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24 results on '"Pariente, Jérémie"'

1. Disfluency patterns in Alzheimer's disease and frontotemporal lobar degeneration.

Author

Pistono, Aurélie, Pariente, Jérémie, and Jucla, Mélanie

Subjects
*ALZHEIMER'S disease, *DATA analysis, *PHONOLOGICAL awareness, *KRUSKAL-Wallis Test, *STUTTERING, *APHASIA, *FRONTOTEMPORAL lobar degeneration, *STATISTICS, *COMPARATIVE studies, *SEMANTICS
Abstract

Disfluencies may reflect various mechanisms: word-finding difficulties, planning strategies, inter-individual cognitive variability, etc. In the current paper, we examined disfluency production in patients with a behavioural variant of Frontotemporal lobar degeneration (bvFTLD), compared to patients with Alzheimer's disease (AD) and healthy older adults. We showed that bvFTLD participants have lower speech rate and produce more incomplete utterances. However, those measures were not correlated with naming and fluency tasks. On the contrary, AD participants did not differ from healthy controls on disfluency production, but discourse measures were correlated with the participants' lexical-semantic impairment. This provides evidence for different causes of disfluency in AD and FTLD, and a distinct role of each disfluency phenomenon. [ABSTRACT FROM AUTHOR]

Published
2024
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3. The functional connectivity of language network across the life span: Disentangling the effects of typical aging from Alzheimer's disease.

Author

Rafiq, Marie, Jucla, Mélanie, Guerrier, Laura, Péran, Patrice, Pariente, Jérémie, and Pistono, Aurélie

Subjects
BRAIN physiology, RESEARCH, ALZHEIMER'S disease, ACTIVE aging, COGNITION, COMPARATIVE studies, AGING, STATISTICAL correlation, SYMPTOMS
Abstract

Language is usually characterized as the most preserved cognitive function during typical aging. Several neuroimaging studies have shown that healthy aging is characterized by inter-network compensation which correlates with better language performance. On the contrary, language deficits occur early in the course of Alzheimer's disease (AD). Therefore, this study compares young participants, healthy older participants, and prodromal AD participants, to characterize functional connectivity changes in language due to healthy aging or prodromal AD. We first compared measures of integrated local correlations (ILCs) and fractional amplitude of low-frequency oscillations (fALFFs) in language areas. We showed that both groups of older adults had lower connectivity values within frontal language-related areas. In the healthy older group, higher integrated local correlation (ILC) and fALFF values in frontal areas were positively correlated with fluency and naming tasks. We then performed seed-based analyses for more precise discrimination between healthy aging and prodromal AD. Healthy older adults showed no functional alterations at a seed-based level when the seed area was not or only slightly impaired compared to the young adults [i.e., inferior frontal gyrus (IFG)], while prodromal AD participants also showed decreased connectivity at a seedbased level. On the contrary, when the seed area was similarly impaired in healthy older adults and prodromal AD participants on ILC and fALFF measures, their connectivity maps were also similar during seed-to-voxel analyses [i.e., superior frontal gyrus (SFG)]. Current results show that functional connectivity measures at a voxel level (ILC and fALFF) are already impacted in healthy aging. These findings imply that the functional compensations observed in healthy aging depend on the functional integrity of brain areas at a voxel level. [ABSTRACT FROM AUTHOR]

Published
2022
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4. Case Report: Presence of Anti-MAG in the CSF Can Be Associated With a Neurodegenerative Process With Frontal Involvement.

Author

Dorcet, Guillaume, Benaiteau, Marie, Ory-Magne, Fabienne, Blancher, Antoine, Pariente, Jérémie, Fortenfant, Françoise, and Bost, Chloé

Subjects
PARANEOPLASTIC syndromes, BIOLOGICAL evolution, PROGRESSIVE supranuclear palsy, ALZHEIMER'S disease, NEURODEGENERATION, CEREBROSPINAL fluid
Abstract

Background: Autoimmune encephalitis (AIE) is an increasingly broad nosological framework that may clinically mimic neurodegenerative diseases (NDDs). Cases Reported: We describe here the clinical, radiological, electrophysiological, and biological evolution of three patients. Two women aged 73 and 72 years and a 69-year-old man presented with complex cognitive and focal neurological symptoms and each had a predominant frontal dysexecutive involvement and an unexpectedly high titer of anti-MAG antibodies in the serum and cerebrospinal fluid (CSF). The question of an autoimmune cause was raised. After 2 years of follow-up and, for two of them, without improvement despite immunosuppressive treatments, diagnoses of NDD were eventually retained: post-radiation encephalopathy, progressive supranuclear palsy (PSP), and Alzheimer's disease. Conclusion: The presence of a high titer of anti-MAG antibodies may be found in NDD. It could reflect cerebral tissue damages, particularly in the case of significant frontal involvement. Atypical presentations may lead to a search for a paraneoplastic neurologic syndrome or AIE. However, the indirect immunofluorescence staining positivity on a monkey cerebellum section linked with anti-MAG antibodies should not lead to those diagnoses being retained. [ABSTRACT FROM AUTHOR]

Published
2022
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5. Explaining the association between social and lifestyle factors and cognitive functions: a pathway analysis in the Memento cohort.

Author

Grasset, Leslie, Proust-Lima, Cécile, Mangin, Jean-François, Habert, Marie-Odile, Dubois, Bruno, Paquet, Claire, Hanon, Olivier, Gabelle, Audrey, Ceccaldi, Mathieu, Annweiler, Cédric, David, Renaud, Jonveaux, Therese, Belin, Catherine, Julian, Adrien, Rouch-Leroyer, Isabelle, Pariente, Jérémie, Locatelli, Maxime, Chupin, Marie, Chêne, Geneviève, and Dufouil, Carole

Subjects
COGNITIVE ability, SOCIAL factors, STRUCTURAL equation modeling, MAGNETIC resonance imaging, UNHEALTHY lifestyles, ALZHEIMER'S disease
Abstract

Background: This work aimed to investigate the potential pathways involved in the association between social and lifestyle factors, biomarkers of Alzheimer's disease and related dementia (ADRD), and cognition. Methods: The authors studied 2323 participants from the Memento study, a French nationwide clinical cohort. Social and lifestyle factors were education level, current household incomes, physical activity, leisure activities, and social network from which two continuous latent variables were computed: an early to midlife (EML) and a latelife (LL) indicator. Brain magnetic resonance imaging (MRI), lumbar puncture, and amyloid-positron emission tomography (PET) were used to define three latent variables: neurodegeneration, small vessel disease (SVD), and AD pathology. Cognitive function was defined as the underlying factor of a latent variable with four cognitive tests. Structural equation models were used to evaluate cross-sectional pathways between social and lifestyle factors and cognition. Results: Participants' mean age was 70.9 years old, 62% were women, 28% were apolipoprotein-ε4 carriers, and 59% had a Clinical Dementia Rating (CDR) score of 0.5. Higher early to midlife social indicator was only directly associated with better cognitive function (direct β = 0.364 (0.322; 0.405), with no indirect pathway through ADRD biomarkers (total β = 0.392 (0.351; 0.429)). In addition to a direct effect on cognition (direct β = 0.076 (0.033; 0.118)), the association between latelife lifestyle indicator and cognition was also mostly mediated by an indirect effect through lower neurodegeneration (indirect β = 0.066 (0.042; 0.090) and direct β = − 0.116 (− 0.153; − 0.079)), but not through AD pathology nor SVD. Conclusions: Early to midlife social factors are directly associated with higher cognitive functions. Latelife lifestyle factors may help preserve cognitive functions through lower neurodegeneration. [ABSTRACT FROM AUTHOR]

Published
2022
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6. Sleep: The Tip of the Iceberg in the Bidirectional Link Between Alzheimer's Disease and Epilepsy.

