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1. DAPHNE: A New Tool for the Assessment of the Behavioral Variant of Frontotemporal Dementia

Author

Claire Boutoleau-Bretonnière, Christelle Evrard, Jean Benoît Hardouin, Laëtitia Rocher, Tiphaine Charriau, Frédérique Etcharry-Bouyx, Sophie Auriacombe, Aurélie Richard-Mornas, Florence Lebert, Florence Pasquier, Anne Sauvaget, Samuel Bulteau, Martine Vercelletto, Pascal Derkinderen, Cédric Bretonnière, and Catherine Thomas-Antérion

Subjects
Frontotemporal dementia, Behavioral disorders, Alzheimer’s disease, Bipolar disorder, Progressive supranuclear palsy, Scale, Neurology. Diseases of the nervous system, RC346-429, Geriatrics, RC952-954.6
Abstract

Background: The diagnosis of behavioral variant of frontotemporal dementia (bvFTD) relies primarily on clinical features and remains challenging. The specificity of the recently revised criteria can be disappointing, justifying development of new clinical tools. Objective: We produced a behavioral inventory named DAPHNE. This scale (adapted from Rascovsky's criteria) explores six domains: disinhibition, apathy, perseverations, hyperorality, personal neglect and loss of empathy. It is composed of ten items (five answer categories). The aim was (1) to assess the validity and reliability of DAPHNE and (2) to evaluate its contribution in differentiating patients. Methods: Two scores were computed: DAPHNE-6 (screening) from the six domains and DAPHNE-40 (diagnosis) from the ten items. Reliability and reproducibility were assessed. External validity was studied with the Frontal Behavioral Inventory (FBI) and the Frontotemporal Behavioral Scale (FBS). Finally, the diagnostic performance of DAPHNE was compared to revised criteria, FBI and FBS. Results: DAPHNE was administered to the caregivers of 89 patients, 36 with bvFTD, 22 with Alzheimer's disease, 15 with progressive supranuclear palsy and 16 with bipolar disorder. Reliability and reproducibility were excellent, as was external validity. DAPHNE-6 allowed bvFTD diagnosis (score ≥4) with a sensitivity of 92%, while DAPHNE-40 (score ≥15) had a specificity of 92%. Conclusion: We demonstrate excellent psychometric features for DAPHNE. This quick tool could help for both diagnosing and screening bvFTD.

Published
2015
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2. How many patients are eligible for disease-modifying treatment in Alzheimer’s disease? A French national observational study over 5 years

Author

Frédéric Blanc, Adrien Julian, Julie Bellet, Julien Dumurgier, Claire Boutoleau-Bretonnière, Renaud David, David Wallon, Jacques Hugon, P. Robert, Emmanuelle Liegey, Aurélie Mouton, Florence Pasquier, Claire Paquet, Samir Bekadar, Marc Paccalin, Stéphane Epelbaum, Didier Hannequin, Thérèse Rivasseau Jonveaux, Annick Besozzi, Bruno Dubois, Caroline Hommet, Roxane Fabre, Laetitia Berly, Olivier Madec, Walter Deberdt, Tiphaine Charriau, Olivier Rouaud, Stéphane Pouponneau, Institut de la Mémoire et de la Maladie d'Alzheimer [Paris] (IM2A), Sorbonne Université (SU), Algorithms, models and methods for images and signals of the human brain (ARAMIS), Sorbonne Université (SU)-Inria de Paris, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP]-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP]-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [APHP], National Reference Center for Rare or Early Dementias and Center of Excellence of Neurodegenerative Disease (CoEN), Hôpital Lariboisière, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Lariboisière-Université Paris Diderot - Paris 7 (UPD7), Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Biomarqueurs CArdioNeuroVASCulaires (BioCANVAS), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Rouen, Normandie Université (NU), Service de neurologie [Rouen], Normandie Université (NU)-Normandie Université (NU), Service de neurologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), CHU Strasbourg, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service de gériatrie [Poitiers], Département de neurologie[Lille], Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de neurologie [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Hôpital Guillaume-et-René-Laennec [Saint-Herblain], Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Hospitalier Universitaire de Nice (CHU Nice), 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 [APHP]-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Eli Lilly and Company [Indianapolis], 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)-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)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de référence sur les démences rares et maladie de Pick, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), 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), Assistance publique - Hôpitaux de Paris (AP-HP) (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 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), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-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)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Département de neurologie [Lille], Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Hôpitaux Universitaires Saint-Louis, Lariboisière, Fernand-Widal, Marqueurs cardiovasculaires en situation de stress (MASCOT (UMR_S_942 / U942)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Université Sorbonne Paris Nord, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Hôpital Charles Nicolle [Rouen], Laboratoire lorrain de psychologie et neurosciences de la dynamique des comportements (2LPN), Université de Lorraine (UL), Centres Mémoire de Ressources et de Recherche [CHRU Nancy] (CMRR de Lorraine), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Service de Neurologie [Strasbourg], CHU Strasbourg-Hopital Civil, Département de Gériatrie [Strasbourg], Les Hôpitaux Universitaires de Strasbourg (HUS)-Hôpital de jour St François [Strasbourg], Hôpital de la Milétrie, Service de Neurologie générale, vasculaire et dégénérative (CHU de Dijon), Centre Mémoire de Ressources et de Recherche [Nice] (CMRR Nice), Université Côte d'Azur (UCA)-Centre Hospitalier Universitaire de Nice (CHU Nice)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA), Service de neurologie 1 [CHU Pitié-Salpétrière], Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université, Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut de la Mémoire et de la Maladie d'Alzheimer [CHU Pitié-Salpétriêre] (IM2A), Assistance publique - Hôpitaux de Paris (AP-HP) (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)-Sorbonne Université (SU), and Epelbaum, Stéphane

