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1. Exploring motor imagery as a therapeutic intervention for Parkinson’s disease patients: a scoping review

Author: Maxime Michel, Elena Terragno, Matthieu Bereau, Eloi Magnin, Nicolas Gueugneau, Antonio Vinicius Soares, and Yoshimasa Sagawa
Subjects: Parkinson’s disease, motor imagery therapy, mental practice, neurorehabilitation, rehabilitation, Neurology. Diseases of the nervous system, RC346-429
Abstract: BackgroundMotor imagery (MI) has emerged as a promising therapeutic approach for Parkinson’s disease (PD). MI entails mentally rehearsing motor actions without executing them. This cognitive process has garnered attention due to its potential benefits in aiding motor function recovery in patients. The purpose of this review was to highlight the findings observed in motor symptoms, balance, gait, and quality of life.MethodsA literature search was carried out in Medline, Embase, Cochrane, and Physiotherapy Evidence Database (PEDro), from the first publication to February 2024. Studies with at least one keyword to PD and MI in the title were included.ResultsThe analysis included 53 studies out of the 262 identified. These comprised 12 randomized controlled trials (RCTs) with an average PEDro score of 6.6 out of 10, as well as 41 non-RCT studies. Notably, the majority of the RCTs focused on balance, gait, and lower limb exercises. The experimental group found an 85.2% improvement on the Timed Up and Go (TUG) with a cognitive task (p
Published: 2024
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2. Phenotype and imaging features associated with APP duplications

Author: Lou Grangeon, Camille Charbonnier, Aline Zarea, Stephane Rousseau, Anne Rovelet-Lecrux, David Bendetowicz, Marion Lemaitre, Cécile Malrain, Muriel Quillard-Muraine, Kevin Cassinari, David Maltete, Jeremie Pariente, Olivier Moreaud, Eloi Magnin, Benjamin Cretin, Marie-Anne Mackowiak, Adeline Rollin Sillaire, Martine Vercelletto, Elsa Dionet, Olivier Felician, Pauline Rod-Olivieri, Catherine Thomas-Antérion, Gaelle Godeneche, Mathilde Sauvée, Leslie Cartz-Piver, Isabelle Le Ber, Valérie Chauvire, Therèse Jonveaux, Anna-Chloé Balageas, Annie Laquerriere, Charles Duyckaerts, Anne Vital, Andre Maues de Paula, David Meyronet, Lucie Guyant-Marechal, Didier Hannequin, Elisabeth Tournier-Lasserve, Dominique Campion, CNR-MAJ collaborators, Gaël Nicolas, and David Wallon
Subjects: Cerebral amyloid angiopathy, Alzheimer disease, APP duplication, Cerebral MRI, Autosomal dominant, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571, Neurology. Diseases of the nervous system, RC346-429
Abstract: Abstract Background APP duplication is a rare genetic cause of Alzheimer disease and cerebral amyloid angiopathy (CAA). We aimed to evaluate the phenotypes of APP duplications carriers. Methods Clinical, radiological, and neuropathological features of 43 APP duplication carriers from 24 French families were retrospectively analyzed, and MRI features and cerebrospinal fluid (CSF) biomarkers were compared to 40 APP-negative CAA controls. Results Major neurocognitive disorders were found in 90.2% symptomatic APP duplication carriers, with prominent behavioral impairment in 9.7%. Symptomatic intracerebral hemorrhages were reported in 29.2% and seizures in 51.2%. CSF Aβ42 levels were abnormal in 18/19 patients and 14/19 patients fulfilled MRI radiological criteria for CAA, while only 5 displayed no hemorrhagic features. We found no correlation between CAA radiological signs and duplication size. Compared to CAA controls, APP duplication carriers showed less disseminated cortical superficial siderosis (0% vs 37.5%, p = 0.004 adjusted for the delay between symptoms onset and MRI). Deep microbleeds were found in two APP duplication carriers. In addition to neurofibrillary tangles and senile plaques, CAA was diffuse and severe with thickening of leptomeningeal vessels in all 9 autopsies. Lewy bodies were found in substantia nigra, locus coeruleus, and cortical structures of 2/9 patients, and one presented vascular amyloid deposits in basal ganglia. Discussion Phenotypes associated with APP duplications were heterogeneous with different clinical presentations including dementia, hemorrhage, and seizure and different radiological presentations, even within families. No apparent correlation with duplication size was found. Amyloid burden was severe and widely extended to cerebral vessels as suggested by hemorrhagic features on MRI and neuropathological data, making APP duplication an interesting model of CAA.
Published: 2023
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3. Adaptations of the balloon analog risk task for neuroimaging settings: a systematic review

Author: Charline Compagne, Juliana Teti Mayer, Damien Gabriel, Alexandre Comte, Eloi Magnin, Djamila Bennabi, and Thomas Tannou
Subjects: balloon analog risk task, functional, neuroimaging, decision making, taking, electroencephalography, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract: IntroductionThe Balloon Analog Risk Task (BART), a computerized behavioral paradigm, is one of the most common tools used to assess the risk-taking propensity of an individual. Since its initial behavioral version, the BART has been adapted to neuroimaging technique to explore brain networks of risk-taking behavior. However, while there are a variety of paradigms adapted to neuroimaging to date, no consensus has been reached on the best paradigm with the appropriate parameters to study the brain during risk-taking assessed by the BART. In this review of the literature, we aimed to identify the most appropriate BART parameters to adapt the initial paradigm to neuroimaging and increase the reliability of this tool.MethodsA systematic review focused on the BART versions adapted to neuroimaging was performed in accordance with PRISMA guidelines.ResultsA total of 105 articles with 6,879 subjects identified from the PubMed database met the inclusion criteria. The BART was adapted in four neuroimaging techniques, mostly in functional magnetic resonance imaging or electroencephalography settings.DiscussionFirst, to adapt the BART to neuroimaging, a delay was included between each trial, the total number of inflations was reduced between 12 and 30 pumps, and the number of trials was increased between 80 and 100 balloons, enabling us to respect the recording constraints of neuroimaging. Second, explicit feedback about the balloon burst limited the decisions under ambiguity associated with the first trials. Third, employing an outcome index that provides more informative measures than the standard average pump score, along with a model incorporating an exponential monotonic increase in explosion probability and a maximum explosion probability between 50 and 75%, can yield a reliable estimation of risk profile. Additionally, enhancing participant motivation can be achieved by increasing the reward in line with the risk level and implementing payment based on their performance in the BART. Although there is no universal adaptation of the BART to neuroimaging, and depending on the objectives of a study, an adjustment of parameters optimizes its evaluation and clinical utility in assessing risk-taking.
Published: 2023
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4. Tools for the Assessment of Risk-Taking Behavior in Older Adults with Mild Dementia: A Cross-Sectional Clinical Study

Author: Charline Compagne, Damien Gabriel, Lénaïc Ferrero, Eloi Magnin, and Thomas Tannou
Subjects: mild cognitive impairment, Alzheimer’s disease, risky decision-making, clinical assessment, behavioral tasks, neuropsychological assessment, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract: Diseases such as Alzheimer’s cause an alteration of cognitive functions, which can lead to increased daily risk-taking in older adults living at home. The assessment of decision-making abilities is primarily based on clinicians’ global analysis. Usual neuropsychological tests such as the MoCA (Montreal Cognitive Assessment) cover most of the cognitive domains and include mental flexibility tasks. Specific behavioral tasks for risk-taking, such as the Balloon Analogue Risk Task (BART) or the Iowa Gambling Task (IGT), have been developed to assess risk-taking behavior, particularly in the field of addictology. Our cross-sectional study aims to determine whether the MoCA global cognitive assessment could be used as a substitute for behavioral tasks in the assessment of risky behavior. In the current study, 24 patients (age: 82.1 ± 5.9) diagnosed with mild dementia completed the cognitive assessment (MoCA and executive function assessment) and two behavioral risk-taking tasks (BART, simplified version of the IGT). Results revealed no relationship between scores obtained in the MoCA and behavioral decision-making tasks. However, the two tasks assessing risk-taking behavior resulted in concordant risk profiles. In addition, patients with a high risk-taking behavior profile on the BART had better Trail Making Test (TMT) scores and thus retained mental flexibility. These findings suggest that MoCA scores are not representative of risk-taking behavioral inclinations. Thus, additional clinical tests should be used to assess risk-taking behavior in geriatric settings. Executive function measures, such as the TMT, and behavioral laboratory measures, such as the BART, are recommended for this purpose.
Published: 2023
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5. Apathy in Parkinson’s Disease: Clinical Patterns and Neurobiological Basis

Author: Matthieu Béreau, Vincent Van Waes, Mathieu Servant, Eloi Magnin, Laurent Tatu, and Mathieu Anheim
Subjects: apathy, motivation, executive functions, Cytology, QH573-671
Abstract: Apathy is commonly defined as a loss of motivation leading to a reduction in goal-directed behaviors. This multidimensional syndrome, which includes cognitive, emotional and behavioral components, is one of the most prevalent neuropsychiatric features of Parkinson’s disease (PD). It has been established that the prevalence of apathy increases as PD progresses. However, the pathophysiology and anatomic substrate of this syndrome remain unclear. Apathy seems to be underpinned by impaired anatomical structures that link the prefrontal cortex with the limbic system. It can be encountered in the prodromal stage of the disease and in fluctuating PD patients receiving bilateral chronic subthalamic nucleus stimulation. In these stages, apathy may be considered as a disorder of motivation that embodies amotivational behavioral syndrome, is underpinned by combined dopaminergic and serotonergic denervation and is dopa-responsive. In contrast, in advanced PD patients, apathy may be considered as cognitive apathy that announces cognitive decline and PD dementia, is underpinned by diffuse neurotransmitter system dysfunction and Lewy pathology spreading and is no longer dopa-responsive. In this review, we discuss the clinical patterns of apathy and their treatment, the neurobiological basis of apathy, the potential role of the anatomical structures involved and the pathways in motivational and cognitive apathy.
Published: 2023
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6. Medical teachers’ opinions about students with neurodevelopmental disorders and their management

Author: Eloi Magnin, Ilham Ryff, and Thierry Moulin
Subjects: Neurodevelopmental disorders, Mainstreaming (education), Staff development, Special aspects of education, LC8-6691, Medicine
Abstract: Abstract Background Some students have neurodevelopmental disorders that might affect their academic and professional careers if they are not identified and addressed by specific pedagogic adaptations. The objective of this work was to describe medical teachers’ opinions of students with neurodevelopmental disorders and their management of these students. Methods An anonymous cross-sectional electronic survey was performed to describe medical teachers’ opinions about the impact of neurodevelopmental disorders on the student’s life and on the medical teachers’ management. aThe survey was created, including visual analogic scales and free text, to assess teachers’ opinions from identification and assessment of neurodevelopemental burden on students and teachers, to their own knowledge about neurodevelopemental disorders and the specific pedagogic management available. The survey was sent to 175 medical teachers in 2019, of whom 67 responded. Quantitative descriptive statistics and qualitative analysis of free text were reported. Results Many medical teachers report having encountered students who might have had neurodevelopmental disorders (dyspraxia 33%; dyslexia 46%; autism spectrum disorders 68%; attention deficit hyperactivity disorders 75%). Impact on students and on teachers was considered as important (mean VAS score for impact over 60/100 for all syndromes except for dyspraxia). Medical teachers’ self-reported knowledge about neurodevelopmental disorders (mean VAS score 43.9/100) and available pedagogical adaptations (mean VAS score 19.0/100) was limited. The teachers were concerned about ethical issues (mean VAS score 72.2/100) but were interested in receiving specialized training (mean VAS score 64.4/100). Conclusion Medical teachers feel unprepared to manage students with neurodevelopmental disorders. They would be interested in specific training and procedures about the pedagogic management of these students.
Published: 2021
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7. Cognitive Impairment in Late-Life Depression: A Comparative Study of Healthy Older People, Late-Life Depression, and Mild Alzheimer's Disease Using Multivariate Base Rates of Low Scores

Author: Caroline Masse, Pierre Vandel, Géraldine Sylvestre, Nicolas Noiret, Djamila Bennabi, Frédéric Mauny, Marc Puyraveau, Yoan Barsznica, Jonathan Dartevelle, Agatha Meyer, Mickaël Binetruy, Marie Lavaux, Ilham Ryff, Julie Giustiniani, Eloi Magnin, Jean Galmiche, Emmanuel Haffen, and Gilles Chopard
Subjects: late-life depression, Alzheimer's disease, older people, base rates, low scores, false positive, Psychology, BF1-990
Abstract: Late-Life Depression (LLD) is often associated with cognitive impairment. However, distinction between cognitive impairment due to LLD and those due to normal aging or mild Alzheimer's Disease (AD) remain difficult. The aim of this study was to present and compare the multivariate base rates of low scores in LLD, mild AD, and healthy control groups on a battery of neuropsychological tests. Participants (ages 60–89) were 352 older healthy adults, 390 patients with LLD, and 234 patients with mild AD (i.e., MMSE ≥ 20). Multivariate base rates of low scores (i.e., ≤ 5th percentile) were calculated for each participant group within different cognitive domains (verbal episodic memory, executive skills, mental processing speed, constructional praxis, and language/semantic memory). Obtaining at least one low score was relatively common in healthy older people controls (from 9.4 to 17.6%), and may thus result in a large number of false positives. By contrast, having at least two low scores was unusual (from 0.3 to 4.6%) and seems to be a more reliable criterion for identifying cognitive impairment in LLD. Having at least three low memory scores was poorly associated with LLD (5.9%) compared to mild AD (76.1%) and may provide a useful way to differentiate between these two conditions [χ(1)2 = 329.8, p < 0.001; Odds Ratio = 50.7, 95% CI = 38.2–77.5]. The multivariate base rate information about low scores in healthy older people and mild AD may help clinicians to identify cognitive impairments in LLD patients, improve the clinical decision-making, and target those who require regular cognitive and clinical follow-up.
Published: 2021
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8. Added value of functional neuroimaging to assess decision-making capacity of older adults with neurocognitive disorders: protocol for a prospective, monocentric, single-arm study (IMAGISION)

