Neuropsychiatric symptoms in patients with possible vascular cognitive impairment, does sex matter?

Background: Neuropsychiatric symptoms (NPS) are common in patients with vascular cognitive impairment (VCI). We aimed to establish sex differences in the manifestation of NPS in memory clinic patients with possible VCI and identify which NPS are determinants of clinical progression in women and men separately. Methods: We included 718 memory clinic patients (age 68 ± 8; 45% women) with cognitive complaints and vascular brain lesions on MRI (i.e. possible VCI). NPS were measured using the 12-item Neuropsychiatric Inventory. Clinical progression after two years (women 18%, men 14%) was defined as increase in CDR ≥1 or institutionalization (available n = 589 without advanced dementia at baseline). The association between NPS and clinical progression was assessed with Cox proportional hazard models stratified by sex, adjusted for age and clinical diagnosis and in a second model additionally for manifestations of vascular brain lesions. Results: Men more often presented with agitation (29% versus 17%, p<.05) and irritability (58% versus 45%, p<.05), the other 10 NPS (delusions, hallucinations, depression, anxiety, euphoria, apathy, disinhibition, aberrant motor behavior, nighttime disturbances and appetite & eating abnormalities) did not differ between sexes. In women the presence of apathy (HR 2.1[1.1;4.3]) was associated with higher risk of clinical progression. In men the presence of depression (HR 2.7[1.4;5.1]) and aberrant motor behavior (HR 2.1[1.1;3.8]) were associated with increased risk of clinical progression. Conclusion: Manifestations of NPS in patients with possible VCI differ by sex. Different NPS are associated with future clinical progression in men and women. Management strategies of NPS could benefit from sex-specific approaches.

Automatic quantification of perivascular spaces in T2-weighted images at 7 T MRI.

Perivascular spaces (PVS) are believed to be involved in brain waste disposal. PVS are associated with cerebral small vessel disease. At higher field strengths more PVS can be observed, challenging manual assessment. We developed a method to automatically detect and quantify PVS. A machine learning approach identified PVS in an automatically positioned ROI in the centrum semiovale (CSO), based on -resolution T2-weighted TSE scans. Next, 3D PVS tracking was performed in 50 subjects (mean age 62.9 years (range 27-78), 19 male), and quantitative measures were extracted. Maps of PVS density, length, and tortuosity were created. Manual PVS annotations were available to train and validate the automatic method. Good correlation was found between the automatic and manual PVS count: ICC (absolute/consistency) is 0.64/0.75, and Dice similarity coefficient (DSC) is 0.61. The automatic method counts fewer PVS than the manual count, because it ignores the smallest PVS (length <2 mm). For 20 subjects manual PVS annotations of a second observer were available. Compared with the correlation between the automatic and manual PVS, higher inter-observer ICC was observed (0.85/0.88), but DSC was lower (0.49 in 4 persons). Longer PVS are observed posterior in the CSO compared with anterior in the CSO. Higher PVS tortuosity are observed in the center of the CSO compared with the periphery of the CSO. Our fully automatic method can detect PVS in a 2D slab in the CSO, and extract quantitative PVS parameters by performing 3D tracking. This method enables automated quantitative analysis of PVS.

Perforating artery flow velocity and pulsatility in patients with carotid occlusive disease. A 7 tesla MRI study.

