Valuing biomarker diagnostics for dementia care: enhancing the reflection of patients, their care-givers and members of the wider public

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Nonfocal transient neurological attacks in patients with carotid artery occlusion

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Cerebrospinal fluid and blood biomarkers for neurodegenerative dementias: An update of the Consensus of the Task Force on Biological Markers in Psychiatry of the World Federation of Societies of Biological Psychiatry

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Differences in cerebral small vessel disease magnetic resonance imaging markers between lacunar stroke and non Lobar intracerebral hemorrhage

Introduction: It is unclear why cerebral small vessel disease (SVD) leads to lacunar stroke in some and to non-lobar intracerebral hemorrhage (ICH) in others. We investigated differences in MRI markers of SVD in patients with lacunar stroke or non-lobar ICH.Patients and methods: We included patients from two prospective cohort studies with either lacunar stroke (RUN DMC) or non-lobar ICH (FETCH). Differences in SVD markers (white matter hyperintensities [WMH], lacunes, cerebral microbleeds [CMB]) between groups were investigated with univariable tests; multivariable logistic regression analysis, adjusted for age, sex, and vascular risk factors; spatial correlation analysis and voxel-wise lesion symptom mapping.Results: We included 82 patients with lacunar stroke (median age 63, IQR 57-72) and 54 with non-lobar ICH (66, 59-75). WMH volumes and distribution were not different between groups. Lacunes were more frequent in patients with a lacunar stroke (44% vs. 17%, adjusted odds ratio [aOR] 5.69, 95% CI [1.66-22.75]) compared to patients with a non-lobar ICH. CMB were more frequent in patients with a non-lobar ICH (71% vs. 23%, aOR for lacunar stroke vs non-lobar ICH 0.08 95% CI [0.02-0.26]), and more often located in non-lobar regions compared to CMB in lacunar stroke.Discussion: Although we obserd different types of MRI markers of SVD within the same patient, ischemic markers of SVD were more frequent in the ischemic type of lacunar stroke, and hemorrhagic markers were more prevalent in the hemorrhagic phenotype of non-lobar ICH.Conclusion: There are differences between MRI markers of SVD between patients with a lacunar stroke and those with a non-lobar ICH.Paroxysmal Cerebral Disorder

Cerebral Perfusion and the Occurrence of Nonfocal Transient Neurological Attacks

INTRODUCTION: Nonfocal transient neurological attacks (TNAs) are associated with an increased risk of cardiac events, stroke and dementia. Their etiology is still unknown. Global cerebral hypoperfusion has been suggested to play a role in their etiology, but this has not been investigated. We assessed whether lower total brain perfusion is associated with a higher occurrence of TNAs. METHODS: Between 2015 and 2018, patients with heart failure were included in the Heart Brain Connection study. Patients underwent brain magnetic resonance imaging, including quantitative magnetic resonance angiography (QMRA) to measure cerebral blood flow (CBF). We calculated total brain perfusion of each participant by dividing total CBF by brain volume. Patients were interviewed with a standardized questionnaire on the occurrence of TNAs by physicians who were blinded to QMRA flow status. We assessed the relation between total brain perfusion and the occurrence of TNAs with Poisson regression analysis. RESULTS: Of 136 patients (mean age 70 years, 68% men), 29 (21%) experienced ≥1 TNAs. Nonrotatory dizziness was the most common subtype of TNA. Patients with TNAs were more often female and more often had angina pectoris than patients without TNAs, but total CBF and total brain perfusion were not different between both groups. Total brain perfusion was not associated with the occurrence of TNAs (adjusted risk ratio 1.12, 95% CI 0.88-1.42). CONCLUSION: We found no association between total brain perfusion and the occurrence of TNAs in patients with heart failure

Cognitive functions in children and adults with Moyamoya Vasculopathy: A systematic review and meta-analysis

