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1. Dementia with Lewy bodies and gait neural basis: a cross-sectional study

Author

Adele Sainsily-Cesarus, Elise Schmitt, Lionel Landre, Anne Botzung, Lucie Rauch, Catherine Demuynck, Nathalie Philippi, Paulo Loureiro de Sousa, Catherine Mutter, Benjamin Cretin, Catherine Martin-Hunyadi, and Frederic Blanc

Subjects
Dementia with lewy bodies, Walking speed, Mid-cingulate cortex, Hippocampi, Magnetic resonance imaging, Voxel-based-morphometry, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571, Neurology. Diseases of the nervous system, RC346-429
Abstract

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

Published
2024
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2. Plasma biomarkers of amyloid, tau, axonal, and neuroinflammation pathologies in dementia with Lewy bodies

Author

Agathe Vrillon, Olivier Bousiges, Karl Götze, Catherine Demuynck, Candice Muller, Alix Ravier, Benoît Schorr, Nathalie Philippi, Claire Hourregue, Emmanuel Cognat, Julien Dumurgier, Matthieu Lilamand, Benjamin Cretin, Frédéric Blanc, and Claire Paquet

Subjects
Dementia with Lewy bodies, Alzheimer’s disease, Plasma biomarkers, Amyloid pathology, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571, Neurology. Diseases of the nervous system, RC346-429
Abstract

Abstract Background Increasing evidence supports the use of plasma biomarkers of amyloid, tau, neurodegeneration, and neuroinflammation for diagnosis of dementia. However, their performance for positive and differential diagnosis of dementia with Lewy bodies (DLB) in clinical settings is still uncertain. Methods We conducted a retrospective biomarker study in two tertiary memory centers, Paris Lariboisière and CM2RR Strasbourg, France, enrolling patients with DLB (n = 104), Alzheimer’s disease (AD, n = 76), and neurological controls (NC, n = 27). Measured biomarkers included plasma Aβ40/Aβ42 ratio, p-tau181, NfL, and GFAP using SIMOA and plasma YKL-40 and sTREM2 using ELISA. DLB patients with available CSF analysis (n = 90) were stratified according to their CSF Aβ profile. Results DLB patients displayed modified plasma Aβ ratio, p-tau181, and GFAP levels compared with NC and modified plasma Aβ ratio, p-tau181, GFAP, NfL, and sTREM2 levels compared with AD patients. Plasma p-tau181 best differentiated DLB from AD patients (ROC analysis, area under the curve [AUC] = 0.80) and NC (AUC = 0.78), and combining biomarkers did not improve diagnosis performance. Plasma p-tau181 was the best standalone biomarker to differentiate amyloid-positive from amyloid-negative DLB cases (AUC = 0.75) and was associated with cognitive status in the DLB group. Combining plasma Aβ ratio, p-tau181 and NfL increased performance to identify amyloid copathology (AUC = 0.79). Principal component analysis identified different segregation patterns of biomarkers in the DLB and AD groups. Conclusions Amyloid, tau, neurodegeneration and neuroinflammation plasma biomarkers are modified in DLB, albeit with moderate diagnosis performance. Plasma p-tau181 can contribute to identify Aβ copathology in DLB.

Published
2024
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3. Who am I with my Lewy bodies? The insula as a core region of the self-concept networks

Author

Alice Tisserand, Frédéric Blanc, Mary Mondino, Candice Muller, Hélène Durand, Catherine Demuynck, Paulo Loureiro de Sousa, Alix Ravier, Léa Sanna, Anne Botzung, and Nathalie Philippi

Subjects
Self, Self-concept, Insula, Dementia with lewy bodies, Lewy bodies, Semantic knowledge, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571, Neurology. Diseases of the nervous system, RC346-429
Abstract

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

Published
2024
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4. MRI data-driven clustering reveals different subtypes of Dementia with Lewy bodies

Author

Anna Inguanzo, Konstantinos Poulakis, Rosaleena Mohanty, Christopher G. Schwarz, Scott A. Przybelski, Patricia Diaz-Galvan, Val J. Lowe, Bradley F. Boeve, Afina W. Lemstra, Marleen van de Beek, Wiesje van der Flier, Frederik Barkhof, Frederic Blanc, Paulo Loureiro de Sousa, Nathalie Philippi, Benjamin Cretin, Catherine Demuynck, Zuzana Nedelska, Jakub Hort, Barbara Segura, Carme Junque, Ketil Oppedal, Dag Aarsland, Eric Westman, Kejal Kantarci, and Daniel Ferreira

Subjects
Neurology. Diseases of the nervous system, RC346-429
Abstract

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

Published
2023
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5. Prodromal characteristics of dementia with Lewy bodies: baseline results of the MEMENTO memory clinics nationwide cohort

Author

Frederic Blanc, Vincent Bouteloup, Claire Paquet, Marie Chupin, Florence Pasquier, Audrey Gabelle, Mathieu Ceccaldi, Paulo Loureiro de Sousa, Pierre Krolak-Salmon, Renaud David, Clara Fischer, Jean-François Dartigues, David Wallon, Olivier Moreaud, Mathilde Sauvée, Catherine Belin, Sandrine Harston, Anne Botzung, Timothée Albasser, Catherine Demuynck, Izzie Namer, Marie-Odile Habert, Stéphane Kremer, Olivier Bousiges, Marc Verny, Candice Muller, Nathalie Philippi, Geneviève Chene, Benjamin Cretin, Jean-François Mangin, and Carole Dufouil

Subjects
Dementia with Lewy bodies, Prodromal, Mild cognitive impairment, Subjective cognitive impairment, Lewy body disease, Mild neurocognitive impairment, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571, Neurology. Diseases of the nervous system, RC346-429
Abstract

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

Published
2022
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6. Me, Myself and My Insula: An Oasis in the Forefront of Self-Consciousness

Author

Alice Tisserand, Nathalie Philippi, Anne Botzung, and Frédéric Blanc

Subjects
insula, self, interoception, autobiographical memory, Biology (General), QH301-705.5
Abstract

The insula is a multiconnected brain region that centralizes a wide range of information, from the most internal bodily states, such as interoception, to high-order processes, such as knowledge about oneself. Therefore, the insula would be a core region involved in the self networks. Over the past decades, the question of the self has been extensively explored, highlighting differences in the descriptions of the various components but also similarities in the global structure of the self. Indeed, most of the researchers consider that the self comprises a phenomenological part and a conceptual part, in the present moment or extending over time. However, the anatomical substrates of the self, and more specifically the link between the insula and the self, remain unclear. We conducted a narrative review to better understand the relationship between the insula and the self and how anatomical and functional damages to the insular cortex can impact the self in various conditions. Our work revealed that the insula is involved in the most primitive levels of the present self and could consequently impact the self extended in time, namely autobiographical memory. Across different pathologies, we propose that insular damage could engender a global collapse of the self.

Published
2023
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7. Differential diagnostic value of total alpha-synuclein assay in the cerebrospinal fluid between Alzheimer’s disease and dementia with Lewy bodies from the prodromal stage

Author

Olivier Bousiges, Nathalie Philippi, Thomas Lavaux, Armand Perret-Liaudet, Ingolf Lachmann, Caroline Schaeffer-Agalède, Pierre Anthony, Anne Botzung, Lucie Rauch, Barbara Jung, Paulo Loureiro de Sousa, Catherine Demuynck, Catherine Martin-Hunyadi, Benjamin Cretin, and Frédéric Blanc

Subjects
Dementia with Lewy bodies, Alzheimer’s disease, Prodromal, Dementia, Cerebrospinal fluid biomarkers, Total alpha-synuclein, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571, Neurology. Diseases of the nervous system, RC346-429
Abstract

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

Published
2020
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8. The insula, a grey matter of tastes: a volumetric MRI study in dementia with Lewy bodies

Author

Nathalie Philippi, Vincent Noblet, Malik Hamdaoui, David Soulier, Anne Botzung, Emmanuelle Ehrhard, Benjamin Cretin, Frédéric Blanc, and AlphaLewyMA study group

Subjects
Insula, Personal tastes, Personal preferences, Self, Dementia with Lewy bodies, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571, Neurology. Diseases of the nervous system, RC346-429
Abstract

Abstract Background Despite the growing number of discoveries during the past decades about its functions, the insula remains a mysterious ‘island’. In addition to its involvement in basic functions such as gustation and interoception, the insular cortex is now considered a key region for integrated functions such as emotion/motivation processing, decision-making and self-consciousness. We hypothesized that this structure, standing at the crossroads of such functions, could ground personal tastes in general, beyond food preferences and aesthetic judgements. Given that dementia with Lewy bodies is characterized by a focal atrophy within the insular cortex from the early stages, this condition provides an opportunity to test such a hypothesis. Methods We developed a questionnaire to assess potential changes in personal tastes, submitted it to a cohort of 23 patients with early-stage dementia with Lewy bodies and compared their questionnaire results to those of 20 age-matched healthy controls. Furthermore, we performed a global and regional neuroimaging study to test for a potential correlation between the patients’ scores for changes in personal tastes and their insular cortex volumes. Results Our results indicate that the patients presented significant changes in personal tastes compared to the controls, in both food and non-food domains. Moreover, imaging analyses confirmed the involvement of the insular cortex atrophy in the changes in personal tastes using global analysis, and in both food and non-food domains using regional analysis. Conclusions These results bring new insights into the role of the insula as a ‘grey matter of tastes’, this structure supporting personal preferences in general, beyond the food domain. The insular cortex could be involved through its role in motivational processes by the representation of subjective awareness of bodily states during the phenomenological experience of stimulus appraisal. However, we also argue that it could support the abstract representations of personal tastes as self-concepts, acutely exemplifying embodied cognition. Finally, the questionnaire on changes in tastes could constitute an interesting tool to help early diagnosis of dementia with Lewy bodies and to assess insular dysfunction more generally.

