Developing blood-brain barrier arterial spin labelling as a non-invasive early biomarker of Alzheimer's disease (DEBBIE-AD): a prospective observational multicohort study protocol.

INTRODUCTION: Loss of blood-brain barrier (BBB) integrity is hypothesised to be one of the earliest microvascular signs of Alzheimer's disease (AD). Existing BBB integrity imaging methods involve contrast agents or ionising radiation, and pose limitations in terms of cost and logistics. Arterial spin labelling (ASL) perfusion MRI has been recently adapted to map the BBB permeability non-invasively. The DEveloping BBB-ASL as a non-Invasive Early biomarker (DEBBIE) consortium aims to develop this modified ASL-MRI technique for patient-specific and robust BBB permeability assessments. This article outlines the study design of the DEBBIE cohorts focused on investigating the potential of BBB-ASL as an early biomarker for AD (DEBBIE-AD). METHODS AND ANALYSIS: DEBBIE-AD consists of a multicohort study enrolling participants with subjective cognitive decline, mild cognitive impairment and AD, as well as age-matched healthy controls, from 13 cohorts. The precision and accuracy of BBB-ASL will be evaluated in healthy participants. The clinical value of BBB-ASL will be evaluated by comparing results with both established and novel AD biomarkers. The DEBBIE-AD study aims to provide evidence of the ability of BBB-ASL to measure BBB permeability and demonstrate its utility in AD and AD-related pathologies. ETHICS AND DISSEMINATION: Ethics approval was obtained for 10 cohorts, and is pending for 3 cohorts. The results of the main trial and each of the secondary endpoints will be submitted for publication in a peer-reviewed journal.

Imaging of Amyloid-Related Imaging Abnormalities (ARIA). / Bildgebung von Amyloid-related Imaging Abnormalities (ARIA).

Patients with Alzheimer's disease (AD) can now be treated with monoclonal antibodies aiming at clearing amyloid plaques from the brain parenchyma. Weeks after initiation of this drug therapy, patients may develop so-called amyloid-related imaging abnormalities (ARIA) on MRI. ARIA comprise vasogenic edema and leptomeningeal effusions (ARIA-E) as well as microbleeds and superficial hemosiderosis (ARIA-H). The prevalence is drug- and dose-dependent (up to 40 % of patients), the apolipoprotein E4 variant and concomitant cerebral amyloid angiopathy (CAA) increase the risk. With regard to MRI characteristics, ARIA strongly resembles the so-called inflammatory subtype of CAA (CAA-ri). While patients with CAA-ri are typically detected due to symptoms such as headaches, lethargy, confusion, and rarely epileptic seizures, around 20 % of ARIA patients show symptoms. Management of ARIA is not yet clearly established. In asymptomatic patients, discontinuation of the drug might be sufficient. KEY POINTS: · Amyloid-related imaging abnormalities (ARIA) occur in around 20 % of patients who are treated with monoclonal antibodies against amyloid ß.. · There are 2 types: ARIA-E (edema effusion) und ARIA-H (hemorrhage).. · Depending on the severity, therapy with monoclonal antibodies is either interrupted or finished.. CITATION FORMAT: · Urbach H, Linn J, Hattingen E et al. Imaging of Amyloid-Related Imaging Abnormalities (ARIA). Fortschr Röntgenstr 2024; 196: 363 - 369.

Improved Visualization and Quantification of Net Water Uptake in Recent Small Subcortical Infarcts in the Thalamus Using Computed Tomography.

