline and each follow-up period.Conclusion: PICASSO-COG is a novel study for assessing the effect on cognitive function of different antiplatelet regimens and the addition of a nonstatin lipid-lowering agent to the current standard statin therapy in patients who have a recent ischemic lesion and prior intracerebral macro- or microbleeds. [ABSTRACT FROM AUTHOR]

We report three cases of traumatic microbleeds evaluated by sequential observation. Hypo-intensities on T2* gradient echo imaging (T2*GEI) appeared just 2-3 h after the injury (the hyper-acute period). However, these hypo-intensities on T2*GEI disappeared or became obscure 2-6 days after the injury (the subacute period). A follow-up MRI again revealed clear hypo-intensities on T2*GEI 1-3 months after the injury (the chronic period). Our cases indicate that hypo-intensities on T2*GEI might change dynamically from the hyper-acute to the chronic period. The differences of susceptibility effects by hematoma age might be the cause of this dynamic change. [ABSTRACT FROM AUTHOR]

Objective In multiple sclerosis (MS) lesions blood-brain-barrier (BBB) breakdown is a common phenomenon delineating the phase of focal inflammation in developing MS lesions. In other pathologies like cerebral amyloid angiopathy or arteriosclerotic cerebral small vessel disease permanent cerebral microbleeds (CMB) have been shown to be sensitive markers indicating BBB dysfunction. We were interested in the potential role of T 2 *-weighted MRI and CMBs as BBB integrity markers in MS. Methods A large cohort of 189 MS patients (179 relapsing remitting MS and 10 secondary progressive MS) was investigated on a 3 T MRI system with conventional and T 2 *-weighted gradient echo MRI (T 2 *w) sequences. T 2 *w images were analysed for CMBs by experienced raters. Results None of the MS patients showed a CMB. Conclusion On T 2 *w MRI the prevalence of CMBs is not higher in MS patients than what is to be expected in young healthy people. In contrast to pathologies with structural vascular changes like small vessel disease or cerebral amyloid angiopathy, CMBs are not seen in MS where the immune reaction is causing a functional change in the BBB. [ABSTRACT FROM AUTHOR]

Background: Homocysteine has been identified as a potential risk factor for stroke, cerebral small-vessel diseases (SVD), and dementia.Objective: The present study aimed to investigate the predictive value of homocysteine levels on incident dementia while simultaneously controlling for MRI findings and vascular risk factors.Methods: Within a Japanese cohort of participants with vascular risk factors in an observational study, we evaluated the association between baseline total homocysteine (tHcy) levels (per 1 μmol/L and the tertile of tHcy), the prevalence of MRI-findings at baseline, and incident all-cause dementia. Baseline brain MRI was used to determine SVD (lacunas, white matter hyperintensities, and cerebral microbleeds [CMBs]) and atrophy (medial-temporal lobe atrophy and bicaudate ratio). Logistic regression analyses were used to estimate the cross-sectional association between tHcy and each of MRI findings. Cox proportional hazards analyses were performed to estimate the longitudinal association between tHcy and dementia.Results: In the 643 subjects (age: 67.2 ± 8.4 years, male: 59% ; education: 12.9 ± 2.6 years), multivariable analyses adjusted for several potential confounders, including estimated glomerular filtration rate (eGFR) and intima-media thickness, showed that highest tHcy tertile was associated with lacunas, CMBs, and strictly deep CMBs. During the mean 7.3-year follow-up (range: 2-13), 47 patients were diagnosed with dementia (Alzheimer's disease: 24; vascular dementia: 18; mixed-type: 3; other: 2). After adjusting for age, gender, APOE ɛ4, education, BMI, MMSE, hypertension, cerebrovascular events, eGFR, and MRI-findings, tHcy level (hazard ratios [HR]: 1.08, p = 0.043) and the highest tertile of tHcy (HR: 2.50, p = 0.047) for all-cause dementia remained significant.Conclusions: Our results provide additional evidence of tHcy that contributes to increased susceptibility to dementia risk. [ABSTRACT FROM AUTHOR]