Published
2020
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9. Changes in gray matter volume and functional connectivity in dementia with Lewy bodies compared to Alzheimer’s disease and normal aging: implications for fluctuations

Author

Eléna Chabran, Vincent Noblet, Paulo Loureiro de Sousa, Catherine Demuynck, Nathalie Philippi, Catherine Mutter, Pierre Anthony, Catherine Martin-Hunyadi, Benjamin Cretin, and Frédéric Blanc

Subjects
Dementia with Lewy bodies, Fluctuations, MRI, Functional connectivity, Voxel-based morphometry, Salience network, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571, Neurology. Diseases of the nervous system, RC346-429
Abstract

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

Published
2020
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10. Pay attention to the basal ganglia: a volumetric study in early dementia with Lewy bodies

Author

Anne Botzung, Nathalie Philippi, Vincent Noblet, Paulo Loureiro de Sousa, and Frédéric Blanc

Subjects
Dementia with Lewy bodies, Prodromal, Mild cognitive impairment, Attention, Processing speed, Neuroimaging, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571, Neurology. Diseases of the nervous system, RC346-429
Abstract

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

Published
2019
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11. CSF in Epileptic Prodromal Alzheimer's Disease: No Diagnostic Contribution but a Pathophysiological One

Author

Benjamin Cretin, Olivier Bousiges, Geoffroy Hautecloque, Nathalie Philippi, Frederic Blanc, Laure Dibitonto, Catherine Martin-Hunyadi, and François Sellal

Subjects
Alzheimer's disease, late onset epilepsy, mild cognitive impairment, cerebrospinal fluid, small vessel disease, Neurology. Diseases of the nervous system, RC346-429
Abstract

Objective: To study whether cerebrospinal fluid (CSF) analysis may serve as a diagnostic test for the screening of epilepsy in sporadic prodromal Alzheimer's disease (AD).Methods: A total of 29 patients with epileptic prodromal sporadic AD patients (epADs) were included and were retrospectively compared with 38 non-epileptic prodromal AD patients (nepADs) for demographics, clinical features, Mini-Mental Status Examination (MMSE) results, CSF biomarkers, and electro-radiological features.Results: Our study did not show any significant differences in CSF biomarkers regarding neurodegeneration, albumin levels, and inflammation between epADs and nepADs. The epADs were significantly older at diagnosis (p = 0.001), more hypertensive (p = 0.01), and displayed larger white matter hyperintensities on brain magnetic resonance imaging (MRI; p = 0.05). There was a significant correlation between the CSF Aβ-42 and Aβ-40 levels with interictal epileptiform discharges and delta slowing on EEGs recordings, respectively (p = 0.03).Conclusions: Our study suggests that CSF may not serve as a surrogate marker of epilepsy in prodromal AD and cannot circumvent the operator-dependent and time-consuming interpretation of EEG recordings. In humans, AD-related epileptogenesis appears to involve the Aβ peptides but likely also additional non-amyloid factors such as small-vessel disease (i.e., white matter hyperintensities).

Published
2021
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12. 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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13. Different Temporal Patterns of Specific and General Autobiographical Memories across the Lifespan in Alzheimer’s Disease

Author

Nathalie Philippi, François Rousseau, Vincent Noblet, Anne Botzung, Olivier Després, Benjamin Cretin, Stéphane Kremer, Frédéric Blanc, and Liliann Manning

Subjects
Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

We compared specific (i.e., associated with a unique time and space) and general (i.e., extended or repeated events) autobiographical memories (AbM) in Alzheimer’s disease (AD). The comparison aims at investigating the relationship between these two components of AbM across the lifespan and the volume of cerebral regions of interest within the temporal lobe. We hypothesized that the ability to elicit specific memories would correlate with hippocampal volume, whereas evoking general memories would be related to lateral temporal lobe. AbM was assessed using the modified Crovitz test in 18 patients with early AD and 18 matched controls. The proportions of total memories—supposed to reflect the ability to produce general memories—and specific memories retrieved were compared between AD patients and controls. Correlations to MRI volumes of temporal cortex were tested. We found different temporal patterns for specific and general memories in AD patients, with (i) relatively spared general memories, according to a temporal gradient that preserved remote memories, predominantly associated with right lateral temporal cortex volume. (ii) Conversely, the retrieval of specific AbMs was impaired for all life periods and correlated with bilateral hippocampal volumes. Our results highlight a shift from an initially episodic to a semantic nature of AbMs during AD, where the abstracted form of memories remains.

Published
2015
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14. Cortical Thickness in Dementia with Lewy Bodies and Alzheimer's Disease: A Comparison of Prodromal and Dementia Stages.

Author

Frederic Blanc, Sean J Colloby, Nathalie Philippi, Xavier de Pétigny, Barbara Jung, Catherine Demuynck, Clélie Phillipps, Pierre Anthony, Alan Thomas, Fabrice Bing, Julien Lamy, Catherine Martin-Hunyadi, John T O'Brien, Benjamin Cretin, Ian McKeith, Jean-Paul Armspach, and John-Paul Taylor

Subjects
Medicine, Science
Abstract

To assess and compare cortical thickness (CTh) of patients with prodromal Dementia with Lewy bodies (pro-DLB), prodromal Alzheimer's disease (pro-AD), DLB dementia (DLB-d), AD dementia (AD-d) and normal ageing.Study participants(28 pro-DLB, 27 pro-AD, 31 DLB-d, 54 AD-d and 33 elderly controls) underwent 3Tesla T1 3D MRI and detailed clinical and cognitive assessments. We used FreeSurfer analysis package to measure CTh and investigate patterns of cortical thinning across groups.Comparison of CTh between pro-DLB and pro-AD (p

Published
2015
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15. Right anterior insula: core region of hallucinations in cognitive neurodegenerative diseases.

Author

Frédéric Blanc, Vincent Noblet, Nathalie Philippi, Benjamin Cretin, Jack Foucher, Jean-Paul Armspach, François Rousseau, and Alzheimer's Disease Neuroimaging Initiative

Subjects
Medicine, Science
Abstract

We investigated the neural basis of hallucinations Alzheimer's disease (AD) by applying voxel-based morphometry (VBM) to anatomical and functional data from the AD Neuroimaging Initiative.AD patients with hallucinations, based on the Neuropsychiatric Inventory (NPI-Q) (AD-hallu group; n = 39), were compared to AD patients without hallucinations matched for age, sex, educational level, handedness and MMSE (AD-c group; n = 39). Focal brain volume on MRI was analyzed and compared between the two groups according to the VBM method. We also performed voxel-level correlations between brain volume and hallucinations intensity. A similar paradigm was used for the PET analysis. "Core regions" (i.e. regions identified in both MRI and PET analyses, simply done by retaining the clusters obtained from the two analyses that are overlapping) were then determined.Regions with relative atrophy in association with hallucinations were: anterior part of the right insula, left superior frontal gyrus and lingual gyri. Regions with relative hypometabolism in association with hallucinations were a large right ventral and dorsolateral prefrontal area. "Core region" in association with hallucinations was the right anterior part of the insula. Correlations between intensity of hallucinations and brain volume were found in the right anterior insula, precentral gyrus, superior temporal gyrus, and left precuneus. Correlations between intensity of hallucinations and brain hypometabolism were found in the left midcingulate gyrus. We checked the neuropathological status and we found that the 4 patients autopsied in the AD-hallu group had the mixed pathology AD and Dementia with Lewy bodies (DLB).Neural basis of hallucinations in cognitive neurodegenerative diseases (AD or AD and DLB) include a right predominant anterior-posterior network, and the anterior insula as the core region. This study is coherent with the top-down/bottom-up hypotheses on hallucinations but also hypotheses of the key involvement of the anterior insula in hallucinations in cognitive neurodegenerative diseases.

Published
2014
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16. MRI-based volumetry correlates of autobiographical memory in Alzheimer's disease.

Author

Nathalie Philippi, Vincent Noblet, Anne Botzung, Olivier Després, Félix Renard, Giorgos Sfikas, Benjamin Cretin, Stéphane Kremer, Lilianne Manning, and Frédéric Blanc

Subjects
Medicine, Science
Abstract

The aim of the present volumetric study was to explore the neuro-anatomical correlates of autobiographical memory loss in Alzheimer's patients and healthy elderly, in terms of the delay of retention, with a particular interest in the medial temporal lobe structures. Fifteen patients in early stages of the disease and 11 matched control subjects were included in the study. To assess autobiographical memory and the effect of the retention delay, a modified version of the Crovitz test was used according to five periods of life. Autobiographical memory deficits were correlated to local atrophy via structural MRI using Voxel Based Morphometry. We used a 'lateralized index' to compare the relative contribution of hippocampal sub-regions (anterior vs posterior, left vs right) according to the different periods of life. Our results confirm the involvement of the hippocampus proper in autobiographical memory retrieval for both recent and very remote encoding periods, with larger aspect for the very remote period on the left side. Contrary to the prominent left-sided involvement for the young adulthood period, the implication of the right hippocampus prevails for the more recent periods and decreases with the remoteness of the memories, which might be associated with the visuo-spatial processing of the memories. Finally, we suggest the existence of a rostrocaudal gradient depending on the retention duration, with left anterior aspects specifically related to retrieval deficits of remote memories from the young adulthood period, whereas posterior aspects would result of simultaneous encoding and/or consolidation and retrieval deficit of more recent memories.