Author

B. Szabo, Anna, Cretin, Benjamin, Gérard, Fleur, Curot, Jonathan, J. Barbeau, Emmanuel, Pariente, Jérémie, Dahan, Lionel, and Valton, Luc

Subjects
ALZHEIMER'S disease, EPILEPSY, COGNITION disorders, COMORBIDITY, SLEEP, MILD cognitive impairment, PEOPLE with epilepsy
Abstract

The observation that a pathophysiological link might exist between Alzheimer's disease (AD) and epilepsy dates back to the identification of the first cases of the pathology itself and is now strongly supported by an ever-increasing mountain of literature. An overwhelming majority of data suggests not only a higher prevalence of epilepsy in Alzheimer's disease compared to healthy aging, but also that AD patients with a comorbid epileptic syndrome, even subclinical, have a steeper cognitive decline. Moreover, clinical and preclinical investigations have revealed a marked sleep-related increase in the frequency of epileptic activities. This characteristic might provide clues to the pathophysiological pathways underlying this comorbidity. Furthermore, the preferential sleep-related occurrence of epileptic events opens up the possibility that they might hasten cognitive decline by interfering with the delicately orchestrated synchrony of oscillatory activities implicated in sleep-related memory consolidation. Therefore, we scrutinized the literature for mechanisms that might promote sleep-related epileptic activity in AD and, possibly dementia onset in epilepsy, and we also aimed to determine to what degree and through which processes such events might alter the progression of AD. Finally, we discuss the implications for patient care and try to identify a common basis for methodological considerations for future research and clinical practice. [ABSTRACT FROM AUTHOR]

Published
2022
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7. Neuroinflammation PET imaging of the translocator protein (TSPO) in Alzheimer's disease: An update.

Author

Gouilly, Dominique, Saint‐Aubert, Laure, Ribeiro, Maria‐Joao, Salabert, Anne‐Sophie, Tauber, Clovis, Péran, Patrice, Arlicot, Nicolas, Pariente, Jérémie, and Payoux, Pierre

Subjects
TRANSLOCATOR proteins, POSITRON emission tomography, ALZHEIMER'S disease, NEUROINFLAMMATION
Abstract

Neuroinflammation is a significant contributor to Alzheimer's disease (AD). Until now, PET imaging of the translocator protein (TSPO) has been widely used to depict the neuroimmune endophenotype of AD. The aim of this review was to provide an update to the results from 2018 and to advance the characterization of the biological basis of TSPO imaging in AD by re‐examining TSPO function and expression and the methodological aspects of interest. Although the biological basis of the TSPO PET signal is obviously related to microglia and astrocytes in AD, the observed process remains uncertain and might not be directly related to neuroinflammation. Further studies are required to re‐examine the cellular significance underlying a variation in the PET signal in AD. [ABSTRACT FROM AUTHOR]

Published
2022
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8. Taking the A Train? Limited Consistency of Aβ42 and the Aβ42/40 Ratio in the AT(N) Classification.

Author

Gouilly, Dominique, Tisserand, Camille, Nogueira, Leonor, Saint-Lary, Laura, Rousseau, Vanessa, Benaiteau, Marie, Rafiq, Marie, Carlier, Jasmine, Milongo-Rigal, Emilie, Pagès, Jean-Christophe, and Pariente, Jérémie

Subjects
ALZHEIMER'S patients, ALZHEIMER'S disease, CEREBROSPINAL fluid, CLASSIFICATION
Abstract

The consistency of cerebrospinal fluid amyloid-β (Aβ)42/40 ratio and Aβ42 has not been assessed in the AT(N) classification system. We analyzed the classification changes of the dichotomized amyloid status (A+/A-) in 363 patients tested for Alzheimer's disease biomarkers after Aβ42 was superseded by the Aβ42/40 ratio. The consistency of Aβ42 and the Aβ42/40 ratio was very low. Notably, the proportions of "false" A+T-patients were considerable (74-91%) and corresponded mostly to patients not clinically diagnosed with Alzheimer's disease. Our results suggest that the interchangeability of Aβ42/40 ratio and Aβ42 is limited for classifying patients in clinical setting using the AT(N) scheme. [ABSTRACT FROM AUTHOR]

Published
2021
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9. Language Network Connectivity Increases in Early Alzheimer's Disease.

Author

Pistono, Aurélie, Senoussi, Mehdi, Guerrier, Laura, Rafiq, Marie, Giméno, Mélanie, Péran, Patrice, Jucla, Mélanie, Pariente, Jérémie, and Gimeno, Mélanie

Subjects
ALZHEIMER'S disease, TEMPORAL lobe, MILD cognitive impairment, BILINGUALISM, FUNCTIONAL connectivity, UNIVARIATE analysis, BRAIN, EXECUTIVE function, RESEARCH, NEURAL pathways, RESEARCH methodology, LANGUAGE & languages, MAGNETIC resonance imaging, MEDICAL cooperation, EVALUATION research, NEUROPSYCHOLOGICAL tests, COMPARATIVE studies, SPEECH, NEUROLOGIC examination
Abstract

Background: Language production deficits occur early in the course of Alzheimer's disease (AD); however, only a few studies have focused on language network's functional connectivity in mild cognitive impairment (MCI) due to AD.Objective: The current study aims to uncover the extent of language alteration at the MCI stage, at a behavioral and neural level, using univariate and multivariate analyses of structural MRI and resting-state fMRI.Methods: Twenty-four MCI due to AD participants and 24 matched healthy controls underwent a comprehensive language evaluation, a structural T1-3D MRI, and resting-state fMRI. We performed seed-based analyses, using the left inferior frontal gyrus and left posterior temporal gyrus as seeds. Then, we analyzed connectivity between executive control networks and language network in each group. Finally, we used multivariate pattern analyses to test whether the two groups could be distinguished based on the pattern of atrophy within the language network; within the executive control networks, as well as the pattern of functional connectivity within the language network and within the executive control networks.Results: MCI due to AD participants had language impairment during standardized language tasks and connected-speech production. Regarding functional connectivity, univariate analyses were not able to discriminate participants, while multivariate pattern analyses could significantly predict participants' group. Language network's functional connectivity could discriminate MCI due to AD participants better than executive control networks. Most notably, they revealed an increased connectivity at the MCI stage, positively correlated with language performance.Conclusion: Multivariate analyses represent a useful tool for investigating the functional and structural (re-)organization of the neural bases of language. [ABSTRACT FROM AUTHOR]

Published
2021
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10. Cerebral microbleeds and CSF Alzheimer biomarkers in primary progressive aphasias

Author

Mendes Aguiar Santos, Aline, Bertrand, Anne, Lamari, Foudil, Colliot, Olivier, Routier, Alexandre, Godefroy, Olivier, Etcharry-Bouyx, Frédérique, Moreaud, Olivier, Pasquier, Florence, Couratier, Philippe, Bennys, Karim, Vercelletto, Martine, Martinaud, Olivier, Laurent, Bernard, Pariente, Jérémie, Puel, Michèle, Epelbaum, Stéphane, Belliard, Serge, Kaaouana, Takoua, Fillon, Ludovic, Chupin, Marie, Dubois, Bruno, Teichmann, Marc, PHRC \\'CAPP\\' Study Group, Instituto Butantan [São Paulo], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Equipe NEMESIS - Centre de Recherches de l'Institut du Cerveau et de la Moelle épinière (NEMESIS-CRICM), Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU), CHU Amiens-Picardie, Laboratoire de Neurosciences Fonctionnelles et Pathologies - UR UPJV 4559 (LNFP), Université de Picardie Jules Verne (UPJV), Service de neurologie [Angers], Université d'Angers (UA)-Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Pôle Psychiatrie et Neurologie [Grenoble], Centre Hospitalier Universitaire [Grenoble] (CHU), Laboratoire de Psychologie et NeuroCognition (LPNC ), Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Département de neurologie [Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Neurologie [CHU Limoges], CHU Limoges, Neuroépidémiologie Tropicale (NET), CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Département de neurologie [Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université de Montpellier (UM), Service de neurologie [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Hôpital Guillaume-et-René-Laennec [Saint-Herblain], Service de neurologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Toulouse Neuro Imaging Center (ToNIC), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de neurologie [Rennes], Université de Rennes (UR), Centre d'Acquisition et de Traitement des Images [Paris], Commissariat à l'énergie atomique et aux énergies alternatives (CEA), FRONTlab - Systèmes frontaux : fonctions et dysfonctions (FRONTlab), 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 Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Service de Biochimie Métabolique [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Département de neurologie[Lille], Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [Montpellier]-Université de Montpellier (UM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], and Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)

