Métodos automatizados de segmentación para cuantificar el grosor cortical en RM en pacientes con deterioro cognitivo y enfermedad de Parkinson

El objetivo del presente estudio es encontrar la relación que existe entre los síntomas de deterioro cognitivo y el grosor cortical cerebral en una muestra de 45 pacientes con Enfermedad de Parkinson diagnosticados y tratados en la consulta externa del Servicio de Neurología del Hospital de la Santa Creu i Sant Pau de Barcelona, quienes fueron sometidos a tests neuropsicológicos que evaluaban su función mental y motora y a quienes se les realizó un estudio de Resonancia Magnética 3 Tesla para evaluar, mediante técnicas de postprocesados, su grosor cortical. Los resultados demostraron una clara disminución del grosor cortical en determinadas áreas que se correlacionaban con las funciones cognitivas afectadas en estos pacientes.L'objectiu d'aquest estudi es trobar la relació que existeix entre els símptomes de deteriorament cognitiu i el gruix cortical cerebral en una mostra de 45 pacients amb Malaltia de Parkinson diagnosticats i tractats en el Servei de Neurologia de l'Hospital de la Santa Creu i Sant Pau de Barcelona, que van ser sotmesos a tests neuropsicològics que avaluaven la seva funció mental i motora i als quals se'ls va realitzar un estudi de ressonància magnètica 3 Tesla per avaluar, mitjançant tècniques de postprocessats, el seu gruix cortical. Els resultats van demostrar una clara disminució del gruix cortical en determinades àrees que es correlacionaven amb les funcions cognitives afectades en aquests pacients

Structural brain correlates of dementia in Huntington's disease

Altres ajuts: The present study was partially funded by the "Human Biology Project Grant" of the Huntington's Disease Society of America (USA).Huntington's disease (HD) is a fatal genetic neurodegenerative disorder with no effective treatment currently available. Progressive basal ganglia and whole-brain atrophy and concurrent cognitive deterioration are prototypical aspects of HD. However, the specific patterns of brain atrophy underlying cognitive impairment of different severity in HD are poorly understood. The aim of this study was to investigate the specific structural brain correlates of major cognitive deficits in HD and to explore its association with neuropsychological indicators. Thirty-five symptomatic early-to-mild HD patients and 15 healthy controls (HC) with available T1-MRI imaging were included in this study. In this cross-sectional study, HD patients were classified as patients with (HD-Dem) and without (HD-ND) major cognitive impairment in the range of dementia. This classification was based on previously validated PD-CRS cutoff scores for HD. Differences in brain atrophy across groups were studied by means of grey-matter volume voxel-based morphometry (GMV-VBM) and cortical thickness (Cth). Voxelwise and vertexwise general linear models were used to assess the group comparisons, controlling for the effects of age, sex, education, CAG repeat length and severity of motor symptoms. Clusters surviving p < 0.05 and family-wise error (FWE) correction were considered statistically significant. In order to characterize the impact on cognitive performance of the observed brain differences across groups, GMV and Cth values in the set of significant regions were computed and correlated with specific neuropsychological tests. All groups had similar sociodemographic profiles, and the HD groups did not significantly differ in terms of CAG repeat length. Compared to HC, both HD groups exhibited significant atrophy in multiple subcortical and parietal brain regions. However, compared to HC and HD-ND groups, HD-Dem patients showed a more prominent pattern of reduced GMV and cortical thinning. Importantly, this thinning was restricted to regions of the parietal-temporal and occipital cortices. Furthermore, these brain alterations were further associated with poorer cognitive performance in tasks assessing frontal-executive and attention domains as well as memory, language and constructional abilities. Major cognitive impairment in the range of dementia in HD is associated with brain and cognitive alterations exceeding the prototypical frontal-executive deficits commonly recognized in HD. The observed posterior-cortical damage identified by MRI and its association with memory, language, and visuoconstructive dysfunction suggest a strong involvement of extra-striatal atrophy in the onset of severe cognitive dysfunction in HD patients. Critically, major cognitive impairment in this sample was not associated with CAG repeat length, age or education. This finding could support a possible involvement of additional neuropathological mechanisms aggravating cognitive deterioration in HD

