Background and Purpose — We investigated whether patients with transient ischemic attack (TIA) have systemic low flow to the brain or an abnormal intracranial flow distribution caused by an abnormal anatomy of the circle of Willis.... more
Background and Purpose — We investigated whether patients with transient ischemic attack (TIA) have systemic low flow to the brain or an abnormal intracranial flow distribution caused by an abnormal anatomy of the circle of Willis. Furthermore, we investigated whether metabolic changes were present in the brain. Methods — Forty-four patients with clinically diagnosed TIA were prospectively included in our study. Clinical and neurological data were compiled. MR imaging; quantitative flow measurements of the internal carotid, middle cerebral, and basilar arteries; MR angiography of the circle of Willis; and 1 H-MR spectroscopy were performed in all patients within 3 days of onset of symptoms. Results — Compared with control subjects, TIA patients did not have altered flow volume in any of the arteries and had normal flow distribution through the circle of Willis. In TIA patients, the N -acetylaspartate (NAA)/choline ratio in noninfarcted regions was significantly decreased in the symp...
Research Interests: Cardiology, Hydrogen, Magnetic Resonance Spectroscopy, Medicine, Brain, and 15 moreHumans, Internal Medicine, Hemodynamics, Female, Male, Clinical Sciences, Aged, Middle Aged, Adult, Asymptomatic, Choline, Lactic Acid, Magnetic resonance angiography, Cardiovascular medicine and haematology, and cerebral arteries
Research Interests:
Research Interests: Neurology, Pediatrics, Medicine, Humans, Mutation, and 8 moreNeuroradiology, Female, Male, Clinical Sciences, Aged, Middle Aged, CADASIL, and Neurosciences
Research Interests:
Research Interests: Psychology, Magnetic Resonance Imaging, Medicine, Humans, Ultrasonography, and 11 moreFemale, Male, Newborn Infant, White matter, Reproducibility of Results, Gestational Age, Intraventricular Hemorrhage, Predictive value of tests, Medical and Health Sciences, Intracranial hemorrhages, and Infant Premature
Research Interests: Chemistry, Magnetic Resonance Imaging, Magnetic Resonance Spectroscopy, Adolescent, Hepatology, and 15 moreBiopsy, Liver diseases, Humans, Liver, Fibrosis, Clinical Sciences, Aged, Adult, Analysis of Variance, Degeneration, Cirrhosis, Liver Disease, Aspartate Aminotransferases, Case Control Studies, and Medical biochemistry and metabolomics
Research Interests:
Research Interests:
Research Interests:
Research Interests:
To better understand the pathogenesis of focal and segmental glomerular hyalinosis and sclerosis (FSGHS), a variety of animal models have been developed--mainly in rats--that allow a comprehensive study of all variables involved, such as... more
To better understand the pathogenesis of focal and segmental glomerular hyalinosis and sclerosis (FSGHS), a variety of animal models have been developed--mainly in rats--that allow a comprehensive study of all variables involved, such as hemodynamic, genetic, and metabolic factors. In this article, we briefly review the role of lipids in the pathogenesis of FSGHS and provide evidence that "atherosclerosis of the glomerular mesangium" contributes to the ultimate histopathologic lesion of FSGHS in susceptible rat strains. Observations in a FSGHS-resistant strain revealed several characteristic features that may protect these rats against chronic renal disease such as high nephron numbers, glomerular visceral epithelial cells with a remarkable resistance to toxic injury, minimal sequestration of serum proteins and cholesterol from the circulation into the mesangium, and a remarkable lipoprotein profile in normal as well as nephrotic states with a very low cholesterol content ...