Subjects
Male, 0301 basic medicine, medicine.medical_specialty, tau Proteins, Neuropathology, Cohort Studies, Primary progressive aphasia, 03 medical and health sciences, Dementia aphasia, 0302 clinical medicine, Alzheimer Disease, Assessment of cognitive disorders/dementia, Internal medicine, Aphasia, Prevalence, medicine, Humans, Aged, Cerebral Hemorrhage, Aged, 80 and over, Amyloid beta-Peptides, medicine.diagnostic_test, business.industry, Brain, Magnetic resonance imaging, Middle Aged, Alzheimer's disease, respiratory system, medicine.disease, Magnetic Resonance Imaging, Peptide Fragments, Hyperintensity, Aphasia, Primary Progressive, Cross-Sectional Studies, 030104 developmental biology, Susceptibility weighted imaging, ddc:618.97, Cardiology, Biomarker (medicine), Female, Neurology (clinical), medicine.symptom, business, Biomarkers, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, MRI
Abstract

ObjectiveTo reveal the prevalence and localization of cerebral microbleeds (CMBs) in the 3 main variants of primary progressive aphasia (PPA) (logopenic, semantic, and nonfluent/agrammatic), to identify the relationship with underlying Alzheimer pathology, and to explore whether CMBs contribute to language breakdown.MethodsWe used a cross-sectional design in a multicenter cohort of 82 patients with PPA and 19 similarly aged healthy controls. MRI allowed for rating CMBs (2-dimensional gradient recalled echo T2*, susceptibility weighted imaging sequences) and white matter hyperintensities. CSF Alzheimer disease biomarker analyses available in 63 of the 82 patients provided the stratification of PPA into subgroups with patients who had or did not have probable underlying Alzheimer pathology.ResultsThe prevalence of CMBs was higher in patients with PPA (28%) than in controls (16%). They were more prevalent in logopenic PPA (50%) than in semantic PPA (18%) and nonfluent/agrammatic PPA (17%). The localization of CMBs was mainly lobar (81%) with no difference between the PPA variants. CMBs were more frequent in PPA patients with positive than with negative CSF Alzheimer disease biomarkers (67% vs 20%). Patients with and without lobar CMBs had similar volumes of white matter hyperintensities. Language and general cognitive impairment in PPA was unrelated to CMB rates.ConclusionsCMB prevalence in PPA is higher than in healthy controls. CMBs were most prevalent in the logopenic variant, were related to underlying Alzheimer pathology, and did not affect the language/cognitive impairment. Our findings also suggest that CMB detection with MRI contributes to PPA variant diagnosis, especially of logopenic PPA, and provides an estimator of the underlying neuropathology.

Published
2018

11. Added value of 18 F-florbetaben amyloid PET in the diagnostic workup of most complex patients with dementia in France: A naturalistic study

