Equivalence of plasma p-tau217 with cerebrospinal fluid in the diagnosis of Alzheimer's disease.

INTRODUCTION: Plasma biomarkers are promising tools for Alzheimer's disease (AD) diagnosis, but comparisons with more established biomarkers are needed. METHODS: We assessed the diagnostic performance of p-tau181 , p-tau217 , and p-tau231 in plasma and CSF in 174 individuals evaluated by dementia specialists and assessed with amyloid-PET and tau-PET. Receiver operating characteristic (ROC) analyses assessed the performance of plasma and CSF biomarkers to identify amyloid-PET and tau-PET positivity. RESULTS: Plasma p-tau biomarkers had lower dynamic ranges and effect sizes compared to CSF p-tau. Plasma p-tau181 (AUC = 76%) and p-tau231 (AUC = 82%) assessments performed inferior to CSF p-tau181 (AUC = 87%) and p-tau231 (AUC = 95%) for amyloid-PET positivity. However, plasma p-tau217 (AUC = 91%) had diagnostic performance indistinguishable from CSF (AUC = 94%) for amyloid-PET positivity. DISCUSSION: Plasma and CSF p-tau217 had equivalent diagnostic performance for biomarker-defined AD. Our results suggest that plasma p-tau217 may help reduce the need for invasive lumbar punctures without compromising accuracy in the identification of AD. HIGHLIGHTS: p-tau217 in plasma performed equivalent to p-tau217 in CSF for the diagnosis of AD, suggesting the increased accessibility of plasma p-tau217 is not offset by lower accuracy. p-tau biomarkers in plasma had lower mean fold-changes between amyloid-PET negative and positive groups than p-tau biomarkers in CSF. CSF p-tau biomarkers had greater effect sizes than plasma p-tau biomarkers when differentiating between amyloid-PET positive and negative groups. Plasma p-tau181 and plasma p-tau231 performed worse than p-tau181 and p-tau231 in CSF for AD diagnosis.

MRI versus CT in the detection of brain lesions in patients with infective endocarditis before or after cardiac surgery.

PURPOSE: Imaging of brain involvement in infective endocarditis can drive the clinical management of this serious condition. MRI is very sensitive, but CT is more readily available. In this retrospective study, we compared the detection rates of CT and MRI. METHODS: After Ethics Committee approval, we retrospectively reviewed a series of 20 patients (13 males, median age 64 years) who underwent both CT and MRI either before or after cardiac surgery for definite infective endocarditis. Plain CT and MRI were evaluated for acute ischemic lesions, both punctuate and large, intraparenchymal hemorrhages, cerebral microbleeds, subarachnoid hemorrhages, abscesses, microabscesses, and meningitis. Qualitative assessment and McNemar test were performed. The value of contrast-enhanced scans (MRI, n = 14; CT, n = 9) and cognitive status were also assessed. RESULTS: A total of 166 lesions were identified on either technique: 137 (83%) on MRI only, 4 (2%) on CT only, and 25 (15%) on both techniques (p < 0.001). For these last 25 lesions, concordance on lesion type was only 16/25 (64%). MRI detected more microbleeds and ischemic lesions, while the 4 CT-only findings were false positives. Contrast-enhanced scans identified 68 enhancing lesions, mainly abscesses and microabscesses, and allowed a better characterization for 61/117 lesions (52%) with MRI, and for 11/81 (14%) with CT. Follow-up identified mild cognitive impairment in 6/13 and dementia in 3/13 patients. CONCLUSION: While CT rapidly excludes large hemorrhages in patients with infective endocarditis, MRI accurately distinguishes the whole spectrum of brain lesions, including small ischemic lesions, microbleeds, and microabscesses.

Videoconference version of the Montreal Cognitive Assessment: normative data for Quebec-French people aged 50 years and older.

