Search

Abstract Background Dementia with Lewy Bodies (DLB) is responsible for cognitive-behavioural disorders but also for gait disorders. The latter are thought to be related to parkinsonism, but the neural bases of these disorders are not well known, especially in the early stages. The aim of this study was to investigate by volumetric Magnetic Resonance Imaging the neuronal basis of gait disorders in DLB patients, compared to Healthy Elderly Controls and Alzheimer’s Disease patients. Methods Clinical examination with motor assessment including 10-meter walking speed, one-leg balance and Timed Up and Go test, a comprehensive neuropsychological evaluation and 3D brain Magnetic Resonance Imaging were performed on 84 DLB patients, 39 Alzheimer’s Disease patients and 22 Healthy Elderly Controls. We used Statistical Parametric Mapping 12 to perform a one-sample t-test to investigate the correlation between each gait score and gray matter volume (P ≤ 0.05 corrected for family-wise error). Results We found a correlation for DLB patients between walking speed and gray matter decrease (P

Abstract Background Dementia with Lewy bodies (DLB) is characterized by insular atrophy, which occurs at the early stage of the disease. Damage to the insula has been associated with disorders reflecting impairments of the most fundamental components of the self, such as anosognosia, which is a frequently reported symptom in patients with Lewy bodies (LB). The purpose of this study was to investigate modifications of the self-concept (SC), another component of the self, and to identify neuroanatomical correlates, in prodromal to mild DLB. Methods Twenty patients with prodromal to mild DLB were selected to participate in this exploratory study along with 20 healthy control subjects matched in terms of age, gender, and level of education. The Twenty Statements Test (TST) was used to assess the SC. Behavioral performances were compared between LB patients and control subjects. Three-dimensional magnetic resonance images (MRI) were acquired for all participants and correlational analyses were performed using voxel-based morphometry (VBM) in whole brain and using a mask for the insula. Results The behavioral results on the TST showed significantly impaired performances in LB patients in comparison with control subjects (p

Abstract Dementia with Lewy bodies (DLB) is a neurodegenerative disorder with a wide heterogeneity of symptoms, which suggests the existence of different subtypes. We used data-driven analysis of magnetic resonance imaging (MRI) data to investigate DLB subtypes. We included 165 DLB from the Mayo Clinic and 3 centers from the European DLB consortium and performed a hierarchical cluster analysis to identify subtypes based on gray matter (GM) volumes. To characterize the subtypes, we used demographic and clinical data, as well as β-amyloid, tau, and cerebrovascular biomarkers at baseline, and cognitive decline over three years. We identified 3 subtypes: an older subtype with reduced cortical GM volumes, worse cognition, and faster cognitive decline (n = 49, 30%); a subtype with low GM volumes in fronto-occipital regions (n = 76, 46%); and a subtype of younger patients with the highest cortical GM volumes, proportionally lower GM volumes in basal ganglia and the highest frequency of cognitive fluctuations (n = 40, 24%). This study shows the existence of MRI subtypes in DLB, which may have implications for clinical workout, research, and therapeutic decisions.

Abstract Background Isolated subjective cognitive impairment (SCI) and mild cognitive impairment (MCI) are the prodromal phases of dementia with Lewy bodies (DLB). MEMENTO is a nationwide study of patients with SCI and MCI with clinic, neuropsychology, biology, and brain imaging data. We aimed to compare SCI and MCI patients with symptoms of prodromal DLB to others in this study at baseline. Methods Participants of the French MEMENTO cohort study were recruited for either SCI or MCI. Among them, 892 were included in the Lewy sub-study, designed to search specifically for symptoms of DLB. Probable prodromal DLB diagnosis (pro-DLB group) was done using a two-criteria cutoff score among the four core clinical features of DLB. This Pro-DLB group was compared to two other groups at baseline: one without any core symptoms (NS group) and the one with one core symptom (1S group). A comprehensive cognitive battery, questionnaires on behavior, neurovegetative and neurosensory symptoms, brain 3D volumetric MRI, CSF, FDG PET, and amyloid PET were done. Results The pro-DLB group comprised 148 patients (16.6%). This group showed more multidomain (59.8%) MCI with slower processing speed and a higher proportion of patients with depression, anxiety, apathy, constipation, rhinorrhea, sicca syndrome, and photophobia, compared to the NS group. The pro-DLB group had isolated lower P-Tau in the CSF (not significant after adjustments for confounders) and on brain MRI widening of sulci including fronto-insular, occipital, and olfactory sulci (FDR corrected), when compared to the NS group. Evolution to dementia was not different between the three groups over a median follow-up of 2.6 years. Conclusions Patients with symptoms of prodromal DLB are cognitively slower, with more behavioral disorders, autonomic symptoms, and photophobia. The occipital, fronto-insular, and olfactory bulb involvement on brain MRI was consistent with symptoms and known neuropathology. The next step will be to study the clinical, biological, and imaging evolution of these patients. Trial registration Clinicaltrials.gov , NCT01926249