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests: Neuroscience, Psychology, Magnetic Resonance Imaging, Medicine, Nucleus Accumbens, and 15 moreBrain Mapping, Brain, Humans, Blood Pressure, Functional Magnetic Resonance Imaging, Functional Imaging, Male, Heart rate, Adult, Backward Masking, Choice Behavior, photic stimulation, Psychology and Cognitive Sciences, hydrocortisone, and Medical and Health Sciences
Research Interests: Computer Science, Algorithms, Magnetic Resonance Imaging, MRI, Medicine, and 15 moreBrain Mapping, Brain, Humans, Injury, Intervention, Female, Images, Classification, Male, Pediatric, Preterm infants, Magnetic resonance image, Premature infants, Automatic segmentation, and Paediatrics and reproductive medicine
Research Interests: Chemistry, Magnetic Resonance Imaging, Kidney transplantation, Magnetic Resonance Spectroscopy, Adolescent, and 15 moreMedicine, Phosphorus, Humans, Child, Kidney, Clinical Sciences, Aged, Middle Aged, Adult, Group, Phosphates, Sensitivity and Specificity, High energy, Adenosine monophosphate, and In Vitro Techniques
The structural correlates of impaired cognition in type 2 diabetes are unclear. The present study compared cognition and brain magnetic resonance imaging (MRI) between type 2 diabetic patients and nondiabetic control subjects and assessed... more
The structural correlates of impaired cognition in type 2 diabetes are unclear. The present study compared cognition and brain magnetic resonance imaging (MRI) between type 2 diabetic patients and nondiabetic control subjects and assessed the relationship between cognition and MRI findings and blood pressure and metabolic control. The study included 113 patients and 51 control subjects. Brain MRI scans were rated for white matter lesions (WMLs), cortical and subcortical atrophy, and infarcts. Neuropsychological test scores were divided into five cognitive domains and expressed as standardized Z values. Type 2 diabetes was associated with deep WMLs (P = 0.02), cortical (P < 0.001) and subcortical (P < 0.05) atrophy, (silent) infarcts (P = 0.06), and impaired cognitive performance (attention and executive function, information-processing speed, and memory, all P < 0.05). Adjustment for hypertension did not affect the results. Within the type 2 diabetic group, cognitive functi...
Research Interests: Cognition, Diabetes, Magnetic Resonance Imaging, Biology, Medicine, and 15 moreExecutive Function, Information Processing, Brain, Humans, Cerebral Cortex, Blood Pressure, Cognitive Performance, Brain atrophy, Aged, Cognitive impairment, Atrophy, Cognitive Function, Cognition disorders, Magnetic resonance image, and Medical and Health Sciences
Research Interests: Immunology, Rheumatoid Arthritis, Medicine, Humans, Basement Membrane, and 10 moreFemale, Leflunomide, Clinical Sciences, Middle Aged, Immunocompromised host, Public health systems and services research, Glomerular Basement Membrane, Immunosuppressive Agents, renal insufficiency, and Kidney glomerulus
Research Interests:
Research Interests:
Research Interests: Magnetic Resonance Imaging, Aging, Positron Emission Tomography, Medicine, Multidisciplinary, and 15 moreBrain, Humans, Female, Male, Flow measurement, PLoS one, Aged, Middle Aged, Atrophy, Multivariate Regression, MR Angiography, Cerebral Blood Flow, Magnetic resonance angiography, Phase Contrast, and Carotid Arteries
Research Interests:
Research Interests:
We aimed to investigate the cross-sectional and longitudinal associations of electrocardiogram (ECG)-based QT, QTc, JT, JTc, and QRS intervals with cognitive function and brain magnetic resonance imaging (MRI) measurements in a cohort of... more
We aimed to investigate the cross-sectional and longitudinal associations of electrocardiogram (ECG)-based QT, QTc, JT, JTc, and QRS intervals with cognitive function and brain magnetic resonance imaging (MRI) measurements in a cohort of older individuals at increased risk for cardiovascular disease, but free of known arrhythmias. We studied 4627 participants (54% female, mean age 75 years) enrolled in the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER). Ten-second ECGs were conducted at baseline. Cognitive function was tested at baseline and repeated during a mean follow-up time of 3.2 years. Structural MRIs were conducted in a subgroup of 535 participants. Analyses were performed with multivariable (repeated) linear regression models and adjusted for cardiovascular risk-factors, co-morbidities, and cardiovascular drug use. At baseline, longer QT, JT, JTc—but not QTc and QRS intervals—were associated with a worse cognitive performance. Most notably, on the Stroop ...
