The EUROASPIRE III stroke-specific module shows that secondary prevention and risk factor control in patients after ischaemic stroke need to be improved in four European centres at the time of the study since about half of patients are not achieving risk factor targets defined in European guidelines.
BackgroundVascular cognitive impairment (VCI) is a heterogeneous entity with multiple aetiologies, all linked to underlying vascular disease. Among these, VCI related to subcortical small vessel disease (SSVD) is emerging as a major homogeneous subtype. Its progressive course raises the need for biomarker identification and/or development for adequate therapeutic interventions to be tested. In order to shed light in the current status on biochemical markers for VCI-SSVD, experts in field reviewed the recent evidence and literature data.MethodThe group conducted a comprehensive search on Medline, PubMed and Embase databases for studies published until 15.01.2017. The proposal on current status of biochemical markers in VCI-SSVD was reviewed by all co-authors and the draft was repeatedly circulated and discussed before it was finalized.ResultsThis review identifies a large number of biochemical markers derived from CSF and blood. There is a considerable overlap of VCI-SSVD clinical symptoms with those of Alzheimer’s disease (AD). Although most of the published studies are small and their findings remain to be replicated in larger cohorts, several biomarkers have shown promise in separating VCI-SSVD from AD. These promising biomarkers are closely linked to underlying SSVD pathophysiology, namely disruption of blood-CSF and blood–brain barriers (BCB-BBB) and breakdown of white matter myelinated fibres and extracellular matrix, as well as blood and brain inflammation. The leading biomarker candidates are: elevated CSF/blood albumin ratio, which reflects BCB/BBB disruption; altered CSF matrix metalloproteinases, reflecting extracellular matrix breakdown; CSF neurofilment as a marker of axonal damage, and possibly blood inflammatory cytokines and adhesion molecules. The suggested SSVD biomarker deviations contrasts the characteristic CSF profile in AD, i.e. depletion of amyloid beta peptide and increased phosphorylated and total tau.ConclusionsCombining SSVD and AD biomarkers may provide a powerful tool to identify with greater precision appropriate patients for clinical trials of more homogeneous dementia populations. Thereby, biomarkers might promote therapeutic progress not only in VCI-SSVD, but also in AD.
Background: Neurological complications after coronary artery bypass grafting (CABG) reduce quality of life, increase mortality, and inflate resource utilization. The risk of postoperative neurological complications parallels the increasing risk burden of the contemporary patient population. We evaluated the efficacy of remote ischemic preconditioning (RIPC) on inducing neuroprotection.Methods: Seventy patients undergoing first-time CABG were randomly assigned to RIPC or a sham procedure. Structural brain magnetic resonance imaging (MRI) was complemented with functional connectivity MRI to gain a whole-brain global connectivity analysis. Paired neurocognitive and MRI data were acquired pre-and postoperatively. The primary end point was a composite of new ischemic brain lesions and neurocognitive impairment. Secondary end points included brain connectivity profiles, pooled ischemic volumes, and individual components of the primary outcome. The Shapiro-Wilk test was used to determine whether a data set followed a normal distribution. The Fisher exact test was used to calculate the measures of association for categorical variables, whereas continuous data were tested with either the Mann-Whitney U test or the Student t test.Results: There was no between-group difference in the incidence of the primary end point (9 [27%] in the RIPC group vs 8 [24%] in the control group, odds ratio, 1.17 [95% confidence interval, 0.34-4.06]; P ¼ 1.0). Although RIPC did not reduce the incidence of brain ischemia (8/33 [24%] vs 7/33 [21%]; P ¼ 1.0), the pooled ischemic volume was lower in the RIPC group (157 [interquartile range, 125-231] vs 777 [interquartile range, 564-965] mm 3 ; P ¼ .004). Postoperative neurocognition was marginally superior in the RIPC group as evidenced by a lower absolute number of abnormal neurocognitive tests in the RIPC group (7/99 [7%] vs 16/99 [16%]; odds ratio, 0.40 [95% confidence interval, 0.14-1.09]; P ¼ .074). Robust reductions of functional connectivity profiles for the associative thalamus were documented in both groups, irrespective of RIPC (RIPC group, t ¼ 3.31; P <.01; and the control group, t ¼ 3.52; P <.01).Conclusions: Silent brain ischemia occurs frequently after CABG. RIPC did not reduce the incidence of the primary outcome. However, RIPC significantly RIPCAGE study summary. Brain-wide postoperative reductions in associative thalamic functional connectivity (shown in green). Central MessageAlthough RIPC did not reduce the incidence of new brain ischemia, it reduced its pooled volume. Surgery adversely affected global brain connectivity, with RIPC conferring no demonstrable protection. PerspectiveIschemic preconditioning mobilizes the endogenous potential for protection against ischemia incurred by alternating periods of sublethal ischemia and reperfusion. Neuronal injury occurs in response to cardiac surgical interventions at the structural and functional levels. RIPC might have the potential to alleviate brain ischemic cellular damage and might thus provide an additional layer of neuroprotect...