Diagnosing recent small subcortical infarcts (RSSIs) via early computed tomography (CT) remains challenging. This study aimed to assess CT attenuation values (Hounsfield Units (HU)) and net water uptake (NWU) in RSSI and explore a postprocessing algorithm's potential to enhance thalamic RSSI detection. We examined non-contrast CT (NCCT) data from patients with confirmed thalamic RSSI on diffusion-weighted magnetic resonance imaging (DW-MRI) between January 2010 and October 2017. Co-registered DW-MRI and NCCT images enabled HU and NWU quantification in the infarct area compared to unaffected contralateral tissue. Results were categorized based on symptom onset to NCCT timing. Postprocessing using window optimization and frequency-selective non-linear blending (FSNLB) was applied, with interpretations by three blinded Neuroradiologists. The study included 34 patients (median age 70 years [IQR 63-76], 14 women). RSSI exhibited significantly reduced mean CT attenuation compared to unaffected thalamus (29.6 HU (±3.1) vs. 33.3 HU (±2.6); p < 0.01). Mean NWU in the infarct area increased from 6.4% (±7.2) at 0-6 h to 16.6% (±8.7) at 24-36 h post-symptom onset. Postprocessed NCCT using these HU values improved sensitivity for RSSI detection from 32% in unprocessed CT to 41% in FSNLB-optimized CT, with specificities ranging from 86% to 95%. In conclusion, CT attenuation values and NWU are discernible in thalamic RSSI up to 36 h post-symptom onset. Postprocessing techniques, particularly window optimization and FSNLB, moderately enhance RSSI detection.

Comorbid cerebral amyloid angiopathy in dementia and prodromal stages-Prevalence and effects on cognition.

OBJECTIVES: To determine the contribution of cerebral amyloid angiopathy to cognitive impairment in MCI and dementia. METHODS: Patients with subjective memory impairment (SMI), amnestic and non-amnestic mild cognitive impairment ((n)aMCI), Alzheimer's disease (AD), mixed and vascular dementia (MD/VD) from our memory clinic were included in this retrospective analysis. Patients underwent neuropsychological testing and cranial magnetic resonance imaging (MRI). Magnetic resonance imaging data sets were analyzed regarding the presence of CAA-related MRI biomarkers to determine CAA prevalence. ANOVAs were used to investigate the contribution of CAA to cognitive impairment within diagnostic groups and to determine whether differences in cognitive test performance between the diagnostic groups are mediated by total CAA burden. RESULTS: 475 patients (222 male, 253 female) with SMI (n = 47), naMCI (n = 41), aMCI (n = 189), early AD (n = 9), AD (n = 114), MD (n = 71) and VD (n = 4) were included. Mean age was 73.2 (9.9) years. CAA prevalence was 14.9% in SMI, 14.6% in naMCI, 24.3% in aMCI, 22.2% in early onset AD, 18.4% in late onset AD, 46.5% in MD and 25% in VD. Patients with possible and probable CAA were older than patients without CAA. In particular, diagnosis of aMCI, early onset AD, MD and VD showed high CAA prevalence. In AD but not in aMCI, CAA diagnosis significantly influenced test performance in the CERAD word list recall (F (1,78) = 4505; p = 0.037; partial eta-square = 0.055). Differences in cognitive test performance between the diagnostic groups of naMCI, aMCI, AD and MD were mediated by total CAA burden within AAT simply nouns subtest (F (2,39) = 4059; p = 0.025; partial eta-square = 0.172) and in CERAD verbal fluency test (F (3,129) = 3533; p = 0.017; partial eta-square = 0.076). CONCLUSION: This retrospective analysis demonstrates high prevalence rates of CAA in cognitive diagnoses. Our data suggest that comorbid CAA independently impacts cognitive test performance in the course of AD with presumably stage-dependent effects. Especially in patients with AD comorbid CAA additionally impairs memory function. Total CAA small vessel disease burden further modulates psychometric differences in cognitive test performance between diagnostic groups regarding word finding and word fluency capabilities.

Triangulating brain alterations in anorexia nervosa: a multimodal investigation of magnetic resonance spectroscopy, morphometry and blood-based biomarkers.

The acute state of anorexia nervosa (AN) is associated with widespread reductions in cortical gray matter (GM) thickness and white matter (WM) volume, suspected changes in myelin content and elevated levels of the neuronal damage marker neurofilament light (NF-L), but the underlying mechanisms remain largely unclear. To gain a deeper understanding of brain changes in AN, we applied a multimodal approach combining advanced neuroimaging methods with analysis of blood-derived biomarkers. In addition to standard measures of cortical GM thickness and WM volume, we analyzed tissue-specific profiles of brain metabolites using multivoxel proton magnetic resonance spectroscopy, T1 relaxation time as a proxy of myelin content leveraging advanced quantitative MRI methods and serum NF-L concentrations in a sample of 30 female, predominately adolescent patients with AN and 30 age-matched female healthy control participants. In patients with AN, we found a reduction in GM cortical thickness and GM total N-acetyl aspartate. The latter predicted higher NF-L levels, which were elevated in AN. Furthermore, GM total choline was elevated. In WM, there were no group differences in either imaging markers, choline levels or N-acetyl aspartate levels. The current study provides evidence for neuronal damage processes as well as for increased membrane lipid catabolism and turnover in GM in acute AN but no evidence for WM pathology. Our results illustrate the potential of multimodal research including tissue-specific proton magnetic resonance spectroscopy analyses to shed light on brain changes in psychiatric and neurological conditions, which may ultimately lead to better treatments.