Research Interests:
Research Interests:
Excessive consumption of sugar-sweetened beverages (SSBs) has been associated with obesity and related diseases. SSBs are often consumed cold, and both the energy content and temperature might influence the consumption behavior for SSBs.... more
Excessive consumption of sugar-sweetened beverages (SSBs) has been associated with obesity and related diseases. SSBs are often consumed cold, and both the energy content and temperature might influence the consumption behavior for SSBs. The main aim of this study was to elucidate whether consumption temperature and energy (i.e., glucose) content modulate homeostatic (hypothalamus) and reward [ventral tegmental area (VTA)] responses. Sixteen healthy men participated in our study [aged 18-25 y; body mass index (kg/m2): 20-23]. High-resolution functional magnetic resonance imaging data were collected after ingestion of 4 different study stimuli: plain tap water at room temperature (22°C), plain tap water at 0°C, a glucose-containing beverage (75 g glucose dissolved in 300 mL water) at 22°C, and a similar glucose drink at 0°C. Blood oxygen level-dependent (BOLD) changes from baseline (7 min preingestion) were analyzed over time in the hypothalamus and VTA for individual stimulus effect...
Research Interests:
Overlapping clinical symptoms often complicate differential diagnosis between patients with Alzheimer's disease (AD) and behavioral variant frontotemporal dementia (bvFTD). Magnetic resonance imaging (MRI) reveals disease specific... more
Overlapping clinical symptoms often complicate differential diagnosis between patients with Alzheimer's disease (AD) and behavioral variant frontotemporal dementia (bvFTD). Magnetic resonance imaging (MRI) reveals disease specific structural and functional differences that aid in differentiating AD from bvFTD patients. However, the benefit of combining structural and functional connectivity measures to-on a subject-basis-differentiate these dementia-types is not yet known. Anatomical, diffusion tensor (DTI), and resting-state functional MRI (rs-fMRI) of 30 patients with early stage AD, 23 with bvFTD, and 35 control subjects were collected and used to calculate measures of structural and functional tissue status. All measures were used separately or selectively combined as predictors for training an elastic net regression classifier. Each classifier's ability to accurately distinguish dementia-types was quantified by calculating the area under the receiver operating character...
Research Interests:
The volume of the lateral ventricles (LV) increases with age and their abnormal enlargement is a key feature of several neurological and psychiatric diseases. Although lateral ventricular volume is heritable, a comprehensive investigation... more
The volume of the lateral ventricles (LV) increases with age and their abnormal enlargement is a key feature of several neurological and psychiatric diseases. Although lateral ventricular volume is heritable, a comprehensive investigation of its genetic determinants is lacking. In this meta-analysis of genome-wide association studies of 23,533 healthy middle-aged to elderly individuals from 26 population-based cohorts, we identify 7 genetic loci associated with LV volume. These loci map to chromosomes 3q28, 7p22.3, 10p12.31, 11q23.1, 12q23.3, 16q24.2, and 22q13.1 and implicate pathways related to tau pathology, S1P signaling, and cytoskeleton organization. We also report a significant genetic overlap between the thalamus and LV volumes (ρ = -0.59, p-value = 3.14 × 10), suggesting that these brain structures may share a common biology. These genetic associations of LV volume provide insights into brain morphology.
Research Interests:
Magnetic resonance imaging visible perivascular spaces in the centrum semiovale (CSO-PVS) have been associated with cerebral amyloid angiopathy (CAA).We aimed to further confirm this link by evaluating CSO-PVS volume in... more
Magnetic resonance imaging visible perivascular spaces in the centrum semiovale (CSO-PVS) have been associated with cerebral amyloid angiopathy (CAA).We aimed to further confirm this link by evaluating CSO-PVS volume in pathologically-demonstrated sporadic and genetically-demonstrated hereditary forms of the disease. We studied a retrospective hospital-based cohort consisting of 63 individuals aged >55 having brain magnetic resonance imaging and pathological assessment of CAA (mean age, 73.6±8.5; 46% female), and a separate cohort consisting of 26 carriers, and 28 noncarriers of the hereditary cerebral hemorrhage with amyloidosis-Dutch type (mean age, 46.7±12.8; 61.1% female). CSO-PVS volume was quantified on a single magnetic resonance imaging slice using a computer-assisted segmentation method and expressed as the relative volume of the intracranial volume in that particular slice (CSO-PVS relative volume). We compared CSO-PVS relative volume (1) between subjects with and witho...