Author

Ceccaldi, Mathieu, Jonveaux, Thérèse, Verger, Antoine, Krolak-Salmon, Pierre, Houzard, Claire, Godefroy, Olivier, Shields, Trevor, Perrotin, Audrey, Gismondi, Rossella, Bullich, Santiago, Jovalekic, Aleksandar, Raffa, Nicola, Pasquier, Florence, Semah, Franck, Dubois, Bruno, Habert, Marie-Odile, Wallon, David, Chastan, Mathieu, Payoux, Pierre, Felician, Olivier, Didic, Mira, Gueriot, Claude, Koric, Lejla, Kletchkova-Gantchev, Radka, Andriuta, Daniela, Devendeville, Agnès, Dupuis, Diane, Binot, Ingrid, Barbay, Mélanie, Meyer, Marc-Etienne, Moullard, Véronique, Magnin, Eloi, Chamard, Ludivine, Haffen, Sophie, Drouet, Clément, Boulahdour, Hatem, Goas, Philippe, Querellou-Lefranc, Solène, de La Sayette, Vincent, Cogez, Julien, Branger, Pierre, Agostini, Denis, Manrique, Alain, Bejot, Yannick, Jacquin-Piques, Agnès, Dygai-Cochet, Inna, Berriolo-Riedinger, Alina, Moreaud, Olivier, Sauvee, Mathilde, Crépin, Céline, Bombois, Stéphanie, Lebouvier, Thibaud, Mackowiak-Cordoliani, Marie-Anne, Deramecourt, Vincent, Rollin-Sillaire, Adeline, Cassagnaud-Thuillet, Pascaline, Chen, Yaohua, Petyt, Grégory, Federico, Denis, Danaila, Keren, Guilhermet, Yves, Magnier, Christophe, Makaroff, Zaza, Rouch, Isabelle, Xie, Jing, Roubaud, Caroline, Coste, Marie-Hélène, David, Kenny, Sarciron, Alain, Waissi, Aziza, Scheiber, Christian, Gabelle-Deloustal, Audrey, Bennys, Karim, Marelli, Cecilia, Touati, Lynda, de Verbizier-Lonjon, Delphine, Benetos, Athanase, Kearney-Schwartz, Anna, Perret-Guillaume, Christine, Vercelletto, Martine, Boutoleau-Bretonniere, Claire, Pouclet-Courtemanche, Hélène, Wagemann, Nathalie, Pallardy, Amandine, Hugon, Jacques, Paquet, Claire, Dumurgier, Julien, Millet, Pascal, Queneau, Mathieu, Epelbaum, Stéphane, Levy, Marcel, Novella, Jean-Luc, Jaidi, Yacine, Morland, David, Belliard, Serge, Salmon, Anne, Lejeune, Florence, Hannequin, Didier, Martinaud, Olivier, Zarea, Aline, Pariente, Jérémie, Thalamas, Claire, Galitzky-Gerber, Monique, Tricoire Ricard, Anne-Marie, Calvas, Fabienne, Rigal, Emilie, Hitzel, Anne, Delrieu, Julien, Ousset, Pierre-Jean, Lala, Françoise, Sastre-Hengan, Nathalie, Morel, Olivier, Rouaud, Olivier, Mariano-Goulart, Denis, Papathanassiou, Dimitri, Le Jeune, Florence, Stephens, Andrew, Guedj, Eric, Hôpital de la Timone [CHU - APHM] (TIMONE), Institut de Neurosciences des Systèmes (INS), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Gériatrie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Imagerie Adaptative Diagnostique et Interventionnelle (IADI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Service de neurologie [Amiens], CHU Amiens-Picardie, Service de Médecine Nucléaire [Amiens], Piramal Imaging, Troubles cognitifs dégénératifs et vasculaires - U 1171 (TCDV), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Institut National de la Santé et de la Recherche Médicale (INSERM), Troubles cognitifs vasculaires et dégénératifs, Université de Lille, Sciences et Technologies, Institut de la Mémoire et de la Maladie d'Alzheimer [Paris] (IM2A), Sorbonne Université (SU), Laboratoire d'Imagerie Biomédicale (LIB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de neurologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Service de médecine nucléaire [Rouen], CRLCC Haute Normandie-CRLCC Henri Becquerel, Toulouse Neuro Imaging Center (ToNIC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Institut de Neurosciences de la Timone (INT), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Neurobiologie intégrative et adaptative (NIA), Université de Provence - Aix-Marseille 1-Centre National de la Recherche Scientifique (CNRS), Service de neurologie et de neuropsychologie, Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Université de Picardie Jules Verne (UPJV), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon), Université de Bourgogne (UB), Université de Lorraine (UL), Nanomédecine, imagerie, thérapeutique - UFC (EA 4662) (NIT / NANOMEDECINE), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Service de neurologie, Centre Hospitalier Universitaire [Grenoble] (CHU), Service de Neurologie [Brest], Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), 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), Groupe coeur et ischémie, CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN), Normandie Université (NU), Service de médecine nucléaire [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), Optimisation - Système - Energie (GEPEA-OSE), Laboratoire de génie des procédés - environnement - agroalimentaire (GEPEA), Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Université Bretagne Loire (UBL)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Université Bretagne Loire (UBL)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS), Cognition, Action, et Plasticité Sensorimotrice [Dijon - U1093] (CAPS), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Neurologie générale, vasculaire et dégénérative (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service de Médecine Nucléaire, Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER, Service de Médecine Nucléaire, Centre Georges-François Leclerc [Dijon] (CGFL), Pôle Psychiatrie et Neurologie [Grenoble], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Neuroendocrinologie et physiopathologie neuronale, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Département de neurologie[Lille], Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital des Charpennes [CHU - HCL], CEA Le Ripault (CEA Le Ripault), Direction des Applications Militaires (DAM), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Unité de Gériatrie, Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL)-Centre Mémoire de Ressources et de Recherche (CMRR Lyon), Système Nerveux Autonome - Epidémiologie, Physiologie, Ingénierie, Santé (SNA-EPIS), Université Jean Monnet [Saint-Étienne] (UJM)-Centre Hospitalier Universitaire de Saint-Etienne, Institut Jacques Monod (IJM (UMR_7592)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Centre Mutualiste de Réeducation Neurologique Propara (PROPARA), Languedoc Mutualité, Département de neurologie [Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [Montpellier]-Université de Montpellier (UM), Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-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), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Université de Lorraine (UL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service de Gérontologie [CHRU Nancy], Clinique neurologique, Hôpital Laennec, Service de neurologie [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Hôpital Guillaume-et-René-Laennec [Saint-Herblain], Service de Médecine Nucléaire [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Neurologie Cognitive [Paris], Université Paris Diderot - Paris 7 (UPD7)-Hôpitaux Universitaires Saint-Louis, Lariboisière, Fernand-Widal-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire de Parasitologie-Immunologie (EA 3677), Université Bordeaux Segalen - Bordeaux 2, Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS), Hôpital de Reims - Service de neuro-gériatrie, Hôpital de Reims, Service de neurologie [Rennes], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Service de médecine nucléaire [Rennes], CRLCC Eugène Marquis (CRLCC), Génétique médicale et fonctionnelle du cancer et des maladies neuropsychiatriques, Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Institut National de la Santé et de la Recherche Médicale (INSERM), CIC - Biotherapie - Toulouse, CHU Clermont-Ferrand, Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps (LEASP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Gérontopôle, Department of Geriatrics, Centre Hospitalier Universitaire de Toulouse, Troubles cognitifs dégénératifs et vasculaires (U1171), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-INSERM, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Bureau de Recherches Géologiques et Minières (BRGM) (BRGM), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université de Franche-Comté (UFC), École pratique des hautes études (EPHE)-Université de Caen Normandie (UNICAEN), Université de Nantes (UN)-Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Centre National de la Recherche Scientifique (CNRS)-Université Bretagne Loire (UBL)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Nantes (UN)-Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Centre National de la Recherche Scientifique (CNRS)-Université Bretagne Loire (UBL)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc (CRLCC - CGFL), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Université Paris Diderot - Paris 7 (UPD7)-Hôpitaux Universitaires Saint-Louis, Lariboisière, Fernand-Widal-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP]-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Neurosciences Fonctionnelles et Pathologies - UR UPJV 4559 (LNFP), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire d'Imagerie Biomédicale [Paris] (LIB), CRLCC Haute Normandie-Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Service d'Obstétrique et de Gynécologie [CHRU Nancy], Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Sciences et Technologies de l'Information et de la Communication - EA 3804 (CRESTIC), Université de Reims Champagne-Ardenne (URCA), Comportement et noyaux gris centraux = Behavior and Basal Ganglia [Rennes], Université de Rennes (UR)-Université européenne de Bretagne - European University of Brittany (UEB)-CHU Pontchaillou [Rennes]-Institut des Neurosciences Cliniques de Rennes = Institute of Clinical Neurosciences of Rennes (INCR), H. Lundbeck A/S, Novartis, Roche, Pfizer, Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Centre National de la Recherche Scientifique (CNRS)-Ecole Polytechnique de l'Université de Nantes (EPUN), Université de Nantes (UN)-Université de Nantes (UN)-Institut Universitaire de Technologie - Nantes (IUT Nantes), Université de Nantes (UN)-Institut Universitaire de Technologie Saint-Nazaire (IUT Saint-Nazaire), Université de Nantes (UN)-Institut Universitaire de Technologie - La Roche-sur-Yon (IUT La Roche-sur-Yon), Université de Nantes (UN)-Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Université Bretagne Loire (UBL)-Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Université Bretagne Loire (UBL), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Pontchaillou [Rennes]-Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université européenne de Bretagne - European University of Brittany (UEB)-Institut des Neurosciences Cliniques de Rennes (INCR)

Subjects
0301 basic medicine, NATIONAL INSTITUTE, Pathology, Epidemiology, IMPACT, Amyloid pet, Clinical practice, BETA PLAQUES, 0302 clinical medicine, MESH: Stilbenes, Diagnosis, MESH: Aged, UTILITY, medicine.diagnostic_test, Health Policy, Alzheimer's disease, MESH: Dementia, MESH: Positron-Emission Tomography, 3. Good health, ALZHEIMERS-DISEASE, Psychiatry and Mental health, Positron emission tomography, Radiology, MESH: Radiopharmaceuticals, medicine.medical_specialty, CSF BIOMARKERS, [SDV.IB.MN]Life Sciences [q-bio]/Bioengineering/Nuclear medicine, Amyloid imaging, 18F-florbetaben, MESH: Aniline Compounds, 03 medical and health sciences, Cellular and Molecular Neuroscience, MESH: Brain, Naturalistic observation, SCANS, Developmental Neuroscience, MESH: Diagnosis, Differential, medicine, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, MANAGEMENT, Dementia, Florbetaben, MESH: Amyloid, MESH: Humans, business.industry, medicine.disease, MESH: Male, MESH: France, 030104 developmental biology, Multicenter study, Etiology, Patient management, Neurology (clinical), Geriatrics and Gerontology, business, MESH: Female, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; Introduction: Although some studies have previously addressed the clinical impact of amyloid positron emission tomography (PET), none has specifically addressed its selective and hierarchical implementation in relation to cerebrospinal fluid analysis in a naturalistic setting.Methods: This multicenter study was performed at French tertiary memory clinics in patients presenting with most complex clinical situations (i.e., early-onset, atypical clinical profiles, suspected mixed etiological conditions, unexpected rate of progression), for whom cerebrospinal fluid analysis was indicated but either not feasible or considered as noncontributory (ClinicalTrials.gov: NCT02681172).Results: Two hundred five patients were enrolled with evaluable florbetaben PET scans; 64.4% of scans were amyloid positive. PET results led to changed diagnosis and improved confidence in 66.8% and 81.5% of patients, respectively, and altered management in 80.0% of cases.Discussion: High-level improvement of diagnostic certainty and management is provided by selective and hierarchical implementation of florbetaben PET into current standard practices for the most complex dementia cases. (C) 2017 The Authors. Published by Elsevier Inc. on behalf of the Alzheimer's Association.