The apolipoprotein APOE4 allele confers greater risk of Alzheimer's disease (AD) for women than men, in conjunction with greater clinical deficits per unit of AD neuropathology (plaques, tangles). Cerebral microbleeds, which contribute to cognitive dysfunctions during AD, also show APOE4 excess, but sex-APOE allele interactions are not described. We report that elderly men diagnosed for mild cognitive impairment and AD showed a higher risk of cerebral cortex microbleeds with APOE4 allele dose effect in 2 clinical cohorts (ADNI and KIDS). Sex-APOE interactions were further analyzed in EFAD mice carrying human APOE alleles and familial AD genes (5XFAD+/-/human APOE+/+). At 7 months, E4FAD mice had cerebral cortex microbleeds with female excess, in contrast to humans. Cerebral amyloid angiopathy, plaques, and soluble Aβ also showed female excess. Both the cerebral microbleeds and cerebral amyloid angiopathy increased in proportion to individual Aβ load. In humans, the opposite sex bias of APOE4 allele for microbleeds versus the plaques and tangles is the first example of organ-specific, sex-linked APOE allele effects, and further shows AD as a uniquely human condition. [ABSTRACT FROM AUTHOR]

Matrix metalloproteinases (MMPs) are a family of enzymes able to degrade components of the extracellular matrix, which is important for normal blood-brain barrier function. Their function is regulated by tissue inhibitors of matrix metalloproteinases (TIMPs). We investigated whether MMPs and TIMPs in cerebrospinal fluid (CSF) and plasma were altered in Alzheimer's disease (AD) and vascular dementia (VaD), and whether this effect was modified by presence of cerebral micro-bleeds in AD patients. In addition, we assessed associations of MMPs and TIMPs with CSF amyloid-β(1-42) (Aβ42), tau, and tau phosphorylated at threonine-181 (p-tau). We measured MMP2, MMP9, and MMP10, and TIMP1 and TIMP2 in CSF and plasma of 52 AD patients, 26 matched controls, and 24 VaD patients. AD patients showed higher plasma MMP2 levels compared to VaD patients (p <  0.05), and higher CSF MMP10 levels compared to controls (p <  0.05). Microbleeds in AD were associated with lower CSF TIMP1, TIMP2 and MMP9 in a dose-response relation. In addition, CSF MMP2 was associated with p-tau (St.B 0.23, p <  0.05), and CSF MMP10 with tau (St.B 0.38, p <  0.001) and p-tau (St.B 0.40, p <  0.001). Our findings suggest involvement of MMP2 and MMP10 in AD pathology. Lower levels of TIMPs in AD patients with microbleeds suggest less MMP inhibition in patients with concurrent cerebral microbleeds, which may hypothetically lead to a more vulnerable blood-brain barrier in these patients. [ABSTRACT FROM AUTHOR]

Imaging plays an essential role in research on neurological diseases in the elderly. The Rotterdam Scan Study was initiated as part of the ongoing Rotterdam Study with the aim to elucidate the causes of neurological disease by performing imaging of the brain in a prospective population-based setting. Initially, in 1995 and 1999, random subsamples of participants from the Rotterdam Study underwent neuroimaging, whereas from 2005 onwards MRI has been implemented into the core protocol of the Rotterdam Study. In this paper, we discuss the background and rationale of the Rotterdam Scan Study. Moreover, we describe the imaging protocol, image post-processing techniques, and the main findings to date. Finally, we provide recommendations for future research, which will also be topics of investigation in the Rotterdam Scan Study. [ABSTRACT FROM AUTHOR]