Patients with carotid occlusive disease express altered hemodynamics in the post-occlusive vasculature and lesions commonly attributed to cerebral small vessel disease (SVD). We addressed the question if cerebral perforating artery flow measures, using a novel 7T MRI technique, are altered and related to SVD lesion burden in patients with carotid occlusive disease. 21 patients were included with a uni- (18) or bilateral (3) carotid occlusion (64±7 years) and 19 controls (65±10 years). Mean flow velocity and pulsatility in the perforating arteries in the semi-oval center (CSO) and basal ganglia (BG), measured with a 2D phase contrast 7T MRI sequence, were compared between patients and controls, and between hemispheres in patients with unilateral carotid occlusive disease. In patients, relations were assessed between perforating artery flow measures and SVD burden score and white matter hyperintensity (WMH) volume. CSO perforating artery flow velocity was lower in patients than controls, albeit non-significant (mean difference [95% confidence interval] 0.08 cm/s [0.00-0.16]; p = 0.053), but pulsatility was similar (0.07  [-0.04-0.18]; p = 0.23). BG flow velocity and pulsatility did not differ between patients and controls (velocity = 0.28 cm/s [-0.32-0.88]; p = 0.34; pulsatility = 0.00 [-0.10-0.11]; p = 0.97). Patients with unilateral carotid occlusive disease showed no significant interhemispheric flow differences. Though non-significant, within patients lower CSO (p = 0.06) and BG (p = 0.11) flow velocity related to larger WMH volume. Our findings suggest that carotid occlusive disease may be associated with abnormal cerebral perforating artery flow and that this relates to SVD lesion burden in these patients, although our observations need corroboration in larger study populations.

Cerebral hemodynamics during atrial fibrillation: Computational fluid dynamics analysis of lenticulostriate arteries using 7 T high-resolution magnetic resonance imaging.

Atrial fibrillation (AF) is the most common cardiac arrhythmia, inducing irregular and faster heart beating. Aside from disabling symptoms-such as palpitations, chest discomfort, and reduced exercise capacity-there is growing evidence that AF increases the risk of dementia and cognitive decline, even in the absence of clinical strokes. Among the possible mechanisms, the alteration of deep cerebral hemodynamics during AF is one of the most fascinating and least investigated hypotheses. Lenticulostriate arteries (LSAs)-small perforating arteries perpendicularly departing from the anterior and middle cerebral arteries and supplying blood flow to basal ganglia-are especially involved in silent strokes and cerebral small vessel diseases, which are considered among the main vascular drivers of dementia. We propose for the first time a computational fluid dynamics analysis to investigate the AF effects on the LSAs hemodynamics by using 7 T high-resolution magnetic resonance imaging (MRI). We explored different heart rates (HRs)-from 50 to 130 bpm-in sinus rhythm and AF, exploiting MRI data from a healthy young male and internal carotid artery data from validated 0D cardiovascular-cerebral modeling as inflow condition. Our results reveal that AF induces a marked reduction of wall shear stress and flow velocity fields. This study suggests that AF at higher HR leads to a more hazardous hemodynamic scenario by increasing the atheromatosis and thrombogenesis risks in the LSAs region.

Brain imaging correlates of mild cognitive impairment and early dementia in patients with type 2 diabetes mellitus.

BACKGROUND AND AIMS: The risk of mild cognitive impairment and dementia is increased in type 2 diabetes mellitus (T2DM). We aimed to identify the neuroanatomical correlates of mild cognitive impairment (MCI) and early dementia in patients with T2DM, using advanced multimodal MRI. METHODS AND RESULTS: Twenty-five patients (≥70 years) with T2DM and MCI (n = 22) or early dementia (n = 3) were included. The reference group consisted of 23 patients with T2DM with intact cognition. All patients underwent a 3 T MRI. Brain volumes and white matter hyperintensity volumes were obtained with automated segmentation methods. White matter connectivity was assessed with diffusion tensor imaging and fiber tractography. Infarcts and microbleeds were rated visually. Compared to patients without cognitive impairment, those with impairment had a lower grey matter volume (effect size: -0.58, p=0.042), especially in the right temporal lobe and subcortical brain regions (effect sizes: -0.45 to -0.91, false discovery rate corrected p < 0.05). White matter volume (effect size: -0.47, p = 0.11) and white matter connectivity (effect size: 0.55, p = 0.054) were also reduced in patients with versus without cognitive impairment, albeit not statistically significant. White matter hyperintensity volumes and occurrence of other vascular lesions did not differ between the two patient groups. CONCLUSION: In patients with T2DM, grey matter atrophy rather than vascular brain injury appears to be the primary imaging correlate of MCI and early dementia.