Measurement(s) spinal cord Technology Type(s) magnetic resonance imaging Factor Type(s) manufacturer • site Sample Characteristic - Organism Homo sapiens Sample Characteristic - Location Canada • Switzerland • Australia • United States of America • United Kingdom • Germany • French Republic • Czech Republic • Italy • Japan • Kingdom of Spain • China Machine-accessible metadata file describing the reported data: https://doi.org/10.6084/m9.figshare.14052269

Narrative discourse (ND) comprehension is a complex task that implies not only linguistic abilities but also other cognitive abilities, including efficient executive functioning. An executive dysfunction has been described in dementia with Lewy bodies (DLB) from the early stage. Here, we question the link between executive dysfunction in DLB and narrative comprehension. The aim of our study was to evaluate ND comprehension and to investigate the neuroanatomical basis for its impairment in the early stage of DLB. DLB patients (N = 26) and controls (N = 19) underwent the ND comprehension test of the Montreal Protocol for Evaluation of Communication (MEC). An additional, qualitative analysis was conducted on their verbal productions. Cognitive tests assessing verbal episodic memory, executive functions, naming and oral syntactic comprehension were also performed. Brain gray matter correlates of the ND comprehension test were examined using voxel-based morphometry (VBM). An ND comprehension impairment was found for prodromal and mild DLB patients as compared to controls. These difficulties were correlated with the Frontal Assessment Battery (FAB) score. ND comprehension impairment in DLB was further characterized by a deficit in the organization and the logic of the discourse. Moreover, VBM analysis revealed a correlation between striatal gray matter volumes and DLB patients’ ability to extract and organize relevant information (p < 0.05, FDR correction, cluster level). The ND comprehension impairment in DLB patients could be related to their executive dysfunction through a deficit of information selection and organization that correlates with the volumetric reduction of striatal gray matter.

Abstract Fibrosis is a key pathological feature in muscle disorders, but its quantification mainly relies on histological and biochemical assays. Muscle fibrosis most frequently is entangled with other pathological processes, as cell membrane lesions, inflammation, necrosis, regeneration, or fatty infiltration, making in vivo assessment difficult. Here, we (1) describe a novel mouse model with variable levels of induced skeletal muscle fibrosis displaying minimal inflammation and no fat infiltration, and (2) report how fibrosis affects non-invasive metrics derived from nuclear magnetic resonance (NMR) and ultrasound shear-wave elastography (SWE) associated with a passive biomechanical assay. Our findings show that collagen fraction correlates with multiple non-invasive metrics. Among them, muscle stiffness as measured by SWE, T2, and extracellular volume (ECV) as measured by NMR have the strongest correlations with histology. We also report that combining metrics in a multi-modality index allowed better discrimination between fibrotic and normal skeletal muscles. This study demonstrates that skeletal muscle fibrosis leads to alterations that can be assessed in vivo with multiple imaging parameters. Furthermore, combining NMR and SWE passive biomechanical assay improves the non-invasive evaluation of skeletal muscle fibrosis and may allow disentangling it from co-occurring pathological alterations in more complex scenarios, such as muscular dystrophies.