BackgroundThe vascular contributions to neurodegeneration and neuroinflammation may be assessed by magnetic resonance imaging (MRI) and ultrasonography (US). This review summarises the methodology for these widely available, safe and relatively low cost tools and analyses recent work highlighting their potential utility as biomarkers for differentiating subtypes of cognitive impairment and dementia, tracking disease progression and evaluating response to treatment in various neurocognitive disorders.MethodsAt the 9th International Congress on Vascular Dementia (Ljubljana, Slovenia, October 2015) a writing group of experts was formed to review the evidence on the utility of US and arterial spin labelling (ASL) as neurophysiological markers of normal ageing, vascular cognitive impairment (VCI) and Alzheimer’s disease (AD). Original articles, systematic literature reviews, guidelines and expert opinions published until September 2016 were critically analysed to summarise existing evidence, indicate gaps in current knowledge and, when appropriate, suggest standards of use for the most widely used US and ASL applications.ResultsCerebral hypoperfusion has been linked to cognitive decline either as a risk or an aggravating factor. Hypoperfusion as a consequence of microangiopathy, macroangiopathy or cardiac dysfunction can promote or accelerate neurodegeneration, blood-brain barrier disruption and neuroinflammation. US can evaluate the cerebrovascular tree for pathological structure and functional changes contributing to cerebral hypoperfusion. Microvascular pathology and hypoperfusion at the level of capillaries and small arterioles can also be assessed by ASL, an MRI signal. Despite increasing evidence supporting the utility of these methods in detection of microvascular pathology, cerebral hypoperfusion, neurovascular unit dysfunction and, most importantly, disease progression, incomplete standardisation and missing validated cut-off values limit their use in daily routine.ConclusionsUS and ASL are promising tools with excellent temporal resolution, which will have a significant impact on our understanding of the vascular contributions to VCI and AD and may also be relevant for assessing future prevention and therapeutic strategies for these conditions. Our work provides recommendations regarding the use of non-invasive imaging techniques to investigate the functional consequences of vascular burden in dementia.
Background: In Central/Eastern European countries, cerebrovascular diseases are among the leading causes of mortality. We aimed to determine the incidence of first-ever stroke (FES) in the north-western part of Croatia. Methods: A population-based prospective incidence study was conducted between July 1, 2007, and June 30, 2009. Cases were sought from multiple overlapping sources. Incidence rates by stroke type and gender were calculated. Results: A total of 1,487 events were recorded, 1,017 of which were FESs. European age-adjusted incidence rates (per 100,000 population) were: total FESs 223.6 [women/men rate ratio (w/m RR) = 0.65 (95% CI 0.57–0.73)]; ischemic stroke 162.4 (w/m RR = 0.65, 0.56–0.76); intracerebral hemorrhage 28.4 (w/m RR = 0.44, 0.30–0.63); subarachnoid hemorrhage 7.2 (w/m RR = 1.18, 0.55–2.54); unknown etiology 25.5 (w/m RR = 0.78, 0.54–1.14). Adjusted incidence rates of ischemic strokes by subtype were: cardioembolic 52.9 (w/m RR = 0.77, 0.59–0.99); large-artery atherosclerosis 14.4 (w/m RR = 0.22, 0.13–0.38); small-artery occlusion 24.5 (w/m RR = 0.53, 0.37–0.77) and ‘other or uncertain causes’ 70.6 (w/m RR = 0.77, 0.62–0.97). Thirty-day case-fatality rate was 23.5% overall and 17.1% for ischemic stroke. Conclusions: The incidence of FES and 30-day mortality of patients with ischemic strokes in the studied population is higher than in Western European countries.