BACKGROUND: The COVID-19 pandemic forced health professionals to rapidly develop and implement telepractice and remote assessments. Recent reviews appear to confirm the validity of a wide range of neuropsychological tests for teleneuropsychology and among these, the Montreal Cognitive Assessment (MoCA), a cognitive screening test widely used in clinical settings. The normative data specific to the context of videoconference administration is essential, particularly that consider sociodemographic characteristics. AIMS: This study had for objective to develop French-Quebec normative data for videoconference-administration of the MoCA that consider sociodemographic characteristics. METHODS: A total of 230 community-dwelling adults aged 50 years and older taking part in clinical trials completed the MoCA by videoconference. Regression analyses were run with sex, education, and age as predictors of the total MoCA scores, based on previously published norms. As an exploratory analysis, a second regression analysis was also run with cardiovascular disease as a predictor. RESULTS: Regression analyses revealed that older age and lower education were associated with poorer total MoCA scores, for medium effect size (p < 0.001, R2 = 0.17). Neither sex nor cardiovascular disease, were significant predictors in our analyses. For clinicians, a regression equation was proposed to calculate Z scores. DISCUSSION: This study provides normative data for the MoCA administered via videoconference in Quebec-French individuals aged 50 years and over. CONCLUSIONS: The present normative data will not only allow clinicians to continue to perform assessments remotely in this pandemic period but will also allow them to perform cognitive assessments to patients located in remote areas.

Striatal Dopamine Deficit and Motor Impairment in Idiopathic Normal Pressure Hydrocephalus.

BACKGROUND: Idiopathic normal pressure hydrocephalus can present with parkinsonism. However, abnormalities of the striatal dopamine reuptake transporter are unclear. OBJECTIVES: To explore presence and features of striatal dopaminergic deficit in subjects with idiopathic normal pressure hydrocephalus as compared to Parkinson's disease (PD) patients and healthy controls. METHODS: We investigated 50 subjects with idiopathic normal pressure hydrocephalus, 25 with PD, and 40 healthy controls. All participants underwent [123 I]-N-ω-fluoropropyl-2ß-carbomethoxy-3ß-(4-iodophenyl)nortropane and single-photon emission computed tomography to quantify the striatal dopamine reuptake transporter binding. All subjects with idiopathic normal pressure hydrocephalus underwent a levodopa (l-dopa) challenge test and magnetic resonance imaging to evaluate ventriculomegaly and white matter changes. Gait, cognition, balance, and continence were assessed with the Idiopathic Normal Pressure Hydrocephalus Rating Scale, and parkinsonism with the motor section of the Movement Disorder Society-Unified Parkinson's Disease Rating Scale. All patients completed a 2-year follow-up. RESULTS: A total of 62% of patients with idiopathic normal pressure hydrocephalus featured a reduced striatal dopamine reuptake transporter binding, which correlated with the severity of parkinsonism but not with features of ventriculomegaly or white matter changes. Unlike PD, this dopaminergic deficit in idiopathic normal pressure hydrocephalus was more symmetric and prominent in the caudate nucleus. CONCLUSIONS: Subjects with idiopathic normal pressure hydrocephalus can present a reduction of striatal dopamine reuptake transporter binding, which is consistent with the severity of parkinsonism and qualitatively differs from that found in PD patients. Longitudinal interventional studies are needed to prove a role for striatal dopamine reuptake transporter deficit in the pathophysiology of idiopathic normal pressure hydrocephalus. © 2020 International Parkinson and Movement Disorder Society.

White Matter Hyperintensities Quantification in Healthy Adults: A Systematic Review and Meta-Analysis.

BACKGROUND: Although white matter hyperintensities (WMH) volumetric assessment is now customary in research studies, inconsistent WMH measures among homogenous populations may prevent the clinical usability of this biomarker. PURPOSE: To determine whether a point estimate and reference standard for WMH volume in the healthy aging population could be determined. STUDY TYPE: Systematic review and meta-analysis. POPULATION: In all, 9716 adult subjects from 38 studies reporting WMH volume were retrieved following a systematic search on EMBASE. FIELD STRENGTH/SEQUENCE: 1.0T, 1.5T, or 3.0T/fluid-attenuated inversion recovery (FLAIR) and/or proton density/T2 -weighted fast spin echo sequences or gradient echo T1 -weighted sequences. ASSESSMENT: After a literature search, sample size, demographics, magnetic field strength, MRI sequences, level of automation in WMH assessment, study population, and WMH volume were extracted. STATISTICAL TESTS: The pooled WMH volume with 95% confidence interval (CI) was calculated using the random-effect model. The I2 statistic was calculated as a measure of heterogeneity across studies. Meta-regression analysis of WMH volume on age was performed. RESULTS: Of the 38 studies analyzed, 17 reported WMH volume as the mean and standard deviation (SD) and were included in the meta-analysis. Mean and SD of age was 66.11 ± 10.92 years (percentage of men 50.45% ± 21.48%). Heterogeneity was very high (I2  = 99%). The pooled WMH volume was 4.70 cm3 (95% CI: 3.88-5.53 cm3 ). At meta-regression analysis, WMH volume was positively associated with subjects' age (ß = 0.358 cm3 per year, P < 0.05, R2  = 0.27). DATA CONCLUSION: The lack of standardization in the definition of WMH together with the high technical variability in assessment may explain a large component of the observed heterogeneity. Currently, volumes of WMH in healthy subjects are not comparable between studies and an estimate and reference interval could not be determined. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 1.