Subjects
Male, Pediatrics, medicine.medical_specialty, Population, Prodromal Symptoms, Disease, 03 medical and health sciences, mild cognitive impairment, 0302 clinical medicine, Alzheimer Disease, Epidemiology, medicine, Humans, 030212 general & internal medicine, Stage (cooking), education, ComputingMilieux_MISCELLANEOUS, Aged, Retrospective Studies, Aged, 80 and over, education.field_of_study, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, Research, prodromal Alzheimer’s disease, Incidence (epidemiology), General Medicine, Middle Aged, Mental Status and Dementia Tests, 3. Good health, Clinical trial, Databases as Topic, Neurology, mild Alzheimer’s disease, [SCCO.PSYC]Cognitive science/Psychology, Medicine, Female, epidemiology, National database, Observational study, France, business, Neurocognitive, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

ObjectiveWe aimed to study the epidemiology of the prodromal and mild stages of Alzheimer’s disease (AD) patients who are eligible for clinical trials with disease-modifying therapies.SettingsWe analysed two large complementary databases to study the incidence and characteristics of this population on a nationwide scope in France from 2014 to 2018. The National Alzheimer Database contains data from 357 memory centres and 90 private neurologists. Data from 2014 to 2018 have been analysed.ParticipantsPatients, 50–85 years old, diagnosed with AD who had an Mini-Mental State Exam (MMSE) score of ≥20 were included. We excluded patients with mixed and non-AD neurocognitive disorders.Primary outcome measureDescriptive statistics of the population of interest was the primary measure.ResultsIn the National Alzheimer Database, 550 198 patients were assessed. Among them, 72 174 (13.1%) were diagnosed with AD and had an MMSE ≥20. Using corrections for specificity of clinical diagnosis of AD, we estimated that about 50 000 (9.1%) had a prodromal or mild AD. In the combined electronic clinical records database of 11 French expert memory centres, a diagnosis of prodromal or mild AD, certified by the use of cerebrospinal fluid AD biomarkers, could be established in 195 (1.3%) out of 14 596 patients.ConclusionsAD was not frequently diagnosed at a prodromal or mild dementia stage in France in 2014 to 2018. Diagnosis rarely relied on a pathophysiological marker even in expert memory centres. National databases will be valuable to monitor early stage AD diagnosis efficacy in memory centres when a disease-modifying treatment becomes available.

Published
2019
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3. Value of Neuropsychological Testing, Imaging, and CSF Biomarkers for the Differential Diagnosis and Prognosis of Clinically Ambiguous Dementia

Author

Tiphaine Charriau, Pascal Derkinderen, Claire Boutoleau-Bretonnière, Christelle Evrard, Martine Vercelletto, Odile Delaroche, Cédric Bretonnière, Thibaud Lebouvier, Estelle Lamy, and Philippe Damier

Subjects
Adult, Male, medicine.medical_specialty, Pathology, tau Proteins, Disease, Neuropsychological Tests, Gastroenterology, Diagnosis, Differential, Technetium Tc 99m Exametazime, Text mining, Internal medicine, medicine, Humans, Dementia, Cognitive decline, Pathological, Aged, Aged, 80 and over, Tomography, Emission-Computed, Single-Photon, business.industry, General Neuroscience, Brain, General Medicine, Middle Aged, Prognosis, medicine.disease, Magnetic Resonance Imaging, Psychiatry and Mental health, Clinical Psychology, Csf biomarkers, Female, Neuropsychological testing, Geriatrics and Gerontology, Differential diagnosis, business, Psychology, Biomarkers, Follow-Up Studies
Abstract