Abstract.Cerebral microbleeds (microbleeds) are small, punctuate hypointense lesions seen in T2* Gradient-Recall Echo (GRE) and Susceptibility-Weighted (SWI) Magnetic Resonance Imaging (MRI) sequences, corresponding to areas of hemosiderin breakdown products from prior microscopic hemorrhages. They occur in the setting of impaired small vessel integrity, commonly due to either hypertensive vasculopathy or cerebral amyloid angiopathy. Microbleeds are more prevalent in individuals with Alzheimer’s disease dementia (AD) and in those with both ischemic and hemorrhagic stroke. However they are also found in asymptomatic individuals, with increasing prevalence with age, particularly in carriers of the Apolipoprotein (APOE) ε4 allele. Other neuroimaging findings that have been linked with microbleeds include lacunar infarcts and white matter hyperintensities on MRI, and increased cerebral β-amyloid burden using 11C-PiB Positron Emission Tomography (PET).The presence of microbleeds has been suggested to confer increased risk of incident intracerebral hemorrhage – particularly in the setting of anticoagulation – and of complications of immunotherapy for AD. Prospective data regarding the natural history and sequelae of microbleeds are currently limited, however there is a growing evidence base that will serve to inform clinical decision-making in the future.

Rationale Prior intracerebral haemorrhage and cerebral microbleeds may increase the risk of haemorrhagic stroke. However, the optimal long-term antiplatelet therapy and lipid management in these patients remain unclear. Aim Prevent Ion of CArdiovascular events in i Schemic Stroke patients with high risk of cerebral hem Orrhage was designed to compare cilostazol and aspirin and to assess the effect of adding probucol, a lipid-lowering and anti-oxidative agent, in patients at high risk of haemorrhagic stroke. Sample size estimate The projected sample size is 1600 patients with at least 12 months of follow-up. Methods and design Prevent Ion of CArdiovascular events in i Schemic Stroke patients with high risk of cerebral hem Orrhage is a randomized trial involving 67 institutes from 3 countries. Patients with non-cardioembolic ischemic stroke or transient ischemic attack within 180 days and with prior intracerebral haemorrhage or multiple cerebral microbleeds on gradient echo imaging are eligible. Enrolled patients are simultaneously randomized in a 2 × 2 factorial design: double-blind for cilostazol 200 mg/day vs. aspirin 100 mg/day, and an open-label, blind end-point evaluation for probucol 500 mg/day vs. non-probucol. Study outcomes The co-primary end-points are the safety end-point of haemorrhagic stroke and the efficacy end-point of a composite of stroke, myocardial infarction, or vascular death. Time-to-event will be analyzed separately for each intervention: superiority testing for the safety of cilostazol over aspirin as well as the efficacy of probucol over non-probucol, and non-inferiority testing for the efficacy of cilostazol to aspirin. Discussion Prevent Ion of CArdiovascular events in i Schemic Stroke patients with high risk of cerebral hem Orrhage is the largest secondary stroke prevention trial for informing antiplatelet therapy and lipid management in patients at high risk of haemorrhagic stroke. [ABSTRACT FROM AUTHOR]

Objective Cerebral hemorrhage has been shown to occur in animals experimentally infected with Streptococcus mutans carrying the collagen-binding Cnm gene. However, the relationship between cerebral microbleeds and oral hygiene, with a focus on Cnm gene-positive S. mutans infection, remains unclear. Material and Methods One hundred and thirty-nine subjects participated. The presence or absence of Cnm-positive S. mutans and its collagen-binding activity were investigated using saliva samples, and relationship with cerebral microbleeds detected on MRI investigated, including clinical information and oral parameters. Results Fifty-one subjects were identified as Cnm-positive S. mutans carriers (36.7%), with cerebral microbleeds being detected in 43 (30.9%). A significantly larger number of subjects carried Cnm-positive S. mutans in the cerebral microbleeds (+) group. S. mutans with Cnm collagen-binding ability was detected in 39 (28.1%) of all subjects, and the adjusted odds ratio for cerebral microbleeds in the Cnm-positive group was 14.4. Regarding the presence of cerebral microbleeds, no significant differences were noted in the number of remaining teeth, dental caries, or in classic arteriosclerosis risk factors. Conclusions The occurrence of cerebral microbleeds was higher in subjects carrying Cnm-positive S. mutans, indicating that the presence of Cnm-positive S. mutans increases cerebral microbleeds, and is an independent risk for the development of cerebrovascular disorders. [ABSTRACT FROM AUTHOR]