Diagnostic Impact of Cerebrospinal Fluid Biomarkers in Atypical Dementias in Canada.

BACKGROUND: In Canada, standard dementia workup consists of clinical, neurological, and cognitive evaluation, as well as structural brain imaging. For atypical dementia presentations, additional FDG-PET brain imaging is recommended. Cerebrospinal fluid (CSF) biomarkers have recently been proposed as the gold standard for in vivo detection of Alzheimer's disease (AD) pathophysiology (NIA-AA research framework, 2018). As clinical implementation of CSF assessment is still limited in Canada, the present study assessed its impact on diagnostic accuracy in atypical neurodegenerative disorders in the clinical practice. METHODS: This retrospective clinical chart review included patients with cognitive complaints who underwent lumbar puncture (LP) in addition to the standard diagnostic workup. CSF analysis determined the presence of biological AD based on reduced amyloid-ß42-to-total-tau index (ATI) and increased phosphorylated-tau (p-tau) levels. CSF-based diagnoses were compared to standard workup and FDG-PET-based diagnoses. RESULTS: A total of 28 patients with atypical dementia presentations were included in the present study after evaluation for cognitive complaints at a specialized dementia clinic between November 2017 and July 2019. CSF analysis changed or better specified the initial clinical diagnosis in 43.0% of cases (alternative diagnosis revealed in 25% and excluded in 18%). In patients with additional FDG-PET imaging (n = 23), FDG-PET and CSF-based diagnosis did not correspond in 35% of patients, even though FDG-PET appeared to increase diagnostic accuracy compared to the initial clinical diagnosis. CONCLUSION: CSF biomarkers improved diagnostic accuracy in atypical cognitively-impaired patients beyond standard workup and FDG-PET imaging. These results support CSF analysis implementation for atypical dementias in Canada, in addition to the standard diagnostic workup.

Progressive apraxia of speech in Quebec French speakers: A case series.