Published
2018

12. App, psen1, and psen2 mutations in early-onset alzheimer disease:a genetic screening study of familial and sporadic cases

Author

Lanoiselée, Hélène-Marie, Nicolas, Gaël, Wallon, David, Rovelet-Lecrux, Anne, Lacour, Morgane, Rousseau, Stéphane, Richard, Anne-Claire, Pasquier, Florence, Rollin-Sillaire, Adeline, Martinaud, Olivier, Quillard-Muraine, Muriel, De La Sayette, Vincent, Boutoleau-Bretonnière, Claire, Etcharry-Bouyx, Frédérique, Chauviré, Valérie, Sarazin, Marie, Le Ber, Isabelle, Epelbaum, Stéphane, Jonveaux, Thérèse, Rouaud, Olivier, Ceccaldi, Mathieu, Felician, Olivier, Godefroy, Olivier, Formaglio, Maite, Croisile, Bernard, Auriacombe, Sophie, Chamard, Ludivine, Vincent, Jean-Louis, Sauvee, Mathilde, Marelli-Tosi, Cecilia, Gabelle, Audrey, Ozsancak, Canan, Pariente, Jérémie, Paquet, Claire, Hannequin, Didier, Campion, Dominique, CHU Lille, CNRS, Inserm, Université de Lille, Troubles cognitifs dégénératifs et vasculaires - U1171, Troubles cognitifs dégénératifs et vasculaires - U 1171 [TCDV], Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de neurologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Centre Hospitalier Régional d'Orléans (CHRO), Service de génétique [Rouen], Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Département de neurologie [Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Troubles cognitifs dégénératifs et vasculaires - U 1171 - EA 1046 (TCDV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Neurologie [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Service de neurologie [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Hôpital Guillaume-et-René-Laennec [Saint-Herblain], Service de neurologie [Angers], Université d'Angers (UA)-Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Centre Hospitalier Sainte Anne [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de neurologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service de Neurologie générale, vasculaire et dégénérative (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Institut de Neurosciences des Systèmes (INS), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de neurologie et de neuropsychologie, Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Service de neurologie [Amiens], CHU Amiens-Picardie, Laboratoire de Neurosciences Fonctionnelles et Pathologies - UR UPJV 4559 (LNFP), Université de Picardie Jules Verne (UPJV), Service de Neurologie [Lyon], CHU Lyon, Service de neurologie [Bordeaux], CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Pôle Psychiatrie et Neurologie [Grenoble], Centre Hospitalier Universitaire [Grenoble] (CHU), Département de neurologie [Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université de Montpellier (UM), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Biomarqueurs CArdioNeuroVASCulaires (BioCANVAS), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Département de neurologie[Lille], Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), 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), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [Montpellier]-Université de Montpellier (UM), CHU Toulouse [Toulouse], Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), 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), Centre Hospitalier Régional d'Orléans (CHR), Troubles cognitifs dégénératifs et vasculaires (U1171), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-INSERM, CHU Pitié-Salpêtrière [APHP], Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP]-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon), and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Lariboisière-Université Paris Diderot - Paris 7 (UPD7)

Subjects
Adult, Male, Heredity, Physiology, Substitution mutation, Gene Identification and Analysis, Research and Analysis Methods, Biochemistry, Nervous System, Amyloid beta-Protein Precursor, Database and Informatics Methods, Alzheimer Disease, Presenilin-2, Mental Health and Psychiatry, Presenilin-1, Genetics, Medicine and Health Sciences, Humans, Genetic Testing, Age of Onset, Cerebrospinal Fluid, Mutation databases, Biology and Life Sciences, Neurodegenerative Diseases, Genetic screens, Middle Aged, Alzheimer's disease, Body Fluids, Mutation detection, Biological Databases, Neurology, Mutation, Female, Dementia, France, Anatomy, Biomarkers, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Research Article
Abstract

Background Amyloid protein precursor (APP), presenilin-1 (PSEN1), and presenilin-2 (PSEN2) mutations cause autosomal dominant forms of early-onset Alzheimer disease (AD-EOAD). Although these genes were identified in the 1990s, variant classification remains a challenge, highlighting the need to colligate mutations from large series. Methods and findings We report here a novel update (2012–2016) of the genetic screening of the large AD-EOAD series ascertained across 28 French hospitals from 1993 onwards, bringing the total number of families with identified mutations to n = 170. Families were included when at least two first-degree relatives suffered from early-onset Alzheimer disease (EOAD) with an age of onset (AOO) ≤65 y in two generations. Furthermore, we also screened 129 sporadic cases of Alzheimer disease with an AOO below age 51 (44% males, mean AOO = 45 ± 2 y). APP, PSEN1, or PSEN2 mutations were identified in 53 novel AD-EOAD families. Of the 129 sporadic cases screened, 17 carried a PSEN1 mutation and 1 carried an APP duplication (13%). Parental DNA was available for 10 sporadic mutation carriers, allowing us to show that the mutation had occurred de novo in each case. Thirteen mutations (12 in PSEN1 and 1 in PSEN2) identified either in familial or in sporadic cases were previously unreported. Of the 53 mutation carriers with available cerebrospinal fluid (CSF) biomarkers, 46 (87%) had all three CSF biomarkers—total tau protein (Tau), phospho-tau protein (P-Tau), and amyloid β (Aβ)42—in abnormal ranges. No mutation carrier had the three biomarkers in normal ranges. One limitation of this study is the absence of functional assessment of the possibly and probably pathogenic variants, which should help their classification. Conclusions Our findings suggest that a nonnegligible fraction of PSEN1 mutations occurs de novo, which is of high importance for genetic counseling, as PSEN1 mutational screening is currently performed in familial cases only. Among the 90 distinct mutations found in the whole sample of families and isolated cases, definite pathogenicity is currently established for only 77%, emphasizing the need to pursue the effort to classify variants., In a cohort including patients with familial Alzheimer disease as well as sporadic cases of early-onset Alzheimer disease, Dominique Campion and colleagues identify previously unreported mutations to PSEN1 and PSEN2., Author summary Why was this study done? Mutations in the amyloid protein precursor (APP), presenilin-1 (PSEN1), and presenilin-2 (PSEN2) genes are a known cause of familial, early-onset Alzheimer disease (EOAD) (onset below age 65). However, in order to improve genetic counseling, it is necessary to report mutational screening from large cohorts of patients. What did the researchers do and find? In the present study, we performed sequencing of the APP, PSEN1, and PSEN2 genes in EOAD families and in 129 sporadic cases. Mutations were identified in 170 EOAD families and in 18 sporadic cases. In 10 sporadic cases, we showed that the mutation was absent in the parents, indicating that it occurred “de novo.” What do these findings mean? Sufficient evidence of pathogenicity is reached for 77% of the 90 distinct mutations identified in this sample, allowing their use in genetic counseling. Our results suggest a potential benefit to screening nonfamilial Alzheimer disease (AD) cases with onset before 50 y for APP, PSEN1, and PSEN2 mutations.