Published
2012
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17. Memory Outcome in Prodromal and Mild Dementia with Lewy Bodies and Alzheimer’s Disease: A Longitudinal Study

Author

Manon Querry, Frédéric Blanc, Olivier Bousiges, Nathalie Philippi, Benjamin Cretin, Catherine Demuynck, Candice Muller, and Anne Botzung

Subjects
Psychiatry and Mental health, Clinical Psychology, General Neuroscience, General Medicine, Geriatrics and Gerontology
Abstract

Background: Dementia with Lewy bodies (DLB) and Alzheimer’s disease (AD) are likely to induce memory impairments from the prodromal stage but, to our knowledge, no longitudinal study of these patients’ memory profile has been conducted to date. Objective: The aim of our study was to describe the characteristics and the evolution of the long-term memory profile of patients with prodromal and mild DLB and AD. Methods: We collected verbal (RL/RI-16) and visual (DMS48) memory scores from 91 DLB patients, 28 AD patients, 15 patients with both conditions (DLB/AD), and 18 healthy control subjects at their inclusion visit and at 12, 24, and 48 months. Results: On the RL/RI-16, DLB patients performed better than AD patients in terms of total recall (p 0.05). Longitudinally, the memory performance of DLB patients was stable over 48 months, unlike that of AD patients. Conclusion: Four indicators were relevant to distinguish between DLB and AD patients in terms of memory performance: DLB patients benefitted greatly from semantic cueing, their recognition and consolidation abilities were well-preserved, and both their verbal and visual memory performance remained remarkably stable over four years. However, no performance differences between DLB and AD patients were found regarding visual memory, either qualitatively (memory profile) or quantitatively (severity of impairment), indicating the lesser relevance of this test in distinguishing between these two diseases.

Published
2023

19. Neural Correlates of Photophobia in Prodromal and Mild Dementia with Lewy Bodies

Author

Alice Tisserand, Benjamin Cretin, Mary Mondino, Anne Botzung, Lea Sanna, Catherine Demuynck, Pierre Anthony, Candice Muller, Olivier Bousiges, Nathalie Philippi, Frédéric Blanc, 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), Laboratoire de neurosciences cognitives et adaptatives (LNCA), and Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Sciences du Vivant [q-bio]/Neurosciences [q-bio.NC], Neurology, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neurology (clinical)
Published
2023

20. Involvement of ApoE4 in dementia with Lewy bodies in the prodromal and demented stages: evaluation of the Strasbourg cohort

Author

Olivier Bousiges, Benjamin Cretin, Candice Muller, Anne Botzung, Lea Sanna, Pierre Anthony, Nathalie Philippi, Catherine Demuynck, and Frédéric Blanc

Abstract

Background: ApoE4 as a risk factor for AD is no longer a matter of debate. However, it is still an issue for dementia with Lewy bodies (DLB). We wanted to determine the involvement of ApoE4 according to different clinical parameters in our cohort of patients from Strasbourg. Methods: ApoE genotyping was performed on the AlphaLewyMA cohort. In this cohort, 197 patients were genotyped. Among them 105 DLB patients, 37 Alzheimer’s disease (AD), 29 comorbidity AD/DLB and 26 control subjects (CS). These groups are also classified according to the stage of evolution of the disease: prodromal or demented. We analyzed other parameters in relation to ApoE4, such as socio-educational levels (SEL) and Alzheimer CSF biomarkers (t-Tau, P-Tau, Aβ-42 and Aβ40). Results: There were significantly more ApoE4 carriers in the AD (51.4%) and AD/DLB (72.4%) groups compared to the DLB (25.7%) and CS (11.5%) groups (PConclusions: ApoE4 does not appear to be a risk factor for “pure” DLB patients with the possible exception of patients with high SEL. In the DLB group, ApoE4 would be responsible for the Aβ42 decrease between the prodromal and demented group, suggesting a strong link between ApoE4 and amyloidopathy thus confirming its strong link with AD. Trial registration: ClinicalTrials.gov, (AlphaLewyMa, Identifier: NCT01876459)

Published
2023

21. Cerebrovascular disease, neurodegeneration, and clinical phenotype in dementia with Lewy bodies

Author

Ketil Oppedal, Benjamin Cretin, Clifford R. Jack, Catherine Demuynck, Timothy G. Lesnick, Dag Aarsland, Scott A. Przybelski, Paulo Loureiro de Sousa, Bradley F. Boeve, Frederik Barkhof, Ronald C. Petersen, Tanis J. Ferman, Hugo Botha, Julie A. Fields, Neill R. Graff-Radford, Zuzana Nedelska, Nathalie Philippi, Val J. Lowe, Daniel Ferreira, Marleen van de Beek, Kejal Kantarci, Jakub Hort, Jonathan Graff-Radford, David S. Knopman, Eric Westman, Matthew L. Senjem, Afina W. Lemstra, Christopher G. Schwarz, Rodolfo Savica, Frédéric Blanc, 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), Neurology, Amsterdam Neuroscience - Neurodegeneration, Radiology and nuclear medicine, Amsterdam Neuroscience - Brain Imaging, and Amsterdam Neuroscience - Neuroinfection & -inflammation

Subjects
0301 basic medicine, Brain Infarction, Lewy Body Disease, Male, Aging, Pathology, medicine.medical_specialty, Hallucinations, Thalamus, Rapid eye movement sleep, REM Sleep Behavior Disorder, Article, 03 medical and health sciences, 0302 clinical medicine, Cognition, mental disorders, medicine, Humans, cardiovascular diseases, Gray Matter, Aged, Aged, 80 and over, Cerebral Cortex, medicine.diagnostic_test, Dementia with Lewy bodies, business.industry, General Neuroscience, Parkinsonism, Neurodegeneration, Magnetic resonance imaging, Middle Aged, medicine.disease, Subcortical gray matter, Magnetic Resonance Imaging, White Matter, Hyperintensity, Cerebrovascular Disorders, 030104 developmental biology, Nerve Degeneration, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Female, Neurology (clinical), Geriatrics and Gerontology, business, 030217 neurology & neurosurgery, Developmental Biology
Abstract

We investigated whether cerebrovascular disease contributes to neurodegeneration and clinical phenotype in dementia with Lewy bodies (DLB). Regional cortical thickness and subcortical gray matter volumes were estimated from structural magnetic resonance imaging (MRI) in 165 DLB patients. Cortical and subcortical infarcts were recorded and white matter hyperintensities (WMHs) were assessed. Subcortical only infarcts were more frequent (13.3%) than cortical only infarcts (3.1%) or both subcortical and cortical infarcts (2.4%). Infarcts, irrespective of type, were associated with WMHs. A higher WMH volume was associated with thinner orbitofrontal, retrosplenial, and posterior cingulate cortices, smaller thalamus and pallidum, and larger caudate volume. A higher WMH volume was associated with the presence of visual hallucinations and lower global cognitive performance, and tended to be associated with the absence of probable rapid eye movement sleep behavior disorder. Presence of infarcts was associated with the absence of parkinsonism. We conclude that cerebrovascular disease is associated with gray matter neurodegeneration in patients with probable DLB, which may have implications for the multifactorial treatment of probable DLB.

Published
2021

22. MRI data-driven clustering reveals different subtypes of Dementia with Lewy bodies

Author

Anna Inguanzo, Konstantinos Poulakis, Rosaleena Mohanty, Christopher G. Schwarz, Scott A. Przybelski, Patricia Diaz-Galvan, Val J. Lowe, Bradley F. Boeve, Afina W. Lemstra, Marleen van de Beek, Wiesje van der Flier, Frederik Barkhof, Frederic Blanc, Paulo Loureiro de Sousa, Nathalie Philippi, Benjamin Cretin, Catherine Demuynck, Zuzana Nedelska, Jakub Hort, Barbara Segura, Carme Junque, Ketil Oppedal, Dag Aarsland, Eric Westman, Kejal Kantarci, Daniel Ferreira, Neurology, Amsterdam Neuroscience - Neurodegeneration, Epidemiology and Data Science, APH - Methodology, APH - Personalized Medicine, Radiology and nuclear medicine, Amsterdam Neuroscience - Brain Imaging, Amsterdam Neuroscience - Neuroinfection & -inflammation, CCA - Cancer Treatment and quality of life, and CCA - Imaging and biomarkers

Subjects
Cellular and Molecular Neuroscience, Neurology, Neurology (clinical)
Abstract

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

Published
2022

23. 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

24. Prodromal characteristics of Dementia with Lewy Bodies: baseline results of the Memento nationwide cohort

Author

Frederic Blanc, Vincent Bouteloup, Claire Paquet, Marie Chupin, Florence Pasquier, Audrey Gabelle, Mathieu Ceccaldi, Paulo Loureiro Sousa, Pierre Krolak-Salmon, Renaud David, Clara Fischer, Jean-François Dartigues, David Wallon, Olivier Moreaud, Mathilde Sauvée, Catherine Belin, Sandrine Harston, Anne Botzung, Timothée Albasser, Catherine Demuynck, Izzie Namer, Marie-Odile Habert, Stéphane Kremer, Olivier Bousiges, Marc Verny, Candice Muller, Nathalie Philippi, Geneviève Chene, Benjamin Cretin, Jean-François Mangin, and Carole Dufouil