BACKGROUND: The term progressive apraxia of speech (PAOS) is used to describe speakers presenting with isolated or dominant apraxia of speech in the context of a neurodegenerative syndrome, including primary progressive apraxia of speech (PPAOS) and dominant progressive apraxia of speech (DAOS), respectively. Its motor speech profile has been increasingly explored in the last decade, but description remains vague and very English oriented, although the effect of speakers' language on motor speech phenotypes is increasingly recognized. Although some studies suggest that speakers presenting with isolated PAOS (PPAOS) versus dominant PAOS with concomitant aphasia (DAOS) should be differentiated, distinct characteristics of the two presentations are unclear. Furthermore, a careful description of their clinical presentation in languages other than English is required. AIMS: To describe the motor speech characteristics of Quebec French-speaking participants with prominent PAOS and to explore the communication profile of those presenting more specifically with isolated PAOS (PPAOS), and with dominant PAOS and concomitant aphasia (DAOS). METHODS & PROCEDURES: A thorough effort to recruit all speakers presenting with PAOS in the larger population areas of the province of Quebec was conducted over a 3-year span. A total of nine participants with PAOS (pwPAOS; PPAOS = 5, DAOS = 4) underwent a comprehensive language and motor speech assessment, and a cognitive screening. Their performance was compared with 30 matched healthy controls. OUTCOMES & RESULTS: As a group, pwPAOS differed from healthy speakers on all acoustic and perceptual measures. The PPAOS and PAOS subgroups were similar on several measures, but participants from the PPAOS subgroup tended to perform better on articulatory measures and maximum speech rate tasks. CONCLUSIONS & IMPLICATIONS: This study provides an in-depth analysis of motor speech characteristics of PAOS in Quebec French speakers and adds further evidence for the differentiation of PPAOS and DAOS. Combining simple perceptual and acoustic analyses represent a promising approach to distinguish the two variants and identify treatment targets. What this paper adds What is already known on this subject Progressive apraxia of speech (PAOS) is a neurodegenerative syndrome characterized by progressive and initially isolated or dominant apraxia of speech (primary progressive apraxia of speech [PPAOS] and dominant progressive apraxia of speech [DAOS], respectively). Studies mostly report articulatory and prosodic deficits in PAOS, but concomitant deficits such as dysarthria and executive dysfunction are also reported. The description of motor speech skills in PAOS remains vague and English-oriented. Studies suggest that speakers presenting with isolated PAOS vs dominant PAOS with concomitant aphasia should be differentiated, but distinct characteristics of the two presentations are unclear. What this study adds to existing knowledge To the best of the authors' knowledge, this study is the first to report transversal data of Quebec-French participants with PPAOS and DAOS. Moreover, this study is a first step towards identifying potential characteristics that could facilitate the diagnosis of PPAOS and DAOS in Quebec French. It makes a significant contribution to our understanding of progressive apraxia of speech in different cultural languages. What are the potential or actual clinical implications of this work? This study also initiates the search for sensitive tasks for the diagnosis of those speakers (which is an important process), in addition to identifying the core characteristics of PAOS, DAOS, and PPAOS in the development of an assessment battery for this population.

Substantia Nigra Volumetry with 3-T MRI in De Novo and Advanced Parkinson Disease.

Background Magnetization transfer-prepared T1-weighted MRI can depict a hyperintense subregion of the substantia nigra involved in the degeneration process of Parkinson disease. Purpose To evaluate quantitative measurement of substantia nigra volume by using MRI to support clinical diagnosis and staging of Parkinson disease. Materials and Methods In this prospective study, a high-spatial-resolution magnetization transfer-prepared T1-weighted volumetric sequence was performed with a 3-T MRI machine between January 2014 and October 2015 for participants with de novo Parkinson disease, advanced Parkinson disease, and healthy control participants. A reproducible semiautomatic quantification analysis method that entailed mesencephalic intensity as an internal reference was used for hyperintense substantia nigra volumetry normalized to intracranial volume. A general linear model with age and sex as covariates was used to compare the three groups. Results Eighty participants were evaluated: 20 healthy control participants (mean age ± standard deviation, 56 years ± 11; 11 women), 29 participants with de novo Parkinson disease (64 years ± 10; 19 men), and 31 participants with advanced Parkinson disease (60 years ± 9; 16 women). Volumetric measurement of hyperintense substantia nigra from magnetization transfer-prepared T1-weighted MRI helped differentiate healthy control participants from participants with advanced Parkinson disease (mean difference for ipsilateral side, 64 mm3 ± 14, P < .001; mean difference for contralateral side, 109 mm3 ± 14, P < .001) and helped distinguish healthy control participants from participants with de novo Parkinson disease (mean difference for ipsilateral side, 45 mm3 ± 15, P < .01; mean difference for contralateral side, 66 mm3 ± 15, P < .001) and participants with de novo Parkinson disease from those with advanced Parkinson disease (mean difference for ipsilateral side, 20 mm3 ± 13, P = .40; mean difference for contralateral side, 43 mm3 ± 13, P = .004). Conclusion Magnetization transfer-prepared T1-weighted MRI volumetry of the substantia nigra helped differentiate the stages of Parkinson disease. © RSNA, 2020 Online supplemental material is available for this article.

Discovering the Italian phenotype of cerebral amyloid angiopathy (CAA): the SENECA project.