Author: Lionel Pazart, Eloi Magnin, Chrystelle Vidal, Régis Aubry, Thomas Tannou, Aurelie Godard-Marceau, Sven Joubert, Serge Daneault, Marie-Jeanne Kergoat, Alexandre Comte, and Damien Gabriel
Subjects: Medicine
Abstract: Introduction Assessment of decision-making capacity (DMC) is essential in daily life as well as for defining a person-centred care plan. Nevertheless, in ageing, especially if signs of dementia appear, it becomes difficult to assess decision-making ability and raises ethical questions. Currently, the assessment of DMC is based on the clinician’s evaluation, completed by neuropsychological tests. Functional MRI (fMRI) could bring added value to the diagnosis of DMC in difficult situations.Methods and analysis IMAGISION is a prospective, monocentric, single-arm study evaluating fMRI compared with clinical assessment of DMC. The study will begin during Fall 2021 and should be completed by Spring 2023. Participants will be recruited from a memory clinic where they will come for an assessment of their cognitive abilities due to decision-making needs to support ageing in place. They will be older people over 70 years of age, living at home, presenting with a diagnosis of mild dementia, and no exclusion criteria of MRI. They will be clinically assessed by a geriatrician on their DMC, based on the neuropsychological tests usually performed. Participants will then perform a behavioural task in fMRI (Balloon Analogue Risk Task) to analyse the activation areas. Additional semistructured interviews will be conducted to explore real life implications. The main analysis will study concordance/discordance between the clinical classification and the activation of fMRI regions of interest. Reclassification as ‘capable’, based on fMRI, of patients for whom clinical diagnosis is ‘questionable’ will be considered as a diagnostic gain.Ethics and dissemination IMAGISION has been authorised by a research ethics board (Comité de Protection des Personnes, Bordeaux, II) in France, in accordance with French legislation on interventional biomedical research, under the reference IDRCB number 2019-A00863-54, since 30 September 2020. Participants will sign an informed consent form. The results of the study will be presented in international peer-reviewed scientific journals, international scientific conferences and public lectures.Trial registration number NCT03931148
Published: 2021
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9. Modification of both functional neurological symptoms and neuroimaging patterns with a good anatomoclinical concordance: a case report

Author: Silvio Galli, Selma Aybek, Sylvie Chokron, Thierry Moulin, and Eloi Magnin
Subjects: Functional neurological disorders, Conversion disorders, Dissociative disorders, SPECT, Neurology. Diseases of the nervous system, RC346-429
Abstract: Abstract Background In the nineteenth century, Jean Martin Charcot explained functional neurological disorder (formerly called conversion disorder) as a “psychodynamic” lesion. Numerous advances in neuroimaging have permitted identification of the neural underpinnings of this disorder. Case presentation Herein we describe a case of functional neurological disorder (FND) with initial left sensorimotor deficit, in-coordinated limb movements, neglect, clouded consciousness, slurred speech and a semiology of visual impairment. A single photon emission computed tomography (SPECT) showed a right thalamic hypoperfusion, which is rather concordant with the initial semiology. Later, the semiology changed, presenting with a predominantly neurovisual complex presentation. The second SPECT showed no more thalamic abnormalities but an hypoperfusion in the right temporo-occipital junction, right inferior parietal lobe and left superior frontal lobe, which is also rather concordant with the changing semiology. Conclusions This case illustrates the evolving neuroimaging patterns of FND but also the concordance between semiology and neuroimaging findings in FND supporting Charcot's theory of “dynamic lesion”.
Published: 2019
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10. Unstable TTTTA/TTTCA expansions in MARCH6 are associated with Familial Adult Myoclonic Epilepsy type 3

Author: Rahel T. Florian, Florian Kraft, Elsa Leitão, Sabine Kaya, Stephan Klebe, Eloi Magnin, Anne-Fleur van Rootselaar, Julien Buratti, Theresa Kühnel, Christopher Schröder, Sebastian Giesselmann, Nikolai Tschernoster, Janine Altmueller, Anaide Lamiral, Boris Keren, Caroline Nava, Delphine Bouteiller, Sylvie Forlani, Ludmila Jornea, Regina Kubica, Tao Ye, Damien Plassard, Bernard Jost, Vincent Meyer, Jean-François Deleuze, Yannick Delpu, Mario D. M. Avarello, Lisanne S. Vijfhuizen, Gabrielle Rudolf, Edouard Hirsch, Thessa Kroes, Philipp S. Reif, Felix Rosenow, Christos Ganos, Marie Vidailhet, Lionel Thivard, Alexandre Mathieu, Thomas Bourgeron, Ingo Kurth, Haloom Rafehi, Laura Steenpass, Bernhard Horsthemke, FAME consortium, Eric LeGuern, Karl Martin Klein, Pierre Labauge, Mark F. Bennett, Melanie Bahlo, Jozef Gecz, Mark A. Corbett, Marina A. J. Tijssen, Arn M. J. M. van den Maagdenberg, and Christel Depienne
Subjects: Science
Abstract: Familial cortical myoclonic tremor with epilepsy (FAME) is a slowly progressing cortical tremor mapping to various genomic loci, including intronic expansions in SAMD12 for FAME1. Here, Florian et al. describe mixed intronic TTTTA/TTTCA expansions of various lengths in the first intron of MARCH6 as a cause of FAME3.
Published: 2019
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11. Evaluation of Attachment Style and Social Support in Patients With Severe Migraine. Applications in Doctor-Patient Relationships and Treatment Adherence

Author: Rose-Angélique Belot, Margaux Bouteloup, Magalie Bonnet, Anne-Laure Parmentier, Eloi Magnin, Frédéric Mauny, and Fabrice Vuillier
Subjects: headaches and migraines, attachment, care, psychological factors, social support, Neurology. Diseases of the nervous system, RC346-429
Abstract: Objectives: The aim of this observational study was to describe social support and patterns of attachment among patients with migraine. We hypothesized that in comparison to the general population, insecure attachment is overrepresented in migraine patients, and that these patients have less social support. We also aimed to study the specific relationship between attachment and social support. We hypothesized that patients with an insecure attachment style have less social support than patients with a secure attachment style.Methods: A total of 101 consecutive patients (88.1% women) aged between 25 and 60 (average age = 41.4) were recruited at the Specialized Center for the Consultation of Primary Headaches at the Regional University Hospital Center of Besançon (France). Migraine impact and disability were evaluated using the Headache Impact Test (HIT-6) questionnaire and Migraine Disability Assessment (MIDAS) questionnaire. Patients also completed several self-administered psychological questionnaires in their validated French versions: the Medical Outcome Survey 36-Item Short-Form Health Survey, the Cungi Scale, the State-Trait Anxiety Inventory, the Beck Depression Inventory, the Relationship Scales Questionnaire and the Sarason's Social Support Questionnaire.Results: The distribution of attachment profiles was different from that of the general population, with an overrepresentation of insecure attachment styles (p = 0.018). Our study showed that migraine patients had less social support than the general population, both in terms of the number of people providing support (p = 0.002) and the level of satisfaction concerning this social support (p = 0.000). We also found that neither the number of available persons score nor the satisfaction score were statistically different between the four attachment categories (p = 0.49). Patient's attachment style and social support influence the patient-doctor relationship, the therapeutic alliance and health behaviors such as treatment adherence.Conclusions: Based on the data we obtained, we developed applications in patient care for people with particular attachment styles and low social support. A treatment plan adapted to the patient's attachment profile should be created to develop “precision medicine” using a personalized approach to the doctor-patient relationship. We would also recommend encouraging patients to participate in support groups, in order to strengthen their attachment systems and gain social support.Clinical Trial Registration:https://clinicaltrials.gov/ct2/show/NCT03577548, identifier NCT03577548.
Published: 2021
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12. Comparison of Noninvasive Imagery Methods to Observe Healthy and Degenerated Olfactory Epithelium in Mice for the Early Diagnosis of Neurodegenerative Diseases

Author: Adeline Etievant, Julie Monnin, Thomas Lihoreau, Brahim Tamadazte, Patrick Rougeot, Eloi Magnin, Laurent Tavernier, Lionel Pazart, and Emmanuel Haffen
Subjects: epithelium olfactory, medical imaging, optical biopsy, neurodegenerative diseases, Alzheimer disease, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571, Human anatomy, QM1-695
Abstract: Olfactory dysfunction could be an early and reliable indicator for the diagnosis of neurodegenerative disorders such as Alzheimer and Parkinson's diseases. In this paper, we compare the potential of different noninvasive medical imaging modalities (optical coherence tomography, confocal microscopy, and fluorescence endomicroscopy) to distinguish how the olfactory epithelium, both at the cellular and the structural levels, is altered. Investigations were carried out on three experimental groups: two pathological groups (mice models with deliberately altered olfactory epithelium and Alzheimer's disease transgenic mice models) were compared with healthy mice models. As histological staining, the three tested noninvasive imaging tools demonstrated the general tubular organization of the olfactory epithelium on healthy mice. Contrary to OCT, confocal microscopy, and endomicroscopy allowed visualizing the inner structure of olfactory epithelium as well as its morphological or functional changes on pathological models, alterations classically observed with histological assessment. The results could lead to relevant development of imaging tools for noninvasive and early diagnosis of neurodegenerative diseases through the in situ characterization of the olfactory epithelium.
Published: 2020
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13. Cognitive Impairment in Secondary Progressive Multiple Sclerosis: Effect of Disease Duration, Age, and Progressive Phenotype

Author: Bruno Brochet, Pierre Clavelou, Gilles Defer, Jérôme De Seze, Céline Louapre, Eloi Magnin, Aurélie Ruet, Catherine Thomas-Anterion, and Patrick Vermersch
Subjects: multiple sclerosis, cognition, secondary progressive MS, neuropsychology, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract: Background: Cognitive deficits are common in multiple sclerosis (MS) and affect patients at all stages of the disease, regardless of phenotype. Aims: This literature review focuses the cognitive deficits observed in secondary progressive MS (SPMS). It is mainly based on studies that compared the frequency and main characteristics of cognitive deficits in SPMS with other phenotypes. Methods: A bibliographic search was carried out using the PubMed database with the following keywords: multiple sclerosis, secondary-progressive, cognition. Results: Thirteen studies were initially selected that were published in English, reporting the neuropsychological data of a sample of at least 30 patients with SPMS, comparing them with patients with other phenotypes. Studies suggest that there is an association between the duration of the disease and the frequency and extent of the cognitive disorders. Studies also showed that the SP form is associated with an increased frequency of cognitive impairment and with an increased severity as compared to relapsing-remitting MS (RRMS). Compared to RRMS, progressive forms of MS are associated with more severe impairment in certain cognitive areas, such as episodic verbal memory, information processing speed, working memory, or verbal fluency. Two studies showed that cognitive performances decline overtime in SPMS. Conclusion: Cognitive disorders are more frequent and more severe in the SP form than in relapsing course of MS. The profile of cognitive impairment encountered in the SP form also appears to be different from those found in the other phenotypes.
Published: 2022
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14. Long-term cognitive outcome of Alzheimer’s disease and dementia with Lewy bodies: dual disease is worse

Author: Frédéric Blanc, Rachid Mahmoudi, Thérèse Jonveaux, Jean Galmiche, Gilles Chopard, Benjamin Cretin, Catherine Demuynck, Catherine Martin-Hunyadi, Nathalie Philippi, François Sellal, Jean-Marc Michel, Gregory Tio, Melanie Stackfleth, Pierre Vandel, Eloi Magnin, Jean-Luc Novella, Georges Kaltenbach, Athanase Benetos, and Erik A. Sauleau
Subjects: Dementia with Lewy bodies, Alzheimer’s disease, Alzheimer’s dementia, Lewy body disease, MMSE, Outcome, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571, Neurology. Diseases of the nervous system, RC346-429
Abstract: Abstract Background Longitudinal studies of dementia with Lewy bodies (DLB) are rare. Clinically, DLB is usually considered to worsen into Alzheimer’s disease (AD). The aim of our study was to compare the rate of the cognitive decline in DLB, AD, and the association of the two diseases (AD + DLB). Methods Using the Regional Network for Diagnostic Aid and Management of Patients with Cognitive Impairment database, which includes all the patients seen at all memory clinics (medical consultation and day hospitals) in four French regions, and beta regression, we compared the longitudinal the Mini-Mental State Examination scores of 1159 patients with AD (n = 1000), DLB (n = 131) and AD + DLB (association of the two) (n = 28) during follow-up of at least 4 years. Results The mean follow-up of the patients was 5.88 years. Using beta regression without propensity scores, the comparison of the decline of patients with AD and patients with DLB did not show a significant difference, but the decline of patients with AD + DLB was worse than that of either patients with DLB (P = 0.006) or patients with AD (P
Published: 2017
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15. Semantic loss marks early Alzheimer's disease‐related neurodegeneration in older adults without dementia