Cognitive functioning and structural brain abnormalities in people with Type 2 diabetes mellitus.

AIMS: Type 2 diabetes mellitus is associated with cognitive dysfunction, but the underlying structural brain correlates are uncertain. This study examined the association between cognitive functioning and structural brain abnormalities in people with long-standing Type 2 diabetes. METHODS: Ninety-three people with Type 2 diabetes (age 62.3 ± 5.4 years, diabetes duration 9.7 ± 6.7 years; HbA1c 65 ± 10 mmol/mol, 8.1 ± 1.3%) were included. Cognitive functioning was assessed by a test battery covering the domains memory, processing speed and executive functioning. Brain tissue volumes and white matter hyperintensity volumes were automatically determined on MRI. Linear regression analyses were performed adjusted for age, sex and education. RESULTS: In people with Type 2 diabetes, increased white matter hyperintensity volume was associated with decreased processing speed [regression B coefficient = -0.22 (-0.38 to -0.06), P = 0.009], but not with memory or executive function (P > 0.05). Brain tissue volumes were not significantly related to cognitive functioning (P > 0.05). CONCLUSIONS: In people with long-standing, less strictly controlled Type 2 diabetes, white matter hyperintensities volumes were associated with decreased processing speed. This suggests that cerebral small vessel disease is an underlying disease mechanism of cognitive dysfunction in these individuals.

[Risk of vitamin K antagonists in cases of cerebral microbleeds]. / Risico's van vitamine K-antagonisten bij cerebrale microbloedingen.

- Cerebral microbleeds are associated with a higher risk of intracerebral hemorrhage.- When microbleeds are detected, the possible underlying pathology should be considered; this includes cerebral amyloid angiopathy and other factors that increase the risk of haemorrhage, particularly hypertension. - No randomised trials have yet been conducted into haemorrhagic complications and cerebral infarctions in patients with microbleeds who take vitamin K antagonists. This means that it is not clear whether the intended prevention of cerebral infarctions outweighs the increased risk of haemorrhage associated with use of vitamin K antagonists by these patients.- When deciding whether or not an older patient should be given anticoagulants the following should be taken into consideration as well: comorbidities, polypharmacy, the risk of falls and the probability that the patient can be optimally titrated to vitamin K antagonists. - If there is an increased risk of intracerebral haemorrhage but anticoagulants are indicated, direct oral anticoagulants (DOACs) might be preferable to vitamin K antagonists in patients with a history of cerebral microbleeds.

Hippocampal volume and the course of depressive symptoms over eight years of follow-up.

OBJECTIVE: To estimate the association between hippocampal and total brain volume and the course of depressive symptoms over eight years of follow-up in patients with a history of vascular disease. METHOD: Within the SMART-Medea study, 636 participants (62 ± 10 years) had a 1.5-tesla brain MRI obtaining hippocampal and total brain volumes. Depressive symptoms were assessed with the Patient Health Questionnaire-9 biannually during eight-year follow-up. Generalized estimating equation models with robust standard errors were used to assess the associations of hippocampal and total brain volumes with depressive symptoms during follow-up adjusting for age, sex, education, and intracranial volume. An interaction term between volume and time (6-month intervals) was included to examine whether the course of depressive symptoms differed according to hippocampal and total brain volume. RESULTS: The mean PHQ-9 score was 2.8 ± 3.5. Smaller hippocampal volumes were associated with an increasing course of depressive symptom levels, while larger volumes were associated with decreasing levels (P-value interaction = 0.07). Smaller total brain volume was associated with consistently higher levels of depressive symptoms, but not with change in course of depressive symptoms (P-value interaction = 0.45). CONCLUSION: Smaller hippocampal volume but not total brain volume is associated with poorer course of depressive symptoms over eight years of follow-up.