Cerebral amyloid angiopathy (CAA) is one of the major types of cerebral small vessel disease, and a leading cause of spontaneous intracerebral hemorrhage and cognitive decline in elderly patients. Although increasingly detected, a number of aspects including the pathophysiology, the clinical and neuroradiological phenotype, and the disease course are still under investigation. The incomplete knowledge of the disease limits the implementation of evidence-based guidelines on patient's clinical management and the development of treatments able to prevent or reduce disease progression. The SENECA (SEarchiNg biomarkErs of Cerebral Angiopathy) project is the first Italian multicenter cohort study aimed at better defining the disease natural history and identifying clinical and neuroradiological markers of disease progression. By a multidisciplinary approach and the collection of a large and well-phenotyped series and biorepository of CAA patients, the study is ultimately expected to improve the diagnosis and the knowledge of CAA pathophysiological mechanisms.

Mild behavioral impairment is associated with ß-amyloid but not tau or neurodegeneration in cognitively intact elderly individuals.

INTRODUCTION: Mild behavioral impairment (MBI) is characterized by the emergence of neuropsychiatric symptoms in elderly persons. Here, we examine the associations between MBI and Alzheimer's disease (AD) biomarkers in asymptomatic elderly individuals. METHODS: Ninety-six cognitively normal elderly individuals underwent MRI, [18 F]AZD4694 ß-amyloid-PET, and [18 F]MK6240 tau-PET. MBI was assessed using the MBI Checklist (MBI-C). Pearson's correlations and voxel-based regressions were used to evaluate the relationship between MBI-C score and [18 F]AZD4694 retention, [18 F]MK6240 retention, and gray matter (GM) volume. RESULTS: Pearson correlations revealed a positive relationship between MBI-C score and global and striatal [18 F]AZD4694 standardized uptake value ratios (SUVRs). Voxel-based regression analyses revealed a positive correlation between MBI-C score and [18 F]AZD4694 retention. No significant correlations were found between MBI-C score and [18 F]MK6240 retention or GM volume. CONCLUSION: We demonstrate for the first time a link between MBI and early AD pathology in a cognitively intact elderly population, supporting the use of the MBI-C as a metric to enhance clinical trial enrolment.

Management of epilepsy in brain tumors.

Epilepsy in brain tumors (BTE) may require medical attention for a variety of unique concerns: epileptic seizures, possible serious adverse effects of antineoplastic and antiepileptic drugs (AEDs), physical disability, and/or neurocognitive disturbances correlated to tumor site. Guidelines for the management of tumor-related epilepsies are lacking. Treatment is not standardized, and overall management might differ according to different specialists. The aim of this document was to provide directives on the procedures to be adopted for a correct diagnostic-therapeutic path of the patient with BTE, evaluating indications, risks, and benefits. A board comprising neurologists, epileptologists, neurophysiologists, neuroradiologists, neurosurgeons, neuro-oncologists, neuropsychologists, and patients' representatives was formed. The board converted diagnostic and therapeutic problems into seventeen questions. A literature search was performed in September-October 2017, and a total of 7827 unique records were retrieved, of which 148 constituted the core literature. There is no evidence that histological type or localization of the brain tumor affects the response to an AED. The board recommended to avoid enzyme-inducing antiepileptic drugs because of their interference with antitumoral drugs and consider as first-choice newer generation drugs (among them, levetiracetam, lamotrigine, and topiramate). Valproic acid should also be considered. Both short-term and long-term prophylaxes are not recommended in primary and metastatic brain tumors. Management of seizures in patients with BTE should be multidisciplinary. The panel evidenced conflicting or lacking data regarding the role of EEG, the choice of therapeutic strategy, and timing to withdraw AEDs and recommended high-quality long-term studies to standardize BTE care.

Brain Gliomas: Multicenter Standardized Assessment of Dynamic Contrast-enhanced and Dynamic Susceptibility Contrast MR Images.