Background: Studies evaluating the association between coffee consumption and neurovascular diseases have frequently yielded contradictory results. The aim of this study was to investigate the association of coffee consumption with small-vessel disease (SVD) incidence in a healthy urban population while accounting for multiple demographic and lifestyle risk factors.Methods: This prospective study conducted from May 2013 through March 2014 included 455 participants (314 men and 141 women) aged 25 to 92 years. All subjects completed a questionnaire on coffee consumption and received a comprehensive neurologic examination, including magnetic resonance imaging, at St. Luke's International Hospital (Tokyo, Japan).Results: Incidence of SVD was lower in male daily coffee drinkers than male nondrinkers and occasional drinkers, whereas incidence of white matter lesions was lower in female daily coffee drinkers than female nondrinkers or occasional drinkers. In multivariate analyses including age, sex, smoking status, and BMI, as well as coffee consumption, incidence of microbleeds was significantly lower in male daily coffee drinkers compared to nondrinkers.Conclusions: Daily coffee consumption is associated with reduced risk of cerebral microbleeds in men. [ABSTRACT FROM AUTHOR]

Background Brain radiotherapy plays a central role in the treatment of certain types of childhood primary central nervous system tumors. However, damage to surrounding normal brain tissue causes different acute and chronic medical and neurological complications. Despite the expected increase in number of childhood primary central nervous system tumor survivors, studies assessing the occurrence of late cerebrovascular complications, such as cavernoma, moyamoya, microbleeds, superficial siderosis, and stroke are sparse. Methods We undertook a retrospective consecutive case series review describing the occurrence and characteristics of late cerebrovascular complications in 100 survivors of childhood primary central nervous system tumors treated with radiotherapy. Demographic, clinical, and radiological findings including gradient echo brain magnetic resonance data were retrieved. Results Late cerebrovascular complications were found in 36 (36%) of the patients included in the study. Mean age at radiotherapy was 8.6 years (3-17) and at diagnosis was 23.9 years (3-38). The majority were males (21; 58%). The most common complications were microbleeds (29/36; 80.6%) and cavernomas 19 (52.8%). In seven (19.4%), late cerebrovascular complications were symptomatic: epilepsy (two), motor and language deficit (two), and sensorineural hearing loss and progressive ataxia (three) associated with cavernomas, stroke, and superficial siderosis, respectively. Follow-up length was associated with an increased diagnosis of late cerebrovascular complications ( P < 0.0001). Late cerebrovascular complications occurred more commonly in children treated with whole-brain radiation therapy ( P = 0.046). Factors such as sex, chemotherapy, and histological type of tumor were not correlated with the occurrence of late cerebrovascular complications. Conclusion Although not usually symptomatic, late cerebrovascular complications occur frequently in survivors of childhood primary central nervous system tumors treated with radiotherapy. Prolonged follow-up increases the probability of diagnosis. The impact and prognostic value of these late cerebrovascular complications is yet to be clarified. [ABSTRACT FROM AUTHOR]