Published
2017

13. Florbetapir Regional Distribution in Cerebral Amyloid Angiopathy and Alzheimer's Disease: A PET Study.

Author

Planton, Mélanie, Saint-Aubert, Laure, Raposo, Nicolas, Payoux, Pierre, Salabert, Anne-Sophie, Albucher, Jean-François, Olivot, Jean-Marc, Péran, Patrice, and Pariente, Jérémie

Subjects
CEREBRAL amyloid angiopathy, ALZHEIMER'S disease, CEREBRAL hemorrhage, POSITRON emission tomography, COMPUTERS in medicine, RESEARCH, RESEARCH methodology, ETHYLENE glycols, MAGNETIC resonance imaging, MEDICAL cooperation, EVALUATION research, AMINES, DIAGNOSTIC imaging, COMPARATIVE studies, RADIOPHARMACEUTICALS, BODY burden, DISEASE complications
Abstract

Background: Sporadic cerebral amyloid angiopathy shows progressive amyloid-β deposition in the wall of small arterioles and capillaries of the leptomeninges and cerebral cortex.Objective: To investigate whether amyloid load and distribution, assessed by florbetapir positron emission tomography (PET), differs between patients with probable CAA-related intracerebral hemorrhage (CAA-ICH) and mild cognitive impairment due to Alzheimer's disease (MCI-AD).Methods: We assessed [18F]florbetapir uptake in 15 patients with probable CAA-ICH and 20 patients with MCI-AD patients. Global and regional florbetapir retention were assessed using standard uptake values ratio (SUVr) in region-based and voxel-wise approaches. Visual reading of florbetapir scans was performed for all participants. Group comparisons were performed using univariate and multivariate analysis.Results: Global florbetapir retention was lower in patients with CAA-ICH than MCI-AD (median SUVr, 1.33 [1.21-1.41] versus 1.44 [1.35-1.66]; p = 0.032). In the region-based analysis, regional florbetapir distribution was similar between the two groups. There was a trend for an increased occipital/global ratio in CAA-ICH patients compared to MCI-AD (p = 0.060). In the voxel-wise approach, two clusters, one in parietal regions and the other in temporal regions, had higher uptake in MCI-AD relative to CAA patients.Conclusions: Patients with CAA-ICH had a lower global florbetapir PET burden than patients with MCI-AD. Relative florbetapir retention in the posterior regions tended to be higher in CAA patients in region-based analysis but was not statistically different between groups. Investigation on differences in amyloid deposits distribution between groups required a fine-grained voxel-wise analysis. In future studies, selective amyloid tracers are needed to differentiate vascular from parenchymal amyloid. [ABSTRACT FROM AUTHOR]

Published
2020
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14. Involvement of the Cingulate Cortex in Anosognosia: A Multimodal Neuroimaging Study in Alzheimer's Disease Patients.

Author

Guerrier, Laura, Le Men, Johanne, Gane, Anaıs, Planton, Mélanie, Salabert, Anne-Sophie, Payoux, Pierre, Dumas, Hervé, Bonneville, Fabrice, Péran, Patrice, Pariente, Jérémie, Gane, Anaıs, Planton, Mélanie, Dumas, Hervé, Péran, Patrice, and Pariente, Jérémie

Subjects
ALZHEIMER'S disease, CINGULATE cortex, FUNCTIONAL magnetic resonance imaging, NEUROPSYCHOLOGICAL tests, ANOSOGNOSIA
Abstract

Background: Anosognosia is a frequent symptom of Alzheimer's disease (AD), but its neural substrates remain in question.Objective: In this study, we combined neuroimaging with a neuropsychological evaluation to assess neural substrates of anosognosia.Methods: We prospectively recruited 30 patients with probable early-stage AD and matched healthy controls. Participants underwent MRI, FDG-PET, and a neuropsychological evaluation that includes an assessment of anosognosia. In the AD group, correlations between the anosognosia score, neuroimaging modalities, and neuropsychological performance were performed.Results: Atrophy and hypometabolism were correlated with the anosognosia score in the left dorsal anterior cingulate cortex. The anosognosia score was also correlated with atrophy of the cerebellar vermis, the left postcentral gyrus, and the right fusiform gyrus. No relation was found between anosognosia and the neuropsychological assessment.Discussion: Structural and metabolic alteration in the dorsal anterior cingulate cortex seems to be associated with a diminution of awareness in patients with early-stage AD. [ABSTRACT FROM AUTHOR]

Published
2018
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15. A genome-wide study reveals rare CNVs exclusive to extreme phenotypes of Alzheimer disease

Author

Rovelet-Lecrux, Anne, Legallic, Solenn, Wallon, David, Flaman, Jean-Michel, Martinaud, Olivier, Bombois, Stéphanie, Rollin-Sillaire, Adeline, Michon, Agnès, Le Ber, Isabelle, Pariente, Jérémie, Puel, Michèle, Paquet, Claire, Croisile, Bernard, Thomas-Antérion, Catherine, Vercelletto, Martine, Lévy, Richard, Frébourg, Thierry, Hannequin, Didier, Campion, Dominique, Renseigné, Non, Moreaud, Olivier, Service de neurologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Génétique médicale et fonctionnelle du cancer et des maladies neuropsychiatriques, Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Normandie Université (NU), 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 de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Imagerie cérébrale et handicaps neurologiques (ICHN), Institut des sciences du cerveau de Toulouse. (ISCT), Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-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), Neurologie générale et maladies inflammatoires du système nerveux [Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Institut du Fer à Moulin, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de Neurologie, Hopital Neurologique, Bron, Centre de Mémoire de Ressource et Recherche (CMRR), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Service de neurologie [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Hôpital Guillaume-et-René-Laennec [Saint-Herblain], Neuro-anatomie fonctionnelle du comportement et de ses troubles, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR70-Institut National de la Santé et de la Recherche Médicale (INSERM), Génétique du cancer et des maladies neuropsychiatriques (GMFC), Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Laboratoire de Psychologie et NeuroCognition (LPNC), Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Joseph Fourier - Grenoble 1 (UJF)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS), Unité de Neuropsychologie, CHU Grenoble, Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U1172 Inserm - U837 (JPArc), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Université de Lille, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], CHU Saint-Etienne-Hôpital Bellevue, Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR70-Université Pierre et Marie Curie - Paris 6 (UPMC), and Centre National de la Recherche Scientifique (CNRS)-Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Joseph Fourier - Grenoble 1 (UJF)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])

Subjects
Male, MESH: Mutation, DNA Copy Number Variations, MESH: Age of Onset, Genome-wide association study, Biology, medicine.disease_cause, MESH: Phenotype, Genome, Article, 03 medical and health sciences, Amyloid beta-Protein Precursor, 0302 clinical medicine, MESH: Aged, 80 and over, Alzheimer Disease, MESH: Amyloid beta-Protein Precursor, PSEN2, Genetics, medicine, PSEN1, Humans, Copy-number variation, Age of Onset, Genetics (clinical), 030304 developmental biology, Aged, Aged, 80 and over, MESH: Aged, 0303 health sciences, Mutation, MESH: Middle Aged, MESH: Humans, Middle Aged, medicine.disease, Phenotype, MESH: Male, 3. Good health, MESH: Genome-Wide Association Study, Female, MESH: DNA Copy Number Variations, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Alzheimer's disease, MESH: Female, 030217 neurology & neurosurgery, MESH: Alzheimer Disease, Genome-Wide Association Study
Abstract

International audience; Studying rare extreme forms of Alzheimer disease (AD) may prove to be a useful strategy in identifying new genes involved in monogenic determinism of AD. Amyloid precursor protein (APP), PSEN1, and PSEN2 mutations account for only 85% of autosomal dominant early-onset AD (ADEOAD) families. We hypothesised that rare copy number variants (CNVs) could be involved in ADEOAD families without mutations in known genes, as well as in rare sporadic young-onset AD cases. Using high-resolution array comparative genomic hybridisation, we assessed the presence of rare CNVs in 21 unrelated ADEOAD cases, having no alteration on known genes, and 12 sporadic AD cases, with an age of onset younger than 55 years. The analysis revealed the presence of 7 singleton CNVs (4 in ADEOAD and 3 in sporadic cases) absent in 1078 controls and 912 late-onset AD cases. Strikingly, 4 out of 7 rearrangements target genes (KLK6, SLC30A3, MEOX2, and FPR2) encoding proteins that are tightly related to amyloid-β peptide metabolism or signalling. Although these variants are individually rare and restricted to particular subgroups of patients, these findings support the causal role, in human pathology, of a set of genes coding for molecules suspected for a long time to modify Aβ metabolism or signalling, and for which animal or cellular models have already been developed.