Purpose To evaluate the feasibility of a standardized protocol for acquisition and analysis of dynamic contrast material-enhanced (DCE) and dynamic susceptibility contrast (DSC) magnetic resonance (MR) imaging in a multicenter clinical setting and to verify its accuracy in predicting glioma grade according to the new World Health Organization 2016 classification. Materials and Methods The local research ethics committees of all centers approved the study, and informed consent was obtained from patients. One hundred patients with glioma were prospectively examined at 3.0 T in seven centers that performed the same preoperative MR imaging protocol, including DCE and DSC sequences. Two independent readers identified the perfusion hotspots on maps of volume transfer constant (Ktrans), plasma (vp) and extravascular-extracellular space (ve) volumes, initial area under the concentration curve, and relative cerebral blood volume (rCBV). Differences in parameters between grades and molecular subtypes were assessed by using Kruskal-Wallis and Mann-Whitney U tests. Diagnostic accuracy was evaluated by using receiver operating characteristic curve analysis. Results The whole protocol was tolerated in all patients. Perfusion maps were successfully obtained in 94 patients. An excellent interreader reproducibility of DSC- and DCE-derived measures was found. Among DCE-derived parameters, vp and ve had the highest accuracy (are under the receiver operating characteristic curve [Az] = 0.847 and 0.853) for glioma grading. DSC-derived rCBV had the highest accuracy (Az = 0.894), but the difference was not statistically significant (P > .05). Among lower-grade gliomas, a moderate increase in both vp and rCBV was evident in isocitrate dehydrogenase wild-type tumors, although this was not significant (P > .05). Conclusion A standardized multicenter acquisition and analysis protocol of DCE and DSC MR imaging is feasible and highly reproducible. Both techniques showed a comparable, high diagnostic accuracy for grading gliomas. © RSNA, 2018 Online supplemental material is available for this article.

Herpes simplex encephalitis in glioma patients: a challenging diagnosis.

OBJECTIVES: In recent years, herpes simplex encephalitis (HSE) has been reported with increasing frequency in settings of immunosuppression, such as acquired immunodeficiency, transplantation and cancer. As observed, in immunocompromised individuals HSE presents peculiar clinical and paraclinical features, and poorer prognosis. METHODS: Here we describe a retrospective series of seven cases of HSE in patients with high-grade glioma (HGG), collected among three institutions in a 5-year period (during this time, a total of 1750 patients with HGG were treated). RESULTS: Diagnosis of the condition was particularly challenging due to the confounding clinical presentation and the atypical biological findings. As a result, antiviral treatment was started with a sharp delay compared with immunocompetent hosts. Prognosis was poor, with high short-term mortality and severe residual disability in survivors. CONCLUSIONS: The substantial incidence of HSE observed in our centres together with the difficulty in diagnosing the condition suggest that the incidence of this complication may be highly underestimated. The aim of our report is to strengthen the observation of HSE in patients with HGG and outline the key elements that may allow its diagnosis.

White matter involvement in sporadic Creutzfeldt-Jakob disease.

Sporadic Creutzfeldt-Jakob disease is considered primarily a disease of grey matter, although the extent of white matter involvement has not been well described. We used diffusion tensor imaging to study the white matter in sporadic Creutzfeldt-Jakob disease compared to healthy control subjects and to correlated magnetic resonance imaging findings with histopathology. Twenty-six patients with sporadic Creutzfeldt-Jakob disease and nine age- and gender-matched healthy control subjects underwent volumetric T1-weighted and diffusion tensor imaging. Six patients had post-mortem brain analysis available for assessment of neuropathological findings associated with prion disease. Parcellation of the subcortical white matter was performed on 3D T1-weighted volumes using Freesurfer. Diffusion tensor imaging maps were calculated and transformed to the 3D-T1 space; the average value for each diffusion metric was calculated in the total white matter and in regional volumes of interest. Tract-based spatial statistics analysis was also performed to investigate the deeper white matter tracts. There was a significant reduction of mean (P=0.002), axial (P=0.0003) and radial (P=0.0134) diffusivities in the total white matter in sporadic Creutzfeldt-Jakob disease. Mean diffusivity was significantly lower in most white matter volumes of interest (P<0.05, corrected for multiple comparisons), with a generally symmetric pattern of involvement in sporadic Creutzfeldt-Jakob disease. Mean diffusivity reduction reflected concomitant decrease of both axial and radial diffusivity, without appreciable changes in white matter anisotropy. Tract-based spatial statistics analysis showed significant reductions of mean diffusivity within the white matter of patients with sporadic Creutzfeldt-Jakob disease, mainly in the left hemisphere, with a strong trend (P=0.06) towards reduced mean diffusivity in most of the white matter bilaterally. In contrast, by visual assessment there was no white matter abnormality either on T2-weighted or diffusion-weighted images. Widespread reduction in white matter mean diffusivity, however, was apparent visibly on the quantitative attenuation coefficient maps compared to healthy control subjects. Neuropathological analysis showed diffuse astrocytic gliosis and activated microglia in the white matter, rare prion deposition and subtle subcortical microvacuolization, and patchy foci of demyelination with no evident white matter axonal degeneration. Decreased mean diffusivity on attenuation coefficient maps might be associated with astrocytic gliosis. We show for the first time significant global reduced mean diffusivity within the white matter in sporadic Creutzfeldt-Jakob disease, suggesting possible primary involvement of the white matter, rather than changes secondary to neuronal degeneration/loss.