Author: Jet M. J. Vonk, Vincent Bouteloup, Jean‐François Mangin, Bruno Dubois, Frédéric Blanc, Audrey Gabelle, Mathieu Ceccaldi, Cédric Annweiler, Pierre Krolak‐Salmon, Catherine Belin, Thérèse Rivasseau‐Jonveaux, Adrien Julian, François Sellal, Eloi Magnin, Marie Chupin, Marie‐Odile Habert, Geneviève Chêne, Carole Dufouil, and and on behalf of the MEMENTO cohort Study Group
Subjects: Alzheimer's disease, amnestic, biomarkers, category fluency, cognitive aging, cohort studies, Neurology. Diseases of the nervous system, RC346-429, Geriatrics, RC952-954.6
Abstract: Abstract Objective To assess progression of semantic loss in early stages of cognitive decline using semantic and letter fluency performance, and its relation with Alzheimer's disease (AD)‐specific neurodegeneration using longitudinal multimodal neuroimaging measures. Methods Change in verbal fluency was analyzed among 2261 non‐demented individuals with a follow‐up diagnosis of no mild cognitive impairment (MCI), amnestic MCI (aMCI), non‐amnestic MCI (naMCI), or incident dementia, using linear mixed models across 4 years of follow‐up, and relations with magnetic resonance imaging (MRI; n = 1536) and 18F‐fluorodeoxyglucose brain positron emission tomography (18F‐FDG‐PET) imaging (n = 756) using linear regression models across 2 years of follow‐up. Results Semantic fluency declined—fastest in those at higher risk for AD (apolipoprotein E [APOE] e4 carriers, Clinical Dementia Rating score of .5, aMCI, or incident dementia)—while letter fluency did not except for those with incident dementia. Lower baseline semantic fluency was associated with an increase in white matter hyperintensities and total mean cortical thinning over time, and regionally with less hippocampal volume as well as more cortical thinning and reduced 18F‐FDG‐PET uptake in the inferior parietal lobule, entorhinal cortex, isthmus cingulate, and precuneus–posterior cingulate area. In contrast, baseline letter fluency was not associated with change in total nor regional neurodegeneration. Whole‐brain neurodegeneration over time was associated with faster decline in both fluencies, while AD‐specific regions were associated with a faster rate of decline in semantic but not letter fluency. Interpretation This study provides strong evidence of distinctive degeneration of semantic abilities early on in relation to both cognitive decline and AD‐specific neurodegeneration.
Published: 2020
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16. Neural Activation in Risky Decision-Making Tasks in Healthy Older Adults: A Meta-Analysis of fMRI Data

Author: Thomas Tannou, Eloi Magnin, Alexandre Comte, Régis Aubry, and Sven Joubert
Subjects: aging, decision making, fMRI, meta-analysis, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract: Decision making is a complex cognitive phenomenon commonly used in everyday life. Studies have shown differences in behavioral strategies in risky decision-making tasks over the course of aging. The development of functional neuroimaging has gradually allowed the exploration of the neurofunctional bases of these behaviors. The purpose of our study was to carry out a meta-analysis on the neural networks underlying risky decision making in healthy older adults. Following the PRISMA guidelines, we systematically searched for fMRI studies of decision making in older adults using risky decision-making tasks. To perform the quantitative meta-analysis, we used the revised version of the activation likelihood estimation (ALE) algorithm. A total of 620 references were selected for initial screening. Among these, five studies with a total of 98 cognitively normal older participants (mean age: 69.5 years) were included. The meta-analysis yielded two clusters. Main activations were found in the right insula, bilateral dorsolateral prefrontal cortex (dlPFC) and left orbitofrontal cortex (OFC). Despite the limited number of studies included, our meta-analysis highlights the crucial involvement of circuits associated with both emotion regulation and the decision to act. However, in contrast to the literature on young adults, our results indicate a different pattern of hemispheric lateralization in older participants. These activations can be used as a minimum pattern of activation in the risky decision-making tasks of healthy older subjects.
Published: 2021
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17. Repetitive Transcranial Magnetic Stimulation as an Add-On Treatment for Cognitive Impairment in Alzheimer’s Disease and Its Impact on Self-Rated Quality of Life and Caregiver’s Burden

Author: Juliana Teti Mayer, Caroline Masse, Gilles Chopard, Magali Nicolier, Matthieu Bereau, Eloi Magnin, Julie Monnin, Gregory Tio, Emmanuel Haffen, Pierre Vandel, and Djamila Bennabi
Subjects: rTMS (repetitive transcranial magnetic stimulation), Alzheimer’s disease, dorsolateral prefrontal cortex, cognitive impairment, quality of life, memory, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract: Alzheimer’s disease (AD) is associated with progressive memory loss and decline in executive functions, as well as neuropsychiatric symptoms. Patients usually consider quality of life (QoL) and mood as more important for their health status than disease-specific physical and mental symptoms. In this open-label uncontrolled trial, 12 subjects diagnosed with AD underwent 10 sessions of repetitive transcranial magnetic stimulation (rTMS) over the left dorsolateral prefrontal cortex (10 Hz, 20 min, 2000 pulses/day, 110% MT). Outcomes were measured before and 30 days after treatment. Our primary objective was to test the efficacy of rTMS as an add-on treatment for AD on the global cognitive function, assessed through the Mini-Mental State Examination (MMSE) and the Mattis Dementia Rating Scale (MDRS). As secondary objectives, the detailed effect on cognitive functions, depression and anxiety symptoms, QoL, and functionality in daily life activities were evaluated, as well as correlations between QoL and cognition, depression and anxiety scores. The treatment significantly enhanced semantic memory and reduced anxiety. Improvement of these features in AD could become an important target for treatment strategies. Although limited by its design, this trial may contribute with another perspective on the analysis and the impact of rTMS on AD.
Published: 2021
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18. Age, Neurological Status MRC Scale, and Postoperative Morbidity are Prognostic Factors in Patients with Glioblastoma Treated by Chemoradiotherapy

Author: Clotilde Verlut, Guillaume Mouillet, Eloi Magnin, Joëlle Buffet-Miny, Gabriel Viennet, Françoise Cattin, Nora Clelia Billon-Grand, Emilie Bonnet, Stéphanie Servagi-Vernat, Joël Godard, Romain Billon-Grand, Antoine Petit, Thierry Moulin, Laurent Cals, Xavier Pivot, and Elsa Curtit
Subjects: Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Published: 2016

19. Cognitive Impairment Involving Social Cognition in SPG4 Hereditary Spastic Paraplegia

Author: Ludivine Chamard, Sabrina Ferreira, Alexa Pijoff, Manon Silvestre, Eric Berger, and Eloi Magnin
Subjects: Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract: Objectives. To describe cognitive assessment including social cognition in SPG4 patients. Methods. We reported a series of nine patients with SPG4 mutation with an extensive neuropsychological examination including social cognition assessment. Results. None of our patients presented with mental retardation or dementia. All presented with mild cognitive impairment with a high frequency of attention deficit (100%), executive disorders (89%), and social cognition impairment (78%). An asymptomatic patient for motor skills presented with the same cognitive profile. No correlation was found in this small sample between cognitive impairment and motor impairment, age at disease onset, or disease duration. Conclusions. SPG4 phenotypes share some cognitive features of frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Cognitive disorders including executive disorders and social cognition impairment are frequent in SPG4 patients and might sometimes occur before motor disorders. Therefore, cognitive functions including social cognition should be systematically assessed in order to improve the clinical management of this population.
Published: 2016
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20. Association of Amyotrophic Lateral Sclerosis and Alzheimer’s Disease: New Entity or Coincidence? A Case Series

Author: Claire Paquet, Pierre Lozeron, Elodie Bouaziz-Amar, Florence Pasquier, Vincent Deramecourt, Eloi Magnin, Agathe Vrillon, and David Wallon
Subjects: Pathology, medicine.medical_specialty, Amyloid, business.industry, General Neuroscience, General Medicine, Disease, Neuropathology, medicine.disease, Psychiatry and Mental health, Clinical Psychology, Cerebrospinal fluid, medicine, Geriatrics and Gerontology, Amyotrophic lateral sclerosis, business, Episodic memory, Pathological, Frontotemporal dementia
Abstract: Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia have a strong clinical, genetic, and pathological connection but association of ALS with Alzheimer’s disease (AD) is seldom reported. We report a series of 5 cases of AD associated with ALS. Our patients presented with cognitive deterioration with episodic memory impairment meeting criteria for AD. ALS occurred subsequently in all cases and its phenotype was not homogenous. Amyloid process was confirmed in four cases with cerebrospinal fluid biomarkers. One case underwent postmortem exam, demonstrating hallmarks lesions of both diseases. This series highlights that ALS-AD phenotype could be a specific underexplored entity.
Published: 2021
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21. Penetrance estimation of Alzheimer disease in SORL1 loss-of-function variant carriers using a family-based strategy and stratification by APOE genotypes

Author: Schramm, Catherine, Charbonnier, Camille, Zaréa, Aline, Lacour, Morgane, Wallon, David, Boland, Anne, Deleuze, Jean-François, Olaso, Robert, Alarcon, Flora, Campion, Dominique, Nuel, Grégory, Nicolas, Gaël, Collaborators Daniela Andriuta, Pierre, Anthony, Sophie, Auriacombe, Anna-Chloé, Balageas, Guillaume, Ballan, Mélanie, Barbay, Emilie, Beaufils, Yannick, Béjot, Serge, Belliard, Marie, Benaiteau, Karim, Bennys, Frédéric, Blanc, Stéphanie, Bombois, Claire Boutoleau Bretonnière, Pierre, Branger, Jasmine, Carlier, Leslie, Cartz-Piver, Pascaline, Cassagnaud, Giovanni, Castelnovo, Christine, Champion, Annabelle, Chaussenot, Mathieu, Ceccaldi, Valérie, Chauviré, Yaohua, Chen, Julien, Cogez, Emmanuel, Cognat, Fabienne, Contegal-Callier, Lea, Corneille, Philippe, Couratier, Hélène, Courtemanche, Benjamin, Cretin, Charlotte, Crinquette, Bernard, Croisille, Benjamin, Dauriat, Sophie, Dautricourt, Vincent de la Sayette, Astrid De Liège, Marie De Verdal, Didier, Deffond, Benoit, Delpont, Florence, Demurger, Vincent, Deramecourt, Céline, Derollez, Mira, Didic, Giulia, Diemert, Elsa, Dionet, Philippe, Diraison, Aude, Doan, Martine Doco Fenzy, Boris, Dufournet, Julien, Dumurgier, Hélène, Durand, Anas, Dutray, Frédérique, Etcharry-Bouyx, Maté, Formaglio, Audrey, Gabelle, Anne, Gainche-Salmon, Jean-Claude, Getenet, Emmanuelle, Ginglinger, Olivier, Godefroy, Mathilde, Graber, Chloé, Gregoire, Stephan, Grimaldi, Julien, Gueniat, Claude, Gueriot, Sophie, Haffen, Lorraine, Hamelin, Didier, Hannequin, Cezara, Hanta, Clémence, Hardy, Geoffroy, Hautecloque, Camille, Heitz, Claire, Hourregue, Thérèse, Jonveaux, Snejana, Jurici, Catia, Khoumri, Lejla, Koric, Pierre, Krolak-Salmon, Pierre, Labauge, Morgane, Lacour, Julien, Lagarde, Hélène-Marie, Lanoiselée, Brice, Laurens, Isabelle Le Ber, Gwenaël Le Guyader, Amélie, Leblanc, Thibaud, Lebouvier, Anas, Lippi, Marie-Anne, Mackowiak, Eloi, Magnin, Cecilia, Marelli, Olivier, Martinaud, Aurélien, Maureille, Emilie, Milongo-Rigal, Sophie, Mohr, Hélène, Mollion, Olivier, Moreaud, Alexandre, Morin, Gaël, Nicolas, Julia, Nivelle, Camille, Noiray, Elisabeth, Ollagnon-Roman, Claire, Paquet, Jérémie, Pariente, Florence, Pasquier, Alexandre, Perron, Nathalie, Philippi, Virginie, Pichon, Vincent, Planche, Céline, Poirsier, Marie, Rafiq, Pauline, Rod-Olivieri, Adeline, Rollin-Sillaire, Carole, Roué-Jagot, Dario, Saracino, Marie, Sarazin, Mathilde, Sauvée, François, Sellal, Lila Sirven Villaros, Christel, Thauvin, Camille, Tisserand, Christophe, Tomasino, Cédric, Turpinat, Laurène Van Damme, Olivier, Vercruysse, Alice, Voilly, Nathalie, Wagemann, David, Wallon, Aline, Zarea, Shahzad, Ahmad, Philippe, Amouyel, Claudine, Berr, Anne, Boland, Paola, Bossu, Femke, Bouwman, Jose, Bras, Dominique, Campion, Camille, Charbonnier, Jordi, Clarimon, Antonio, Daniele, Jean-François, Dartigues, Stéphanie, Debette, Jean-François, Deleuze, Nicola, Denning, Oriol, Dols-Icardo, Nick, C Fox, Daniela, Galimberti, Emmanuelle, Génin, Hans, Gille, Benjamin, Grenier-Boley, Detelina, Grozeva, Rita, Guerreiro, John, J Hardy, Clive, Holmes, Henne, Holstege, Marc, Hulsman, Holger, Hummerich, M Arfan Ikram, M Kamran Ikram, Iris, Jansen, Amit, Kawalia, Robert, Kraaij, Jean-Charles, Lambert, Marc, Lathrop, Afina, W Lemstra, Alberto, Lleo, Lauren, Luckcuck, Marcel M A, M Mannens, Rachel, Marshall, Carlo, Masullo, Simon, Mead, Mecocci, Patrizia, Alun, Meggy, Merel, O Mol, Kevin, Morgan, Benedetta, Nacmias, Penny, J Norsworthy, Pau, Pastor, Olivier, Quenez, Alfredo, Ramirez, Rachel, Raybould, Richard, Redon, Marcel J, T Reinders, Anne-Claire, Richard, Steffi, G Riedel-Heller, Fernando, Rivadeneira, Stéphane, Rousseau, Natalie, S Ryan, Salha, Saad, Pascual, Sanchez-Juan, Philip, Scheltens, Jonathan, M Schott, Davide, Seripa, Daoud, Sie, Rebecca, Sims, Erik, Sistermans, Sandro, Sorbi, Resie van Spaendonk, Gianfranco, Spalleta, Nicćolo, Tesi, Betty, Tijms, André, G Uitterlinden, Wiesje, M van der Flier, Sven, J van der Lee, Cornelia, M van Duijn, Jeroen G, J van Rooij, John, C van Swieten, Pieter, J de Visser, Michael, Wagner, and Julie, Williams
Subjects: Genotype, Membrane Transport Proteins, Penetrance, Lifetime risk, Pedigree, Expectation-maximization algorithm, Settore MED/26 - NEUROLOGIA, Apolipoproteins E, Missing genotypes, Alzheimer Disease, Case-Control Studies, SORL1, Alzheimer, Genetics, Humans, Molecular Medicine, Molecular Biology, LDL-Receptor Related Proteins, APOE, Genetics (clinical)
Abstract: Background Alzheimer disease (AD) is a common complex disorder with a high genetic component. Loss-of-function (LoF) SORL1 variants are one of the strongest AD genetic risk factors. Estimating their age-related penetrance is essential before putative use for genetic counseling or preventive trials. However, relative rarity and co-occurrence with the main AD risk factor, APOE-ε4, make such estimations difficult. Methods We proposed to estimate the age-related penetrance of SORL1-LoF variants through a survival framework by estimating the conditional instantaneous risk combining (i) a baseline for non-carriers of SORL1-LoF variants, stratified by APOE-ε4, derived from the Rotterdam study (N = 12,255), and (ii) an age-dependent proportional hazard effect for SORL1-LoF variants estimated from 27 extended pedigrees (including 307 relatives ≥ 40 years old, 45 of them having genotyping information) recruited from the French reference center for young Alzheimer patients. We embedded this model into an expectation-maximization algorithm to accommodate for missing genotypes. To correct for ascertainment bias, proband phenotypes were omitted. Then, we assessed if our penetrance curves were concordant with age distributions of APOE-ε4-stratified SORL1-LoF variant carriers detected among sequencing data of 13,007 cases and 10,182 controls from European and American case-control study consortia. Results SORL1-LoF variants penetrance curves reached 100% (95% confidence interval [99–100%]) by age 70 among APOE-ε4ε4 carriers only, compared with 56% [40–72%] and 37% [26–51%] in ε4 heterozygous carriers and ε4 non-carriers, respectively. These estimates were fully consistent with observed age distributions of SORL1-LoF variant carriers in case-control study data. Conclusions We conclude that SORL1-LoF variants should be interpreted in light of APOE genotypes for future clinical applications.
Published: 2022
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22. Neurodevelopmental and Neurodegenerative Similarities and Interactions: A Point of View About Lifelong Neurocognitive Trajectories