Background: We explored the association between cerebral microbleeds (CMBs) and cognitive impairment in patients with ischemic stroke/transient ischemic attack (TIA). Methods: A total of 488 ischemic stroke/TIA patients received magnetic resonance imaging. Montreal Cognitive Assessment (MoCA) was used to evaluate global cognitive function and cognitive domains. The association of CMB quantity with cognitive function and the impact of CMB locations (strictly lobar, strictly deep, and mixed regions) on cognitive impairment were examined in regression models with adjustments for confounders. Results: A total of 113 subjects (23.2%) had ≥1 CMB. Strictly lobar, strictly deep, and mixed CMBs were identified in 36, 40, and 37 patients, respectively. The presence of ≥5 CMBs or strictly deep CMBs was associated with the MoCA total score (p = 0.007 and 0.020, respectively). Of all MoCA domains tested, a lower score in the attention domain was related to the presence of ≥5 CMBs (p = 0.014) and strictly deep CMBs (p = 0.028). Conclusion: CMBs were associated with cognitive dysfunction in stroke/TIA patients, especially in the attention domain. This association was mainly driven by CMBs in the deep region, underlining the role of hypertensive microangiopathy in stroke-related cognitive impairment. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to implement and evaluate the utility of a multi-echo sequence at 7 Tesla (T) for simultaneous time-of-flight (TOF) MR-angiography (MRA) and susceptibility-weighted imaging (SWI) of radiation-induced cerebral microbleeds (CMBs), intracranial arteries, and veins. Methods: A four-echo gradient-echo sequence was implemented on a 7T scanner. The first echo was used to create TOF-MRA images, while the remaining echoes were combined to visualize CMBs and veins on SWI images. The sequence was evaluated on eight brain tumor patients with known radiation-induced CMBs. Single-echo images were also acquired to visually and quantitatively compare the contrast-to-noise ratio (CNR) of small- and intermediate-vessels between acquisitions. The number of CMBs detected with each acquisition was also quantified. Statistical significance was determined using a Wilcoxon signed-rank test. Results: Compared with the single-echo sequences, the CNR of small and intermediate arteries increased 7.6% (P < 0.03) and 9.5% (P = 0.06), respectively, while the CNR of small and intermediate veins were not statistically different between sequences (P = 0.95 and P = 0.46, respectively). However, these differences were not discernible by visual inspection. Also the multi-echo sequence detected 18.3% more CMBs (P < 0.008) due to higher slice resolution. Conclusion: The proposed 7T multi-echo sequence depicts arteries, veins, and CMBs on a single image to facilitate quantitative evaluation of radiation-induced vascular injury. [ABSTRACT FROM AUTHOR]

Background: Microbleeds in the brain have been shown to occur in Alzheimer's disease (AD), affecting approximately a third of subjects that present with typical dementia of the Alzheimer's type (DAT). However, little is known about the frequency or distribution of microbleeds in subjects with AD that present with atypical clinical presentations. Objective: To determine whether the frequency and regional distribution of microbleeds in atypical AD differs from that observed in subjects with DAT, and to determine whether microbleeds in atypical AD are associated with age, demographics, or cognitive impairment. Methods: Fifty-five subjects with amyloid-β deposition on Pittsburgh compound B (PiB) PET who presented with predominant language (n = 37) or visuospatial/perceptual (n = 18) deficits underwent T2*weighted MRI. These subjects were compared to 41 PiB-positive subjects with DAT. Microbleeds were identified and assigned a lobar location. Results: The proportion of subjects with microbleeds did not differ between atypical AD (42%) and DAT (32%). However, atypical AD had larger numbers of microbleeds than DAT. In addition, the topographic distribution of microbleeds differed between atypical AD and DAT, with atypical AD showing the highest density of microbleeds in the frontal lobes. Among atypical AD, number of microbleeds was associated with age, but not gender or cognition. Microbleeds were more common in subjects with language (51%) versus visuospatial/perceptual deficits (22%). Conclusions: Microbleeds are relatively common in both DAT and atypical AD, although atypical AD subjects appear to be at particular risk for developing large numbers of microbleeds and for developing microbleeds in the frontal lobe. [ABSTRACT FROM AUTHOR]

Objectives: CNS dengue infection is a rare condition and the pattern of brain involvement has not been well described. We report the MR imaging (MRI) features in eight cases of dengue encephalitis. Materials and methods: We retrospectively searched cases of dengue encephalitis in which imaging was performed. Eight cases (three men, five women; age range: 8-42 years) diagnosed with dengue encephalitis were included in the study. MR studies were performed on 3-T and 1.5-T MR clinical systems. Two neuroradiologists retrospectively reviewed the MR images and analysed the type of lesions, as well as their distribution and imaging features. Results: All eight cases exhibited MRI abnormalities and the cerebellum was involved in all cases. In addition, MRI signal changes were also noted in the brainstem, thalamus, basal ganglia, internal capsule, insula, mesial temporal lobe, and cortical and cerebral white matter. Areas of susceptibility, diffusion restriction, and patchy post-contrast enhancement were the salient imaging features in our cohort of cases. Conclusion: A pattern of symmetrical cerebellar involvement and presence of microbleeds/haemorrhage may serve as a useful imaging marker and may help in the diagnosis of dengue encephalitis. Key Points: • MR images of eight cases diagnosed with dengue encephalitis were retrospectively reviewed. • Symmetrical cerebellar involvement may serve as an imaging marker on MRI. • Presence of microbleeds/haemorrhage and diffusion restriction are other salient features. [ABSTRACT FROM AUTHOR]