Cerebrospinal fluid volumetric MRI mapping as a simple measurement for evaluating brain atrophy.

OBJECTIVES: To assess whether volumetric cerebrospinal fluid (CSF) MRI can be used as a surrogate for brain atrophy assessment and to evaluate how the T2 of the CSF relates to brain atrophy. METHODS: Twenty-eight subjects [mean age 64 (sd 2) years] were included; T1-weighted and CSF MRI were performed. The first echo data of the CSF MRI sequence was used to obtain intracranial volume, CSF partial volume was measured voxel-wise to obtain CSF volume (VCSF) and the T2 of CSF (T2,CSF) was calculated. The correlation between VCSF/T2,CSF and brain atrophy scores [global cortical atrophy (GCA) and medial temporal lobe atrophy (MTA)] was evaluated. RESULTS: Relative total, peripheral subarachnoidal, and ventricular VCSF increased significantly with increased scores on the GCA and MTA (R = 0.83, 0.78 and 0.78 and R = 0.72, 0.62 and 0.86). Total, peripheral subarachnoidal, and ventricular T2 of the CSF increased significantly with higher scores on the GCA and MTA (R = 0.72, 0.70 and 0.49 and R = 0.60, 0.57 and 0.41). CONCLUSION: A fast, fully automated CSF MRI volumetric sequence is an alternative for qualitative atrophy scales. The T2 of the CSF is related to brain atrophy and could thus be a marker of neurodegenerative disease. KEY POINTS: • A 1:11 min CSF MRI volumetric sequence can evaluate brain atrophy. • CSF MRI provides accurate atrophy assessment without partial volume effects. • CSF MRI data can be processed quickly without user interaction. • The measured T 2 of the CSF is related to brain atrophy.

Case-finding for cognitive impairment among people with Type 2 diabetes in primary care using the Test Your Memory and Self-Administered Gerocognitive Examination questionnaires: the Cog-ID study.

AIM: To evaluate two cognitive tests for case-finding for cognitive impairment in older patients with Type 2 diabetes. METHODS: Of 1243 invited patients with Type 2 diabetes, aged ≥70 years, 228 participated in a prospective cohort study. Exclusion criteria were: diagnosis of dementia; previous investigation at a memory clinic; and inability to write or read. Patients first filled out two self-administered cognitive tests (Test Your Memory and Self-Administered Gerocognitive Examination). Secondly, a general practitioner, blinded to Test Your Memory and Self-Administered Gerocognitive Examination scores, performed a structured evaluation using the Mini-Mental State Examination. Subsequently, patients suspected of cognitive impairment (on either the cognitive tests or general practitioner evaluation) and a random sample of 30% of patients not suspected of cognitive impairment were evaluated at a memory clinic. Diagnostic accuracy and area under the curve were determined for the Test Your Memory, Self-Administered Gerocognitive Examination and general practitioner evaluation compared with a memory clinic evaluation to detect cognitive impairment (mild cognitive impairment or dementia). RESULTS: A total of 44 participants were diagnosed with cognitive impairment. The Test Your Memory and Self-Administered Gerocognitive Examination questionnaires had negative predictive values of 81 and 85%, respectively. Positive predictive values were 39 and 40%, respectively. The general practitioner evaluation had a negative predictive value of 83% and positive predictive value of 64%. The area under the curve was ~0.70 for all tests. CONCLUSIONS: Both the tests evaluated in the present study can easily be used in case-finding strategies for cognitive impairment in patients with Type 2 diabetes in primary care. The Self-Administered Gerocognitive Examination had the best diagnostic accuracy and therefore we would have a slight preference for this test. Applying the Self-Administered Gerocognitive Examination would considerably reduce the number of patients in whom the general practitioner needs to evaluate cognitive functioning to tailor diabetes treatment.

Assessment of blood flow velocity and pulsatility in cerebral perforating arteries with 7-T quantitative flow MRI.