Abstract Background Several studies have investigated the value of alpha-synuclein assay in the cerebrospinal fluid (CSF) of Alzheimer’s disease (AD) and dementia with Lewy bodies (DLB) patients in the differential diagnosis of these two pathologies. However, very few studies have focused on this assay in AD and DLB patients at the MCI stage. Methods All patients were enrolled under a hospital clinical research protocol from the tertiary Memory Clinic (CM2R) of Alsace, France, by an experienced team of clinicians. A total of 166 patients were included in this study: 21 control subjects (CS), 51 patients with DLB at the prodromal stage (pro-DLB), 16 patients with DLB at the demented stage (DLB-d), 33 AD patients at the prodromal stage (pro-AD), 32 AD patients at the demented stage (AD-d), and 13 patients with mixed pathology (AD+DLB). CSF levels of total alpha-synuclein were assessed using a commercial enzyme-linked immunosorbent assay (ELISA) for alpha-synuclein (AJ Roboscreen). Alzheimer’s biomarkers (t-Tau, P-Tau, Aβ42, and Aβ40) were also measured. Results The alpha-synuclein assays showed a significant difference between the AD and DLB groups. Total alpha-synuclein levels were significantly higher in AD patients than in DLB patients. However, the ROC curves show a moderate discriminating power between AD and DLB (AUC = 0.78) which does not improve the discriminating power of the combination of Alzheimer biomarkers (AUC = 0.95 with or without alpha-synuclein). Interestingly, the levels appeared to be altered from the prodromal stage in both AD and DLB. Conclusions The modification of total alpha-synuclein levels in the CSF of patients occurs early, from the prodromal stage. The adding of alpha-synuclein total to the combination of Alzheimer’s biomarker does not improve the differential diagnosis between AD and DLB. Trial registration ClinicalTrials.gov, NCT01876459 (AlphaLewyMa)

Abstract Background Central nervous system damage in multiple sclerosis (MS) is responsible for serious deficiencies. Current therapies are focused on the treatment of inflammation; however, there is an urgent need for innovative therapies promoting neuroregeneration, particularly myelin repair. It is demonstrated that testosterone can act through neural androgen receptors and several clinical observations stimulated an interest in the potential protective effects of testosterone treatment for MS. Here, we sought to demonstrate the effects of a testosterone supplementation in testosterone-deficient men with relapsing-remitting MS. Methods/design This report presents the rationale and methodology of TOTEM RRMS, a French, phase 2, multicenter, randomized, placebo-controlled, and double-blind trial, which aims to prevent the progression of MS in men with low testosterone levels by administration of testosterone undecanoate, who were kept under natalizumab (Tysabri®) to overcome the anti-inflammatory effect of testosterone. Forty patients will be randomized into two groups receiving either a testosterone treatment (Nebido®) or a matching placebo. The intervention period for each group will last 66 weeks (treatment will be injected at baseline, week 6, and then every 12 weeks). The main objective is to determine the neuroprotective and remyelinating effects of testosterone using tensor diffusion imaging techniques and thalamic atrophy analyses. As secondary objectives, impacts of the testosterone supplementation will be studied using other conventional and unconventional MRI parameters and with clinical outcomes. Discussion The action of testosterone is observed in different experimental autoimmune encephalomyelitis models and epidemiological studies in humans. However, despite several preclinical data and some small clinical trials in MS, clear evidence for a therapeutic effect of hormone therapy is still missing. Therefore, our goal is to demonstrate the effects of testosterone therapies in MS. As there is no effective treatment currently available on fatigue in MS, careful attention should also be paid to secondary endpoints: fatigue, cognitive functions, and other symptoms that may improve life quality. Assuming a positive outcome of the trial, this treatment could be considered as a new neuroprotective and remyelinating therapy in relapsing-remitting MS and could be applicable to other demyelinating diseases. Trial registration ClinicalTrials.gov NCT03910738. Registered on 10 April 2019.

Abstract Background Fluctuations are one of the core clinical features characterizing dementia with Lewy bodies (DLB). They represent a determining factor for its diagnosis and strongly impact the quality of life of patients and their caregivers. However, the neural correlates of this complex symptom remain poorly understood. This study aimed to investigate the structural and functional changes in DLB patients, compared to Alzheimer’s disease (AD) patients and healthy elderly subjects, and their potential links with fluctuations. Methods Structural and resting-state functional MRI data were collected from 92 DLB patients, 70 AD patients, and 22 control subjects, who also underwent a detailed clinical examination including the Mayo Clinic Fluctuation Scale. Gray matter volume changes were analyzed using whole-brain voxel-based morphometry, and resting-state functional connectivity was investigated using a seed-based analysis, with regions of interest corresponding to the main nodes of the salience network (SN), frontoparietal network (FPN), dorsal attention network (DAN), and default mode network (DMN). Results At the structural level, fluctuation scores in DLB patients did not relate to the atrophy of insular, temporal, and frontal regions typically found in this pathology, but instead showed a weak correlation with more subtle volume reductions in different regions of the cholinergic system. At the functional level, the DLB group was characterized by a decreased connectivity within the SN and attentional networks, while the AD group showed decreases within the SN and DMN. In addition, higher fluctuation scores in DLB patients were correlated to a greater connectivity of the SN with the DAN and left thalamus, along with a decreased connectivity between the SN and DMN, and between the right thalamus and both the FPN and DMN. Conclusions Functional connectivity changes, rather than significant gray matter loss, could play an important role in the emergence of fluctuations in DLB. Notably, fluctuations in DLB patients appeared to be related to a disturbed external functional connectivity of the SN, which may lead to less relevant transitions between different cognitive states in response to internal and environmental stimuli. Our results also suggest that the thalamus could be a key region for the occurrence of this symptom.