Author: Eloi Magnin
Subjects: 0301 basic medicine, Point (typography), General Neuroscience, Neurodegenerative Diseases, Diagnostic accuracy, Cognition, General Medicine, 03 medical and health sciences, Psychiatry and Mental health, Clinical Psychology, 030104 developmental biology, 0302 clinical medicine, Neurodevelopmental Disorders, Animals, Humans, Geriatrics and Gerontology, Psychology, Neurocognitive, 030217 neurology & neurosurgery, Cognitive psychology
Abstract: Neurodevelopmental and neurodegenerative disorders are both growing major public health topics with similarities and frequent complex interactions with each other. Taking these aspects into account can provide a new point of view on lifelong neurocognitive trajectories. Assessing both neurodevelopmental and neurodegenerative dimensions during cognitive and behavioral clinical assessments is challenging but might improve diagnostic accuracy and physiopathological understanding. It is therefore necessary to understand the lifelong specific neurocognitive trajectory of each patient in order to develop personalized precision cognitive medicine.
Published: 2021
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23. Medical teachers’ opinions about students with neurodevelopmental disorders and their management

Author: Ilham Ryff, Thierry Moulin, and Eloi Magnin
Subjects: 020205 medical informatics, education, lcsh:Medicine, 02 engineering and technology, Mainstreaming, Affect (psychology), Education, 03 medical and health sciences, 0302 clinical medicine, Surveys and Questionnaires, mental disorders, 0202 electrical engineering, electronic engineering, information engineering, medicine, Humans, 030212 general & internal medicine, Students, Mainstreaming (education), Vas score, Medical education, lcsh:LC8-6691, Descriptive statistics, lcsh:Special aspects of education, Professional development, Neurodevelopmental disorders, lcsh:R, Dyslexia, General Medicine, medicine.disease, Faculty, Staff development, Cross-Sectional Studies, Attitude, Attention deficit, Autism, Psychology, Research Article
Abstract: Background Some students have neurodevelopmental disorders that might affect their academic and professional careers if they are not identified and addressed by specific pedagogic adaptations. The objective of this work was to describe medical teachers’ opinions of students with neurodevelopmental disorders and their management of these students. Methods An anonymous cross-sectional electronic survey was performed to describe medical teachers’ opinions about the impact of neurodevelopmental disorders on the student’s life and on the medical teachers’ management. aThe survey was created, including visual analogic scales and free text, to assess teachers’ opinions from identification and assessment of neurodevelopemental burden on students and teachers, to their own knowledge about neurodevelopemental disorders and the specific pedagogic management available. The survey was sent to 175 medical teachers in 2019, of whom 67 responded. Quantitative descriptive statistics and qualitative analysis of free text were reported. Results Many medical teachers report having encountered students who might have had neurodevelopmental disorders (dyspraxia 33%; dyslexia 46%; autism spectrum disorders 68%; attention deficit hyperactivity disorders 75%). Impact on students and on teachers was considered as important (mean VAS score for impact over 60/100 for all syndromes except for dyspraxia). Medical teachers’ self-reported knowledge about neurodevelopmental disorders (mean VAS score 43.9/100) and available pedagogical adaptations (mean VAS score 19.0/100) was limited. The teachers were concerned about ethical issues (mean VAS score 72.2/100) but were interested in receiving specialized training (mean VAS score 64.4/100). Conclusion Medical teachers feel unprepared to manage students with neurodevelopmental disorders. They would be interested in specific training and procedures about the pedagogic management of these students.
Published: 2021

24. Contribution of cerebrospinal fluid Alzheimer biomarkers to the diagnosis of Creutzfeldt‐Jakob disease

Author: Elise Faraut, Maïté Formaglio, Audrey Gabelle, Lou Grangeon, Eloi Magnin, Olivier Martinaud, Claire Boutoleau‐Bretonnière, Emmanuel Cognat, Muriel Quillard‐Muraine, David Maltête, and David Wallon
Subjects: Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Epidemiology, Health Policy, Neurology (clinical), Geriatrics and Gerontology
Published: 2021
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25. Added value of functional neuroimaging to assess decision-making capacity of older adults with neurocognitive disorders: protocol for a prospective, monocentric, single-arm study (IMAGISION)

Author: Alexandre Comte, Eloi Magnin, Lionel Pazart, Thomas Tannou, Damien Gabriel, Serge Daneault, Sven Joubert, Chrystelle Vidal, Régis Aubry, Aurélie Godard-Marceau, Marie-Jeanne Kergoat, Laboratoire d'Imagerie et de Neurosciences Cognitives (LINC), Université Louis Pasteur - Strasbourg I-IFR37-Centre National de la Recherche Scientifique (CNRS), Centre d'Investigation Clinique de Besançon (Inserm CIC 1431), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre de Recherche de l'Institut Universitaire de Gériatrie de Montréal (CRIUGM), Université de Montréal (UdeM), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), and Malbec, Odile
Subjects: Gerontology, protocol for a prospective, Concordance, [SDV]Life Sciences [q-bio], Geriatric Medicine, Decision Making, 050105 experimental psychology, 03 medical and health sciences, 0302 clinical medicine, Informed consent, Medicine, Dementia, magnetic resonance imaging, Humans, 0501 psychology and cognitive sciences, Prospective Studies, single-arm study (IMAGISION). BMJ Open, Aged, Aged, 80 and over, Research ethics, business.industry, Functional Neuroimaging, 05 social sciences, Memory clinic, Neuropsychology, monocentric, Cognition, General Medicine, 16. Peace & justice, medicine.disease, 3. Good health, [SDV] Life Sciences [q-bio], medical ethics, Independent Living, business, Neurocognitive, 030217 neurology & neurosurgery
Abstract: IntroductionAssessment of decision-making capacity (DMC) is essential in daily life as well as for defining a person-centred care plan. Nevertheless, in ageing, especially if signs of dementia appear, it becomes difficult to assess decision-making ability and raises ethical questions. Currently, the assessment of DMC is based on the clinician’s evaluation, completed by neuropsychological tests. Functional MRI (fMRI) could bring added value to the diagnosis of DMC in difficult situations.Methods and analysisIMAGISION is a prospective, monocentric, single-arm study evaluating fMRI compared with clinical assessment of DMC. The study will begin during Fall 2021 and should be completed by Spring 2023. Participants will be recruited from a memory clinic where they will come for an assessment of their cognitive abilities due to decision-making needs to support ageing in place. They will be older people over 70 years of age, living at home, presenting with a diagnosis of mild dementia, and no exclusion criteria of MRI. They will be clinically assessed by a geriatrician on their DMC, based on the neuropsychological tests usually performed. Participants will then perform a behavioural task in fMRI (Balloon Analogue Risk Task) to analyse the activation areas. Additional semistructured interviews will be conducted to explore real life implications. The main analysis will study concordance/discordance between the clinical classification and the activation of fMRI regions of interest. Reclassification as ‘capable’, based on fMRI, of patients for whom clinical diagnosis is ‘questionable’ will be considered as a diagnostic gain.Ethics and disseminationIMAGISION has been authorised by a research ethics board (Comité de Protection des Personnes, Bordeaux, II) in France, in accordance with French legislation on interventional biomedical research, under the reference IDRCB number 2019-A00863-54, since 30 September 2020. Participants will sign an informed consent form. The results of the study will be presented in international peer-reviewed scientific journals, international scientific conferences and public lectures.Trial registration numberNCT03931148
Published: 2021
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26. What Are the Minimal Detectable Changes in SDMT and Verbal Fluency Tests for Assessing Changes in Cognitive Performance in Persons with Multiple Sclerosis and Non-Multiple Sclerosis Controls?

Author: Yoshimasa Sagawa, Pierre Decavel, Thierry Moulin, and Eloi Magnin
Subjects: Adult, Male, medicine.medical_specialty, Multiple Sclerosis, Activities of daily living, Intraclass correlation, Population, Neuropsychological Tests, 030204 cardiovascular system & hematology, Audiology, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Verbal fluency test, Cognitive Dysfunction, Effects of sleep deprivation on cognitive performance, education, education.field_of_study, business.industry, Multiple sclerosis, Reproducibility of Results, Cognition, Middle Aged, medicine.disease, Cognitive test, Neurology, Female, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract: Introduction: Cognitive impairment is frequent in persons with multiple sclerosis (PwMS) and can impact on activities of daily living. The capacity to differentiate real changes from background statistical noise induced by human, instrumentational, and environmental variations inherent to the evaluation would improve cognitive assessments. Objective: To assess the short-term reproducibility of cognitive tests in non-multiple sclerosis (non-MS) persons and PwMS. Methods: Sixty-two PwMS and 19 non-MS persons performed 2 measurements, 1 week apart, of the Symbol Digit Modalities Test (SDMT) and phonological and semantic verbal fluency. Test-retest reliability was evaluated by the intraclass correlation coefficients (ICC) and agreement by standard error of measurement (SEM) and minimum detectable change (MDC). Results: The reliability of the cognitive variables studied had moderate to high ICC values (ICC > 0.8) in both populations. The threshold to consider a significant cognitive modification evaluated by SEM and MDC was lower in PwMS compared with non-MS persons. Conclusions: SDMT and verbal fluency have good short-term reproducibility in PwMS. Specific SEM and MDC cutoffs based on the same design of evaluation (especially retest timing) and to the targeted pathological population (MS vs. healthy) should systematically be used to consider cognitive modification as significant in research protocol as well as in clinical practice.
Published: 2020
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27. Neural Activation in Risky Decision-Making Tasks in Healthy Older Adults: A Meta-Analysis of fMRI Data

Author: Alexandre Comte, Régis Aubry, Eloi Magnin, Sven Joubert, and Thomas Tannou
Subjects: General Neuroscience, aging, fMRI, Cognition, Neurosciences. Biological psychiatry. Neuropsychiatry, Lateralization of brain function, decision making, Dorsolateral prefrontal cortex, meta-analysis, medicine.anatomical_structure, Functional neuroimaging, Meta-analysis, medicine, Orbitofrontal cortex, Systematic Review, Young adult, Everyday life, Psychology, Cognitive psychology, RC321-571
Abstract: Decision making is a complex cognitive phenomenon commonly used in everyday life. Studies have shown differences in behavioral strategies in risky decision-making tasks over the course of aging. The development of functional neuroimaging has gradually allowed the exploration of the neurofunctional bases of these behaviors. The purpose of our study was to carry out a meta-analysis on the neural networks underlying risky decision making in healthy older adults. Following the PRISMA guidelines, we systematically searched for fMRI studies of decision making in older adults using risky decision-making tasks. To perform the quantitative meta-analysis, we used the revised version of the activation likelihood estimation (ALE) algorithm. A total of 620 references were selected for initial screening. Among these, five studies with a total of 98 cognitively normal older participants (mean age: 69.5 years) were included. The meta-analysis yielded two clusters. Main activations were found in the right insula, bilateral dorsolateral prefrontal cortex (dlPFC) and left orbitofrontal cortex (OFC). Despite the limited number of studies included, our meta-analysis highlights the crucial involvement of circuits associated with both emotion regulation and the decision to act. However, in contrast to the literature on young adults, our results indicate a different pattern of hemispheric lateralization in older participants. These activations can be used as a minimum pattern of activation in the risky decision-making tasks of healthy older subjects.
Published: 2021