Interaction between sex and neurofilament light chain on brain structure and clinical severity in Huntington's disease

Altres ajuts: Huntington's Disease Society of AmericaFemale Huntington's disease (HD) patients have consistently shown a faster clinical worsening than male, but the underlying mechanisms responsible for this observation remain unknown. Here, we describe how sex modifies the impact of neurodegeneration on brain atrophy and clinical severity in HD. Cerebrospinal fluid neurofilament light chain (NfL) levels were used as a biological measure of neurodegeneration, and brain atrophy was assessed by structural magnetic resonance imaging. We found that larger NfL values in women reflect higher brain atrophy and clinical severity than in men (p < 0.05 for an interaction model). This differential vulnerability could have important implications in clinical trials

Increased plasma neurofilament light chain levels in patients with type-1 diabetes with impaired awareness of hypoglycemia

Altres ajuts: This work was financially supported by a grant from the SPANISH DIABETES SOCIETY.Impaired awareness of hypoglycemia (IAH) is a common complication in patients with type-1 diabetes (T1D). IAH is a major risk factor for severe hypoglycemic events, leading to adverse clinical consequences and cerebral damage. Non-invasive, cost-effective, and logistically efficient biomarkers for this condition have not been validated. Here, we propose plasma neurofilament light chain (NfL) levels as a biomarker of neuroaxonal damage in patients with T1D-IAH. 54 patients were included into the study (18 T1D-IAH, 18 T1D with normal awareness of hypoglycemia (NAH) and 18 healthy controls). We measured plasma NfL levels and studied cerebral gray matter alterations on MRI. We found that NfL levels were increased in patients with T1D-IAH compared with patients with T1D-NAH and healthy controls. Importantly, increased NfL levels correlated with reduced cerebral gray matter volume and increased IAH severity in patients with T1D-IAH. Overall, our findings identify plasma NfL levels as a potential biomarker of cerebral damage in this population, motivating further confirmatory studies with potential implications in clinical trials

Structure and Dynamics of Large-Scale Cognitive Networks in Huntington's Disease

Altres ajuts: La Marató de TV3 (20142910).Background: Huntington's disease is a neurodegenerative disorder characterized by clinical alterations in the motor, behavioral, and cognitive domains. However, the structure and disruptions to large-scale brain cognitive networks have not yet been established. Objective: We aimed to profile changes in large-scale cognitive networks in premanifest and symptomatic patients with Huntington's disease. Methods: We prospectively recruited premanifest and symptomatic Huntington's disease mutation carriers as well as healthy controls. Clinical and sociodemographic data were obtained from all participants, and resting-state functional connectivity data, using both time-averaged and dynamic functional connectivity, was acquired from whole-brain and cognitively oriented brain parcellations. Results: A total of 64 gene mutation carriers and 23 healthy controls were included; 21 patients with Huntington's disease were classified as premanifest and 43 as symptomatic Huntington's disease. Compared with healthy controls, patients with Huntington's disease showed decreased network connectivity within the posterior hubs of the default-mode network and the medial prefrontal cortex, changes that correlated with cognitive (t = 2.25, P = 0.01) and disease burden scores (t = −2.42, P = 0.009). The salience network showed decreased functional connectivity between insular and supramarginal cortices and also correlated with cognitive (t = 2.11, P = 0.02) and disease burden scores (t = −2.35, P = 0.01). Dynamic analyses showed that network variability was decreased for default-central executive networks, a feature already present in premanifest mutation carriers (dynamic factor 8, P = 0.02). Conclusions: Huntington's disease shows an early and widespread disruption of large-scale cognitive networks. Importantly, these changes are related to cognitive and disease burden scores, and novel dynamic functional analyses uncovered subtler network changes even in the premanifest stages

Depression and Anxiety Scores Are Associated with Amygdala Volume in Cushing's Syndrome : Preliminary Study