Proper name anomia in poststroke aphasics: evidence from a multiple-case study.

We aimed to characterize difficulties in famous face naming in three poststroke aphasic patients with a lesion limited to the left mid-posterior temporal language regions, sparing the anterior temporal lobe. The patients did not present semantic deficits specific to known people. Nonetheless, they showed difficulties naming famous buildings in addition to famous faces, but they were comparable to healthy controls in generating proper names. Our results support the critical role of the mid-posterior temporal language regions in the lexical retrieval of proper names, namely from pictorial stimuli, in absence of semantic impairments.

Finding the limits of deep learning clinical sensitivity with fractional anisotropy (FA) microstructure maps.

Background: Quantitative maps obtained with diffusion weighted (DW) imaging, such as fractional anisotropy (FA) -calculated by fitting the diffusion tensor (DT) model to the data,-are very useful to study neurological diseases. To fit this map accurately, acquisition times of the order of several minutes are needed because many noncollinear DW volumes must be acquired to reduce directional biases. Deep learning (DL) can be used to reduce acquisition times by reducing the number of DW volumes. We already developed a DL network named "one-minute FA," which uses 10 DW volumes to obtain FA maps, maintaining the same characteristics and clinical sensitivity of the FA maps calculated with the standard method using more volumes. Recent publications have indicated that it is possible to train DL networks and obtain FA maps even with 4 DW input volumes, far less than the minimum number of directions for the mathematical estimation of the DT. Methods: Here we investigated the impact of reducing the number of DW input volumes to 4 or 7, and evaluated the performance and clinical sensitivity of the corresponding DL networks trained to calculate FA, while comparing results also with those using our one-minute FA. Each network training was performed on the human connectome project open-access dataset that has a high resolution and many DW volumes, used to fit a ground truth FA. To evaluate the generalizability of each network, they were tested on two external clinical datasets, not seen during training, and acquired on different scanners with different protocols, as previously done. Results: Using 4 or 7 DW volumes, it was possible to train DL networks to obtain FA maps with the same range of values as ground truth - map, only when using HCP test data; pathological sensitivity was lost when tested using the external clinical datasets: indeed in both cases, no consistent differences were found between patient groups. On the contrary, our "one-minute FA" did not suffer from the same problem. Conclusion: When developing DL networks for reduced acquisition times, the ability to generalize and to generate quantitative biomarkers that provide clinical sensitivity must be addressed.

CT Arthrography of the Elbow: What Radiologists Should Know.

Computed tomography (CT) arthrography is a quickly available imaging modality to investigate elbow disorders. Its excellent spatial resolution enables the detection of subtle pathologic changes of intra-articular structures, which makes this technique extremely valuable in a joint with very tiny chondral layers and complex anatomy of articular capsule and ligaments. Radiation exposure has been widely decreased with the novel CT scanners, thereby increasing the indications of this examination. The main applications of CT arthrography of the elbow are the evaluation of capsule, ligaments, and osteochondral lesions in both the settings of acute trauma, degenerative changes, and chronic injury due to repeated microtrauma and overuse. In this review, we discuss the normal anatomic findings, technical tips for injection and image acquisition, and pathologic findings that can be encountered in CT arthrography of the elbow, shedding light on its role in the diagnosis and management of different orthopedic conditions. We aspire to offer a roadmap for the integration of elbow CT arthrography into routine clinical practice, fostering improved patient outcomes and a deeper understanding of elbow pathologies.

Comparison of immunoassay- with mass spectrometry-derived p-tau quantification for the detection of Alzheimer's disease pathology.