28. Clinical and neuropathological diversity of tauopathy in MAPT duplication carriers

Author: Isabelle Le Ber, Marie Sarazin, Olivier Quenez, Florence Clavaguera, Catherine Schramm, Anne Rovelet-Lecrux, Camille Heitz, Mathieu Mula, Stéphane Epelbaum, Susana Boluda, Charles Duyckaerts, Manon Thierry, Didier Hannequin, Magalie Lecourtois, Serge Marty, Michel Bottlaender, Julien Lagarde, David Wallon, Natsuko Nakamura, François Sellal, Antoine Bonnevalle, Laetitia Miguel, Gaël Nicolas, Stéphane Rousseau, Dominique Campion, Thérèse Rivasseau Jonveaux, Aline Zarea, Eloi Magnin, Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Neurologie de la mémoire et du langage [CHU Ste Anne], Université Paris Descartes - Paris 5 (UPD5), Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Sainte Anne [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), LaBoratoire d'Imagerie biOmédicale MultimodAle Paris-Saclay (BIOMAPS), Service Hospitalier Frédéric Joliot (SHFJ), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Neuropathologie Raymond Escourolle, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Unité BioMaps (BIOMAPS), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Proband, Adult, Male, Pathology, medicine.medical_specialty, Heterozygote, [SDV]Life Sciences [q-bio], Tau protein, tau Proteins, Pathology and Forensic Medicine, Progressive supranuclear palsy, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Extrapyramidal symptoms, Alzheimer Disease, Basal ganglia, medicine, Humans, Cognitive Dysfunction, Age of Onset, ComputingMilieux_MISCELLANEOUS, Inclusion Bodies, biology, business.industry, Brain, Middle Aged, medicine.disease, 030104 developmental biology, Tauopathies, Chromosomal region, biology.protein, Female, Neurology (clinical), Tauopathy, Alzheimer's disease, medicine.symptom, business, 030217 neurology & neurosurgery
Abstract: Microduplications of the 17q21.31 chromosomal region encompassing the MAPT gene, which encodes the Tau protein, were identified in patients with a progressive disorder initially characterized by severe memory impairment with or without behavioral changes that can clinically mimic Alzheimer disease. The unique neuropathological report showed a primary tauopathy, which could not be unanimously classified in a given known subtype, showing both 4R- and 3R-tau inclusions, mainly within temporal cortical subregions and basal ganglia, without amyloid deposits. Recently, two subjects harboring the same duplication were reported with an atypical extrapyramidal syndrome and gait disorder. To decipher the phenotypic spectrum associated with MAPT duplications, we studied ten carriers from nine families, including two novel unrelated probands, gathering clinical (n = 10), cerebrospinal fluid (n = 6), MRI (n = 8), dopamine transporter scan (n = 4), functional (n = 5), amyloid (n = 3) and Tau-tracer (n = 2) PET imaging data as well as neuropathological examination (n = 4). Ages at onset ranged from 37 to 57 years, with prominent episodic memory impairment in 8/10 patients, associated with behavioral changes in four, while two patients showed atypical extrapyramidal syndrome with gait disorder at presentation, including one with associated cognitive deficits. Amyloid imaging was negative but Tau imaging showed significant deposits mainly in both mesiotemporal cortex. Dopaminergic denervation was found in 4/4 patients, including three without extrapyramidal symptoms. Neuropathological examination exclusively showed Tau-immunoreactive lesions. Distribution, aspect and 4R/3R tau aggregates composition suggested a spectrum from predominantly 3R, mainly cortical deposits well correlating with cognitive and behavioral changes, to predominantly 4R deposits, mainly in the basal ganglia and midbrain, in patients with prominent extrapyramidal syndrome. Finally, we performed in vitro seeding experiments in HEK-biosensor cells. Morphological features of aggregates induced by homogenates of three MAPT duplication carriers showed dense/granular ratios graduating between those induced by homogenates of a Pick disease and a progressive supranuclear palsy cases. These results suggest that MAPT duplication causes a primary tauopathy associated with diverse clinical and neuropathological features.
Published: 2021
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29. [Neurodevelopmental disorders modify neurodegenerative diseases: a medical history to screen in memory clinic]

Author: Sandrine Basaglia-Pappas, Sylvie Chokron, Ilham Ryff, Olivier Martinaud, Mathilde Sauvée, Isabelle Bernard, Servane Mouton, Laure Pisella, Aurélie Richard-Mornas, Julie Monnin, Catherine Thomas Antérion, Eloi Magnin, Centre Mémoire Ressources et Recherche [Dijon] (CMRR Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre d'expertise de la performance Gilles Cometti [Dijon] (CEP), Université de Bourgogne (UB), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Laboratoire de Neurosciences Intégratives et Cliniques - UFC (EA 481) (NEURO), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Hôpital de la Fondation Ophtalmologique Adolphe de Rothschild [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire d'Etude des Mécanismes Cognitifs (EMC), Université Lumière - Lyon 2 (UL2), Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Université de Mons (UMons), Centre de recherche en neurosciences de Lyon (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Neuropsychologie et imagerie de la mémoire humaine (NIMH), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Mémoire de Ressources et de Recherche [Grenoble] (CMRR), Centre Hospitalier Universitaire [Grenoble] (CHU), Laboratoire de Psychologie et NeuroCognition (LPNC ), Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), and Hospices Civils de Lyon (HCL)
Subjects: education.field_of_study, medicine.medical_specialty, business.industry, [SDV]Life Sciences [q-bio], Memory clinic, Perspective (graphical), Population, Cognition, Diagnostic accuracy, Neurodegenerative Diseases, atypical dementia, 3. Good health, Neuropsychology and Physiological Psychology, Neurodevelopmental Disorders, Medicine, Humans, Medical history, Neurology (clinical), Geriatrics and Gerontology, business, education, Psychiatry, Neurocognitive, Biological Psychiatry
Abstract: International audience; Neurodevelopmental disorders are frequent in the general population and are often lifelong conditions despite sometimes being masked by conscious or unconscious compensation and avoidance mechanisms. These conditions are often unknown or underestimated in adults, even when diagnosed in childhood. Neurodevelopmental disorders share similarities with and frequently interact in a complex way with neurodegenerative disorders. Considering these aspects during memory clinic assessments can provide a new perspective on lifelong neurocognitive trajectories. Assessing both neurodevelopmental and neurodegenerative dimensions is challenging but should improve diagnostic accuracy. It is therefore necessary to understand the lifelong specific neurocognitive trajectory of each patient in order to develop personalized and focused cognitive medicine and care.
Published: 2021
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30. Characteristics of Bipolar Patients with Cognitive Impairment of Suspected Neurodegenerative Origin: A Multicenter Cohort

Author: Emilie Olié, Emmanuel Cognat, Djamila Bennabi, Esteban Munoz Musat, Frédéric Blanc, Florence Lebert, Eloi Magnin, Audrey Gabelle, Claire Paquet, Mélanie Leroy, Emeline Marlinge, Magnin, Eloi, Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Lille Neurosciences & Cognition - U 1172 (LilNCog), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre Mémoire de Ressources et de Recherche [Lille-Bailleul] (CMRR), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Hôpital Roger Salengro [Lille], Institut des Neurosciences de Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Laboratoire de Neurosciences Intégratives et Cliniques - UFC (UR 481) (NEURO), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre d'Investigation Clinique de Besançon (Inserm CIC 1431), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Centre Mémoire Ressources et Recherche [Strasbourg] (CMRR Strasbourg), CHU Strasbourg, Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Université de Strasbourg (UNISTRA)-Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), and Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC)
Subjects: cognition, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Medicine (miscellaneous), Parkinsonism, Article, Internal medicine, medicine, Dementia, Bipolar disorder, bipolar disorder, business.industry, neurodegenerescence, Neuropsychology, biomarkers, Cognition, medicine.disease, [SDV] Life Sciences [q-bio], Biomarker (medicine), Medicine, business, Neurocognitive, Alzheimer’s disease, Executive dysfunction, dementia
Abstract: Bipolar disorder is associated with an increased risk of dementia with aging. Little is known regarding this association, limiting appropriate diagnosis and management. We aimed to describe the characteristics of bipolar patients with late cognitive impairment for whom the hypothesis of an underlying neurodegenerative disease had been raised. We performed a retrospective multicenter study, recruiting bipolar patients over 50 years old from five French tertiary memory centers who had undergone cerebrospinal fluid (CSF) biomarker assessment for Alzheimer’s disease (AD). Clinical, neuropsychological, and paraclinical characteristics were analyzed and 78 patients were included. The mean age at the onset of cognitive impairment was 62.4 years (±9.2). The mean MMSE score was 22.8 (±4.5), the mean FAB was 11.7 (±3.9), and the mean FCRST was 15.8 (±7.4)/36.8 (±9.7) (free/total recall). A total of 48.6% of the patients displayed cognitive fluctuations, and 38.2% showed cognitive improvement during follow-ups, and 56.3% of the patients showed Parkinsonism, of which 12.7% had never received antipsychotics. Among patients who underwent DAT-scans, 35.3% displayed dopaminergic denervation, 10.3% of patients had CSF AD biological signature (“A+ T+” profile), while 56.4% had other abnormal CSF profiles. Thus, clinical presentation was dominated by executive dysfunction, episodic memory impairment, fluctuating cognition, and a high frequency of Parkinsonism. Specifically, high frequency of delusional episodes suggests limited tolerance of psychotropic drugs. Most patients had abnormal CSF biomarker profiles, but only a minority displayed AD’s specific biomarker signature. Therefore, while our results unveil shared common neurocognitive features in bipolar patients with cognitive impairment of suspected neurodegenerative origin they suggest a participation of various underlying pathologies rather than a common degenerative mechanism in the pathophysiology of this condition.
Published: 2021
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31. Social and emotional cognition in patients with severe migraine consulting in a tertiary headache center: a preliminary study

Author: Margaux Bouteloup, Eloi Magnin, Rose-Angélique Belot, Geraldine Sylvestre, Maxime Bertoux, Fabrice Vuillier, Nicolas Noiret, Laboratoire de Psychologie - UFC (UR 3188) (PSYCHO), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre de Recherches sur la Cognition et l'Apprentissage (CeRCA), Université de Poitiers-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Lille Neurosciences & Cognition - U 1172 (LilNCog), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Laboratoire de Psychologie - UFC (EA 3188) (PSYCHO), and Lille Neurosciences & Cognition - U 1172 (LilNCog (ex-JPARC))
Subjects: Migraine Disorders, Emotions, 03 medical and health sciences, Cognition, 0302 clinical medicine, Alexithymia, medicine, Humans, Affective Symptoms, 030212 general & internal medicine, Depression (differential diagnoses), Headache, medicine.disease, Neurology, Mentalization, Migraine, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Anxiety, Faux pas, Normative, Neurology (clinical), medicine.symptom, Psychology, 030217 neurology & neurosurgery, Clinical psychology
Abstract: Twenty-three severe migraine participants were studied to investigate social and emotional cognition features and explore their relationship with depression, anxiety and alexithymia. In comparison to normative data, 74% were under the norm for the Faux Pas subtest, 13% for the facial emotion recognition subtest and 52% for the overall composite score of the mini-SEA. Factor 1, Factor 3, and the total score of the TAS-20 were negatively correlated with the Faux Pas subtest. Our preliminary study shows that severe migraine patients present difficulties in inferring mental states, which could be related to alexithymia. It would be useful to identify these impairments in order to improve the quality of care provided. Clinical Trials registration number: NCT03577548.
Published: 2021
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32. Phenotypes associated with MAPT duplications

Author: Stéphane Epelbaum, Muriel Quillard-Muraine, David Wallon, Dominique Campion, François Sellal, Antoine Bonnevalle, Gaël Nicolas, Michel Bottlaender, Susana Boluda, Marie Sarazin, Camille Heitz, Isabelle Le Ber, Didier Hannequin, Thérèse Rivasseau Jonveaux, Anne-Claire Richard, Anne Rovelet-Lecrux, Stéphane Rousseau, Charles Duyckaerts, Julien Lagarde, Olivier Quenez, Camille Charbonnier, Eloi Magnin, and Mathieu Chastan
Subjects: Genetics, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Epidemiology, Health Policy, Neurology (clinical), Geriatrics and Gerontology, Biology, Phenotype
Published: 2020
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33. lncRNAs as a novel source of diagnostic applications for early Alzheimer’s disease and other dementia types

Author: Moira Marizzoni, Hüseyin Firat, Sabrina Danilin, Frédéric Blanc, Eloi Magnin, Jean-François Démonet, Hakan Gurvit, Bruno Dubois, Giovanni B. Frisoni, Eric Schordan, Florence Pasquier, Stéphanie Boutillier, François Sellal, Sami Ait Abbi Nazi, Jean Christophe Bier, Saliha Moussaoui, Audrey Gabelle, Catherine Mutter, Renaud David, and Adrian Ivanoiu
Subjects: Epidemiology, business.industry, Health Policy, Disease, medicine.disease, Bioinformatics, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Neuroimaging, medicine, Dementia, Neurology (clinical), Geriatrics and Gerontology, business
Published: 2020
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34. Cerebrospinal Fluid Levels of Kininogen‐1 Indicate Early Cognitive Impairment in Parkinson's Disease

Author: Anna Månberg, Wassilios G. Meissner, Kimmo Sorjonen, Julia Remnestål, Stephanie Carvalho, Wojciech Paslawski, Peter Nilsson, Mathias Uhlén, Eloi Magnin, Ioanna Markaki, Sofia Bergström, Ellen Hertz, Graziella Mangone, Olivier Rascol, Jean-Christophe Corvol, Ullrich Wüllner, Panagiota Tsitsi, Per Svenningsson, Karolinska Institutet [Stockholm], Royal Institute of Technology [Stockholm] (KTH ), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre d'investigation clinique de Toulouse (CIC 1436), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d’Excellence en Maladies Neurodégénératives (NeuroToul), CHU Toulouse [Toulouse], Institut des Maladies Neurodégénératives [Bordeaux] (IMN), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), University of Otago [Dunedin, Nouvelle-Zélande], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), University Hospital Bonn, German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Gestionnaire, Hal Sorbonne Université, Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Pôle Santé publique et médecine publique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), and Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)
Subjects: 0301 basic medicine, Kininogen 1, Oncology, cognition, medicine.medical_specialty, Parkinson's disease, Movement disorders, [SDV]Life Sciences [q-bio], Neuropsychological Tests, etiology [Cognitive Dysfunction], kininogen-1, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Medicine, Dementia, Humans, Cognitive Dysfunction, ddc:610, diagnosis [Cognition Disorders], business.industry, Kininogens, Confounding, Neuropsychology, neurodegeneration, etiology [Cognition Disorders], Montreal Cognitive Assessment, Cognition, Parkinson Disease, medicine.disease, Mental Status and Dementia Tests, 3. Good health, [SDV] Life Sciences [q-bio], 030104 developmental biology, Neurology, Neurology (clinical), complications [Parkinson Disease], medicine.symptom, business, Cognition Disorders, 030217 neurology & neurosurgery
Abstract: International audience; Background: Cognitive impairment is common in patients with PD. Core markers of Alzheimer's dementia have been related also to PD dementia, but no disease-specific signature to predict PD dementia exists to date.Objectives: The aim of this study was to investigate CSF markers associated with cognition in early PD.Methods: A high-throughput suspension bead array examined 216 proteins in CSF of 74 PD patients in the AETIONOMY project. Cognitive function was assessed with Repeatable Battery for the Assessment of the Neuropsychological Status, Montreal Cognitive Assessment, and Mini-Mental State Examination.Results: Of 69 patients with complete data, 34 had high (≥90) and 35 had low Repeatable Battery for the Assessment of the Neuropsychological Status total score (
Published: 2020
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35. Lexique des troubles cognitifs dans la sclérose en plaques