German guidelines on community-acquired acute bacterial meningitis in adults.

INTRODUCTION: The incidence of community-acquired acute bacterial meningitis has decreased during the last decades. However, outcome remains poor with a significant proportion of patients not surviving and up to 50% of survivors suffering from long-term sequelae. These guidelines were developed by the Deutsche Gesellschaft für Neurologie (DGN) under guidance of the Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften (AWMF) to guide physicians through diagnostics and treatment of adult patients with acute bacterial meningitis. RECOMMENDATIONS: The most important recommendations are: (i) In patients with suspected acute bacterial meningitis, we recommend that lumbar cerebrospinal fluid (with simultaneous collection of serum to determine the cerebrospinal fluid-serum glucose index and blood cultures) is obtained immediately after the clinical examination (in the absence of severely impaired consciousness, focal neurological deficits, and/or new epileptic seizures). (ii) Next, we recommend application of dexamethasone and empiric antibiotics intravenously. (iii) The recommended initial empiric antibiotic regimen consists of ampicillin and a group 3a cephalosporin (e.g., ceftriaxone). (iv) In patients with severely impaired consciousness, new onset focal neurological deficits (e.g. hemiparesis) and/or patients with newly occurring epileptic seizures, we recommend that dexamethasone and antibiotics are started immediately after the collection of blood; we further recommend that -if the imaging findings do not indicate otherwise -a lumbar CSF sample is taken directly after imaging. (v) Due to the frequent occurrence of intracranial and systemic complications, we suggest that patients with acute bacterial meningitis are treated at an intensive care unit in the initial phase of the disease. In the case of impaired consciousness, we suggest that this is done at an intensive care unit with experience in the treatment of patients with severe CNS diseases. CONCLUSIONS: The German S2k-guidelines give up to date recommendations for workup, diagnostics and treatment in adult patients with acute bacterial meningitis.

Olfactory brain activations in patients with Major Depressive Disorder.

Depression is associated with reduced olfactory function. This relationship is assumed to be based on either a reduced olfactory bulb volume or diminished functioning of higher cortical areas. As previous results are controversial, we aimed to re-evaluate central olfactory processing in depression. We recorded the BOLD signal of 21 patients with Major Depressive Disorder and 21 age and gender matched healthy controls during odor presentation. In addition, we measured the individual olfactory bulb volume, tested odor identification and odor threshold, and asked for hedonic odor perception. In both groups, odor presentation led to a pronounced activation of primary olfactory areas. However, secondary olfactory areas were significantly less activated in depressed individuals. The two groups did not differ in olfactory bulb volume. Our results point towards altered olfactory processing in patients in those regions that relate to sensory integration and attention allocation. Difficulties in cognitive processing could impact olfactory function in depression. We are therefore in favor of a top-down mechanism originating in higher cortical areas explaining parts of the relation between depression and olfaction.

Unchanged perfusion in normal-appearing white and grey matter of glioma patients nine months after proton beam irradiation.