Published
2012

16. High prevalence of cognitive impairment after intracerebral hemorrhage.

Author

Planton, Mélanie, Saint-Aubert, Laure, Raposo, Nicolas, Branchu, Laura, Lyoubi, Aicha, Bonneville, Fabrice, Albucher, Jean-François, Olivot, Jean-Marc, Péran, Patrice, and Pariente, Jérémie

Subjects
INTRACEREBRAL hematoma, MILD cognitive impairment, DISEASE prevalence, CEREBRAL amyloid angiopathy, ALZHEIMER'S disease
Abstract

Background: Cognitive impairment seems to be frequent in intracerebral hemorrhage (ICH) survivors, but remains widely understudied. In this study, we investigated the frequency and patterns of vascular cognitive disorders (VCDs) in patients with cerebral amyloid angiopathy (CAA)-related and deep ICH compared to patients with mild cognitive impairment due to Alzheimer’s disease (MCI-AD) and healthy controls. Methods: We prospectively recruited 20 patients with CAA-related lobar ICH, 20 with deep ICH, 20 with MCI-AD and 17 healthy controls. Patients with cognitive decline pre-ICH were excluded from the analysis. Each participant underwent a comprehensive neuropsychological assessment and a structural brain MRI. Cognitive assessment was performed at a median delay of 4 months after the acute phase in ICH patients, and more than 6 months after the first complaint in MCI-AD patients. Cognitive profiles were compared between groups. The prevalence of VCDs in the ICH groups was estimated using the recent VASCOG criteria. Results: “Mild” and “major VCDs” were respectively observed in 87.5% and 2.5% of all ICH patients. Every patient in the CAA group had mild VCDs. No significant difference was observed in cognitive functioning between CAA-related and deep ICH patients. The most impaired process in the CAA group was naming, with a mean (±standard deviation) z-score of -5.2 ±5.5, followed by processing speed (-4.1±3.3), executive functioning (-2.6 ±2.5), memory (-2.4 ±3.5) and attention (-0.9 ±1.3). This cognitive pattern was different from the MCI-AD patients, but the groups were only different in gestural praxis, and by construction, in memory processes. Conclusions: VCDs are frequent after ICH. Cognitive patterns of patients with deep or CAA-related ICH did not differ, but there was impaired performance in specific domains distinct from the effects of Alzheimer’s disease. Clinical trial registration: URL: . Unique identifier: . [ABSTRACT FROM AUTHOR]

Published
2017
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17. Long-term safety and tolerability of bapineuzumab in patients with Alzheimer's disease in two phase 3 extension studies.

Author

Ivanoiu, Adrian, Pariente, Jérémie, Booth, Kevin, Lobello, Kasia, Luscan, Gerald, Hua, Lisa, Lucas, Prisca, Styren, Scot, Lingfeng Yang, Li, David, Black, Ronald S., Robert Brashear, H., and McRae, Thomas

Subjects
*THERAPEUTIC use of monoclonal antibodies, *ALZHEIMER'S disease treatment, *AMYLOID beta-protein, *APOLIPOPROTEIN E, *IMMUNOTHERAPY, *PATIENT safety, *DRUG efficacy
Abstract

Background: Immunotherapy with monoclonal antibodies that target amyloid beta has been under investigation as a treatment for patients with Alzheimer's disease (AD). The 3000 and 3001 phase 3 clinical studies of intravenous bapineuzumab assessed safety and efficacy in patients with mild to moderate AD recruited in over 26 countries. This article describes the long-term safety and tolerability of bapineuzumab in the extension studies for these two protocols. Methods: The long-term safety and tolerability of intravenous-administered bapineuzumab in patients with AD was evaluated in apolipoprotein E ε4 allele noncarriers (Study 3002, extension of Study 3000) and apolipoprotein E ε4 allele carriers (Study 3003, extension of Study 3001). Those receiving bapineuzumab in the parent study were continued at the same dose; if receiving placebo, patients began bapineuzumab. Bapineuzumab doses were 0. 5 mg/kg in both studies and also 1.0 mg/kg in the noncarrier study. Clinical efficacy of bapineuzumab was also assessed in exploratory analyses. Results: Because of lack of efficacy in two other phase 3 trials, the parent protocols were stopped early. As a result, Studies 3002 and 3003 were also terminated. In total, 492 and 202 patients were enrolled in Studies 3003 and 3002, respectively. In apolipoprotein E ε4 carriers (Study 3003), treatment-emergent adverse events occurred in 70.7 % of the patients who originally received placebo and 66.9 % of those who originally received bapineuzumab. In noncarriers, treatment-emergent adverse events occurred in 82.1 % and 67.6 % of patients who received placebo + bapineuzumab 0.5 mg/kg and placebo + bapineuzumab 1.0 mg/kg, respectively, and in 72.7 % and 64.3 % of those who received bapineuzumab + bapineuzumab 0.5 mg/kg and 1.0 mg/kg, respectively. Amyloid-related imaging abnormalities with edema or effusions were the main bapineuzumab-associated adverse events in both studies, occurring in approximately 11 % of placebo + bapineuzumab and 4 % of bapineuzumab + bapineuzumab groups overall. Exploratory analyses of clinical efficacy were not significantly different between groups in either study. Conclusions: In these phase 3 extension studies, intravenous bapineuzumab administered for up to approximately 3 years showed no unexpected safety signals and a safety profile consistent with previous bapineuzumab trials. [ABSTRACT FROM AUTHOR]

Published
2016
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18. Pauses During Autobiographical Discourse Reflect Episodic Memory Processes in Early Alzheimer's Disease.

Author

Pistono, Aurélie, Jucla, Mélanie, Barbeau, Emmanuel J., Saint-Aubert, Laure, Lemesle, Béatrice, Calvet, Benjamin, Köpke, Barbara, Puel, Michèle, and Pariente, Jérémie

Subjects
EPISODIC memory, MILD cognitive impairment, LANGUAGE & languages, BRAIN imaging, BRAIN mapping, ALZHEIMER'S disease, BRAIN, NEUROPSYCHOLOGICAL tests, MEMORY, MEMORY disorders, PROTEINS, PSYCHOLOGICAL tests, STATISTICS, POSITRON emission tomography, DISEASE complications
Abstract

There is a large body of research on discourse production in Alzheimer's disease (AD). Some studies have focused on pause production, revealing that patients make extensive use of pauses during speech. This has been attributed to lexical retrieval difficulties, but pausing may also reflect other forms of cognitive impairment as it increases with cognitive load. The aim of the present study was to analyze autobiographical discourse impairment in AD from a broad perspective, looking at pausing behavior (frequency, duration, and location). Our first objective was to characterize discourse changes in mild cognitive impairment (MCI) due to AD. Our second objective was to determine the cognitive and neuroanatomical correlates of these changes. Fifteen patients with MCI due to AD and 15 matched cognitively normal controls underwent an ecological episodic memory task, a full neuropsychological assessment, and a 3D T1-weighted MRI scans. Autobiographical discourse collected from the ecological episodic memory task was recorded, transcribed, and analyzed, focusing on pausing. Intergroup comparisons showed that although patients did not produce more pauses than controls overall, they did make more between-utterance pauses. The number of these specific pauses was positively correlated with patients' episodic memory performance. Furthermore, neuroimaging analysis showed that, in the patient group, their use was negatively correlated with frontopolar area (BA 10) grey matter density. This region may therefore play an important role in the planning of autobiographical discourse production. These findings demonstrate that pauses in early AD may reflect a compensatory mechanism for improving mental time travel and memory retrieval. [ABSTRACT FROM AUTHOR]

Published
2016
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19. A Case of Logopenic Primary Progressive Aphasia with C9ORF72 Expansion and Cortical Florbetapir Binding.