Thus far, blood flow velocity measurements with MRI have only been feasible in large cerebral blood vessels. High-field-strength MRI may now permit velocity measurements in much smaller arteries. The aim of this proof of principle study was to measure the blood flow velocity and pulsatility of cerebral perforating arteries with 7-T MRI. A two-dimensional (2D), single-slice quantitative flow (Qflow) sequence was used to measure blood flow velocities during the cardiac cycle in perforating arteries in the basal ganglia (BG) and semioval centre (CSO), from which a mean normalised pulsatility index (PI) per region was calculated (n = 6 human subjects, aged 23-29 years). The precision of the measurements was determined by repeated imaging and performance of a Bland-Altman analysis, and confounding effects of partial volume and noise on the measurements were simulated. The median number of arteries included was 14 in CSO and 19 in BG. In CSO, the average velocity per volunteer was in the range 0.5-1.0 cm/s and PI was 0.24-0.39. In BG, the average velocity was in the range 3.9-5.1 cm/s and PI was 0.51-0.62. Between repeated scans, the precision of the average, maximum and minimum velocity per vessel decreased with the size of the arteries, and was relatively low in CSO and BG compared with the M1 segment of the middle cerebral artery. The precision of PI per region was comparable with that of M1. The simulations proved that velocities can be measured in vessels with a diameter of more than 80 µm, but are underestimated as a result of partial volume effects, whilst pulsatility is overestimated. Blood flow velocity and pulsatility in cerebral perforating arteries have been measured directly in vivo for the first time, with moderate to good precision. This may be an interesting metric for the study of haemodynamic changes in aging and cerebral small vessel disease. © 2015 The Authors NMR in Biomedicine Published by John Wiley & Sons Ltd.

Major depressive episodes over the course of 7 years and hippocampal subfield volumes at 7 tesla MRI: the PREDICT-MR study.

INTRODUCTION: Smaller hippocampal volumes have been associated with major depressive disorder (MDD). The hippocampus consists of several subfields that may be differentially related to MDD. We investigated the association of occurrence of major depressive episodes (MDEs), assessed five times over seven years, with hippocampal subfield and entorhinal cortex volumes at 7 tesla MRI. METHODS: In this prospective study of randomly selected general practice attendees, MDEs according to DSM-IV-R criteria were assessed at baseline and after 6, 12, 39 and 84 months follow-up. At the last follow-up, a T2 (0.7 mm(3)) 7 tesla MRI scan was obtained in 47 participants (60±10 years). The subiculum, cornu ammonis (CA) 1 to 3, dentate gyrus&CA4 and entorhinal cortex volumes were manually segmented according a published protocol. RESULTS: Of the 47 participants, 13 had one MDE and 5 had multiple MDEs. ANCOVAs, adjusted for age, sex, education and intracranial volume, revealed no significant differences in hippocampal subfield or entorhinal cortex volumes between participants with and without an MDE in the preceding 84 months. Multiple episodes were associated with smaller subiculum volumes (B=-0.03 mL/episode; 95% CI -0.06; -0.003), but not with the other hippocampal subfield volumes, entorhinal cortex, or total hippocampal volume. LIMITATIONS: A limitation of this study is the small sample size which makes replication necessary. CONCLUSIONS: In this exploratory study, we found that an increasing number of major depressive episodes was associated with smaller subiculum volumes in middle-aged and older persons, but not with smaller volumes in other hippocampal subfields or the entorhinal cortex.

Cognitive performance and the course of depressive symptoms over 7 years of follow-up: the SMART-MR study.