PURPOSE: Radio(chemo)therapy is used as a standard treatment for glioma patients. The surrounding normal tissue is inevitably affected by the irradiation. The aim of this longitudinal study was to investigate perfusion alterations in the normal-appearing tissue after proton irradiation and assess the dose sensitivity of the normal tissue perfusion. METHODS: In 14 glioma patients, a sub-cohort of a prospective clinical trial (NCT02824731), perfusion changes in normal-appearing white matter (WM), grey matter (GM) and subcortical GM structures, i.e. caudate nucleus, hippocampus, amygdala, putamen, pallidum and thalamus, were evaluated before treatment and at three-monthly intervals after proton beam irradiation. The relative cerebral blood volume (rCBV) was assessed with dynamic susceptibility contrast MRI and analysed as the percentage ratio between follow-up and baseline image (ΔrCBV). Radiation-induced alterations were evaluated using Wilcoxon signed rank test. Dose and time correlations were investigated with univariate and multivariate linear regression models. RESULTS: No significant ΔrCBV changes were found in any normal-appearing WM and GM region after proton beam irradiation. A positive correlation with radiation dose was observed in the multivariate regression model applied to the combined ΔrCBV values of low (1-20 Gy), intermediate (21-40 Gy) and high (41-60 Gy) dose regions of GM (p < 0.001), while no time dependency was detected in any normal-appearing area. CONCLUSION: The perfusion in normal-appearing brain tissue remained unaltered after proton beam therapy. In further studies, a direct comparison with changes after photon therapy is recommended to confirm the different effect of proton therapy on the normal-appearing tissue.

A Systematic Literature Review and Meta-Analysis of the Treatment of Ruptured Intracranial Aneurysms with Hydrophilic Polymer and Phosphorylcholine-Coated Flow Diverters Under Single Antiplatelet Therapy.

OBJECTIVE: Flow diverters coated with antithrombogenic substances were recently introduced and have shown encouraging results in the preclinical setting. Our aim was to analyze their clinical application in patients with ruptured intracranial aneurysms using single antiplatelet therapy (SAPT). METHODS: We performed a PRISMA-compliant systematic review and meta-analysis covering 3 major data bases until March 2022.Two reviewers independently reviewed clinical studies for eligibility.Random-effects analysis of proportions was used to pool safety outcomes (hemorrhagic, thrombembolic, and overall complications). Studies were tested for publication bias and heterogeneity. RESULTS: Five studies reporting 43 patients with 46 aneurysms were identified. More than 1 stent was implanted in 16%, and additional coil embolization was performed in 53.8% of patients. SAPT with one of various acetylsalicylic acid regimens was used in 86%, altogether antiplatelet protocols were variable. The pooled risks of thromboembolic (23.9%; 95% confidence interval [CI], 9.6-47.9), hemorrhagic (9.4%; 95% CI, 3.6-22.6), and overall complications (28.3%; 95% CI, 12.4-52.5) were calculated in the absence of publication bias with low to moderate study heterogeneity measures. All complications occurred in patients under acetylsalicylic acid SAPT. Adequate aneurysm occlusion was described in 65.5% of patients.few retrospective observational studies with moderate heterogeneity, encompassing a limited number of patients treated with variable SAPT regimens. CONCLUSIONS: Flow diversion for ruptured aneurysms under SAPT with coated stents is feasible. Although the risk of hemorrhagic complications was low, thromboembolic complications occurred in a significant number of patients, all under ASA SAPT.

Flow diversion for compressive unruptured internal carotid artery aneurysms with neuro-ophthalmological symptoms: a systematic review and meta-analysis.

BACKGROUND: Data on the safety and efficacy of flow diverters (FD) for the treatment of unruptured internal carotid artery (ICA) aneurysms with compressive neuro-ophthalmological symptoms (NOS) are scarce and comprise mainly small case series. METHODS: We performed a search of three databases and included series with ≥10 patients, with unruptured aneurysms of the ICA and NOS, treated with FD. Random-effects analysis of treatment results and safety was performed. RESULTS: A total of 22 studies reporting on 594 patients were included. Pooled proportions of NOS recovery, improvement, transient and permanent worsening were: 47.4% (95% CI 35.0% to 60.1%); 74.5% (95% CI 67.9% to 80.2%); 7.1% (95% CI 3.3% to 14.7%); and 4.9% (95% CI 3.2% to 7.4%), respectively. Rates of complete recovery and improvement in patients with isolated visual symptoms were 30.6% (95% CI 12.5% to 57.7%) and 56.6% (95% CI 42.3% to 69.9%). Isolated oculomotor symptoms recovered completely in 47.8% (95% CI 29.9% to 66.3%) and improved in 78% (95% CI 69.2% to 84.9%). Morbidity occurred in 5% (95% CI 2.8% to 9%) and mortality in 3.9% (95% CI 2% to 7.5%) of patients. An increased likelihood of symptom improvement was observed when treatment was performed early (<1 month) after symptom onset (OR=11.22, 95% CI 3.9% to 32.5%). CONCLUSION: Flow diversion promotes recovery or improvement of compressive symptoms in a large proportion of patients but is associated with significant rates of morbidity and mortality. Transient and permanent NOS worsening is not uncommon. Early treatment is of utmost importance, as it increases the likelihood of symptom improvement more than 10-fold.