The objective of this study was to examine the diagnostic accuracy of imaging and CSF biomarkers in clinically ambiguous dementia (CAD). 69 patients were prospectively followed. The endpoint was clinical diagnosis at follow-up of 24 months based upon existing criteria. Medial temporal lobe atrophy score on MRI, distinctive patterns on 99 mTc-HMPAO- SPECT, and CSF levels of amyloid- peptide, total tau protein, and P-tau181P were used together with neuropsychological testing to assess Se (sensitivity) and Sp (specificity) of separate and combined markers. 60 patients reached the endpoint. A definite diagnosis was achieved in 48 patients. CSF biomarkers had a Sp of 71% and a Se of 100% for Alzheimer's disease (AD) diagnosis. Sp increased to 88% and 93% when MRI and MRI + SPECT were combined, at the expense of Se. CSF biomarkers levels also provided clues to frontotemporal (FTD) or vascular dementias (VaD) diagnosis when situated in an intermediate range between normal and pathological values. MRI and SPECT contributed mostly to the diagnosis of VaD (Se 88%, Sp 75%) and FTD (Se 73%, Sp 78%), respectively. Initial neuropsychological testing had a poor diagnostic accuracy, except for a neuropsychiatric inventory score >40 for the diagnosis of FTD (Se 73%, Sp 84%). Independent of the clinical diagnosis, medial temporal lobe atrophy and total-tau were best correlated with cognitive decline at 2 years. In conclusion, CSF biomarkers efficiently predict evolution toward an AD phenotype in CAD. Imaging biomarkers mostly contribute to the differential diagnosis between non-AD dementias. Initial neuropsychological testing was poorly contributive in CAD diagnosis.

Published
2012
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4. DAPHNE: A New Tool for the Assessment of the Behavioral Variant of Frontotemporal Dementia

Author

Christelle Evrard, Samuel Bulteau, Claire Boutoleau-Bretonnière, Catherine Thomas-Antérion, Frédérique Etcharry-Bouyx, Martine Vercelletto, Laëtitia Rocher, Tiphaine Charriau, Aurélie Richard-Mornas, Florence Lebert, Florence Pasquier, Sophie Auriacombe, Jean-Benoit Hardouin, Anne Sauvaget, Cédric Bretonnière, Pascal Derkinderen, MethodS in Patients-centered outcomes and HEalth ResEarch (SPHERE), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université de Nantes (UN)-Université de Nantes (UN), Service de Neurologie [Lille], Hôpital Roger Salengro [Lille]-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Département de neurologie [Lille], and Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)

Subjects
medicine.medical_specialty, Bipolar disorder, Cognitive Neuroscience, Perseveration, media_common.quotation_subject, [SDV]Life Sciences [q-bio], Validity, lcsh:Geriatrics, lcsh:RC346-429, Alzheimer’s disease, Progressive supranuclear palsy, Neglect, External validity, medicine, Apathy, Original Research Article, Psychiatry, lcsh:Neurology. Diseases of the nervous system, ComputingMilieux_MISCELLANEOUS, media_common, Alzheimer's disease, medicine.disease, Scale, Behavioral disorders, lcsh:RC952-954.6, Psychiatry and Mental health, medicine.symptom, Psychology, Frontotemporal dementia, Clinical psychology
Abstract

Background: The diagnosis of behavioral variant of frontotemporal dementia (bvFTD) relies primarily on clinical features and remains challenging. The specificity of the recently revised criteria can be disappointing, justifying development of new clinical tools. Objective: We produced a behavioral inventory named DAPHNE. This scale (adapted from Rascovsky's criteria) explores six domains: disinhibition, apathy, perseverations, hyperorality, personal neglect and loss of empathy. It is composed of ten items (five answer categories). The aim was (1) to assess the validity and reliability of DAPHNE and (2) to evaluate its contribution in differentiating patients. Methods: Two scores were computed: DAPHNE-6 (screening) from the six domains and DAPHNE-40 (diagnosis) from the ten items. Reliability and reproducibility were assessed. External validity was studied with the Frontal Behavioral Inventory (FBI) and the Frontotemporal Behavioral Scale (FBS). Finally, the diagnostic performance of DAPHNE was compared to revised criteria, FBI and FBS. Results: DAPHNE was administered to the caregivers of 89 patients, 36 with bvFTD, 22 with Alzheimer's disease, 15 with progressive supranuclear palsy and 16 with bipolar disorder. Reliability and reproducibility were excellent, as was external validity. DAPHNE-6 allowed bvFTD diagnosis (score ≥4) with a sensitivity of 92%, while DAPHNE-40 (score ≥15) had a specificity of 92%. Conclusion: We demonstrate excellent psychometric features for DAPHNE. This quick tool could help for both diagnosing and screening bvFTD.

Published
2015
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