Subjects
nervous system, mental disorders, behavioral disciplines and activities, nervous system diseases
Abstract

Background: Isolated subjective cognitive impairment (SCI) and mild neurocognitive impairment (MCI) are prodromal phase of dementia with Lewy bodies (DLB). Memento is a nationwide study of patients with SCI and MCI with clinic, neuropsychology, biology and brain imaging data. We aimed to compare SCI and MCI patients with symptoms of prodromal DLB to others in this study at baseline. Methods: Participants of the French Memento cohort study recruited for either SCI or MCI. Among them, 892 were included in the Lewy sub-study, designed to search specifically for symptoms of DLB. Probable prodromal DLB group (pro-DLB) was done using a two-criteria cut-off score among the four core clinical features of DLB. This Pro-DLB group was compared to two other groups at baseline: one without any core symptoms (NS group), and the one with one core symptom (1S group). A comprehensive cognitive battery, questionnaires on behavior, neurovegetative and neurosensory symptoms, brain 3D volumetric MRI, CSF, FDG PET and amyloid PET were done.Results: The Pro-DLB group comprised 148 patients (16.6%). This group showed more multidomain (59.8%) MCI with slower processing speed and a higher proportion of patients with depression, anxiety, apathy, constipation, rhinorrhea, sicca syndrome, and photophobia. The Pro-DLB group had isolated lower P-Tau and on brain MRI widening of sulci including fronto-insular, occipital, and olfactory sulci (FDR corrected). Conclusions: Patients with symptoms of prodromal DLB are cognitively slower, with more behavioral disorders, autonomic symptoms, and photophobia. Biomarkers confirmed the non-Alzheimer profile. The occipital, fronto-insular, and olfactory bulb involvement on brain MRI was consistent with symptoms and known neuropathology. The next step will be to study the clinical, biological, and imaging evolution of these patients.Trial registration: Clinicaltrials.gov, NCT01926249 .

Published
2022

25. Does Culture Shape Our Understanding of Others’ Thoughts and Emotions? An Investigation Across 12 Countries

Author

François Quesque, Antoine Coutrot, Sharon Cox, Leonardo Cruz de Souza, Sandra Baez, Juan Felipe Cardona, Hannah Mulet-Perreault, Emma Flanagan, Alejandra Neely-Prado, Maria Florencia Clarens, Luciana Cassimiro, Gada Musa, Jennifer Kemp, Anne Botzung, Nathalie Philippi, Maura Cosseddu, Catalina Trujillo-Llano, Johan Sebastián Grisales-Cardenas, Sol Fittipaldi, Nahuel Magrath Guimet, Ismael Luis Calandri, Lucia Crivelli, Lucas Sedeno, Adolfo M. Garcia, Fermin Moreno, Begoña Indakoetxea, Alberto Benussi, Millena Vieira Brandão Moura, Hernando Santamaria-Garcia, Diana Matallana, Galina Pryanishnikova, Anna Morozova, Olga Iakovleva, Nadezda Veryugina, Oleg Levin, Lina Zhao, Junhua Liang, Thomas Duning, Thibaud Lebouvier, Florence Pasquier, David Huepe, Myriam Barandiaran, Andreas Johnen, Elena Lyashenko, Ricardo F. Allegri, Barbara Borroni, Frederic Blanc, Fen Wang, Mônica Sanches Yassuda, Patricia Lillo, Antônio Lúcio Teixeira, Paulo Caramelli, Carol Hudon, Andrea Slachevsky, Agustin Ibáñez, Michael Hornberger, and Maxime Bertoux

Subjects
Mental Disorders, Emotions, Culture, Mentalizing, Social cognition, Cognition, Neuropsychology and Physiological Psychology, COGNIÇÃO SOCIAL, Neuropsychology, Theory of mind, Emotion recognition, Educational Status, Humans
Abstract

Measures of social cognition have now become central in neuropsychology, being essential for early and differential diagnoses, follow-up, and rehabilitation in a wide range of conditions. With the scientific world becoming increasingly interconnected, international neuropsychological and medical collaborations are burgeoning to tackle the global challenges that are mental health conditions. These initiatives commonly merge data across a diversity of populations and countries, while ignoring their specificity.In this context, we aimed to estimate the influence of participants' nationality on social cognition evaluation. This issue is of particular importance as most cognitive tasks are developed in highly specific contexts, not representative of that encountered by the world's population.Through a large international study across 18 sites, neuropsychologists assessed core aspects of social cognition in 587 participants from 12 countries using traditional and widely used tasks.Age, gender, and education were found to impact measures of mentalizing and emotion recognition. After controlling for these factors, differences between countries accounted for more than 20% of the variance on both measures. Importantly, it was possible to isolate participants' nationality from potential translation issues, which classically constitute a major limitation.Overall, these findings highlight the need for important methodological shifts to better represent social cognition in both fundamental research and clinical practice, especially within emerging international networks and consortia. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Published
2022

26. Pay attention to the basal ganglia: a volumetric study in early dementia with Lewy bodies

Author

Frédéric Blanc, Paulo Loureiro de Sousa, Anne Botzung, Vincent Noblet, Nathalie Philippi, univOAK, Archive ouverte, 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), 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), and 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)

Subjects
Male, Trail Making Test, Dementia with Lewy bodies, Caudate nucleus, Neuropsychological Tests, Audiology, Basal Ganglia, lcsh:RC346-429, 0302 clinical medicine, Basal ganglia, Attention, VBM, Aged, 80 and over, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Putamen, 05 social sciences, Cognition, Organ Size, Middle Aged, Magnetic Resonance Imaging, Neurology, Disease Progression, Female, Processing speed, MRI, Lewy Body Disease, medicine.medical_specialty, Cognitive Neuroscience, Prodromal Symptoms, Neuroimaging, Sciences du Vivant [q-bio]/Médecine humaine et pathologie, 050105 experimental psychology, lcsh:RC321-571, 03 medical and health sciences, mental disorders, Reaction Time, medicine, Humans, 0501 psychology and cognitive sciences, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, lcsh:Neurology. Diseases of the nervous system, Aged, Cerebral atrophy, business.industry, Research, Mild cognitive impairment, medicine.disease, Prodromal, Digit symbol substitution test, Neurology (clinical), business, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

Background Cortical and subcortical cognitive impairments are usually found in dementia with Lewy bodies (DLB). Roughly, they comprise visuo-constructive/executive function and attention/processing speed impairments, whereas memory would remain relatively spared. In this study, we focused on the neuro-anatomical substrates of attention and processing speed, which is still poorly understood. For the purpose of the study, we examined the correlations between behavioral scores measuring the speed of processing and the degree of cerebral atrophy in patients with prodromal to moderate DLB. Methods Ninety-three prodromal to moderate DLB patients (mean MMSE = 25.5) were selected to participate in the study as well as 28 healthy elderly subjects (mean MMSE = 28.9), matched in terms of age and educational level. The Trail Making Test A (TMTA) and the Digit Symbol Substitution Test (DSST) were used to assess attention and processing speed. Behavioral performances were compared between patients and healthy control subjects. Three-dimensional MRI images were acquired for all participants, and correlational analyses were performed in the patient group using voxel-based morphometry (VBM). Results The behavioral results on both the TMTA (p = .026) and the DSST (p p p Conclusions The behavioral results are in line with the literature on the DLB cognitive profile and confirm the existence of attention and processing speed impairment. Interestingly, VBM analysis revealed the involvement of the basal ganglia, in particular, the left caudate nucleus, which is part of the attention cerebral network, suggesting an important role of this structure for attentional processing speed. This also suggests the clinical implication of damage in this region relatively early in the course of the disease.

Published
2019

27. Dementia with Lewy bodies subtypes identified by cluster analysis on structural MRI

Author

Anna Inguanzo, Konstantinos Poulakis, Rosaleena Mohanty, Christopher G. Schwarz, Scott A. Przybelski, Afina W. Lemstra, Marleen van de Beek, Wiesje M van der Flier, Frederik Barkhof, Frédéric Blanc, Paulo Loureiro de Sousa, Nathalie Philippi, Benjamin Cretin, Catherine Demuynck, Zuzana Nedelska, Jakub Hort, Barbara Segura, Carme Junqué, Ketil Oppedal, Dag Aarsland, Eric Westman, Kejal Kantarci, and Daniel Ferreira

Subjects
Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Epidemiology, Health Policy, Neurology (clinical), Geriatrics and Gerontology
Published
2021

29. Self, insula and dementia with Lewy bodies

Author

Alice Tisserand, Nathalie Philippi, Anne Botzung, and Frédéric Blanc

Subjects
Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Epidemiology, Health Policy, Neurology (clinical), Geriatrics and Gerontology
Published
2021

30. Memories defining the self in Alzheimer’s disease

Author

Benjamin Cretin, Hédi Ben Malek, Fabrice Berna, Frédéric Blanc, Liliann Manning, Anne Botzung, and Nathalie Philippi

Subjects
Male, Memory, Episodic, media_common.quotation_subject, Disease, 050105 experimental psychology, 03 medical and health sciences, 0302 clinical medicine, Arts and Humanities (miscellaneous), Alzheimer Disease, Humans, 0501 psychology and cognitive sciences, In patient, Valence (psychology), Potential mechanism, General Psychology, Aged, media_common, Autobiographical memory, Self, 05 social sciences, Mental Status and Dementia Tests, Self Concept, Case-Control Studies, Mental Recall, Personal identity, Female, Psychology, 030217 neurology & neurosurgery, Cognitive psychology
Abstract

There is a debate over the extent to which personal identity or the self is preserved in patients with Alzheimer's disease (AD). Autobiographical memory deficits at early stages of AD could contribute to altering patients' self. However, the nature of the relationship between autobiographical memory deficits and the self in AD has not been much investigated experimentally. In the present study, we aimed to investigate the integrative meaning of self-defining memories (SDMs) in early stages of AD and to analyse its relationship with the self-concept. The results showed that, when compared to the control group, AD patients less frequently extracted meaning from their SDMs and the meaning was less frequently tied to the self. Patients exhibited some altered aspects of the self-concept (i.e., complexity and strength), though some other components still persisted (i.e., valence and certainty). Correlation analyses showed that the impaired integrative meaning in the AD group was correlated with some changes in self-concept. We suggest that integrative meaning may act as a bridge between autobiographical memories and the self-concept, with reduced integration abilities appearing as a potential mechanism for the deterioration of the self-concept in AD.