BACKGROUND: Depressive symptoms and cognitive impairment often co-occur, but their interactive relationship is complex and the direction of causation is still a topic of research. We examined the influence of cognitive performance on the course of depressive symptoms during 7 years of follow-up in patients with vascular disease. METHOD: Within the SMART-MR study, 736 patients (mean age 62 ± 10 years) had neuropsychological assessment on four cognitive domains at baseline [memory (MEM), working memory (WMEM), executive functioning (EXEC), and information processing speed (SPEED)]. Depressive symptoms were assessed with the Patient Health Questionnaire-9 (PHQ-9) at baseline and every 6 months during 7 years of follow-up. Generalized Estimating Equation (GEE) models were used to assess the association between cognitive performance with depressive symptoms at multiple time points during follow-up. Interaction terms between the respective cognitive domains and time was included to examine if the course of depressive symptoms differed according to baseline cognitive performance. RESULTS: The GEE analyses showed no significant interactions between the respective cognitive domains and time indicating no different course of depressive symptoms according to baseline cognitive performance. Lower MEM, EXEC or SPEED, but not WMEM performance, was significantly associated with more depressive symptoms during follow-up per z score decrease: MEM [B = 0.70, 95% confidence interval (CI) 0.35-1.05]; EXEC (B = 0.88, 95% CI 0.41-1.36), and SPEED (B = 0.57, 95% CI 0.21-0.92). CONCLUSIONS: Poorer cognitive performance on the domains MEM, EXEC and SPEED, but not WMEM, was associated with higher levels of depressive symptoms over 7 years of follow-up, but not with a different course of depressive symptoms over time.

Phenotyping animal models of diabetic neuropathy: a consensus statement of the diabetic neuropathy study group of the EASD (Neurodiab).

NIDDK, JDRF, and the Diabetic Neuropathy Study Group of EASD sponsored a meeting to explore the current status of animal models of diabetic peripheral neuropathy. The goal of the workshop was to develop a set of consensus criteria for the phenotyping of rodent models of diabetic neuropathy. The discussion was divided into five areas: (1) status of commonly used rodent models of diabetes, (2) nerve structure, (3) electrophysiological assessments of nerve function, (4) behavioral assessments of nerve function, and (5) the role of biomarkers in disease phenotyping. Participants discussed the current understanding of each area, gold standards (if applicable) for assessments of function, improvements of existing techniques, and utility of known and exploratory biomarkers. The research opportunities in each area were outlined, providing a possible roadmap for future studies. The meeting concluded with a discussion on the merits and limitations of a unified approach to phenotyping rodent models of diabetic neuropathy and a consensus formed on the definition of the minimum criteria required for establishing the presence of the disease. A neuropathy phenotype in rodents was defined as the presence of statistically different values between diabetic and control animals in 2 of 3 assessments (nocifensive behavior, nerve conduction velocities, or nerve structure). The participants propose that this framework would allow different research groups to compare and share data, with an emphasis on data targeted toward the therapeutic efficacy of drug interventions.

Physical activity, structural brain changes and cognitive decline. The SMART-MR study.

OBJECTIVE: We aimed to examine the cross-sectional and prospective relationship between leisure time physical activity, brain MRI abnormalities and cognitive performance in patients with vascular disease. METHODS: Within the SMART-MR study, 1.5 T MRI of the brain and neuropsychological examinations were performed at baseline (n = 1232) and after 3.9 ± 0.4 years follow-up (n = 663). Automatic brain segmentation was used to quantify intracranial (ICV), total brain, ventricular, and white matter lesion (WML) volumes. Brain infarcts were rated visually. Level of physical activity was expressed in metabolic equivalents (MET) hours p/week. With linear regression analysis we examined associations of level of physical activity with brain MRI measures and with cognitive performance, adjusted for potential confounders. For the association with brain infarcts relative risks (RR) were calculated with Poisson regression. RESULTS: At baseline, an increase in physical activity of one SD (39.7 METh/w) was significantly associated with larger total brain volume (B = 0.20% of ICV; 95% CI 0.06; 0.33%). A trend was found for the association of physical activity with smaller ventricular volume (B = -0.04% of ICV; 95% CI -0.09; 0.02%) and with a decreased risk for brain infarcts (RR = 0.91, 95% CI: 0.82-1.02). No association was found with smaller WML volume (B = -0.02% of ICV; 95% CI -0.07; 0.04%). No associations with change in brain structures over time were observed. Also, no associations between physical activity and cognitive performance or cognitive decline were found. CONCLUSION: These data suggest that leisure time physical activity does not have a significant contribution in preventing or slowing down brain abnormalities and cognitive decline in this cohort of middle-aged individuals already burdened with vascular disease.