Research Interests:
The aim of the present study is to explore whether using 7 Tesla magnetic resonance imaging, additional brain changes can be observed in hereditary cerebral hemorrhage with amyloidosis-Dutch type (HCHWA-D) patients as compared with the... more
The aim of the present study is to explore whether using 7 Tesla magnetic resonance imaging, additional brain changes can be observed in hereditary cerebral hemorrhage with amyloidosis-Dutch type (HCHWA-D) patients as compared with the established magnetic resonance imaging features of sporadic cerebral amyloid angiopathy. The local institutional review board approved this prospective cohort study. In all cases, informed consent was obtained. This prospective parallel cohort study was conducted between 2012 and 2014. We performed T*-weighted magnetic resonance imaging performed at 7 Tesla in presymptomatic mutation carriers (n=11, mean age 35±12 years), symptomatic HCHWA-D patients (n=15, mean age 45±14 years), and in control subjects (n=29, mean age 45±14 years). Images were analyzed for the presence of changes that have not been reported before in sporadic cerebral amyloid angiopathy and HCHWA-D. Innovative observations comprised intragyral hemorrhaging and cortical changes. The p...
Research Interests:
Cytosine-adenine-guanine (CAG) repeat expansions in the coding regions of nine polyglutamine (polyQ) genes (HTT, ATXN1, ATXN2, ATXN3, CACNA1A, ATXN7, ATN1, AR, and TBP) are the cause of several neurodegenerative diseases including... more
Cytosine-adenine-guanine (CAG) repeat expansions in the coding regions of nine polyglutamine (polyQ) genes (HTT, ATXN1, ATXN2, ATXN3, CACNA1A, ATXN7, ATN1, AR, and TBP) are the cause of several neurodegenerative diseases including Huntington's disease (HD), six different spinocerebellar ataxias (SCAs), dentatorubral-pallidoluysian atrophy, and spinobulbar muscular atrophy. The expanded CAG repeat length in the causative gene is negatively related to the age-at-onset (AAO) of clinical symptoms. In addition to the expanded CAG repeat length in the causative gene, the normal CAG repeats in the other polyQ genes can affect the AAO, suggesting functional interactions between the polyQ genes. However, there is no detailed assessment of the relationships among polyQ genes in pathologically relevant brain regions. We used gene co-expression analysis to study the functional relationships among polyQ genes in different brain regions using the Allen Human Brain Atlas (AHBA), a spatial map ...
Research Interests:
Alzheimer's disease (AD) patients show altered patterns of functional connectivity (FC) on resting state functional magnetic resonance imaging (RSfMRI) scans. It is yet unclear which RSfMRI measures are most informative for the... more
Alzheimer's disease (AD) patients show altered patterns of functional connectivity (FC) on resting state functional magnetic resonance imaging (RSfMRI) scans. It is yet unclear which RSfMRI measures are most informative for the individual classification of AD patients. We investigated this using RSfMRI scans from 77 AD patients (MMSE = 20.4 ± 4.5) and 173 controls (MMSE = 27.5 ± 1.8). We calculated i) FC matrices between resting state components as obtained with independent component analysis (ICA), ii) the dynamics of these FC matrices using a sliding window approach, iii) the graph properties (e.g., connection degree, and clustering coefficient) of the FC matrices, and iv) we distinguished five FC states and administered how long each subject resided in each of these five states. Furthermore, for each voxel we calculated v) FC with 10 resting state networks using dual regression, vi) FC with the hippocampus, vii) eigenvector centrality, and viii) the amplitude of low frequency...