Published
2018

31. Transient epileptic amnesia is significantly associated with discrete CA1-located hippocampal calcifications but not with atrophic changes on brain imaging

Author

Benjamin Cretin, Frédéric Blanc, François Sellal, Antoine Blain, Nathalie Philippi, Mécanismes Centraux et Périphériques de la Neurodégénérescence, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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, 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
Pathology, medicine.medical_specialty, business.industry, Brain, Neuroimaging, Hippocampal formation, medicine.disease, Hippocampus, Magnetic Resonance Imaging, Pathophysiology, Epilepsy, Transient epileptic amnesia, Neurology, Etiology, Medicine, Humans, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neurology (clinical), Amnesia, Cognitive decline, Atrophy, business, Cortical atrophy, Aged
Abstract

The exact etiology of transient epileptic amnesia (TEA) is currently unknown. In older individuals, common neurodegenerative dementias and small-vessel diseases (SVDs) could be major contributors. We examined these hypotheses on the basis of imaging analysis.In total, 36 TEA patients were compared with 25 healthy controls for (1) cortical atrophic changes (in the mesial temporal, frontal, anterior temporal, and parietal regions) using four established MRI-based visual rating scales, and for (2) SVD evidence using two MRI-based visual rating scales (Fazekas and MARS scores). In 24 TEAs cases, there were also brain CT scans available that were compared with 57 controls for the presence of hippocampal calcifications (HCs).We did not find significant differences in cortical atrophy between TEAs and controls, nor did we observe a different SVD brain load on MRI. However, TEAs were significantly associated (p0.01) with uni- or bilateral CA1-located HCs in half of the patients compared with the controls (less than 20 %).This study argues in favor of a hippocampal-restricted SVD (as indicated by HCs) as one of the major etiologies of TEA, while neurodegenerative dementias are probably minor causes. It furthermore highlights the pivotal role of the CA1 hippocampal subfield in the pathophysiology of this syndrome.

Published
2021

32. Who am I with my Lewy bodies? A self‐concept study

Author

Alice Tisserand, Vincent Noblet, Nathalie Philippi, Anne Botzung, and Frédéric Blanc

Subjects
Cognitive science, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Epidemiology, Health Policy, Self-concept, Neurology (clinical), Geriatrics and Gerontology, Psychology
Published
2020

33. Dementia with Lewy bodies: A differential diagnosis of normal pressure hydrocephalus

Author

François Proust, Mathieu Anheim, Irène Ollivier, Seyyid Baloglu, Frédéric Blanc, Mathias Bilger, Benjamin Cretin, Hélène Durand, and Nathalie Philippi

Subjects
Pediatrics, medicine.medical_specialty, Epidemiology, Dementia with Lewy bodies, business.industry, Behavioral neurology, Health Policy, Neuropsychiatry, medicine.disease, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Normal pressure hydrocephalus, medicine, Dementia, Neurology (clinical), Geriatrics and Gerontology, Differential diagnosis, business
Published
2020

34. The impact of culture on neuropsychological performance: A global social cognition study across 12 countries

Author

Anne Botzung, Sandra Baez, Ricardo F. Allegri, Begoña Indakoetxea, Catalina Trujillo, Lucia Crivelli, Fermin Moreno, Andrea Slachevsky, Sol Fittipaldi, Leonardo Cruz de Souza, Frédéric Blanc, François Quesque, Johan S. Grisales, Gada Musa, Alberto Benussi, Olga Iakovlena, Michael Hornberger, Maxime Bertoux, María Florencia Clarens, Antoine Coutrot, Antônio Lúcio Teixeira, Galina Prianishnikova, Junhua Liang, Thomas Duning, Ismael Calandri, David Huepe, Juan F. Cardona, Lina Zhao, Myriam Barandiaran, Luciana Cassimiro, Elena Lyashenko, Nahuel Magrath, Patricia Lillo, Paulo Caramelli, Thibaud Lebouvier, Anna Morozova, Nathalie Philippi, Carol Hudon, Florence Pasquier, Nadezda Veryugina, Adolfo M. García, Maura Cosseddu, Agustín Ibáñez, Fen Wang, Emma Flanagan, Hannah Mulet‐Perreault, Millena Vieira Brandão Moura, Carolina Delgado, Lucas Sedeño, Jennifer Kemp, Alejandra Neely-Prado, Sharon Cox, Mônica Sanches Yassuda, Andreas Johnen, and Barbara Borroni

Subjects
Epidemiology, Health Policy, media_common.quotation_subject, Neuropsychology, medicine.disease, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Social cognition, Multiculturalism, medicine, Dementia, Neurology (clinical), Geriatrics and Gerontology, Psychology, media_common, Clinical psychology
Published
2020

35. Dementia with Lewy bodies: Characteristics of the prodromal stage in a nationwide longitudinal cohort

Author

Anne Botzung, Izzie Jacques Namer, Carole Dufouil, Frédéric Blanc, Jean-François Dartigues, Catherine Martin-Hunyadi, Jean-François Mangin, Marie Chupin, Clara Fischer, Marie-Odile Habert, Paulo Loureiro de Sousa, Claire Paquet, Vincent Bouteloup, Mathieu Ceccaldi, Nathalie Philippi, Pierre Krolak Salmon, Florence Pasquier, Renaud David, David Wallon, Geneviève Chêne, Catherine Demuynck, Olivier Bousiges, Stéphane Kremer, Catherine Belin, Timothée Albasser, Olivier Moreaud, Mathilde Sauvée, Benjamin Cretin, and Audrey Gabelle

Subjects
medicine.medical_specialty, Epidemiology, Dementia with Lewy bodies, Behavioral neurology, business.industry, Health Policy, Prodromal Stage, Neuropsychiatry, medicine.disease, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, medicine, Neurology (clinical), Geriatrics and Gerontology, Longitudinal cohort, Psychiatry, business
Published
2020

36. Subcortical atrophy in dementia with Lewy bodies

Author

Anne Botzung, Frédéric Blanc, Nathalie Philippi, and Vincent Noblet

Subjects
Pathology, medicine.medical_specialty, Epidemiology, Dementia with Lewy bodies, business.industry, Health Policy, medicine.disease, Subcortical atrophy, 03 medical and health sciences, Psychiatry and Mental health, Cellular and Molecular Neuroscience, 0302 clinical medicine, Developmental Neuroscience, 030225 pediatrics, medicine, Neurology (clinical), Geriatrics and Gerontology, business, 030217 neurology & neurosurgery
Published
2020

37. CASPR2 antibody encephalitis presenting as transient epileptic amnesia

Author

Benjamin Cretin, Mathias Bilger, Nathalie Philippi, Frédéric Blanc, 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), CHU Strasbourg, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), 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), and CCSD, Accord Elsevier

Subjects
[SDV]Life Sciences [q-bio], Nerve Tissue Proteins, 03 medical and health sciences, Epilepsy, 0302 clinical medicine, Seizures, medicine, Humans, case report, ComputingMilieux_MISCELLANEOUS, Autoantibodies, 030304 developmental biology, Autoimmune encephalitis, 0303 health sciences, biology, business.industry, Membrane Proteins, transient epileptic amnesia, General Medicine, Middle Aged, medicine.disease, autoimmune encephalitis, 3. Good health, anti-CASPR2, [SDV] Life Sciences [q-bio], Transient epileptic amnesia, Neurology, Immunology, biology.protein, Encephalitis, Amnesia, Neurology (clinical), Antibody, business, 030217 neurology & neurosurgery
Abstract

International audience; No abstract available

Published
2020

38. Association of cerebral microbleeds with cerebrospinal fluid Alzheimer-biomarkers and clinical symptoms in early dementia with Lewy bodies

Author

Anne Archenault, Michel Casanovas, Frédéric Blanc, Aline Mendes, Nathalie Philippi, Olivier Bousiges, Seyyid Baloglu, Vincent Noblet, Sumayya Manji, Paulo Loureiro de Sousa, Lucie Rauch, Benjamin Cretin, Mary Mondino, Catherine Demuynck, and Catherine Martin-Hunyadi

Subjects
Lewy Body Disease, medicine.medical_specialty, Disease, Fluid-attenuated inversion recovery, behavioral disciplines and activities, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Cerebrospinal fluid, Alzheimer Disease, Internal medicine, mental disorders, medicine, Humans, Effects of sleep deprivation on cognitive performance, Cerebral Hemorrhage, Retrospective Studies, Amyloid beta-Peptides, 030214 geriatrics, business.industry, Dementia with Lewy bodies, Parkinsonism, medicine.disease, Hyperintensity, Peptide Fragments, nervous system diseases, Psychiatry and Mental health, Cross-Sectional Studies, Cerebral amyloid angiopathy, Geriatrics and Gerontology, business, Biomarkers
Abstract