Markers of low-grade inflammation and endothelial dysfunction are related to reduced information processing speed and executive functioning in an older population - the Hoorn Study.

Low-grade inflammation and endothelial dysfunction are related to cognitive decline and dementia, in a complex interplay with vascular factors and aging. We investigated, in an older population, low-grade inflammation and endothelial dysfunction in relation to detailed assessment of cognitive functioning. Furthermore, we explored this association within the context of vascular factors. 377 participants (73 ± 6 years) of the population-based Hoorn Study were included. In plasma samples of 2000-2001 (n=363) and/or 2005-2008 (n=323), biomarkers were determined of low-grade inflammation (CRP, TNF-alpha, IL-6, IL-8, SAA, MPO, and sICAM-1) and endothelial dysfunction (vWF, sICAM-1, sVCAM-1, sTM, sE-selectin). In 2005-2008, all participants underwent neuropsychological examination. Composite z-scores were computed for low-grade inflammation and endothelial dysfunction at both time points, and for six domains of cognitive functioning (abstract reasoning, memory, information processing speed, attention and executive functioning, visuoconstruction, and language). The association between low-grade inflammation and endothelial dysfunction, and cognitive functioning was evaluated with linear regression analysis. In secondary analyses, we explored the relation with vascular risk factors and cardiovascular disease. Low-grade inflammation and endothelial dysfunction were associated with worse performance on information processing speed and attention and executive functioning, in prospective and cross-sectional analyses (standardized betas ranging from -0.20 to -0.10). No significant relation with other cognitive domains was observed. Adjusting for vascular factors slightly attenuated the associations. Low-grade inflammation and endothelial dysfunction accounted for only 2.6% explained variance in cognitive functioning, on top of related vascular risk factors and cardiovascular disease. Bootstrapping analyses show that low-grade inflammation and endothelial dysfunction mediate the relation between vascular risk factors and cognitive functioning. This study shows that low-grade inflammation and endothelial dysfunction contribute to reduced information processing speed and executive functioning in an older population.

Predictive value of thrombus attenuation on thin-slice non-contrast CT for persistent occlusion after intravenous thrombolysis.

BACKGROUND: In stroke erythrocyte-rich thrombi are more sensitive to intravenous thrombolysis with recombinant tissue plasminogen activator (IV-rtPA) and have higher density on non-contrast CT (NCCT). We investigated the relationship between thrombus density and recanalization and whether persistent occlusions can be predicted by Hounsfield unit (HU) measurements. METHODS: In 88 IV-rtPA-treated patients with intracranial ICA or MCA occluding thrombus and follow-up imaging, thrombus and contralateral vessel attenuation measurements were performed on thin-slice NCCT. Mean absolute and relative HU were compared between patients with persistent occlusion (modified Thrombolysis in Cerebral Infarction system, grade 0/1/2a) and recanalization (grade 2b/3). Univariate and multivariate (adjusted for stroke subtype, clot burden score, occlusion site and time to thrombolysis) odds ratios for persistent occlusion were calculated. Additional prognostic value for persistent occlusion was estimated by adding HU measurements to the area under the curve (AUC) of known determinants and calculating optimal cut-off values. RESULTS: Patients with persistent occlusion (n = 19) had significant lower mean HU (absolute 52.2 ± 9.5, relative 1.29 ± 0.20) compared to recanalization (absolute 63.1 ± 10.7, relative 1.54 ± 0.23, both p < 0.0001). Odds ratios for persistent occlusion were 3.1 (95% confidence interval, CI 1.6-6.0) univariate and 3.1 (95% CI 1.7-5.7) multivariate per 10 absolute HU decrease and 3.2 (95% CI 1.6-6.5) univariate and 4.1 (95% CI 1.8-9.1) multivariate per 0.20 relative HU decrease. Attenuation measurements significantly increased the AUC (0.67) of the known determinants to 0.84 (absolute HU) and 0.86 (relative HU). Cut-off values of <56.5 absolute HU and <1.38 relative HU showed optimal predictive values for persistent occlusion. CONCLUSIONS: Thrombus density is related to recanalization rate. Lower absolute and relative HU are independently related to persistent occlusion and HU measurements significantly increase discriminative performances of known recanalization determinants.