Author: J.-P. Delabrousse-Mayoux, Jean-Jacques Pere, Eloi Magnin, B. Durand, Olivier Heinzlef, Gilles-Louis Defer, Christine Lebrun-Frenay, Aurélie Ruet, Bruno Brochet, Pierre Clavelou, J. de Seze, Catherine Thomas-Antérion, Service de Neurologie [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Service de Neurologie [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Service de Neurologie [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Laboratoire d'Etude des Mécanismes Cognitifs (EMC), and Université Lumière - Lyon 2 (UL2)
Subjects: 03 medical and health sciences, 0302 clinical medicine, [SDV]Life Sciences [q-bio], 030212 general & internal medicine, Neurology (clinical), 030217 neurology & neurosurgery, 3. Good health
Abstract: Resume Les troubles cognitifs sont frequents chez les patients atteints de sclerose en plaques, avec des degres d’intensite divers. Ils peuvent impacter de maniere significative la vie quotidienne et professionnelle des patients, ainsi que leur qualite de vie. Le depistage de ces troubles est donc important et les neurologues doivent s’investir dans leur evaluation afin de proposer une prise en charge adaptee. Les liens entre cognition et comportement sont souvent intriques. Il peut etre utile de rappeler le vocabulaire neuropsychologique definissant les differents symptomes les plus souvent observes dans la sclerose en plaques. Ceci permet aussi de visiter clinique et anatomie. Nous proposons un lexique qui definit 118 termes susceptibles d’aider les neurologues dans la comprehension des troubles de la cognition et du comportement chez leurs patients, de faciliter leur ecoute dans un entretien, de prescrire quand il le faut une expertise de premiere ligne ou plus specialisee, de lire des travaux scientifiques ou ces donnees sont de plus en plus citees et de communiquer en utilisant un vocabulaire commun.
Published: 2020
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36. Diffuse neurofibrillary tangles with calcification: A single entity or two disorders in a single patient?

Author: Guillaume Nicolas, Xavier Ayrignac, and Eloi Magnin
Subjects: Pathology, medicine.medical_specialty, business.industry, Calcinosis, Neurofibrillary Tangles, medicine.disease, Single patient, Neurology, Diffuse Neurofibrillary Tangles with Calcification, Single entity, Medicine, Humans, Neurology (clinical), business, Calcification
Published: 2020

37. C’est pas ça mais vous n’aurez pas de mal à trouver le diagnostic !

Author: Pierre Bernard, Emilie Claeys, Thierry Moulin, Eloi Magnin, and Nathalie Devys-Meyer
Subjects: Neurology, Neurology (clinical)
Published: 2022
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38. Apports de la scintigraphie dans les TND neurovisuels

Author: Cyrielle Huguenot, Eloi Magnin, Florent Caetta, Karim Farid, Gordon Dutton, and Sylvie Chokron
Subjects: Neurology, Neurology (clinical)
Published: 2022
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39. Relevance of Follow-Up in Patients with Core Clinical Criteria for Alzheimer Disease and Normal CSF Biomarkers

Author: Olivier Vercruysse, Claire Paquet, Audrey Gabelle, Xavier Delbeuck, Frederic Blanc, David Wallon, Julien Dumurgier, Eloi Magnin, Olivier Martinaud, Barbara Jung, Olivier Bousiges, Sylvain Lehmann, Constance Delaby, Muriel Quillard-Murain, Katell Peoc`h, Jean-Louis Laplanche, Elodie Bouaziz-Amar, Didier Hannequin, Bernard Sablonniere, Luc Buee, Jacques Hugon, Susanna Schraen, Florence Pasquier, Stephanie Bombois, null for the e-PLM group, Troubles cognitifs dégénératifs et vasculaires - U 1171 (TCDV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Biomarqueurs CArdioNeuroVASCulaires (BioCANVAS), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université de Strasbourg (UNISTRA), Service de neurologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Plateforme de Protéomique Clinique, CHU Saint-Eloi, Université Paris Diderot - Paris 7 (UPD7), Génétique du cancer et des maladies neuropsychiatriques (GMFC), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Lille, Troubles cognitifs dégénératifs et vasculaires - U 1171 - EA 1046 (TCDV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), and Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)
Subjects: Male, medicine.medical_specialty, [SDV]Life Sciences [q-bio], tau Proteins, 030218 nuclear medicine & medical imaging, Diagnosis, Differential, 03 medical and health sciences, 0302 clinical medicine, Alzheimer Disease, Internal medicine, medicine, Humans, Dementia, Cognitive Dysfunction, Diagnostic Errors, Phosphorylation, Vascular dementia, ComputingMilieux_MISCELLANEOUS, Depression (differential diagnoses), Aged, Retrospective Studies, Hippocampal sclerosis, Amyloid beta-Peptides, business.industry, Brain, medicine.disease, Peptide Fragments, 3. Good health, Neurology, Mood disorders, Biomarker (medicine), Female, Neurology (clinical), Alzheimer's disease, business, Biomarkers, 030217 neurology & neurosurgery, Follow-Up Studies, Frontotemporal dementia
Abstract: Background: Few patients with a normal cerebrospinal fluid (CSF) biomarker profile fulfill the clinical criteria for Alzheimer disease (AD). Objective: The aim of this study was to test the hypothesis of misdiagnoses for these patients. Method: Patients from the e-PLM centers fulfilling the core clinical criteria for probable AD dementia or mild cognitive impairment due to AD (AD-MCI), with normal CSF Aβ1-42, T-tau and P-tau biomarkers and clinical follow-up, were included. Clinical and imaging data were reviewed by an independent board, from baseline (visit with clinical evaluation and CSF analysis) to the end of the follow-up, for a final diagnosis. Results: In the e-PLM cohort of 1098 AD patients with CSF analysis, 37 (3.3%) patients (20 with AD dementia core clinical criteria and 17 with AD-MCI core clinical criteria) had normal CSF biomarker profile and a clinical follow-up. All patients presented with episodic memory impairment and 27 (73%) had medial temporal lobe atrophy on MRI-scan. After a median follow-up of 36 months (range 7-74), the final diagnosis was AD MCI or dementia for 9 (24%) patients, and unlikely due to AD for 28 (76%) patients. A misdiagnosis was corrected in 18 (49%) patients (mood disorders, non-AD degenerative dementia, vascular cognitive impairment, alcohol cognitive disorders, temporal epilepsy and hippocampal sclerosis), and 10 (27%) patients had cognitive disorders of undetermined etiology. Conclusion: AD diagnosis (MCI or dementia) with normal CSF biomarkers is a rare condition. A clinical follow- up is particularly recommended to consider an alternative diagnosis.
Published: 2018
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40. Evidence for a neural signature of musical preference during silence

Author: Magali Nicolier, Julie Giustiniani, Gaelle Brunotte, Pierre Vandel, Thierry Moulin, Julie Monnin, Nicolas Noiret, Emmanuel Haffen, Eloi Magnin, Coralie Joucla, Damien Gabriel, Lionel Pazart, Centre Mémoire de Ressources et de Recherche [CHRU de Besançon] (CMRR), Hôpital Saint-Jacques [CHRU de Besançon] -Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Laboratoire de Psychologie - UFC (EA 3188) (PSYCHO), Université de Franche-Comté (UFC), and Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)
Subjects: Adult, Male, Time Factors, Choice Behavior, 050105 experimental psychology, 03 medical and health sciences, Superior temporal gyrus, 0302 clinical medicine, Physiology (medical), Humans, 0501 psychology and cognitive sciences, Active listening, Set (psychology), ComputingMilieux_MISCELLANEOUS, Brain Mapping, Neural correlates of consciousness, General Neuroscience, 05 social sciences, Electroencephalography, Recognition, Psychology, Preference, Neuropsychology and Physiological Psychology, Acoustic Stimulation, Auditory Perception, Evoked Potentials, Auditory, Imagination, Auditory imagery, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Psychology, Insula, Music, 030217 neurology & neurosurgery, Cognitive psychology, Mental image
Abstract: One of the most basic and person-specific affective responses to music is liking. The present investigation sought to determine whether liking was preserved during spontaneous auditory imagery. To this purpose, we inserted two-second silent intervals into liked and disliked songs, a method known to automatically recreate a mental image of these songs. Neural correlates of musical preference were measured by high-density electroencephalography in twenty subjects who had to listen to a set of five pre-selected unknown songs the same number of times for two weeks. Time frequency analysis of the two most liked and the two most disliked songs confirmed the presence of neural responses related to liking. At the beginning of silent intervals (400–900 ms and 1000–1300 ms), significant differences in theta activity were originating from the inferior frontal and superior temporal gyrus. These two brain structures are known to work together to process various aspects of music and are also activated when measuring liking while listening to music. At the end of silent intervals (1400–1900 ms), significant alpha activity differences originating from the insula were observed, whose exact role remains to be explored. Although exposure was controlled for liked and disliked songs, liked songs were rated as more familiar, underlying the strong relationship that exists between liking, exposure, and familiarity.
Published: 2018
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41. Cerebrospinal fluid Alzheimer biomarkers can be useful for discriminating dementia with Lewy bodies from Alzheimer’s disease at the prodromal stage

Author: Frédéric Blanc, Eloi Magnin, Muriel Quillard, Elodie Amar-Bouaziz, David Wallon, Olivier Bousiges, Nathalie Philippi, Sylvain Lehmann, Audrey Gabelle, Stéphanie Bombois, Xavier Delbeuck, Claire Paquet, Susanna Schraen, Pierre Anthony, Carole Miguet-Alfonsi, Thomas Lavaux, Université de Strasbourg (UNISTRA), Université de Lille, Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Service de neurologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Plateforme de Protéomique Clinique, CHU Saint-Eloi, Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), CHU Montpellier, Biomarqueurs CArdioNeuroVASCulaires (BioCANVAS), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Université Lille Nord (France), Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Réseau nanophotonique et optique, Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Matériaux et nanosciences d'Alsace (FMNGE), Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Université de Strasbourg (UNISTRA)-Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, and Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Lewy Body Disease, Male, 0301 basic medicine, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Prodromal Symptoms, tau Proteins, behavioral disciplines and activities, Gastroenterology, Diagnosis, Differential, 03 medical and health sciences, 0302 clinical medicine, Cerebrospinal fluid, Alzheimer Disease, Internal medicine, mental disorders, Humans, Medicine, Dementia, Stage (cooking), ComputingMilieux_MISCELLANEOUS, Aged, Retrospective Studies, Amyloid beta-Peptides, business.industry, Dementia with Lewy bodies, Prodromal Stage, Case-control study, Retrospective cohort study, Middle Aged, medicine.disease, Peptide Fragments, nervous system diseases, Psychiatry and Mental health, 030104 developmental biology, nervous system, Case-Control Studies, Female, Surgery, Neurology (clinical), Differential diagnosis, business, Biomarkers, 030217 neurology & neurosurgery
Abstract: BackgroundDifferential diagnosis between dementia with Lewy bodies (DLB) and Alzheimer’s disease (AD) is not straightforward, especially in the early stages of disease. We compared AD biomarkers (phospho-Tau181, total-Tau, Aβ42 and Aβ40) in cerebrospinal fluid (CSF) of patients with DLB and AD, focusing especially on the prodromal stage.MethodsA total of 1221 CSF were collected in different memory centres (ePLM network) in France and analysed retrospectively. Samples were obtained from patients with prodromal DLB (pro-DLB; n=57), DLB dementia (DLB-d; n=154), prodromal AD (pro-AD; n=132) and AD dementia (n=783), and control subjects (CS; n=95). These centres use the same diagnostic procedure and criteria to evaluate the patients.ResultsIn patients with pro-DLB, CSF Aβ42 levels appeared much less disrupted than in patients at the demented stage (DLB-d) (Ppro-DLB; PDLB-d). On average, Aβ40 levels in patients with DLB (pro-DLB and DLB-d) were much below those in patients with pro-AD (P181 levels were unaltered in patients with DLB (pro-DLB and DLB-d).ConclusionsReduced levels of CSF Aβ42 were found in patients with DLB but rather at a later stage, reaching those of patients with AD, in whom Aβ42 levels were decreased even at the prodromal stage. At the prodromal stage of DLB, the majority of patients presented a normal CSF profile. CSF t-Tau and phospho-Tau181 were the best biomarkers to discriminate between AD and DLB, whatever the stage of disease.
Published: 2018
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42. Multicenter Alzheimer's and Parkinson's disease immune biomarker verification study