Aim: The aim of this study was standardization and validation of the Mini-Mental State Examination (MMSE) in the general Croatian aging population. Methods: Three-hundred and forty-four participants underwent the MMSE test, 217 cognitively healthy subjects without neurological and psychiatric disorders and 127 patients with mild cognitive impairment (MCI) or dementia. Results: The optimal cutoff point for screening of the general Croatian population (cognitively healthy vs. MCI and dementia) is 26/27; in the Croatian population aged ≥65 years, the cutoff point is 24/25, whereas for screening of highly educated persons (≥14 years of education) aged ≥65 years a higher cutoff point should be used (26/27). Conclusions: MMSE results when standardized and validated in a certain population might better contribute to recognition of the individuals at risk that should be directed to dementia outpatient clinics.
Background: Stroke is reported as a consequence of SARS-CoV-2 infection. However, there is a lack of regarding comprehensive stroke phenotype and characteristics Methods: We conducted a multinational observational study on features of consecutive acute ischemic stroke (AIS), intracranial hemorrhage (ICH), and cerebral venous or sinus thrombosis (CVST) among SARS-CoV-2 infected patients. We further investigated the association of demographics, clinical data, geographical regions, and countrie's health expenditure among AIS patients with the risk of large vessel occlusion (LVO), stroke severity as measured by National Institute of Health stroke scale (NIHSS), and stroke subtype as measured by the TOAST criteria. Additionally, we applied unsupervised machine learning algorithms to uncover possible similarities among stroke patients. Results: Among the 136 tertiary centers of 32 countries who participated in this study, 71 centers from 17 countries had at least one eligible stroke patient. Out of 432 patients included, 323(74.8%) had AIS, 91(21.1%) ICH, and 18(4.2%) CVST. Among 23 patients with subarachnoid hemorrhage, 16(69.5%) had no evidence of aneurysm. A total of 183(42.4%) patients were women, 104(24.1%) patients were younger than 55 years, and 105(24.4%) patients had no identifiable vascular risk factors. Among 380 patients who had known interval onset of the SARS-CoV-2 and stroke, 144(37.8%) presented to the hospital with chief complaints of stroke-related symptoms, with asymptomatic or undiagnosed SARS-CoV-2 infection. Among AIS patients 44.5% had LVO; 10% had small artery occlusion according to the TOAST criteria. We observed a lower median NIHSS (8[3-17], versus 11[5-17]; p=0.02) and higher rate of mechanical thrombectomy (12.4% versus 2%; p<0.001) in countries with middle to high-health expenditure when compared to countries with lower health expenditure. The unsupervised machine learning identified 4 subgroups, with a relatively large group with no or limited comorbidities. Conclusions: We observed a relatively high number of young, and asymptomatic SARS-CoV-2 infections among stroke patients. Traditional vascular risk factors were absent among a relatively large cohort of patients. Among hospitalized patients, the stroke severity was lower and rate of mechanical thrombectomy was higher among countries with middle to high-health expenditure.
In this investigation, we explored the impact of mild traumatic brain injury (mTBI) upon short term or working memory and attention. The performance of 37 individuals with mTBI was compared with that of 53 age, sex and education-matched controls. All participants were staff members or individuals seeking medical care at a University hospital serving a large metropolitan area. A battery of computerized tests measured sustained visual attention, short-term memory (STM), simple reaction time, and decision time. Individuals with mTBI showed a performance deficit at sustained visual attention, STM scanning and a trend towards slowing in choice decision making. These observed changes in the cognitive performance of mTBI individuals are hypothesized to be a consequence of impaired central information processing. Our results suggest that mTBI can elicit meaningful cognitive deficits for several months post-injury. Additionally, we believe that the tasks employed in the current investigation demonstrate their utility for understanding cognitive deficits in mTBI individuals.
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