Abstract Background Cortical and subcortical cognitive impairments are usually found in dementia with Lewy bodies (DLB). Roughly, they comprise visuo-constructive/executive function and attention/processing speed impairments, whereas memory would remain relatively spared. In this study, we focused on the neuro-anatomical substrates of attention and processing speed, which is still poorly understood. For the purpose of the study, we examined the correlations between behavioral scores measuring the speed of processing and the degree of cerebral atrophy in patients with prodromal to moderate DLB. Methods Ninety-three prodromal to moderate DLB patients (mean MMSE = 25.5) were selected to participate in the study as well as 28 healthy elderly subjects (mean MMSE = 28.9), matched in terms of age and educational level. The Trail Making Test A (TMTA) and the Digit Symbol Substitution Test (DSST) were used to assess attention and processing speed. Behavioral performances were compared between patients and healthy control subjects. Three-dimensional MRI images were acquired for all participants, and correlational analyses were performed in the patient group using voxel-based morphometry (VBM). Results The behavioral results on both the TMTA (p = .026) and the DSST (p

Imaging has become a valuable tool in the assessment of neuromuscular diseases, and, specifically, quantitative MR imaging provides robust biomarkers for the monitoring of disease progression. Quantitative evaluation of fat infiltration and quantification of the T2 values of the muscular tissue's water component (wT2) are two of the most essential indicators currently used. As each voxel of the image can contain both water and fat, a two-component model for the estimation of wT2 must be used. In this work, we present a fast method for reconstructing wT2 maps obtained from conventional multi-echo spin-echo (MESE) acquisitions and released as Free Open Source Software. The proposed software is capable of fast reconstruction thanks to extended phase graphs (EPG) simulations and dictionary matching implemented on a general-purpose graphic processing unit. The program can also perform more conventional biexponential least-squares fitting of the data and incorporate information from an external water-fat acquisition to increase the accuracy of the results. The method was applied to the scans of four healthy volunteers and five subjects suffering from facioscapulohumeral muscular dystrophy (FSHD). Conventional multi-slice MESE acquisitions were performed with 17 echoes, and additionally, a 6-echo multi-echo gradient-echo (MEGE) sequence was used for an independent fat fraction calculation. The proposed reconstruction software was applied on the full datasets, and additionally to reduced number of echoes, respectively, to 8, 5, and 3, using EPG and biexponential least-squares fitting, with and without incorporating information from the MEGE acquisition. The incorporation of external fat fraction maps increased the robustness of the fitting with a reduced number of echoes per datasets, whereas with unconstrained fitting, the total of 17 echoes was necessary to retain an independence of wT2 from the level of fat infiltration. In conclusion, the proposed software can successfully be used to calculate wT2 maps from conventional MESE acquisition, allowing the usage of an optimized protocol with similar precision and accuracy as a 17-echo acquisition. As it is freely released to the community, it can be used as a reference for more extensive cohort studies.

A "Rede Nós de Água" se origina de um processo de construção e sistematização de experiências agroecológicas emergentes na região de Araponga/MG no início dos anos 90, a partir de uma parceria entre o Centro de Tecnologias Alternativas da Zona da Mata (CTA-ZM), a Universidade Federal de Viçosa (UFV) e agricultores familiares da região. Destas experiências, surge a demanda pelo melhor entendimento sobre a dinâmica dos recursos hídricos nestes sistemas agroflorestais, incitando a criação, em 2009, do Grupo de Trabalho das Águas (GT-Água). A partir daí, inúmeras ações de formação e pesquisa foram iniciadas e outras entidades foram se associando ao grupo, constituindo, em 2014, a Rede Nós de Água, que atua em diversos municípios da Zona da Mata mineira e além, com técnicas e tecnologias sociais que promovam a conservação dos recursos hídricos através de metodologias colaborativas e participativas, visando a autonomia e construção coletiva do conhecimento agroecológico.