Relationship between thrombus attenuation and different stroke subtypes.

INTRODUCTION: More insights in the etiopathogenesis of thrombi could be helpful in the treatment of patients with acute ischemic stroke. The aim of our study was to determine the relationship between presence of a hyperdense vessel sign and thrombus density with different stroke subtypes. METHODS: We included 123 patients with acute ischemic anterior circulation stroke and a visible occlusion on CT-angiography caused by cardioembolism (n = 53), large artery atherosclerosis (n = 55), or dissection (n = 15). Presence or absence of a hyperdense vessel sign was assessed and thrombus density was measured in Hounsfield Units (HU) on non-contrast 1 mm thin slices CT. Subsequently, occurrence of hyperdense vessel sign and thrombus density (absolute HU and rHU (=HU thrombus/HU contralateral)) were related with stroke subtypes. RESULTS: The presence of hyperdense vessel signs differed significantly among subtypes and was found in 45, 64 and 93 % of patients with cardioembolism, large artery atherosclerosis and dissection, respectively (p = 0.003). The mean HU and rHU (+95 % CI) of the thrombi in all vessels were respectively 56.1 (53.2-59.0) and 1.39 (1.33-1.45) in cardioembolism, 64.6 (62.2-66.9) and 1.59 (1.54-1.64) in large artery atherosclerosis and 76.4 (73.0-79.8) and 1.88 (1.79-1.97) in dissection (p < 0.0001). We found the same significant ranking order in the density of thrombi with hyperdense vessel signs (mean HU and rHU (+95 % CI), respectively): cardioembolism 61.3 (57.4-65.3) and 1.49 (57.4-65.3); large artery atherosclerosis 67.3 (64.9-69.7) and 1.65 (1.58-1.71); dissection 76.4 (72.6-80.1) and 1.89 (1.79-1.99, p < 0.0001). CONCLUSION: Presence of a hyperdense vessel sign and thrombus density are related to stroke subtype.

Diagnostic accuracy of CT perfusion imaging for detecting acute ischemic stroke: a systematic review and meta-analysis.

BACKGROUND: The aim of the current study was to determine the sensitivity and specificity of CT perfusion (CTP) for the detection of ischemic stroke by performing a systematic review and meta-analysis of published reports. METHODS: We searched PubMed, Embase and the Cochrane library using the terms 'perfusion computed tomography', 'ischemic stroke' and synonyms. We included studies that: (1) reported original data, (2) studied the diagnostic value of CTP for detecting ischemic stroke, (3) used MRI-DWI, follow-up MRI or follow-up CT as the reference standard, (4) included at least 10 patients who were suspected of ischemic stroke, and (5) reported the number of true positives, true negatives, false positives and false negatives for the diagnosis of ischemic stroke. RESULTS: Fifteen studies were finally included in the current review with a total of 1,107 patients. A pooled analysis resulted in a sensitivity of 80% (95% confidence interval, CI: 72-86%) and a specificity of 95% (95% CI: 86-98%). Almost two thirds of the false negatives were due to small lacunar infarcts; the remaining false negatives were mostly due to limited coverage. CONCLUSIONS: The current systematic review shows that CTP has a high sensitivity and a very high specificity for detecting infarcts.