Objectives To determine the prevalence, localization and associations of cerebral microbleeds (CMB) in dementia with Lewy bodies (DLB) with its core clinical symptoms and cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD). We hypothesize DLB patients with CMB have increased amyloid burden compared to those without CMB, which could also translate into clinical differences. Methods Retrospective cross-sectional analysis from the AlphaLewyMA study (https://clinicaltrials.gov/ct2/show/NCT01876459). Patients underwent a standardized protocol of brain MRI including 3D T1, 3D FLAIR and T2* sequences, and CSF analysis of AD biomarkers. CMB and white matter hyperintensities (WMHs) were visually assessed in prodromal and mild demented (DLB, N = 91) and AD (AD, N = 67) patients. Results CMB prevalence did not differ among DLB and AD (24.2% vs. 37.3%; p = 0.081). CMB were mainly distributed in lobar topographies in both DLB (74%) and AD (89%). CMB in DLB was not associated with global cognitive performance, executive functioning, speed of information processing, or AD CSF biomarkers. Similarly, there was no difference regarding specific clinical symptoms: fluctuations, psychotic phenomena, sleep behavior disorder and Parkinsonism between DLB patients with and without CMB. AD patients with CMB had increased burden of WMH compared to those without (2.1 ± 0.86 vs. 1.4 ± 0.89; p = 0.005), according to Fazekas scale, whereas no significant difference was observed in DLB patients (1.68 ± 0.95 vs. 1.42 ± 0.91; p = 0.25). Conclusion CMB were equally prevalent with similar topographic distribution in both DLB and AD patients. CMB was not associated with CSF AD biomarkers or core clinical symptoms in DLB.

Published
2020

39. Differential diagnostic value of total alpha-synuclein assay in the cerebrospinal fluid between Alzheimer's disease and dementia with Lewy bodies from the prodromal stage

Author

Paulo Loureiro de Sousa, Benjamin Cretin, Anne Botzung, Nathalie Philippi, Pierre Anthony, Frédéric Blanc, Lucie Rauch, Caroline Schaeffer-Agalède, Armand Perret-Liaudet, Olivier Bousiges, Barbara Jung, Thomas Lavaux, Catherine Martin-Hunyadi, Catherine Demuynck, Ingolf Lachmann, Laboratoire de neurosciences cognitives et adaptatives (LNCA), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), 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), Biomatériaux et Bioingénierie (BB), Université de Strasbourg (UNISTRA)-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)-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 National de la Santé et de la Recherche Médicale (INSERM), 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), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Matériaux et Nanosciences Grand-Est (MNGE), and 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)

Subjects
Neurology, Dementia with Lewy bodies, Gastroenterology, lcsh:RC346-429, 0302 clinical medicine, Cerebrospinal fluid biomarkers, Stage (cooking), ComputingMilieux_MISCELLANEOUS, 0303 health sciences, Prodromal Stage, Total alpha-synuclein, alpha-Synuclein, Biomarker (medicine), [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], France, Alzheimer’s disease, Lewy Body Disease, medicine.medical_specialty, Sciences du Vivant [q-bio]/Neurosciences [q-bio.NC], Cognitive Neuroscience, Prodromal Symptoms, tau Proteins, behavioral disciplines and activities, lcsh:RC321-571, Diagnosis, Differential, 03 medical and health sciences, Alzheimer Disease, Internal medicine, mental disorders, medicine, Humans, Dementia, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, lcsh:Neurology. Diseases of the nervous system, 030304 developmental biology, Amyloid beta-Peptides, business.industry, Research, Memory clinic, medicine.disease, nervous system diseases, nervous system, Prodromal, Neurology (clinical), Differential diagnosis, business, Biomarkers, 030217 neurology & neurosurgery
Abstract

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

Published
2020

40. Total alpha-synuclein assay in cerebrospinal fluid is of interest in the differential diagnosis between Alzheimer's disease and dementia with Lewy bodies from the prodromal stage

Author

Benjamin Cretin, Ingolf Lachmann, Nathalie Philippi, Anne Botzung, Caroline Schaeffer-Agalède, Catherine Martin-Hunyadi, Thomas Lavaux, Lucie Rauch, Pierre Anthony, Barbara Jung, Armand Perret-Liaudet, Catherine Demuynck, Olivier Bousiges, Paulo Loureiro de Sousa, and Frédéric Blanc

Subjects
Alpha-synuclein, Pathology, medicine.medical_specialty, business.industry, Dementia with Lewy bodies, Prodromal Stage, Disease, medicine.disease, behavioral disciplines and activities, nervous system diseases, chemistry.chemical_compound, Cerebrospinal fluid, nervous system, chemistry, mental disorders, Medicine, Differential diagnosis, business
Abstract

Background: Several studies have investigated the value of alpha-synuclein assay in the cerebrospinal fluid (CSF) of Alzheimer’s disease (AD) and dementia with Lewy bodies (DLB) patients in the differential diagnosis of these two pathologies. However, very few studies have focused on this assay in AD and DLB patients at the MCI stage.Methods: All patients were enrolled under a hospital clinical research protocol from the tertiary Memory Clinic (CM2R) of Alsace, France, by an experienced team of clinicians. A total of 166 patients were included in this study: 21 control subjects (CS), 51 patients with DLB at the prodromal stage (pro-DLB), 16 patients with DLB at the demented stage (DLB-d), 33 AD patients at the prodromal stage (pro-AD), 32 AD patients at the demented stage (AD-d) and 13 patients with mixed pathology (AD+DLB). CSF levels of total alpha-synuclein were assessed using a commercial enzyme-linked immunosorbent assay (ELISA) for alpha-synuclein (AJ Roboscreen). Alzheimer’s biomarkers (t-Tau, P-Tau, Aβ42 and Aβ40) were also measured.Results: The alpha-synuclein assays showed a significant difference between the AD and DLB groups. Total alpha-synuclein levels were significantly higher in AD patients than in DLB patients. Interestingly, the levels appeared to be altered from the prodromal stage in both AD and DLB. Furthermore, alpha-synuclein levels were elevated not only in AD patients with a typical “Alzheimer” profile (i.e. 2 or 3 pathological biomarkers) but also in AD patients with an atypical “Alzheimer” profile (i.e. one or no pathological biomarkers).Conclusions: The modification of total alpha-synuclein levels in the CSF of patients occurs early, from the prodromal stage. Moreover, alpha-synuclein assay appears to be of particular interest in the differential diagnosis of AD in cases where the Alzheimer biomarkers do not have a typical profile of the disease, i.e. when there is only one or no pathological biomarkers.Trial registration: ClinicalTrials.gov, (AlphaLewyMa, Identifier: NCT01876459)

Published
2020

41. Total alpha-synuclein assay in the Cerebro-Spinal-Fluid is of interest in the differential diagnosis between Alzheimer's disease and dementia with Lewy bodies from the prodromal stage

Author

Olivier BOUSIGES, Nathalie Philippi, Thomas Lavaux, Armand Perret-Liaudet, Ingolf Lachmann, Caroline Schaeffer-Agalède, Pierre Anthony, Anne Botzung, Lucie Rauch, Barbara Jung, Paulo Loureiro de Sousa, Catherine Demuynck, Catherine Martin-Hunyadi, Benjamin Cretin, and Frédéric Blanc

Subjects
nervous system, mental disorders, nervous system diseases
Abstract

Background: Several studies have investigated the value of alpha-synuclein assay in the cerebrospinal fluid (CSF) of Alzheimer’s disease (AD) and Dementia with Lewy Bodies (DLB) patients in the differential diagnosis of these two pathologies. However, very few studies have focused on this assay in AD and DLB patients at the MCI stage. Methods: All patients were enrolled under a hospital clinical research protocol from the tertiary Memory Clinic (CM2R) of Alsace by an experienced team of clinicians. A total of 166 patients were included in this study: 21 control subjects (CS), 51 patients with DLB at the prodromal stage (pro-DLB), 16 patients with DLB at the demented stage (DLB-d), 33 AD patients at the prodromal stage (pro-AD) and 32 AD patients at the demented stage (AD-d). CSF levels of total alpha-synuclein were assessed using commercial enzyme-linked immunosorbent assay (ELISA) for alpha-synuclein (AJ Roboscreen). Alzheimer's biomarkers (t-Tau, P-Tau, Aβ42 and Aβ40) were also measured.Results: The alpha-synuclein assays showed a significant difference between the AD and DLB groups. Total alpha-synuclein levels are significantly higher in AD patients than in DLB patients. Interestingly is that the levels seem to be altered from the prodromal stage in both AD and DLB. Furthermore, by dividing the patients according to the profiles of Alzheimer's biomarkers typically found or not for each of the two pathologies and then classifying the patients according to the level of alpha-synuclein, we find that alpha-synuclein levels are elevated not only for AD patients with typical “Alzheimer” profile (i.e. 2 or 3 pathological biomarkers) but also for AD patients with a non-typical “Alzheimer” profile (i.e. none or one pathological biomarker).Conclusions: The modification of total alpha-synuclein levels in the CSF of patients occurs early from the prodromal stage. Moreover, alpha-synuclein assay appears to be of particular interest in the differential diagnosis of AD in cases where the Alzheimer biomarkers do not have a typical profile of the disease, i.e. when there is only one or no pathological biomarker.Trial registration: ClinicalTrials.gov, (AlphaLewyMa, Identifier: NCT01876459)