Modified Look-Locker Inversion recovery (MOLLI) sequence is increasingly performed for myocardial T1 mapping but is known to underestimate T1 values. The aim of the study was to quantitatively analyze several sources of errors when T1 maps are derived using standard post-processing of the sequence and to propose a reconstruction approach that takes into account inversion efficacy (η), T2 relaxation during balanced steady-state free-precession readouts and B1+ inhomogeneities. Contributions of the different sources of error were analyzed using Bloch equations simulations of MOLLI sequence. Bloch simulations were then combined with the acquisition of fast B1+ and T2 maps to derive more accurate T1 maps. This novel approach was evaluated on phantoms and on five healthy volunteers. Simulations show that T2 variations, B1+ heterogeneities and inversion efficiency represent major confounders for T1 mapping when MOLLI is processed with standard 3-parameters fitting. In vitro data indicate that T1 values are accurately derived with the simulation approach and in vivo data suggest that myocardium T1 are 15% underestimated when processed with the standard 3-parameters fitting. At the cost of additional acquisitions, this method might be suitable in clinical research protocols for precise tissue characterization as it decorrelates T1 and T2 effects on parametric maps provided by MOLLI sequence and avoids inaccuracies when B1+ is not homogenous throughout the myocardium.

Quantitative nuclear magnetic resonance imaging (MRI) has been considered a promising non-invasive tool for monitoring therapeutic essays in small size mouse models of muscular dystrophies. Here, we combined MRI (anatomical images and transverse relaxation time constant-T2-measurements) to texture analyses in the study of four mouse strains covering a wide range of dystrophic phenotypes. Two still unexplored mouse models of muscular dystrophies were analyzed: The severely affected Largemyd mouse and the recently generated and worst double mutant mdx/Largemyd mouse, as compared to the mildly affected mdx and normal mice. The results were compared to histopathological findings. MRI showed increased intermuscular fat and higher muscle T2 in the three dystrophic mouse models when compared to the wild-type mice (T2: mdx/Largemyd: 37.6±2.8 ms; mdx: 35.2±4.5 ms; Largemyd: 36.6±4.0 ms; wild-type: 29.1±1.8 ms, p

We conducted a prospective multinational study of muscle pathology using magnetic resonance imaging (MRI) in patients with limb-girdle muscular dystrophy 2I (LGMD2I). Thirty eight adult ambulant LGMD2I patients (19 male; 19 female) with genetically identical mutations (c.826C>A) in the fukutin-related protein (FKRP) gene were recruited. In each patient, T1-weighted (T1w) imaging was assessed by qualitative grading for 15 individual lower limb muscles and quantitative Dixon imaging was analysed on 14 individual lower limb muscles by region of interest analysis. We described the pattern and appearance of muscle pathology and gender differences, not previously reported for LGMD2I. Diffuse fat infiltration of the gastrocnemii muscles was demonstrated in females, whereas in males fat infiltration was more prominent in the medial than the lateral gastrocnemius (p = 0.05). In the anterior thigh of males, in contrast to females, median fat infiltration in the vastus medialis muscle (45.7%) exceeded that in the vastus lateralis muscle (11.2%) (p

BackgroundTNF-related lymphotoxin alpha (LTalpha) is essential for the development of Plasmodium berghei ANKA (PbA)-induced experimental cerebral malaria (ECM). The pathway involved has been attributed to TNFR2. Here we show a second arm of LTalpha-signaling essential for ECM development through LTbeta-R, receptor of LTalpha1beta2 heterotrimer.Methodology/principal findingsLTbetaR deficient mice did not develop the neurological signs seen in PbA induced ECM but died at three weeks with high parasitaemia and severe anemia like LTalphabeta deficient mice. Resistance of LTalphabeta or LTbetaR deficient mice correlated with unaltered cerebral microcirculation and absence of ischemia, as documented by magnetic resonance imaging and angiography, associated with lack of microvascular obstruction, while wild-type mice developed distinct microvascular pathology. Recruitment and activation of perforin(+) CD8(+) T cells, and their ICAM-1 expression were clearly attenuated in the brain of resistant mice. An essential contribution of LIGHT, another LTbetaR ligand, could be excluded, as LIGHT deficient mice rapidly succumbed to ECM.Conclusions/significanceLTbetaR expressed on radioresistant resident stromal, probably endothelial cells, rather than hematopoietic cells, are essential for the development of ECM, as assessed by hematopoietic reconstitution experiment. Therefore, the data suggest that both functional LTbetaR and TNFR2 signaling are required and non-redundant for the development of microvascular pathology resulting in fatal ECM.