Cushing's syndrome (CS) has repeatedly been associated with hippocampal volume reductions, while little information is available on the amygdala, another structure rich in glucocorticoid receptors. The aim of the study was to analyze amygdala volume in patients with CS and its relationship with anxiety, depression, and hormone levels. 39 CS patients (16 active and 23 patients in remission) and 39 healthy controls matched for age, sex, and education level completed anxiety (STAI) and depression tests (BDI-II) and underwent a 3 Tesla brain MRI and endocrine testing. Amygdala volumes were analysed with FreeSurfer software. Active CS patients had smaller right (but not left) amygdala volumes when compared to controls (P = 0.045). Left amygdala volumes negatively correlated with depression scores (r = −0.692, P = 0.003) and current anxiety state scores (r = −0.617, P = 0.011) in active CS patients and with anxiety trait scores (r = −0.440, P = 0.036) in patients in remission. No correlations were found between current ACTH, urinary free cortisol or blood cortisol levels, and amygdala volumes in either patient group. Patients with active CS have a smaller right amygdala volume in comparison to controls, while left amygdala volumes are associated with mood state in both patient groups

The Free and Cued Selective Reminding Test in Parkinson's Disease Mild Cognitive Impairment : Discriminative Accuracy and Neural Correlates

Altres ajuts: This work was partially supported by grants from La Marató TV3 (20142910, 2014/U/477); FIS (PI14/02058, PI15/00962); CIBERNED.Introduction: Memory alterations are common in Parkinson's disease (PD) patients but the mechanisms involved in these deficits remain poorly understood. The study aims to explore the profile of episodic memory deficits in non-demented early PD patients. Methods: We obtained neurological, cognitive and behavioral data from 114 PD patients and 41 healthy controls (HC). PD participants were grouped as normal cognition (PD-NC) and mild cognitive impairment (PD-MCI) according to the Level II criteria of the Movement Disorders Society Task Force (MDS-TF). We evaluate the performance amongst groups on an episodic memory task using the Free and Cued Selective Reminding Test (FCSRT). Additionally, gray matter volume (GMV) voxel based morphometry, and mean diffusivity (MD) analyses were conducted in a subset of patients to explore the structural brain correlates of FCSRT performance. Results: Performance on all subscores of the FCSRT was significantly worse in PD-MCI than in PD-NC and HC. Delayed total recall (DTR) subscore was the best at differentiating PD-NC from PD-MCI. Using crosstabulation, DTR allowed identification of PD-MCI patients with an accuracy of 80%. Delayed free and cued recall was associated with decreased GMV and increased MD in multiple fronto-temporal and parietal areas. Conclusion: Encoding and retrieval deficits are a main characteristic of PD-MCI and are associated with structural damage in temporal, parietal and prefrontal areas

A visual quality control scale for clinical arterial spin labeling images

Background: Image-quality assessment is a fundamental step before c linical evaluation of mag netic resonance images. The aim of this study was to introduce a vi sual scoring system that provides a qual ity control standard for arterial spin labeling (ASL) and that can be applied to cerebral blood flow (CBF) maps, as well as to ancillary ASL images. Methods: The proposed image quality control (QC) system had two components: (1) contrast-based QC (cQC), describing the visual contrast between anatomical structures; a nd (2) artifact-based QC (aQC), evaluating image quality of theCBFmapforthepresenceofcommontypesofartifacts. Three raters evaluated cQC an d aQC for 158 quantitative signal targeting with alternating radiofrequency labelling o f arterial regions (QUASAR) ASL scans (CBF, T1 relaxation rate, arterial blood volume, and arterial transie nt time). Spearman correlation coefficient ( r ), intraclass correlation coefficients (ICC), and receiver operating characteristic analysis were used. Results: Intra/inter-rater agreement ranged from moderate to excellent; inter-rater ICC was 0.72 for cQC, 0.60 for aQC, and 0.74 for the combined QC (cQC + aQC). Intra-rater ICC was 0.90 for cQC; 0.80 for aQC, and 0.90 for the combined QC. Strong correlations were found between aQC and CBF maps quality ( r = 0.75), and between aQC and cQC ( r = 0.70). A QC score of 18 was optimal to discriminate between high and low quality clinical scans. Conclusions: The proposed QC system provided high reproducibility and a reliable threshold for discarding low quality scans. Future research should compare this v isualQCsystemwithanautomaticQCsystem