Cerebral microbleeds (CMBs) have emerged as a new imaging marker of small vessel disease. Composed of hemosiderin, CMBs are paramagnetic and can be detected with MRI sequences sensitive to magnetic susceptibility (typically, gradient recalled echo T2* weighted images). Nevertheless, their identification remains challenging on T2* magnitude images because of confounding structures and lesions. In this context, T2* phase image may play a key role in better characterizing CMBs because of its direct relationship with local magnetic field variations due to magnetic susceptibility difference. To address this issue, susceptibility-based imaging techniques were proposed, such as Susceptibility Weighted Imaging (SWI) and Quantitative Susceptibility Mapping (QSM). But these techniques have not yet been validated for 2D clinical data in multicenter settings. Here, we introduce 2DHF, a fast 2D phase processing technique embedding both unwrapping and harmonic filtering designed for data acquired in 2D, even with slice-to-slice inconsistencies. This method results in internal field maps which reveal local field details due to magnetic inhomogeneity within the region of interest only. This technique is based on the physical properties of the induced magnetic field and should yield consistent results. A synthetic phantom was created for numerical simulations. It simulates paramagnetic and diamagnetic lesions within a ‘brain-like’ tissue, within a background. The method was evaluated on both this synthetic phantom and multicenter 2D datasets acquired in standardized clinical setting, and compared with two state-of-the-art methods. It proved to yield consistent results on synthetic images and to be applicable and robust on patient data. As a proof-of-concept, we finally illustrate that it is possible to find a magnetic signature of CMBs and CMCs on internal field maps generated with 2DHF on 2D clinical datasets that give consistent results with CT-scans in a subsample of 10 subjects acquired with both modalities. [ABSTRACT FROM AUTHOR]

Background T2*-weighted gradient echo magnetic resonance imaging is sensitive in detecting cerebral microbleeds (MBs), but there are few reports on the risk factors of MBs in different brain regions. Therefore, we aimed to investigate whether the risk factors associated with the presence of MBs in strictly deep or lobar brain regions were different. Methods This study consisted of 696 consecutive acute ischemic stroke patients from 6 hospitals in the Chinese IntraCranial AtheroSclerosis Study. We evaluated the number and location of MBs, severity of lacune and leukoaraiosis (LA), and etiologic subtype of ischemic stroke. Multivariable logistic regression was used to analyze risk factors of MBs in different brain regions. Results Among 696 acute ischemic stroke patients, 162 patients (23.3%) had MBs. Of them, 62 patients had strictly deep brain MBs, 49 patients had strictly lobar MBs. There was a significant correlation between the number of MBs, the number of lacune, and the severity of LA ( P < .0001). In multivariable logistic regression analysis, both strictly deep and strictly lobar brain, MBs were significantly associated with history of cerebral hemorrhage ( P = .037 and P = .026, respectively), presence of lacune ( P = .004 and P = .032, respectively), and severe LA ( P = .002 and P = .008, respectively). However, MBs in strictly deep regions were significantly associated with higher mean arterial pressure ( P = .030), and those in strictly lobar brain regions were significantly associated with older age ( P = .023). Conclusions The risk factors of MBs in strictly deep or lobar regions differ modestly, which may be related to heterogeneous vascular pathologic changes. [ABSTRACT FROM AUTHOR]