BACKGROUND: Antibody-based immunoassays have enabled quantification of very low concentrations of phosphorylated tau (p-tau) protein forms in cerebrospinal fluid (CSF), aiding in the diagnosis of AD. Mass spectrometry enables absolute quantification of multiple p-tau variants within a single run. The goal of this study was to compare the performance of mass spectrometry assessments of p-tau181, p-tau217 and p-tau231 with established immunoassay techniques. METHODS: We measured p-tau181, p-tau217 and p-tau231 concentrations in CSF from 173 participants from the TRIAD cohort and 394 participants from the BioFINDER-2 cohort using both mass spectrometry and immunoassay methods. All subjects were clinically evaluated by dementia specialists and had amyloid-PET and tau-PET assessments. Bland-Altman analyses evaluated the agreement between immunoassay and mass spectrometry p-tau181, p-tau217 and p-tau231. P-tau associations with amyloid-PET and tau-PET uptake were also compared. Receiver Operating Characteristic (ROC) analyses compared the performance of mass spectrometry and immunoassays p-tau concentrations to identify amyloid-PET positivity. RESULTS: Mass spectrometry and immunoassays of p-tau217 were highly comparable in terms of diagnostic performance, between-group effect sizes and associations with PET biomarkers. In contrast, p-tau181 and p-tau231 concentrations measured using antibody-free mass spectrometry had lower performance compared with immunoassays. CONCLUSIONS: Our results suggest that while similar overall, immunoassay-based p-tau biomarkers are slightly superior to antibody-free mass spectrometry-based p-tau biomarkers. Future work is needed to determine whether the potential to evaluate multiple biomarkers within a single run offsets the slightly lower performance of antibody-free mass spectrometry-based p-tau quantification.

Predicting functional decline in aging and Alzheimer's disease with PET-based Braak staging.

The progression of PET-based Braak stages correlates with cognitive deterioration in aging and Alzheimer's disease. Here, we investigate the association between PET-based Braak stages and functional impairment and assess whether PET-based Braak staging predicts a longitudinal decline in the performance of activities of daily living. In this cohort study, we evaluated cognitively unimpaired individuals and individuals with mild cognitive impairment or Alzheimer's disease dementia. Participants underwent [18F]MK6240 tau-PET, were assigned a PET-based Braak stage at baseline and were followed for a mean (SD) of 1.97 (0.66) years. Functional performance was evaluated with the Functional Activities Questionnaire, Everyday Cognition and functional Clinical Dementia Rating sum of boxes. Multiple linear regressions assessed the association of PET-based Braak stages with baseline functionality and with the longitudinal rate of change in functional scores, adjusting for age, sex and amyloid-ß load. We employed voxel-based regression models to investigate the association between functionality and tau-PET signal and assessed the voxel overlap with Braak regions of interest. We included 291 individuals (181 cognitively unimpaired, 56 amyloid-ß+ mild cognitive impairment and 54 amyloid-ß+ Alzheimer's disease) aged 70.60 (7.48) years. At baseline, PET-based Braak stages III-IV (ß = 0.43, P = 0.03) and V-VI (ß = 1.20, P < 0.0001) showed associations with poorer Functional Activities Questionnaire scores. Similarly, stages III-IV (ß = 0.43, P = 0.02) and V-VI (ß = 1.15, P < 0.0001) were associated with worse Everyday Cognition scores. Only stages V-VI were associated with higher functional Clinical Dementia Rating sum of boxes (ß = 1.17, P < 0.0001) scores. Increased tau-PET signals in all Braak regions of interest were linked to worse performance in all tools. The voxelwise analysis showed widespread cortical associations between functional impairment and tau-PET and high voxel overlap with Braak regions of interest. Baseline PET-based Braak stages V-VI predicted significant longitudinal functional decline as assessed by the Functional Activities Questionnaire (ß = 1.69, P < 0.0001), the Everyday Cognition (ß = 1.05, P = 0.001) and the functional Clinical Dementia Rating sum of boxes (ß = 1.29, P < 0.0001). Our results suggest that functional impairment increases with the severity of tau accumulation. These findings also indicate that PET-based Braak staging is a good predictor of functional impairment in the Alzheimer's disease continuum. Finally, our study provides evidence for the clinical significance of the PET-based Braak staging framework.