Research Interests:
Research Interests: Psychology and Medicine
Previous work suggests that impairments of cerebrovascular flow or reactivity might be early markers of cerebral amyloid angiopathy (CAA). Hereditary cerebral haemorrhage with amyloidosis-Dutch type (HCHWA-D) is a genetic form of CAA that... more
Previous work suggests that impairments of cerebrovascular flow or reactivity might be early markers of cerebral amyloid angiopathy (CAA). Hereditary cerebral haemorrhage with amyloidosis-Dutch type (HCHWA-D) is a genetic form of CAA that can be diagnosed before the onset of clinical symptoms by DNA testing. We aimed to investigate whether haemodynamic measures are decreased in presymptomatic and symptomatic HCHWA-D mutation carriers compared with healthy controls. In this case-control study, we included presymptomatic and symptomatic HCHWA-D mutation carriers diagnosed through genetic testing and recruited through the HCHWA-D patient association (Katwijk, Netherlands) and the outpatient clinic of the Department of Neurology of the Leiden University Medical Center (Leiden, Netherlands), and healthy controls. We measured regional cerebral blood flow (rCBF) using pseudo-continuous arterial spin labelling. Quantitative flow was measured by phase-contrast magnetic resonance angiography ...
Research Interests:
Research Interests:
The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common... more
The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for…
Research Interests:
Early markers for cerebral amyloid angiopathy are largely unknown. We aimed to identify which magnetic resonance imaging (MRI) (performed at 7 and 3T) and cognitive markers are an early sign in (pre) symptomatic subjects with hereditary... more
Early markers for cerebral amyloid angiopathy are largely unknown. We aimed to identify which magnetic resonance imaging (MRI) (performed at 7 and 3T) and cognitive markers are an early sign in (pre) symptomatic subjects with hereditary cerebral hemorrhage with amyloidosis-Dutch type. Twenty-seven DNA-proven Dutch-type mutation carriers (15 symptomatic and 12 presymptomatic) (mean age of 45.9 years) and 33 controls (mean age of 45.6 years) were included. 7T and 3T MRI was performed, cerebral amyloid angiopathy and small-vessel disease type MRI markers were estimated, and cognitive performance was assessed. Univariate general linear modeling analysis was used to assess the association between MRI markers and cognitive performance on the one hand and on the other, mutation status, adjusted for age, sex, and education. In symptomatic patients, all established cerebral amyloid angiopathy MRI markers (microbleeds, intracerebral hemorrhages, subarachnoid hemorrhages, superficial siderosis...
Research Interests:
Objective:To investigate CSF biomarkers in presymptomatic and symptomatic mutation carriers with hereditary cerebral hemorrhage with amyloidosis–Dutch type (HCHWA-D), a model for sporadic cerebral amyloid angiopathy, and to determine the... more
Objective:To investigate CSF biomarkers in presymptomatic and symptomatic mutation carriers with hereditary cerebral hemorrhage with amyloidosis–Dutch type (HCHWA-D), a model for sporadic cerebral amyloid angiopathy, and to determine the earliest deposited form of β-amyloid (Aβ).Methods:HCHWA-D mutation carriers and controls were enrolled in the cross-sectional EDAN (Early Diagnosis of Amyloid Angiopathy Network) study. The HCHWA-D group was divided into symptomatic carriers with a previous intracerebral hemorrhage and presymptomatic carriers. CSF concentrations of Aβ40, Aβ42, total tau, and phosphorylated tau181 proteins were compared to those of controls of a similar age. Correlations between CSF biomarkers, MRI markers, and age were investigated with multivariate linear regression analyses.Results:We included 10 symptomatic patients with HCHWA-D (mean age 55 ± 6 years), 5 presymptomatic HCHWA-D carriers (mean age 36 ± 13 years), 31 controls <50 years old (mean age 31 ± 7 years...