Author

Saint-Aubert, Laure, Sagot, Catherine, Wallon, David, Hannequin, Didier, Payoux, Pierre, Nemmi, Federico, Bezy, Catherine, Chauveau, Nicolas, Campion, Dominique, Puel, Michèle, Chollet, François, and Pariente, Jérémie

Subjects
AMYLOID
Abstract

We report the case of a 65-year-old woman, clinically diagnosed with the logopenic variant of primary progressive aphasia (PPA), and carrier of C9ORF72 expansion, despite cerebrospinal fluid biomarkers suggesting Alzheimer's disease (AD). She underwent structural MRI, metabolic PET, and amyloid PET imaging using florbetapir. Comparison with healthy controls revealed widespread hypometabolism, left sided cortical atrophy, and an increased cortical amyloid load. No difference in amyloid binding was found between the patient and predemential AD patients. This case provides evidence of amyloidopathy in a carrier of C9ORF72 expansion exhibiting a clinical profile of the logopenic variant of PPA. [ABSTRACT FROM AUTHOR]

Published
2014
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20. The French Series of Autosomal Dominant Early Onset Alzheimer's Disease Cases: Mutation Spectrum and Cerebrospinal Fluid Biomarkers.

Author

Wallon, David, Rousseau, Stéphane, Rovelet-Lecrux, Anne, Quillard-Muraine, Muriel, Guyant-Maréchal, Lucie, Martinaud, Olivier, Pariente, Jérémie, Puel, Michèle, Rollin-Sillaire, Adeline, Pasquier, Florence, Le Ber, Isabelle, Sarazin, Marie, Croisile, Bernard, Boutoleau-Bretonnière, Claire, Thomas-Antérion, Catherine, Paquet, Claire, Moreaud, Olivier, Gabelle, Audrey, Sellal, François, and Sauvée, Mathilde

Subjects
ALZHEIMER'S disease, CEREBROSPINAL fluid, BIOMARKERS, PATIENTS, GENETIC determinism
Abstract

We describe 56 novel autosomal dominant early-onset Alzheimer disease (ADEOAD) families with PSEN1, PSEN2, and AβPP mutations or duplications, raising the total of families with mutations on known genes to 111 (74 PSEN1, 8 PSEN2, 16 AβPP, and 13 AβPP duplications) in the French series. In 33 additional families (23% of the series), the genetic determinism remained uncharacterized after this screening. Cerebrospinal fluid (CSF) biomarker levels were obtained for patients of 58 families (42 with known mutations and 16 without genetic characterization). CSF biomarkers profile was consistent with an AD diagnosis in 90% of families carrying mutations on known genes. In families without mutation, CSF biomarkers were consistent with AD diagnosis in 14/16 cases. Overall, these results support further genetic heterogeneity in the determinism of ADEOAD and suggest that other major genes remain to be characterized. [ABSTRACT FROM AUTHOR]

Published
2012

21. Amyloid Imaging with AV45 (18F-florbetapir) in a Cognitively Normal AβPP Duplication Carrier.

Author

Saint-Aubert, Laure, Planton, Mélanie, Hannequin, Didier, Albucher, Jean-François, Delisle, Marie-Bernadette, Payoux, Pierre, Hitzel, Anne, Viallard, Gérard, Péran, Patrice, Campion, Dominique, Laquerrière, Annie, Barbeau, Emmanuel J., Puel, Michéle, Raposo, Nicolas, Chollet, François, and Pariente, Jérémie

Subjects
GENETICS of Alzheimer's disease, CHROMOSOME duplication, AMYLOID, MAGNETIC resonance imaging, NEUROLOGICAL disorders
Abstract

We report the case of a 62-year-old asymptomatic carrier of AβPP gene duplication. He was investigated by MRI and the amyloid ligand 18F-AV45, and compared to Alzheimer's disease patients (n = 11) and healthy controls (n = 11). The neuropsychological examination was normal. Cortical thickness and AV45 retention were comparable to Alzheimer's disease patients. AβPP duplication was diagnosed because cerebral amyloid angiopathy and Alzheimer's disease pathology were found on the neuropathological examination of his youngest brother, who died at 42 from intracerebral hemorrhage. This is the first description of a pre-symptomatic AβPP duplication carrier over 60, despite widespread cerebral amyloid angiopathy, 'Alzheimer's like' atrophy, and amyloid deposition. [ABSTRACT FROM AUTHOR]

Published
2012
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22. Can neurodevelopmental disorders influence the course of neurodegenerative diseases? A scoping review.

Author

Siguier, Perrine L.M., Planton, Mélanie, Baudou, Eloise, Chaix, Yves, Delage, Alix, Rafiq, Marie, Wolfrum, Marie, Gérard, Fleur, Jucla, Mélanie, and Pariente, Jérémie

Subjects
*NEURODEGENERATION, *ALZHEIMER'S disease, *DISEASE progression, *LEARNING disabilities, *DISEASE risk factors
Abstract

This scoping review aims at giving an overview of the possible influence of neurodevelopmental disorders (NDDs) on cognitive-behavioral neurodegenerative diseases (CBNDs). Based on the PRISMA-ScR checklist, it details the methods of NDDs screening, the identified NDDs-CBNDs associations, as well as the criteria and types of association. The last literature search was performed in June 2023. In the final study, 32 articles were included. Analysis first showed that NDDs were mainly detected through medical records screening. Second, the association of specific learning disorders and major or mild neurocognitive disorder due to Alzheimer's disease was the most investigated. Third, associations were mostly based on prevalence comparisons. Finally, 66 % of studies reported a positive association between NDDs and CBNDs. Notably, up to 67 % of positive associations were observed with atypical forms of certain CBNDs. Authors' interpretations suggest that NDDs could constitute a risk factor for CBNDs. However, the influence of NDDs on CBNDs still lacks evidence and biological support, possibly due to the heterogeneity of methods and criteria employed. Developing validated assessment tools for all NDDs and conducting cohort studies could be beneficial for research, and clinical practice. Indeed, this review also underlines the importance of adopting a life-span approach regarding CBNDs. • NDDs may be a risk factor for dementia, especially for atypical variants. • The biological and temporal processes involved remain hypothetical. • A lifespan approach should be adopted in both clinical practice and research. • This lifespan approach requires methodological breakthroughs. [ABSTRACT FROM AUTHOR]

Published
2024
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24. Alteration of rhythmic unimanual tapping and anti-phase bimanual coordination in Alzheimer's disease: A sign of inter-hemispheric disconnection?

Author

Martin, Elodie, Blais, Mélody, Albaret, Jean-Michel, Pariente, Jérémie, and Tallet, Jessica

Subjects
*ALZHEIMER'S disease, *CORPUS callosum, *NEUROPSYCHOLOGY, *PSYCHOLOGY of movement, *SYNCHRONIZATION, *BRAIN diseases, *ATTENTION, *CEREBRAL dominance, *CYCLES, *TIME, *TRANSFER of training, *BODY movement
Abstract

Little attention is paid to motor control in Alzheimer's disease (AD) although it is a relevant sign of central nervous system integrity and functioning. In particular, unimanual and bimanual tapping is a relevant paradigm because it requires intra- and inter-hemispheric transfer (IHT). Previous results indicate that both unimanual and anti-phase tapping requires more IHT than in-phase tapping, especially produced without external stimulation. The aim of the present study was to test the production of unimanual, bimanual in-phase and anti-phase tapping with a synchronization-continuation paradigm with and without visual stimulation in AD patients (N=9) and control participants (N=12). In accordance with our hypothesis, these results suggest that unimanual and anti-phase tapping is more altered in AD than in control participants. Moreover, performance is globally more variable in the AD group. These alterations are discussed in terms of possible IHT modulation, in line with functional and structural findings in AD, revealing changes in the connectivity of brain regions across hemispheres and white matter damage. [ABSTRACT FROM AUTHOR]

Published
2017
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