Exploring in vivo lesion myelination dynamics: Longitudinal Myelin Water Imaging in early Multiple Sclerosis.

BACKGROUND: Multiple Sclerosis (MS) lesions are pathologically heterogeneous and the temporal behavior in terms of growth and myelination status of individual lesions is highly variable, especially in the early phase of the disease. Thus, monitoring the development of individual lesion myelination by using quantitative magnetic resonance myelin water imaging (MWI) could be valuable to capture the variability of disease pathology and get an individual insight into the subclinical disease activity. OBJECTIVE: The goal of this work was (1) to observe the variation and longitudinal change of in vivo lesion myelination by means of MWI and its parameter Myelin Water Fraction (MWF), and, (2) to identify individual lesion myelination patterns in early MS. METHODS: In this study n = 12 patients obtained conventional MRI and quantitative MWI derived from multi-component driven equilibrium single pulse observation of T1 and T2 (mcDESPOT) within four weeks after presenting a clinically isolated syndrome and remained within the study if clinically definitive MS was diagnosed within the 12 months study period. Four MRI sessions were acquired at baseline, 3, 6, and 12 months. The short-term and long-term variability of MWF maps was evaluated by scan-rescan measures and the coefficient of variation was determined in four healthy controls. Tracking of individual lesions was performed using the Automatic Follow-up of Individual Lesions (AFIL) algorithm. Lesion volume and MWF were evaluated for every individual lesion in all patients. Median lesion MWF change was used to define lesion categories as decreasing, varying, increasing and invariant for MWF variation. RESULTS: In total n = 386 T2 lesions were detected with a subset of n = 225 permanent lesions present at all four time-points. Among those, a heterogeneous lesion MWF reduction was found, with the majority of lesions bearing only mild MWF reduction, approximately a third with an intermediate MWF decrease and highest MWF reduction in acute-inflammatory active lesions. A moderate negative correlation was determined between individual lesion volumes and median MWF consistent across all time-points. Permanent lesions featured variable temporal dynamics with the majority of varying MWF (58 %), however decreasing (16 %), increasing (15 %) and invariant (11 %) subgroups could be identified resembling demyelinating activity and post-demyelinating inactivity known from histopathology studies. Inflammatory-active enhancing lesions showed a distinct pattern of MWF reduction followed by partial recovery after 3 months. This was similar in new enhancing lesions and those with a non-enhancing precursor lesion. CONCLUSION: This work provides in vivo evidence for an individual evolution of early demyelinated MS lesions measured by means of MWF imaging. Our results support the hypothesis, that MS lesions undergo multiple demyelination and remyelination episodes in the early acute phase. The in vivo MRI surrogate of myelin turnover bears capacity as a novel biomarker to select and potentially monitor personalized MS treatment.

Optimizing Time Management for Drip-and-Ship Stroke Patients Qualifying for Endovascular Therapy-A Single-Network Study.

BACKGROUND: We sought to identify factors for delayed drip-and-ship (DS) management in stroke patients transferred from primary hospitals to our comprehensive stroke center (CSC) for endovascular therapy (EVT). METHODS: We conducted a retrospective study of all patients transferred to our CSC for EVT between 2016 and 2020. We analyzed emergency and hospital records to assess DS process times and factors predictive of delays. We dichotomized the admission period to 2016−2017 and 2018−2020 according to the main process optimization, including the introduction of a prenotification call. RESULTS: We included 869 DS patients (median age 76 years (IQR 65−82), NIHSS 16 (IQR 11−21), 278 min (IQR 243−335) from onset to EVT); 566 were transferred in 2018−2020. Admission in 2016−2017, during on-call, longer tranfer distance, and general anesthesia were factors independently associated with delayed onset to EVT time (F(5, 352) = 14.76, p < 0.000). Other factors associated with delayed DS management were: transfer mode, primary hospital type, site of large-vessel occlusion, and intravenous thrombolysis. Total transfer time was faster for distances <50 km by ambulance and for distances >71 km by helicopter. CONCLUSION: Assessment of DS processes and times throughout the patient pathway allows identification of potentially modifiable factors for improvement of the very time-critical workflow for stroke patients.