Research Interests:
Research Interests:
Recently, cerebral structural covariance networks (SCNs) have been shown to partially overlap with functional networks. However, although for some of these SCNs a strong association with age is reported, less is known about the... more
Recently, cerebral structural covariance networks (SCNs) have been shown to partially overlap with functional networks. However, although for some of these SCNs a strong association with age is reported, less is known about the association of individual SCNs with separate cognition domains and the potential mediation effect in this of cerebral small vessel disease (SVD). In 219 participants (aged 75-96 years) with mild cognitive deficits, 8 SCNs were defined based on structural covariance of gray matter intensity with independent component analysis on 3DT1-weighted magnetic resonance imaging (MRI). Features of SVD included volume of white matter hyperintensities (WMH), lacunar infarcts, and microbleeds. Associations with SCNs were examined with multiple linear regression analyses, adjusted for age and/or gender. In addition to higher age, which was associated with decreased expression of subcortical, premotor, temporal, and occipital-precuneus networks, the presence of SVD and especially higher WMH volume was associated with a decreased expression in the occipital, cerebellar, subcortical, and anterior cingulate network. The temporal network was associated with memory (p = 0.005), whereas the cerebellar-occipital and occipital-precuneus networks were associated with psychomotor speed (p = 0.002 and p &lt; 0.001). Our data show that a decreased expression of specific networks, including the temporal and occipital lobe and cerebellum, was related to decreased cognitive functioning, independently of age and SVD. This indicates the potential of SCNs in substantiating cognitive functioning in older persons.
Research Interests:
Intracranial volume reflects the maximally attained brain size during development, and remains stable with loss of tissue in late life. It is highly heritable, but the underlying genes remain largely undetermined. In a genome-wide... more
Intracranial volume reflects the maximally attained brain size during development, and remains stable with loss of tissue in late life. It is highly heritable, but the underlying genes remain largely undetermined. In a genome-wide association study of 32,438 adults, we discovered five previously unknown loci for intracranial volume and confirmed two known signals. Four of the loci were also associated with adult human stature, but these remained associated with intracranial volume after adjusting for height. We found a high genetic correlation with child head circumference (ρgenetic = 0.748), which indicates a similar genetic background and allowed us to identify four additional loci through meta-analysis (Ncombined = 37,345). Variants for intracranial volume were also related to childhood and adult cognitive function, and…
Research Interests:
Research Interests:
Accumulation of brain iron has been suggested as a biomarker of neurodegeneration. Increased iron has been seen in the cerebral cortex in postmortem studies of neurodegenerative diseases and healthy aging. Until recently, the diminutive... more
Accumulation of brain iron has been suggested as a biomarker of neurodegeneration. Increased iron has been seen in the cerebral cortex in postmortem studies of neurodegenerative diseases and healthy aging. Until recently, the diminutive thickness of the cortex and its relatively low iron content have hampered in vivo study of cortical iron accumulation. Using phase images of a T2*-weighted sequence at ultrahigh field strength (7 Tesla), we examined the iron content of 22 cortical regions in 70 healthy subjects aged 22-80 years. The cortex was automatically segmented and parcellated, and phase shift was analyzed using an in-house developed method. We found a significant increase in phase shift with age in 20 of 22 cortical regions, concurrent with current understanding of cortical iron accumulation. Our findings suggest that increased cortical iron content can be assessed in healthy aging in vivo. The high spatial resolution and sensitivity to iron of our method make it a potentially useful tool for studying cortical iron accumulation in healthy aging and neurodegenerative diseases.
Research Interests:
To determine whether hereditary cerebral hemorrhage with amyloidosis-Dutch type (HCHWA-D), a monogenetic disease model for the sporadic variant of amyloid angiopathy (sCAA), has a comparable recurrent intracerebral hemorrhage (ICH) risk... more
To determine whether hereditary cerebral hemorrhage with amyloidosis-Dutch type (HCHWA-D), a monogenetic disease model for the sporadic variant of amyloid angiopathy (sCAA), has a comparable recurrent intracerebral hemorrhage (ICH) risk and mortality after a first symptomatic ICH. We included patients with HCHWA-D from the Leiden University Medical Center and patients with sCAA from the Massachusetts General Hospital in a cohort study. Baseline characteristics, hemorrhage recurrence, and short- and long-term mortality were compared. Hazard ratios (HRs) adjusted for age and sex were calculated with Cox regression analyses. We included 58 patients with HCHWA-D and 316 patients with sCAA. Patients with HCHWA-D had fewer cardiovascular risk factors (≥1 risk factor 24% vs 70% in sCAA) and were younger at the time of presenting hemorrhage (mean age 54 vs 72 years in sCAA). Eight patients (14%) with HCHWA-D and 46 patients (15%) with sCAA died before 90 days. During a mean follow-up time o...