Author: Sarah Bujac, Samir Bekadar, Marc Stauch, Reinhard Schneider, Holger Froehlich, Bruno Dubois, Albert Lladó, Wassilios G. Meissner, Viktor K. Jirsa, Ina Schmitt, Cecile Gaudebout, Michael T. Heneka, Jean-Christophe Corvol, Nathan Lawless, Tamas Letoha, Aishwarya Alex Namasivayam, Grégory Operto, Anna Antonell, Johan Van der Lei, Eloi Magnin, Phil Scordis, Ana Graf, Oriol Grau, Ana Diaz, Per Svenningsson, Mircea alasam, José Luis Molinuevo, Sofia Bergström, Stephanie Carvalho, Dianne Gove, Ioanna Markaki, Stéphane Epelbaum, Lorena Rami, Raffaele Cacciaglia, Panagiota Tsitsi, Raquel Sánchez-Valle, Jean Georges, Carl-Christian Kolbe, Olivier Rascol, Ullrich Wüllner, Frederic Brosseron, Boris Labrador, Frederic rosseron, Sergio Castro-Gomez, Noemí Carranza, Pawel Tacik, Matthew Page, Jacqueline Marovac, Eicke Latz, Luc Canard, Graziella Mangone, Martin Hofmann-Apitius, Nikolaus Forgo, Beatriz Bosch, Peter Nilsson, Francesco Santarelli, Stephan Springstubbe, University of Bonn, German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Luxembourg Centre For Systems Biomedicine (LCSB), University of Luxembourg [Luxembourg], Universitat de Barcelona (UB), Service de neurologie 1 [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Gestionnaire, Hal Sorbonne Université, Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: 0301 basic medicine, Apolipoprotein E, Male, Cellular pathology, Aging, Parkinson's disease, Epidemiology, [SDV]Life Sciences [q-bio], Disease, Cohort Studies, 0302 clinical medicine, cerebrospinal fluid [Parkinson Disease], Multicenter, Aged, 80 and over, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Health Policy, Neurodegeneration, Age Factors, Parkinson Disease, Middle Aged, Alzheimer's disease, 3. Good health, [SDV] Life Sciences [q-bio], cerebrospinal fluid [Alzheimer Disease], Europe, Psychiatry and Mental health, Cerebrospinal fluid, cerebrospinal fluid [Biomarkers], Biomarker (medicine), Female, Amyloid, tau Proteins, 03 medical and health sciences, Cellular and Molecular Neuroscience, Immune system, Sex Factors, Developmental Neuroscience, Immunity, Alzheimer Disease, medicine, Humans, ddc:610, Aged, Inflammation, business.industry, Mild cognitive impairment, Biomarker, medicine.disease, 030104 developmental biology, cerebrospinal fluid [tau Proteins], Immunology, cerebrospinal fluid [Amyloid], Neurology (clinical), Geriatrics and Gerontology, Tau, business, 030217 neurology & neurosurgery, Biomarkers, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; INTRODUCTION:Multiple immunity biomarkers have been suggested as tracers of neuroinflammation in neurodegeneration. This study aimed to verify findings in cerebrospinal fluid (CSF) samples of Alzheimer's disease (AD) and Parkinson's disease (PD) subjects from the network of the European, Innovative Medicines Initiative-funded project AETIONOMY.METHODS:A total of 227 samples from the studies/centres AETIONOMY, ICEBERG, and IDIBAPS were used to analyse 21 selected immunity biomarkers in CSF. Results were compared to data of an independent cohort of 399 subjects previously published.RESULTS:Immunity markers were predominantly and reproducibly associated with pathological levels of tau isoforms, but also with amyloid levels, aging, sex, APOE genotype, and center-specific factors.DISCUSSION:Immunity biomarker levels in CSF reflect molecular and cellular pathology rather than diagnosis in neurodegenerative disorders. Assay standardization and stratification for age and other covariates could improve the power of such markers in clinical applications or intervention studies targeting immune responses in neurodegeneration.
Published: 2020
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43. Semantic loss marks early Alzheimer's disease-related neurodegeneration in older adults without dementia

Author: Cédric Annweiler, Marie-Odile Habert, Audrey Gabelle, François Sellal, Geneviève Chêne, Vincent Bouteloup, Frédéric Blanc, Eloi Magnin, Jet M.J. Vonk, Catherine Belin, Carole Dufouil, Adrien Julian, Marie Chupin, Jean-François Mangin, Bruno Dubois, Pierre Krolak-Salmon, Mathieu Ceccaldi, Thérèse Rivasseau-Jonveaux, Admin, Oskar, Columbia University [New York], University Medical Center [Utrecht], Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Bordeaux [Bordeaux], Service NEUROSPIN (NEUROSPIN), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), CATI Multicenter Neuroimaging Platform (CATI), Institut de la Mémoire et de la Maladie d'Alzheimer [CHU Pitié-Salpétriêre] (IM2A), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Université de Strasbourg (UNISTRA)-Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centres Mémoire de Ressources et de Recherche Montpellier (CMRR), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [Montpellier], Institut de Neurosciences des Systèmes (INS), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Psychologie des Pays de la Loire (LPPL), Université d'Angers (UA)-Université de Nantes - UFR Lettres et Langages (UFRLL), Université de Nantes (UN)-Université de Nantes (UN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire lorrain de psychologie et neurosciences de la dynamique des comportements (2LPN), Université de Lorraine (UL), Hôpital de la Milétrie, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Mécanismes Centraux et Périphériques de la Neurodégénérescence, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Mémoire de Ressources et de Recherche [CHRU de Besançon] (CMRR), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Hôpital Saint-Jacques [CHRU de Besançon], Laboratoire de Neurosciences Intégratives et Cliniques - UFC (UR 481) (NEURO), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Laboratoire d'Imagerie Biomédicale (LIB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Laboratoire d'Imagerie Biomédicale [Paris] (LIB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Institut de la Mémoire et de la Maladie d'Alzheimer [Paris] (IM2A), Sorbonne Université (SU), Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Réseau nanophotonique et optique, Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Matériaux et nanosciences d'Alsace (FMNGE), Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), and Laboratoire de Neurosciences Intégratives et Cliniques - UFC (EA 481) (NEURO)
Subjects: medicine.medical_specialty, Clinical Dementia Rating, Audiology, lcsh:Geriatrics, lcsh:RC346-429, 03 medical and health sciences, Fluency, 0302 clinical medicine, Neuroimaging, cohort studies, medicine, Brain positron emission tomography, MORPH3Eus, Dementia, Verbal fluency test, Cognitive decline, 10. No inequality, lcsh:Neurology. Diseases of the nervous system, 030304 developmental biology, 0303 health sciences, neuroimaging, amnestic, business.industry, cognitive aging, semantic fluency, verbal fluency, biomarkers, [SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, letter fluency, Alzheimer's disease, medicine.disease, Hyperintensity, MCI, Psychiatry and Mental health, lcsh:RC952-954.6, VINTAGE, Cognitive & Behavioral Assessment, Neurology (clinical), category fluency, business, Alzheimer’s disease, 030217 neurology & neurosurgery, [SDV.NEU.SC] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, Research Article
Abstract: International audience; Objective: To assess progression of semantic loss in early stages of cognitive decline using semantic and letter fluency performance, and its relation with Alzheimer's disease (AD)‐specific neurodegeneration using longitudinal multimodal neuroimaging measures.Methods: Change in verbal fluency was analyzed among 2261 non‐demented individuals with a follow‐up diagnosis of no mild cognitive impairment (MCI), amnestic MCI (aMCI), non‐amnestic MCI (naMCI), or incident dementia, using linear mixed models across 4 years of follow‐up, and relations with magnetic resonance imaging (MRI; n = 1536) and 18F‐fluorodeoxyglucose brain positron emission tomography (18F‐FDG‐PET) imaging (n = 756) using linear regression models across 2 years of follow‐up.Results: Semantic fluency declined—fastest in those at higher risk for AD (apolipoprotein E [APOE] e4 carriers, Clinical Dementia Rating score of .5, aMCI, or incident dementia)—while letter fluency did not except for those with incident dementia. Lower baseline semantic fluency was associated with an increase in white matter hyperintensities and total mean cortical thinning over time, and regionally with less hippocampal volume as well as more cortical thinning and reduced 18F‐FDG‐PET uptake in the inferior parietal lobule, entorhinal cortex, isthmus cingulate, and precuneus–posterior cingulate area. In contrast, baseline letter fluency was not associated with change in total nor regional neurodegeneration. Whole‐brain neurodegeneration over time was associated with faster decline in both fluencies, while AD‐specific regions were associated with a faster rate of decline in semantic but not letter fluency.Interpretation: This study provides strong evidence of distinctive degeneration of semantic abilities early on in relation to both cognitive decline and AD‐specific neurodegeneration.
Published: 2020
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44. Comparison of Noninvasive Imagery Methods to Observe Healthy and Degenerated Olfactory Epithelium in Mice for the Early Diagnosis of Neurodegenerative Diseases

Author: Adeline Etievant, Julie Monnin, Thomas Lihoreau, Brahim Tamadazte, Patrick Rougeot, Eloi Magnin, Laurent Tavernier, Lionel Pazart, Emmanuel Haffen, Laboratoire de Neurosciences Intégratives et Cliniques - UFC (UR 481) (NEURO), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre d'Investigation Clinique de Besançon (Inserm CIC 1431), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies (UMR 6174) (FEMTO-ST), Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Institut des Systèmes Intelligents et de Robotique (ISIR), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Université Bourgogne Franche-Comté [COMUE] (UBFC), Etiévant, Adeline, Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Franche-Comté (UFC), and Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Genetically modified mouse, Pathology, medicine.medical_specialty, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, medical imaging, Neuroscience (miscellaneous), lcsh:RC321-571, lcsh:QM1-695, law.invention, 03 medical and health sciences, Cellular and Molecular Neuroscience, optical biopsy, 0302 clinical medicine, Optical coherence tomography, Confocal microscopy, law, Methods, Medical imaging, Endomicroscopy, Medicine, neurodegenerative diseases, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], epithelium olfactory, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, Pathological, medicine.diagnostic_test, business.industry, lcsh:Human anatomy, medicine.disease, [SDV.IB.IMA] Life Sciences [q-bio]/Bioengineering/Imaging, 030104 developmental biology, medicine.anatomical_structure, [SDV.IB]Life Sciences [q-bio]/Bioengineering, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Alzheimer disease, Anatomy, Alzheimer's disease, business, Olfactory epithelium, 030217 neurology & neurosurgery, Neuroscience
Abstract: International audience; Olfactory dysfunction could be an early and reliable indicator for the diagnosis of neurodegenerative disorders such as Alzheimer and Parkinson's diseases. In this paper, we compare the potential of different noninvasive medical imaging modalities (optical coherence tomography, confocal microscopy, and fluorescence endomicroscopy) to distinguish how the olfactory epithelium, both at the cellular and the structural levels, is altered. Investigations were carried out on three experimental groups: two pathological groups (mice models with deliberately altered olfactory epithelium and Alzheimer's disease transgenic mice models) were compared with healthy mice models. As histological staining, the three tested noninvasive imaging tools demonstrated the general tubular organization of the olfactory epithelium on healthy mice. Contrary to OCT, confocal microscopy, and endomicroscopy allowed visualizing the inner structure of olfactory epithelium as well as its morphological or functional changes on pathological models, alterations classically observed with histological assessment. The results could lead to relevant development of imaging tools for noninvasive and early diagnosis of neurodegenerative diseases through the in situ characterization of the olfactory epithelium.
Published: 2019
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45. AETIONOMY, a Cross-Sectional Study Aimed at validating a new taxonomy of Neurodegenerative Diseases: Study design and subject characteristics

Author: Panagiota Tsitsi, Michael T. Heneka, Stephanie Carvalho, Sarah Bujac, Eloi Magnin, Wassilios G. Meissner, Per Svenningsson, José-Luis Molinuevo, Olivier Rascol, Ioanna Markaki, Jean-Christophe Corvol, Ullrich Wuellner, Hélène Catala, Martin Hofmann-Apitius, Raquel Sánchez-Valle, Graziella Mangone, Alexandra Foubert-Samier, Jacqueline Marovac, Bethan Clarke, and Phil Scordis
Subjects: 0303 health sciences, medicine.medical_specialty, Levodopa, Cross-sectional study, business.industry, Subject Characteristics, Disease, medicine.disease, Missing data, 3. Good health, Part iii, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Alzheimer's disease, Multi centre, business, 030217 neurology & neurosurgery, 030304 developmental biology, medicine.drug
Abstract: BackgroundAlthough advances in the understanding of neurodegenerative diseases (NDDs) have led to improvements in classification and diagnosis and most importantly to new therapies, the unmet medical needs remain significant due to high treatment failure rates. The AETIONOMY project funded by the Innovative Medicine Initiative (IMI) aims at using multi-OMICs and bioinformatics to identify new classifications for NDDs based on common molecular pathophysiological mechanisms in view of improving the availability of personalised treatments.ObjectivesThe purpose of the AETIONOMY cross-sectional study is to validate novel patient classification criteria provided by these tools.MethodsThis was a European multi centre, cross-sectional, clinical study conducted at 6 sites in 3 countries. Standardised clinical data, biosamples from peripheral blood, cerebrospinal fluid, skin biopsies, and data from a multi-OMICs approach were collected in patients suffering from Alzheimer’s and Parkinson’s disease, as well as healthy controls.ResultsFrom September 2015 to December 2017 a total of 421 participants were recruited including 95 Healthy Controls. Nearly 1,500 biological samples were collected. The study achieved its objective with respect to Parkinson’s disease (PD) recruitment, however it was unable to recruit many new Alzheimer Disease (AD) patients. Overall, data from 413 evaluable subjects (405 PD and 8 AD) are available for analysis. PD patients and controls were well matched with respect to age (mean 63.4 years), however, close gender matching was not achieved. Approximately half of all PD patients and one At-Risk subject were taking dopamine agonists; rates of Levodopa usage were slightly higher (∼60%). Median MDS-UPDRS Part III Scores (OFF state) ranged from 45 (SD 18) in those with Genetic PD to 2 (SD 3) in Healthy Controls. The standardised methodologies applied resulted in a high-quality database with very few missing data.ConclusionThis is one of the collaborative multi-OMICs studies in individuals suffering from PD and AD involving a control group. It is expected that the integration of data will provide new biomarker-led descriptions of clusters of patient subgroups.
Published: 2019
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46. Causative Mutations and Genetic Risk Factors in Sporadic Early Onset Alzheimer’s Disease Before 51 Years