The Boston criteria version 2.0 for cerebral amyloid angiopathy: a multicentre, retrospective, MRI-neuropathology diagnostic accuracy study.

BACKGROUND: Cerebral amyloid angiopathy (CAA) is an age-related small vessel disease, characterised pathologically by progressive deposition of amyloid ß in the cerebrovascular wall. The Boston criteria are used worldwide for the in-vivo diagnosis of CAA but have not been updated since 2010, before the emergence of additional MRI markers. We report an international collaborative study aiming to update and externally validate the Boston diagnostic criteria across the full spectrum of clinical CAA presentations. METHODS: In this multicentre, hospital-based, retrospective, MRI and neuropathology diagnostic accuracy study, we did a retrospective analysis of clinical, radiological, and histopathological data available to sites participating in the International CAA Association to formulate updated Boston criteria and establish their diagnostic accuracy across different populations and clinical presentations. Ten North American and European academic medical centres identified patients aged 50 years and older with potential CAA-related clinical presentations (ie, spontaneous intracerebral haemorrhage, cognitive impairment, or transient focal neurological episodes), available brain MRI, and histopathological assessment for CAA diagnosis. MRI scans were centrally rated at Massachusetts General Hospital (Boston, MA, USA) for haemorrhagic and non-haemorrhagic CAA markers, and brain tissue samples were rated by neuropathologists at the contributing sites. We derived the Boston criteria version 2.0 (v2.0) by selecting MRI features to optimise diagnostic specificity and sensitivity in a prespecified derivation cohort (Boston cases 1994-2012, n=159), then externally validated the criteria in a prespecified temporal validation cohort (Boston cases 2012-18, n=59) and a geographical validation cohort (non-Boston cases 2004-18; n=123), comparing accuracy of the new criteria to the currently used modified Boston criteria with histopathological assessment of CAA as the diagnostic standard. We also assessed performance of the v2.0 criteria in patients across all cohorts who had the diagnostic gold standard of brain autopsy. FINDINGS: The study protocol was finalised on Jan 15, 2017, patient identification was completed on Dec 31, 2018, and imaging analyses were completed on Sept 30, 2019. Of 401 potentially eligible patients presenting to Massachusetts General Hospital, 218 were eligible to be included in the analysis; of 160 patient datasets from other centres, 123 were included. Using the derivation cohort, we derived provisional criteria for probable CAA requiring the presence of at least two strictly lobar haemorrhagic lesions (ie, intracerebral haemorrhages, cerebral microbleeds, or foci of cortical superficial siderosis) or at least one strictly lobar haemorrhagic lesion and at least one white matter characteristic (ie, severe visible perivascular spaces in centrum semiovale or white matter hyperintensities in a multispot pattern). The sensitivity and specificity of these criteria were 74·8% (95% CI 65·4-82·7) and 84·6% (71·9-93·1) in the derivation cohort, 92·5% (79·6-98·4) and 89·5% (66·9-98·7) in the temporal validation cohort, 80·2% (70·8-87·6) and 81·5% (61·9-93·7) in the geographical validation cohort, and 74·5% (65·4-82·4) and 95·0% (83·1-99·4) in all patients who had autopsy as the diagnostic standard. The area under the receiver operating characteristic curve (AUC) was 0·797 (0·732-0·861) in the derivation cohort, 0·910 (0·828-0·992) in the temporal validation cohort, 0·808 (0·724-0·893) in the geographical validation cohort, and 0·848 (0·794-0·901) in patients who had autopsy as the diagnostic standard. The v2.0 Boston criteria for probable CAA had superior accuracy to the current Boston criteria (sensitivity 64·5% [54·9-73·4]; specificity 95·0% [83·1-99·4]; AUC 0·798 [0·741-0854]; p=0·0005 for comparison of AUC) across all individuals who had autopsy as the diagnostic standard. INTERPRETATION: The Boston criteria v2.0 incorporate emerging MRI markers of CAA to enhance sensitivity without compromising their specificity in our cohorts of patients aged 50 years and older presenting with spontaneous intracerebral haemorrhage, cognitive impairment, or transient focal neurological episodes. Future studies will be needed to determine generalisability of the v.2.0 criteria across the full range of patients and clinical presentations. FUNDING: US National Institutes of Health (R01 AG26484).