Background: Normal aging is associated with a decline in cognitive abilities, particularly in the domains of psychomotor speed and executive functioning. However, 'aging,' per se, is not a cause of cognitive decline but rather a variable that likely captures multiple accumulating biological changes over time that collectively affect mental abilities. Recent work has focused on the role of cerebrovascular disease as one of the biological changes. In the current study, we examined whether lobar microbleeds - magnetic resonance imaging (MRI) signal voids due to hemosiderin deposits secondary to cerebral amyloid angiopathy - are associated with cognitive decline in normal aging. Previous studies that reported a relationship between the presence of lobar microbleeds and decreased cognitive abilities have been primarily cross-sectional. Here, we used a retrospective longitudinal design to examine whether the presence of lobar microbleeds is associated with the rate of cognitive decline among non-demented older adults. Methods: Participants came from an ongoing longitudinal community-based aging study, in which subjects are evaluated at 18-24 months intervals and received a full medical, neurological, and neuropsychological examination at each of the follow-up visits. Gradient echo MRI scans were available on 197 non-demented participants (mean age: 84.15 ± 5.02 years). Microbleeds were rated visually on axial view and divided into subcortical (basal ganglia, cerebellum) and lobar (frontal, temporal, parietal, occipital lobe) regions, and confirmed with coronal and sagittal views to exclude artifacts. Cognition was assessed with a neuropsychological battery, providing summary scores for memory, language, executive, and visuospatial abilities. Using general estimating equations (GEE), we compared cognition cross-sectionally between individuals with 2 or more (n = 11) and fewer than 2 (n = 186) lobar microbleeds and examined longitudinal cognitive change beginning 9.47 ± 3.13 years before the MRI scan. Results: Subjects with 2 or more lobar microbleeds had worse executive functioning at the visit closest to the MRI scan (β = -0.044; p < 0.001)and had a faster decline in executive function over time (β = -0.072; p = 0.012) than subjects with fewer than 2 lobar microbleeds. The two groups were similar in age at scan date, education, ethnicity, sex distribution, and cognitive performance at first visit. Conclusions: Lobar microbleeds, a marker of cerebral amyloid angiopathy, are associated with an accelerated rate of executive function decline. The presence of cerebral amyloid angiopathy may be an important source of cognitive decline in aging. Future work should examine how cerebral amyloid angiopathy interacts with neurodegenerative processes, such as Alzheimer's disease. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background and purpose: Cardiac myxoma is a rare etiology of stroke. Both cerebral microbleeds and cardiac myxoma may increase the risk of intracerebral hemorrhage after intravenous (IV) thrombolysis. However, data are still limited.We report a case of multiple cerebral microbleeds treated with IV thrombolysis with later findings of cardiac myxoma. Summary of case: A 58-year-old-man presented with right-sided hemiplegia and global aphasia. The presumptive diagnosis of acute left middle cerebral artery (MCA) infarction was made. Previous magnetic resonance imaging showed multiple cerebral microbleeds. The patient received IV thrombolysis. Bilateral cerebellar hemorrhage occurred after thrombolysis, and a median suboccipital craniectomy and hematoma removal was performed. Transthoracic echocardiogram found a left atrial myxoma. The tumor was then surgically removed. Six months later, neurological deficit improved. Conclusion: Cerebral microbleeds may be associated with atrial myxoma. IV thrombolysis could benefit acute ischemic stroke patients with both baseline cerebral microbleeds and atrial myxoma. [ABSTRACT FROM AUTHOR]