Author: Aline Zarea, Eloi Magnin, Stéphane Epelbaum, Claire Paquet, Valérie Chauviré, Florence Pasquier, Anne Boland, Marie Sarazin, David Wallon, Bruno Salomon, Dominique Campion, Olivier Godefroy, Olivier Martinaud, Mathilde Sauvée, Sophie Auriacombe, Cecilia Marelli, Frédérique Etcharry-Bouyx, Gaël Nicolas, Jean-François Deleuze, Anne-Claire Richard, Vincent de la Sayette, Audrey Gabelle, Thérèse Rivasseau Jonveaux, Stéphane Rousseau, Jérémie Pariente, Mathieu Ceccaldi, Maïté Formaglio, Anne Rovelet-Lecrux, Didier Hannequin, Adeline Rollin-Sillaire, Bernard Croisile, Isabelle Le Ber, Morgane Lacour, Olivier Quenez, Olivier Rouaud, Muriel Quillard-Muraine, Claire Boutoleau-Bretonnière, Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Normandie Université (NU)-Normandie Université (NU), CHU Rouen, Normandie Université (NU), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de neurologie [Rouen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Service de neurologie [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Hôpital Guillaume-et-René-Laennec [Saint-Herblain], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Centre Hospitalier Sainte Anne [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Algorithms, models and methods for images and signals of the human brain (ARAMIS), Sorbonne Université (SU)-Inria de Paris, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service de neurologie et de neuropsychologie, Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Laboratoire de Neurosciences Fonctionnelles et Pathologies (LNFP), Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique (CNRS), Service de Neurologie [Lyon], CHU Lyon, Hospices Civils de Lyon (HCL), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre Hospitalier Universitaire [Grenoble] (CHU), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut National de la Santé et de la Recherche Médicale (INSERM), Biomarqueurs CArdioNeuroVASCulaires (BioCANVAS), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Male, MESH: Mutation, 03 medical and health sciences, Amyloid beta-Protein Precursor, 0302 clinical medicine, MESH: Whole Exome Sequencing, Alzheimer Disease, Risk Factors, MESH: Risk Factors, MESH: Amyloid beta-Protein Precursor, PSEN2, Genotype, Genetic variation, Presenilin-2, Exome Sequencing, medicine, PSEN1, Presenilin-1, Humans, Early-onset Alzheimer's disease, Genetic Predisposition to Disease, Risk factor, Allele, Exome sequencing, Genetics, MESH: Humans, MESH: Middle Aged, business.industry, General Neuroscience, MESH: Genetic Predisposition to Disease, General Medicine, Middle Aged, medicine.disease, MESH: Presenilin-1, MESH: Male, 3. Good health, MESH: Presenilin-2, Psychiatry and Mental health, Clinical Psychology, 030104 developmental biology, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Mutation, Female, Geriatrics and Gerontology, business, MESH: Female, 030217 neurology & neurosurgery, MESH: Alzheimer Disease
Abstract: International audience; Background:Pathogenic variants in the autosomal dominant genes PSEN1, PSEN2, or APP, APOE4 alleles, and rare variants within TREM2, SORL1, and ABCA7 contribute to early-onset Alzheimer’s disease (EOAD). However, sporadic EOAD patients have been insufficiently studied to define the probability of being a carrier of one of these variants.Objective:To describe the proportion of each genetic variation among patients with very young-onset sporadic AD. Methods:We first screened PSEN1, PSEN2, and APP in 154 EOAD patients with an onset before 51 years and a negative family history. Among 99 patients with no mutation (NMC), whole exome sequencing (WES) was performed. We analyzed the APOE genotype and rare protein-truncating or missense predicted damaging variants of TREM2, SORL1, and ABCA7. Neurological examination and cerebrospinal fluid (CSF) biomarkers were systematically retrieved. Results:Nineteen (12.3%) mutation carriers (MC) harbored an APP or PSEN1 pathogenic or likely pathogenic variant. Among the NMC, 54/99 carried at least one genetic risk factor, including 9 APOE4/E4 homozygous, 37 APOE4 heterozygous, and 14 with a rare variant in another risk factor gene: 3 SORL1, 4 TREM2, and 9 ABCA7. MC presented an earlier disease onset (p
Published: 2019
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47. Diagnosis associated with Tau higher than 1200 pg/mL: Insights from the clinical and laboratory practice

Author: C Malaplate-Armand, Frédéric Blanc, Jean-Louis Laplanche, Constance Delaby, Eloi Magnin, Jacques Hugon, Audrey Gabelle, David Wallon, S. Schraen, Julien Dumurgier, Claire Paquet, Bernard Sablonnière, Elodie Bouaziz-Amar, Muriel Quillard-Muraine, Olivier Bousiges, Sylvain Lehmann, Katell Peoc'h, Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hôpitaux Universitaire Saint-Louis, Lariboisière, Fernand-Widal, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, CHU Rouen, Normandie Université (NU), Laboratoire de neurosciences cognitives et adaptatives (LNCA), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Biochimie et de Biologie Moléculaire [AP-HP Hôpital Lariboisière] (Inserm U942), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Neurologie [Strasbourg], CHU Strasbourg-Hopital Civil, Service de neurologie [Rouen], Normandie Université (NU)-Normandie Université (NU), CCSD, Accord Elsevier, Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U1172 Inserm - U837 (JPArc), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Université de Lille
Subjects: 0301 basic medicine, Adult, Male, medicine.medical_specialty, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Clinical Biochemistry, Tau protein, Context (language use), tau Proteins, Disease, Biochemistry, Diagnosis, Differential, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Cerebrospinal fluid, Internal medicine, Medicine, Dementia, Humans, Medical diagnosis, Aged, Aged, 80 and over, biology, Lewy body, business.industry, [SCCO.NEUR]Cognitive science/Neuroscience, Biochemistry (medical), [SCCO.NEUR] Cognitive science/Neuroscience, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, 14-3-3 protein, General Medicine, Middle Aged, Alzheimer's disease, medicine.disease, Phosphoproteins, Creutzfeldt-Jakob disease, 3. Good health, 030104 developmental biology, 030220 oncology & carcinogenesis, biology.protein, Female, business, Laboratories, Biomarkers, Frontotemporal dementia
Abstract: International audience; Context: Cerebrospinal fluid (CSF) biomarkers are valuable tools for the diagnosis of neurological diseases. We aimed to investigate within a retrospective multicentric study the final diagnosis associated with very high CSF Tau levels and to identify patterns of biomarkers that would differentiate them in clinical practice, to help clinical biologists into physicians' counseling.Patients and methods: Within the national multicentric network ePLM, we included 1743 patients from January 1, 2008, to December 31, 2013, with CSF biomarkers assayed by the same Innotest assays (protein Tau, phospho-Tau [pTau], and Aβ 1-42). We identified 205 patients with protein Tau concentration higher than 1200 pg/mL and final diagnosis.Results: Among those patients, 105 (51.2%) were suffering from Alzheimer's disease, 37 (18%) from sporadic Creuztfeldt-Jakob disease, and 63 (30.7%) from other neurological diseases including paraneoplastic/ central nervous system tumor, frontotemporal dementia, other diagnoses, amyloid angiopathy, Lewy body dementia, and infections of the central nervous system. Phospho-Tau, Aβ1-42 and Aβ1-42/pTau values differed significantly between the three groups of patients (p < .001). An Aβ1-42/pTau ratio between 4.7 and 9.7 was suggestive of other neurological diseases (threshold in AD: 8.3). CSF 14-3-3 was useful to discriminate Alzheimer's disease from Creuztfeldt-Jakob disease in case of Aβ1-42 concentrations 60 pg/mL.Conclusion: This work emphasizes the interest of a well-thought-out interpretation of CSF biomarkers in neurological diseases, particularly in the case of high Tau protein concentrations in the CSF.
Published: 2019
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48. Functional movement disorders

Author: Thierry Moulin, Eloi Magnin, Matthieu Bereau, Selma Aybek, Silvio Galli, Service de Neurologie [CHRU Besançon], and Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)
Subjects: medicine.medical_specialty, Tics, [SDV]Life Sciences [q-bio], Diagnostic Techniques, Neurological, History, 21st Century, 03 medical and health sciences, 0302 clinical medicine, Physical medicine and rehabilitation, mental disorders, Medicine, Psychogenic disease, Humans, 030212 general & internal medicine, Functional movement disorder, Conversion disorder, Dystonia, Movement Disorders, business.industry, Parkinsonism, Chorea, medicine.disease, nervous system diseases, 3. Good health, Diagnostic and Statistical Manual of Mental Disorders, Neurology, Neurology (clinical), medicine.symptom, business, Myoclonus, 030217 neurology & neurosurgery
Abstract: Functional movement disorders (FMD) represent a complex and disabling entity characterized by a broad range of clinical symptoms not explained by a classical neurological disease. In 2013, the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) added a clinical criterion based on incongruence and inconsistency, supported by recent literature highlighting the role of "positive clinical signs". These clinical signs allow a "rule-in" procedure in making a diagnosis of FMD so that the diagnosis is no longer a "rule-out" or "by default" diagnosis made after exclusion of other neurological conditions. This review summarizes current evidence on common clinical features and highlights bedside signs in FMD, such as tremor, dystonia, myoclonus and parkinsonism. Tics, chorea and hemiballism are also briefly discussed.
Published: 2019
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49. What (more) can verbal fluency tell us about multiple sclerosis?

Author: Suveyla Yilmaz, Pierre Decavel, Yoshimasa Sagawa, Elise Barois, and Eloi Magnin
Subjects: 030506 rehabilitation, medicine.medical_specialty, Multiple Sclerosis, Verbal Behavior, Rehabilitation, Linguistics, Cognition, Neuropsychological Tests, Audiology, Semantics, Test (assessment), 03 medical and health sciences, Fluency, 0302 clinical medicine, Inflection, medicine, Humans, Verbal fluency test, Orthopedics and Sports Medicine, Observational study, 0305 other medical science, Psychology, 030217 neurology & neurosurgery, Word (group theory), Variable (mathematics)
Abstract: Background Clinical symptoms of multiple sclerosis (MS) are variable and may include cognitive impairment, which can be assessed with the verbal fluency test (VFT). This test is evaluated by counting words spoken during a 2-min period, which is not a functional approach. Objective The objectives of this observational study were to: (1) determine new parameters that reflect communication and cognitive functions in persons with multiple sclerosis (PwMS) considering the evaluation of real-time word production in the VFT; (2) compare the results with those of a control group; and (3) evaluate the impact of including errors. Methods A phonological fluency test (“letter P”) and a semantic fluency test (“animals”) were used. The real-time word production was recorded. The main variables studied were the total number of words, first word delay, moment of inflection of the curve corresponding to the change in the cognitive process, speed of word production before inflection, and maximum delay between 2 consecutive words. These variables were studied by taking into account or not errors. Results We included 68 PwMS and 33 healthy controls. VFT results were impaired in PwMS. The total number of words, first word delay, speed before inflection, and maximum delay were relevant to the study of phonologic fluency. For studying semantic fluency, the total number of words, first word delay, speed before inflection, and inflection time of the curve seemed relevant. Taking into account errors was significant only for total number of words. Conclusion Taking into account errors in evaluating real-time word production in PwMS is of interest only for the total number of words performed but has no impact on the variables studied. These variables should be used to quantitatively evaluate verbal fluency with the objective of evaluating functionally relevant parameters (communication).
Published: 2021
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50. Multiple Sclerosis and Clinical Gait Analysis before and after Fampridine: A Systematic Review

Author: Vincent Gremeaux, Yoshimasa Sagawa, Pierre Decavel, Eloi Magnin, Magaly Lecat, Brigitte Lucas, Laboratoire d'exploration fonctionnelle clinique du mouvement [CHRU Besançon], Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ), Centre de Rééducation Fonctionnelle Divio [Dijon] ( CRF COS Divio ), Laboratoire de Neurosciences Intégratives et Cliniques - UFC ( NEURO ), Université Bourgogne Franche-Comté ( UBFC ) -Université de Franche-Comté ( UFC ), Service de neurologie [Besançon], Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Jean Minjoz, Pôle Rééducation - Réadaptation (Médecine Physique et Réadaptation) (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Service de Physiologie et Exploration fonctionnelle [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre de Rééducation Fonctionnelle Divio [Dijon] (CRF COS Divio), Laboratoire de Neurosciences Intégratives et Cliniques - UFC (EA 481) (NEURO), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Service de Neurologie [CHRU Besançon], and Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)
Subjects: Adult, Male, medicine.medical_specialty, Multiple sclerosis, 03 medical and health sciences, 0302 clinical medicine, Physical medicine and rehabilitation, Gait (human), [ SDV.MHEP ] Life Sciences [q-bio]/Human health and pathology, Potassium Channel Blockers, Long term, medicine, Humans, 030212 general & internal medicine, 4-Aminopyridine, Gait, Gait Disorders, Neurologic, business.industry, Middle Aged, medicine.disease, Fampridine, Gait speed, Gait impairment, Neurology, [ SDV.NEU ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Gait analysis, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neurology (clinical), business, human activities, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030217 neurology & neurosurgery
Abstract: Background: Gait impairment is one of the most disabling symptoms in people with multiple sclerosis (PwMS). Fampridine, has demonstrated a positive effect on gait speed in PwMS after 14 days of treatment but the long-term effects have not yet been demonstrated. This study reviews the long-term effects of fampridine on gait in PwMS. Summary: This systematic review was conducted according to the PRISMA statement. Studies were considered long term if treatment exceeded 28 days. From the 498 studies identified, 18 (2,200 patients) fulfilled all eligibility criteria. Only 3 studies followed-up patients for >1 year and one of these showed a non-significant improvement in the gait speed. Key Messages: Fampridine seems to be beneficial at improving gait speed in PwMS in the long term. Further long-term studies are needed on related gait and functional parameters.
Published: 2017
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