Background and Purpose Patients with moyamoya vasculopathy (MMV) may experience cognitive impairment, but its reported frequency, severity, and nature vary. In a systematic review and meta-analysis, we aimed to assess the presence, severity, and nature of cognitive impairments in children and adults with MMV. Methods We followed the MOOSE guidelines for meta-analysis and systematic reviews of observational studies. We searched Ovid Medline and Embase for studies published between January 1, 1969 and October 4, 2016. Independent reviewers extracted data for mean intelligence quotient (IQ) and standardized z-scores for cognitive tests, and determined percentages of children and adults with cognitive deficits, before and after conservative or surgical treatment. We explored associations between summary measures of study characteristics and cognitive impairments by linear regression analysis. Results We included 17 studies (11 studies reporting on 281 children, six on 153 adults). In children, the median percentage with impaired cognition was 30% (range, 13% to 67%); median IQ was 98 (range, 71 to 107). Median z-score was –0.39 for memory, and –0.43 for processing speed. In adults, the median percentage with impaired cognition was 31% (range, 0% to 69%); median IQ was 95 (range, 94 to 99). Median z-scores of cognitive domains were between –0.9 and –0.4, with multiple domains being affected. We could not identify determinants of cognitive impairment. Conclusions A large proportion of children and adults with MMV have cognitive impairment, with modest to large deficits across various cognitive domains. Further studies should investigate determinants of cognitive deficits and deterioration, and the influence of revascularization treatment on cognitive functioning

Cerebellar superficial siderosis in cerebral amyloid angiopathy

Background and Purpose: Although evidence accumulates that the cerebellum is involved in cerebral amyloid angiopathy (CAA), cerebellar superficial siderosis is not considered to be a disease marker. The objective of this study is to investigate cerebellar superficial siderosis frequency and its relation to hemorrhagic magnetic resonance imaging markers in patients with sporadic and Dutch-type hereditary CAA and patients with deep perforating arteriopathy-related intracerebral hemorrhage. Methods: We recruited patients from 3 prospective 3 Tesla magnetic resonance imaging studies and scored siderosis and hemorrhages. Cerebellar siderosis was identified as hypointense linear signal loss (black) on susceptibility-weighted or T2*-weighted magnetic resonance imaging which follows at least one folia of the cerebellar cortex (including the vermis). Results: We included 50 subjects with Dutch-type hereditary CAA, (mean age 50 years), 45 with sporadic CAA (mean age 72 years), and 43 patients with deep perforating arteriopathy-related intracerebral hemorrhage (mean age 54 years). Cerebellar superficial siderosis was present in 5 out of 50 (10% [95% CI, 2-18]) patients with Dutch-type hereditary CAA, 4/45 (9% [95% CI, 1-17]) patients with sporadic CAA, and 0 out of 43 (0% [95% CI, 0-8]) patients with deep perforating arteriopathy-related intracerebral hemorrhage. Patients with cerebellar superficial siderosis had more supratentorial lobar (median number 9 versus 2, relative risk, 2.9 [95% CI, 2.5-3.4]) and superficial cerebellar macrobleeds (median number 2 versus 0, relative risk, 20.3 [95% CI, 8.6-47.6]) compared with patients without the marker. The frequency of cortical superficial siderosis and superficial cerebellar microbleeds was comparable. Conclusions: We conclude that cerebellar superficial siderosis might be a novel marker for CAA.Paroxysmal Cerebral Disorder

Risk factors for lobar and non-lobar intracerebral hemorrhage in patients with vascular disease