Susceptibility-weighted and gradient-recalled echo T2* magnetic resonance imaging have enabled the detection of very small foci of blood within the brain, which have been termed "cerebral microbleeds." These petechial intraparenchymal hemorrhages have begun to emerge as diagnostically and prognostically useful markers in a variety of disease states. Severe hypertension and cerebral amyloid angiopathy are perhaps the best established microhemorrhagic conditions from neuroimaging literature; however, many others are also recognized including cerebral autosomal dominant arteriopathy, subcortical infarcts, and leukoencephalopathy (CADASIL), moyamoya disease, fat embolism, cerebral malaria, and infective endocarditis. Microbleeds are also a common finding in the setting of trauma and stroke. The purpose of this review is to broadly describe the neuroimaging of cerebral microbleeds in a wide variety of conditions, including the differences in their appearance and distribution in different disease states. In a few situations, the presence of microbleeds may influence clinical management, and we discuss these situations in detail. The major importance of this emerging field in neuroimaging is the potential to identify microvascular pathology at an asymptomatic or minimally symptomatic stage and create a window of therapeutic opportunity. [ABSTRACT FROM AUTHOR]

Background and Purpose: Sex differences in cerebral microbleeds (CMBs) are not well-known. We aimed to assess the impact of sex on the progression of CMBs., Methods: The CHALLENGE (Comparison Study of Cilostazol and Aspirin on Changes in Volume of Cerebral Small Vessel Disease White Matter Changes) database was analyzed. Out of 256 subjects, 189 participants with a follow-up brain scan were included in the analysis. The linear mixed-effect model was used to compare the 2-year changes in the number of CMBs between men and women., Results: A total of 65 men and 124 women were analyzed. There were no significant differences in the prevalence (70.8 vs. 71.8%; P = 1.000) and the median [interquartile range (IQR)] number of total CMBs [1 (0-7) vs. 2 (0-7); P = 0.810] at baseline between men and women. The median (IQR) increase over 2 years in the number of CMBs was statistically higher in women than in men [1 (0-2) vs. 0 (0-1), P = 0.026]. The multivariate linear mixed-effects model showed that women had a significantly greater increase in the number of total, deep, and lobar CMBs compared to men after adjusting for age and the baseline number of CMBs [estimated log-transformed mean of difference between women and men: 0.040 ( P = 0.028) for total CMBs, 0.037 ( P = 0.047) for deep CMBs, and 0.047 ( P = 0.009) for lobar CMBs]., Conclusion: The progression of CMB over 2 years was significantly greater in women than in men., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yoon, Rha, Park, Park, Kwon, Kim, Youn, Jeong, Han and Choi.)

Background: 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., Methods: 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 3 days of admission. The association between CMBs and cognitive function as well as clinical characteristics was explored., Results: 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)., Conclusions: 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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Xie, Zhuang, Zhang and Liu.)

Background: Limited data exist regarding the prevalence of clinical, neuroimaging, and genetic markers among patients diagnosed with Cerebral Amyloid Angiopathy−related inflammation (CAA-ri). We sought to determine these characteristics in patients diagnosed in our center and to summarize available literature published either as single-case reports or small case series (<5 patients). Methods: We reported our single-center experience of patients diagnosed with CAA-ri according to international criteria during a seven-year period (2015−2022), and we abstracted data from 90 previously published cases. Results: Seven patients (43% women, mean age 70 ± 13 years) were diagnosed with CAA-ri in our center. The most common symptom at presentation was focal neurological dysfunction (71%), and the most prevalent radiological finding was the presence of T2/FLAIR white matter hyperintensities (100%). All patients were treated with corticosteroids and had a favorable functional outcome. Among 90 previously published CAA-ri cases (51% women, mean age 70 ± 9 years), focal neurological dysfunction was the most common symptom (76%), followed by a cognitive decline (46%) and headache (34%). The most prevalent neuroimaging findings were cerebral microbleeds (85%), asymmetric T2/FLAIR white matter hyperintensities (81%), and gadolinium-enhancing T1-lesions (37%). Genetic testing for the Apolipoprotein-E gene was available in 27 cases; 59% carried the APOE ε4/ε4 genotype. The majority of the published CAA-ri cases (78%) received corticosteroid monotherapy, while 17 patients (19%) were treated with additional immunosuppressive treatment. Favorable functional outcome following treatment was documented in 70% of patients. Conclusion: Improving the vigilance of clinicians regarding the early recognition and accurate diagnosis of CAA-ri is crucial for swift therapy initiation, which may result in improved functional outcomes.