Subjective memory impairment in glioma patients with curative radiotherapy.

BACKGROUND: Radiotherapy in patients with primary brain tumors may affect hippocampal structure and cause dyscognitive side-effects. PATIENTS AND METHODS: Using structural MRI and comprehensive neurocognitive evaluation, we investigated associations between hippocampal structure and memory deficits in 15 patients with WHO grade 3 and grade 4 gliomas receiving standard radio(chemo)therapy. RESULTS: We did not find changes in hippocampal thickness or cognitive abilities three months after completing radiotherapy. However, subjective memory impairment was associated with symptoms of depression, but not with objective memory performance, cortical thickness of the hippocampus or radiation dose. CONCLUSIONS: Irrespective of whether there is a bidirectional relationship between affective changes and subjective cognitive dysfunction in these patients, depressive symptoms remain a target for intervention to improve their quality of life. The results of our pilot study highlight that future assessment of side effects of radiotherapy concerning memory should include assessments of depressive symptoms.

Ultrasonography Grading of Internal Carotid Artery Disease: Multiparametric German Society of Ultrasound in Medicine (DEGUM) versus Society of Radiologists in Ultrasound (SRU) Consensus Criteria.

PURPOSE: We sought to determine the diagnostic agreement between the revised ultrasonography approach by the German Society of Ultrasound in Medicine (DEGUM) and the established Society of Radiologists in Ultrasound (SRU) consensus criteria for the grading of carotid artery disease. MATERIALS AND METHODS: Post-hoc analysis of a prospective multicenter study, in which patients underwent ultrasonography and digital subtraction angiography (DSA) of carotid arteries for validation of the DEGUM approach. According to DEGUM and SRU ultrasonography criteria, carotid arteries were independently categorized into clinically relevant NASCET strata (normal, mild [1-49 %], moderate [50-69 %], severe [70-99 %], occlusion). On DSA, carotid artery findings according to NASCET were considered the reference standard. RESULTS: We analyzed 158 ultrasonography and DSA carotid artery pairs. There was substantial agreement between both ultrasonography approaches for severe (κw 0.76, CI95 %: 0.66-0.86), but only fair agreement for moderate (κw 0.38, CI95 %: 0.19-0.58) disease categories. Compared with DSA, both ultrasonography approaches were of equal sensitivity (79.7 % versus 79.7 %; p = 1.0) regarding the identification of severe stenosis, yet the DEGUM approach was more specific than the SRU approach (70.2 % versus 56.4 %, p = 0.0002). There was equality of accuracy parameters (p > 0.05) among both ultrasonography approaches for the other ranges of carotid artery disease. CONCLUSION: While the sensitivity was equivalent, false-positive identification of severe carotid artery stenosis appears to be more frequent when using the SRU ultrasonography approach than the revised multiparametric DEGUM approach.

Predictors of subjective cognitive deficits in patients with mild cognitive impairment.

BACKGROUND: Detailed examination of cognitive deficits in patients with mild cognitive impairment (MCI) yields substantial diagnostic and prognostic value, specifically with respect to memory. Magnitude and characteristics of subjective cognitive deficits, however, often receive less attention in this population at risk for developing dementia. METHODS: We investigated predictors of subjective cognitive deficits in patients with MCI, using a detailed assessment for such impairments associated with different cognitive domains, as well as demographic and clinical variables including magnetic resonance imaging data. RESULTS: The strongest predictor for subjective memory deficits was depressed mood, whereas subjective performance issues associated with attention or executive functions also corresponded to measurable impairments in the respective cognitive domains. Reduced hippocampal thickness and hemispheric entorhinal cortex thickness asymmetry were associated with objective memory impairment but not with subjective deficits or symptoms of depression. CONCLUSIONS: Whereas low objective memory performance and reduced cortical thickness within medial temporal lobe subregions could be associated with neurodegeneration, greater subjective memory deficits in patients with MCI may indicate psychological burden.