Introduction Lobar and non-lobar non-traumatic intracerebral hemorrhage (ICH) are presumably caused by different types of small vessel diseases. The aim of this study was to assess risk factors for ICH according to location. Methods In two large prospective studies, SMART (n = 9088) and ESPRIT (n = 2625), including patients with manifest cardiovascular, cerebrovascular or peripheral artery disease or with vascular risk factors, we investigated potential risk factors for ICH during follow-up according to lobar or non-lobar location by Cox proportional hazards analyses. Results During 65,156 patient years of follow up 19 patients had lobar ICH (incidence rate 29, 95% CI 19-42 per 100,000 person-years) and 24 non-lobar ICH (incidence rate 37, 95% CI 26-51 per 100,000 person-years). Age significantly increased the risk of lobar ICH (HR per 10 years increase 1.90; 95% CI 1.17-3.10) in the multivariable analysis, but not of non-lobar hemorrhage. Anticoagulant medication (HR 3.49; 95% CI 1.20-10.2) and male sex (HR 3.79; 95% CI 1.13-12.8) increased the risk of non-lobar but not lobar ICH. Conclusion This study shows an elevated risk of future ICH in patients with manifestations of, or risk factors for, cardiovascular, cerebrovascular or peripheral artery disease. Our data suggest that risk factors for ICH vary according to location, supporting the hypothesis of a differential pathophysiology of lobar and non-lobar ICH

A replication study of genetic risk loci for ischemic stroke in a Dutch population: A case-control study

We aimed to replicate reported associations of 10 SNPs at eight distinct loci with overall ischemic stroke (IS) and its subtypes in an independent cohort of Dutch IS patients. We included 1,375 IS patients enrolled in a prospective multicenter hospital-based cohort in the Netherlands, and 1,533 population-level controls of Dutch descent. We tested these SNPs for association with overall IS and its subtypes (large artery atherosclerosis, small vessel disease and cardioembolic stroke (CE), as classified by TOAST) using an additive multivariable logistic regression model, adjusting for age and sex. We obtained odds ratios (OR) with 95% confidence intervals (95% CI) for the risk allele of each SNP analyzed and exact p-values by permutation. We confirmed the association at 4q25 (PITX2) (OR 1.43; 95% CI, 1.13-1.81, p = 0.029) and 16q22 (ZFHX3) (OR 1.62; 95% CI, 1.26-2.07, p = 0.001) as risk loci for CE. Locus 16q22 was also associated with overall IS (OR 1.24; 95% CI, 1.08-1.42, p = 0.016). Other loci previously associated with IS and/or its subtypes were not confirmed. In conclusion, we validated two loci (4q25, 16q22) associated with CE. In addition, our study may suggest that the association of locus 16q22 may not be limited to CE, but also includes overall IS

Diagnostic yield and accuracy of CT angiography, MR angiography, and digital subtraction angiography for detection of macrovascular causes of intracerebral haemorrhage: Prospective, multicentre cohort study

Study question What are the diagnostic yield and accuracy of early computed tomography (CT) angiography followed by magnetic resonance imaging/angiography (MRI/MRA) and digital subtraction angiography (DSA) in patients with non-traumatic intracerebral haemorrhage? Methods This prospective diagnostic study enrolled 298 adults (18-70 years) treated in 22 hospitals in the Netherlands over six years. CT angiography was performed within seven days of haemorrhage. If the result was negative, MRI/MRA was performed four to eight weeks later. DSA was performed when the CT angiography or MRI/MRA results were inconclusive or negative. The main outcome was a macrovascular cause, including arteriovenous malformation, aneurysm, dural arteriovenous fistula, and cavernoma. Three blinded neuroradiologists independently evaluated the images for macrovascular causes of haemorrhage. The reference standard was the best available evidence from all findings during one year's follow-up. Study answer and limitations A macrovascular cause was identified in 69 patients (23%). 291 patients (98%) underwent CT angiography; 214 with a negative result underwent additional MRI/MRA and 97 with a negative result for both CT angiography and MRI/MRA underwent DSA. Early CT angiography detected 51 macrovascular causes (yield 17%, 95% confidence interval 13% to 22%). CT angiography with MRI/MRA identified two additional macrovascular causes (18%, 14% to 23%) and these modalities combined with DSA another 15 (23%, 18% to 28%). This last extensive strategy failed to detect a cavernoma, which was identified on MRI during follow-up (reference strategy). The positive predictive value of CT angiography was 72% (60% to 82%), of additional MRI/MRA was 35% (14% to 62%), and of additional DSA was 100% (75% to 100%). None of the patients experienced complications with CT angiography or MRI/MRA; 0.6% of patients who underwent DSA experienced p