Published
2020

42. 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

43. Insular cognitive impairment at the early stage of dementia with Lewy bodies: a preliminary study

Author

Anne Botzung, Frédéric Blanc, Malik Hamdaoui, Morgane Constans-Erbs, Olivier Després, Geraldine Heim, Laetitia Berly, Jennifer Kemp, Laetitia Monjoin, Nathalie Philippi, Mathias Bilger, Catherine Martin-Hunyadi, David Soulier, Timothée Albasser, Emmanuelle Ehrhard, Benjamin Cretin, and Catherine Demuynck

Subjects
Lewy Body Disease, Male, medicine.medical_specialty, media_common.quotation_subject, Empathy, Neuropsychological Tests, Audiology, behavioral disciplines and activities, Diagnosis, Differential, 03 medical and health sciences, 0302 clinical medicine, Alzheimer Disease, mental disorders, Humans, Medicine, Cognitive Dysfunction, Emotional expression, Biological Psychiatry, Aged, media_common, business.industry, Dementia with Lewy bodies, Neuropsychology, Cognition, Middle Aged, medicine.disease, Disgust, nervous system diseases, Comprehension, Neuropsychology and Physiological Psychology, nervous system, 030220 oncology & carcinogenesis, Disease Progression, Female, Neurology (clinical), Geriatrics and Gerontology, business, Insula, 030217 neurology & neurosurgery
Abstract

Background The anterior part of the insula appears atrophied in the early stage of dementia with Lewy bodies (DLB) whereas it is not the case in early Alzheimer's disease (AD). Objective The objective of this study was to develop neuropsychological markers supposed to reflect insular dysfunction, which would facilitate early diagnosis of DLB, namely in comparison to AD. Methods Twelve patients with DLB, 12 patients with AD, all at the stage of Mild cognitive impairment (MCI) or mild dementia, as well as 10 Controls subjects (CS) participated in the study. Cognitive functions supposedly related to the insula were evaluated with a battery of tests: a facial expression recognition test, a test assessing the feeling of disgust with images, a test evaluating idioms' comprehension, an empathy questionnaire and a questionnaire screening for disgusting behaviors. Results Compared to AD patients and CS, DLB patients experienced less disgust when they were shown disgusting images, whereas their ability to recognize emotional expression of disgust appeared to be preserved. Furthermore, DLB patients seemed less empathetic than AD patients. Finally, compared to CS, DLB patients were less effective to provide an intuitive decision about idioms' signification since they needed significantly more time to answer. Conclusion This preliminary study suggests the existence of a potential « insular cognitive impairment » profile in DLB at the early stage. These results provide interesting leads to develop tools facilitating the differential diagnosis of DLB and AD.

Published
2017

44. Insular atrophy at the prodromal stage of dementia with Lewy bodies: a VBM DARTEL study

Author

Benjamin Cretin, Daniel Roquet, Frédéric Blanc, Pierre Anthony, Paulo Loureiro de Sousa, Catherine Martin-Hunyadi, Vincent Noblet, Nathalie Philippi, and Catherine Demuynck

Subjects
Lewy Body Disease, Male, 0301 basic medicine, medicine.medical_specialty, lcsh:Medicine, Severity of Illness Index, behavioral disciplines and activities, Article, White matter, 03 medical and health sciences, 0302 clinical medicine, Atrophy, Internal medicine, mental disorders, medicine, Humans, Dementia, Gray Matter, Psychiatry, lcsh:Science, Aged, Aged, 80 and over, Cerebral Cortex, Multidisciplinary, medicine.diagnostic_test, business.industry, Dementia with Lewy bodies, Prodromal Stage, lcsh:R, Magnetic resonance imaging, Middle Aged, medicine.disease, Magnetic Resonance Imaging, nervous system diseases, 030104 developmental biology, medicine.anatomical_structure, nervous system, Case-Control Studies, Cardiology, Female, lcsh:Q, business, Insula, 030217 neurology & neurosurgery, Parahippocampal gyrus
Abstract

Diffuse atrophy including the insula was previously demonstrated in dementia with Lewy bodies (DLB) patients but little is known about the prodromal stage of DLB (pro-DLB). In this prospective study, we used SPM8-DARTEL to measure gray matter (GM) and white matter (WM) atrophy in pro-DLB patients (n = 54), prodromal Alzheimer’s disease (pro-AD) patients (n = 16), DLB patients at the stage of dementia (mild-DLB) (n = 15), and Alzheimer’s disease patients at the stage of dementia (mild-AD) (n = 28), and compared them with healthy elderly controls (HC, n = 22). Diminished GM volumes were found in bilateral insula in pro-DLB patients, a trend to significance in right hippocampus and parahippocampal gyrus in pro-AD patients, in left insula in mild-DLB patients, and in medial temporal lobes and insula in mild-AD patients. The comparison between prodromal groups did not showed any differences. The comparison between groups with dementia revealed atrophy around the left middle temporal gyrus in mild-AD patients. Reduced WM volume was observed in mild-DLB in the pons. The insula seems to be a key region in DLB as early as the prodromal stage. MRI studies looking at perfusion, and functional and anatomical connectivity are now needed to better understand the role of this region in DLB.

Published
2017

45. Long-term cognitive outcome of Alzheimer’s disease and dementia with Lewy bodies: dual disease is worse

Author

Rachid Mahmoudi, Erik Sauleau, Jean-Luc Novella, Catherine Martin-Hunyadi, Mélanie Stackfleth, Jean Galmiche, Jean-Marc Michel, Georges Kaltenbach, Athanase Benetos, François Sellal, Pierre Vandel, Catherine Demuynck, Benjamin Cretin, Thérèse Rivasseau Jonveaux, Nathalie Philippi, Grégory Tio, Frédéric Blanc, Eloi Magnin, Gilles Chopard, 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), Laboratoire de Biostatistique, Faculté de Médecine, Strasbourg and Pôle Santé Publique, Hôpitaux Universitaires de Strasbourg, 67085 Strasbourg Cedex, France, Laboratoire de biostatistiques, Centre de Mémoire de Ressource et Recherche [Champagne-Ardenne-Reims] (CMRR Reims - Champagne-Ardenne), Hôpital Maison Blanche, Centre Hospitalier Universitaire de Reims (CHU Reims)-Centre Hospitalier Universitaire de Reims (CHU Reims)-Fédération nationale des Centres de Mémoire de Ressources et de Recherche (FCMRR), Service Gériatrique (CHU Reims), Centre Hospitalier Universitaire de Reims (CHU Reims), Service de Gériatrie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre de Mémoire de Ressource et Recherche [Lorraine-Nancy] (CMRR Nancy-Lorraine), Association pour le développement de la neuropsychologie appliquée, CH Colmar, 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], Département de psychiatrie [CHRU de Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Service de Neurologie [CHRU Besançon], Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), 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), and MAHMOUDI, Rachid

Subjects
Male, Neurology, Dementia with Lewy bodies, Disease, Comorbidity, lcsh:RC346-429, 0302 clinical medicine, Risk Factors, Prevalence, 030212 general & internal medicine, Longitudinal Studies, Cognitive decline, ComputingMilieux_MISCELLANEOUS, Outcome, [SDV.MHEP.GEG] Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, [SDV.MHEP.GEG]Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, Cognition, Prognosis, 3. Good health, Causality, Female, France, Alzheimer’s disease, medicine.medical_specialty, Alzheimer’s dementia, Cognitive Neuroscience, Lewy body disease, behavioral disciplines and activities, MMSE, lcsh:RC321-571, 03 medical and health sciences, Alzheimer Disease, Internal medicine, mental disorders, medicine, Humans, Cognitive Dysfunction, Psychiatry, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, lcsh:Neurology. Diseases of the nervous system, Aged, business.industry, Research, Significant difference, medicine.disease, nervous system diseases, nervous system, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Propensity score matching, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Neurology (clinical), business, 030217 neurology & neurosurgery, Geriatric psychiatry
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

46. Do we know how to diagnose epilepsy early in Alzheimer's disease?

Author

Catherine Martin-Hunyadi, Nathalie Philippi, François Sellal, Olivier Bousiges, L. Dibitonto, Frédéric Blanc, and Benjamin Cretin

Subjects
0301 basic medicine, Pediatrics, medicine.medical_specialty, Prodromal Symptoms, Disease, Electroencephalography, Temporal lobe, 03 medical and health sciences, Epilepsy, 0302 clinical medicine, Alzheimer Disease, medicine, Humans, Dementia, Cognitive Dysfunction, Generalized epilepsy, Psychiatry, medicine.diagnostic_test, medicine.disease, Comorbidity, Early Diagnosis, 030104 developmental biology, Neurology, Disease Progression, Neurology (clinical), Alzheimer's disease, Psychology, 030217 neurology & neurosurgery
Abstract

Epilepsy is an increasingly recognized comorbidity in Alzheimer's disease (AD). First described as generalized in dementia patients, epileptic AD patients are nowadays fully described in earlier stages of the disease (with mild or subjective cognitive impairment). At such early stages, patients may present not only with generalized seizures, but also with focal seizures (commonly localized in the frontal or temporal lobe). Thus, partial or generalized epilepsy is part of the semiological spectrum of AD that should be borne in mind at all stages of disease to ensure early identification and prevent the risk of repeated seizures (such as accidents, injury, progression of cognitive impairment). This review of the available (and still growing) literature shows that there are already sufficient data to inform physicians on seizure semiology, and on the diagnostic value of electroencephalography and brain imaging. Taken together, these tools can help to rapidly identify epilepsy in AD patients. Nevertheless, epilepsy diagnosis can be challenging, and test medication is sometimes necessary. Some cerebrospinal fluid biomarkers (or their ratios) may also prove to be good predictors of seizures in AD, but further studies are needed. Epilepsy in AD patients is frequently pharmacosensitive, and a good response can be obtained with standard doses of antiepileptic drugs. For all these reasons and based on our review of the literature, it appears that, at present, the diagnosis of epilepsy in AD is not only possible at any stage of the disease, but also to be recommended to improve the patient's prognosis.

Published
2017

47. Epilepsy at the prodromal stages of neurodegenerative diseases

Author

Frédéric Blanc, Laure Dibitonto, Nathalie Philippi, and Benjamin Cretin

Subjects
Aged, 80 and over, Pediatrics, medicine.medical_specialty, Epilepsy, business.industry, Prodromal Symptoms, Neurodegenerative Diseases, Cognition, Degeneration (medical), Disease, medicine.disease, Temporal lobe, Neuropsychology and Physiological Psychology, Atrophy, Neuroimaging, medicine, Humans, Neurology (clinical), Geriatrics and Gerontology, business, Biological Psychiatry, Aged, Frontotemporal dementia
Abstract

This review provides a clinically grounded description of the links between epilepsy and early common neurodegenerative diseases (i.e. Alzheimer's disease, Lewy body disease, vascular cognitive impairment, fronto-temporal lobar degeneration). It shows that epilepsy does not only concern demented patients displaying convulsive seizures (whether focal or generalized) and obvious atrophy on brain imaging. On the contrary, unprovoked seizures and epilepsy - commonly involving the temporal lobe - are now reported at the prodromal stages of these diseases, when cognitive complaints are mild or even minimal and brain imaging inconstantly abnormal. Thus epilepsy must be considered as a part of the phenotypic spectrum at any stages of the neurodegenerative diseases. This must be kept in mind in everyday practice, and when defining these diseases with clinic-biological criteria. Such entanglement also explains the growing prevalence of elderly epileptic subjects and the need of a close collaboration between geriatricians, cognitivists and epileptologists.

Published
2017

49. What is the clinical impact of cerebrospinal fluid biomarkers on final diagnosis and management in patients with mild cognitive impairment in clinical practice? Results from a nation-wide prospective survey in France

Author

Philippe Robert, Jacques Hugon, David Wallon, Bernard Croisile, Alain Jager, Emilie Beaufils, Florence Pasquier, Claire Paquet, Frédéric Blanc, Eloi Magnin, François Mouton Liger, Emmanuelle Duron, Susanna Schraen, Didier Hannequin, Anne-Cécile Troussière, Vincent de la Sayette, Julien Dumurgier, Muriel Quillard, Nathalie Philippi, Carole Miguet-Alfonsi, Audrey Gabelle, Elodie Bouaziz-Amar, Emmanuel Cognat, Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), 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 Lille Nord (France), 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), CHU Rouen, Normandie Université (NU), Hôpital Lariboisière, 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), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Groupe hospitalier Broca, Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hospices Civils de Lyon, Departement de Neurologie (HCL), Neuropsychologie cognitive et neuroanatomie fonctionnelles de la mémoire humaine, Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Neurologie [CHU Caen], Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre hospitalier régional Metz-Thionville (CHR Metz-Thionville), Laboratoire de Neuroimagerie in Vivo (LNV), CHU Strasbourg-Centre National de la Recherche Scientifique (CNRS), CHU Strasbourg, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Université Pierre et Marie Curie - Paris 6 (UPMC)-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), Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre d'Investigation Clinique [CHU Rouen] (CIC Rouen), Hôpital Charles Nicolle [Rouen], Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), 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), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), 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), Service de neurologie [Rouen], Normandie Université (NU)-Normandie Université (NU), Centre Hospitalier Universitaire de Nice (CHU Nice), Service d'Histologie, cytologie, cytogénétique, biologie cellulaire [CHU Limoges], CHU Limoges, Institut du Fer à Moulin, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Salvy-Córdoba, Nathalie, Normandie Université (NU)-Normandie Université (NU)-École Pratique des Hautes Études (EPHE), 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), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), 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), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Charles Nicolle [Rouen]-CHU Rouen, Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U1172 Inserm - U837 (JPArc), 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 de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Université Paris Diderot - Paris 7 (UPD7)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Université de Lille, and Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)

Subjects
Male, medicine.medical_specialty, Databases, Factual, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Disease, Clinical practice, 03 medical and health sciences, 0302 clinical medicine, Cerebrospinal fluid, Alzheimer Disease, Internal medicine, Surveys and Questionnaires, medicine, Humans, In patient, Cognitive Dysfunction, 030212 general & internal medicine, Prospective Studies, Stage (cooking), Cognitive impairment, Aged, medicine.diagnostic_test, Lumbar puncture, business.industry, Research, [SCCO.NEUR]Cognitive science/Neuroscience, [SCCO.NEUR] Cognitive science/Neuroscience, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Mild cognitive impairment, General Medicine, Confidence interval, 3. Good health, Clinical Practice, Neurology, Disease Progression, Female, France, business, Alzheimer’s disease, 030217 neurology & neurosurgery, Biomarkers
Abstract

ObjectivesNew diagnostic criteria for Alzheimer’s disease (AD) include cerebrospinal fluid (CSF) biomarkers that allow diagnosis at the stage of mild cognitive impairment (MCI). However, the impact of CSF biomarkers in MCI populations in clinical practice has been poorly evaluated. The objective of this study is to assess the use and impact in clinical practice of AD CSF biomarkers in French memory clinics.DesignWe performed a nation-wide, prospective survey between March 2012 and September 2014. Data over the same period was extracted from the French National Database (Banque Nationale Alzheimer, BNA) and compared with the results of the survey.Setting29 secondary and tertiary memory clinics in France.ParticipantsClinicians prescribing lumbar puncture (LP) in order to measure AD CSF biomarkers. Clinicians completed a two-part questionnaire for each of their patients undergoing LP.Primary and secondary outcome measuresAssessment of diagnosis, level of confidence before and after CSF biomarkers and impact on management in patients who underwent LP for CSF AD biomarkers in clinical routine.Results977 questionnaires were completed, of which 61 were excluded because of unknown initial/final diagnosis or non-contributory CSF results. Of 916 patients reported, 153 (16.7%) had MCI as the initial diagnosis, of which 51 (33.3%) displayed an AD profile. CSF biomarkers resulted in a change in diagnosis in 44 patients (28.8%). Confidence level significantly increased after LP (8.3±1.4vs 6.73±1.18, pConclusionThis nation-wide survey, reflecting clinical practice in French memory clinics, describes the impact of CSF AD biomarkers in patients with MCI in clinical practice.

Published
2019

50. Epileptic Prodromal Alzheimer’s Disease, a Retrospective Study of 13 New Cases: Expanding the Spectrum of Alzheimer’s Disease to an Epileptic Variant?

Author

François Sellal, Laure Di Bitonto, Olivier Bousiges, Catherine Martin-Hunyadi, Nathalie Philippi, Benjamin Cretin, and Frédéric Blanc

Subjects
Male, 0301 basic medicine, Pediatrics, medicine.medical_specialty, Prodromal Symptoms, Neuropsychological Tests, Cohort Studies, 03 medical and health sciences, Epilepsy, 0302 clinical medicine, Alzheimer Disease, medicine, Humans, Psychiatry, Aged, Amyloid beta-Peptides, General Neuroscience, Prodromal Stage, Memory clinic, Electroencephalography, Retrospective cohort study, General Medicine, Middle Aged, medicine.disease, Magnetic Resonance Imaging, Psychiatry and Mental health, Clinical Psychology, 030104 developmental biology, Epilepsy, Temporal Lobe, Epilepsy syndromes, Cohort, Disease Progression, Anticonvulsants, Female, Geriatrics and Gerontology, Alzheimer's disease, Mental Status Schedule, Psychology, 030217 neurology & neurosurgery, Cohort study
Abstract

BACKGROUND Aside from rare case reports, only one study, with 12 patients, has addressed the phenotypic presentation of epilepsy in clinically defined amnestic mild cognitive impairment (aMCI, presumed to correspond to the AD prodromal stage): the authors highlighted a pharmacosensitive non-convulsive partial epileptic syndrome most probably related to the temporal or temporo-frontal cortices. OBJECTIVE The objective of this study was to verify the existence and the syndromic features of epileptic prodromal AD in a tertiary Memory Clinic. METHODS We conducted a retrospective, single-center study of the electro-radio-clinical features of 13 cases of epileptic prodromal AD patients (3.1% of a cohort of MCI, n = 430 subjects), selected on both clinical criteria and CSF biomarkers. RESULTS In our patients, a pharmacosensitive temporal lobe epilepsy syndrome, inaugurating prodromal AD, started at a mean age of 63 years (±12.8 years) and preceded MCI diagnosis by 4 to 7 years. At the stage of aMCI, median MMSE score was 26 and imaging showed mild hippocampal atrophy. After almost one year under treatment, cognitive complaints were not relieved but the MMSE score remained stable at 26 for 11 patients (2 patients were excluded from analysis because of the onset of aphasic or neurovisual symptoms altering MMSE scoring). CONCLUSION Our data, in conjunction with those of the 12 previously described subjects, suggest the existence of a currently unrecognized inaugural epilepsy syndrome of sporadic AD. Such a syndrome could be called the epileptic variant of AD because seizures are its sole feature for more than 2.5 years.

Published
2016

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