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January 2008 - present
January 1990 - December 2012
Publications
Publications (752)
Clinical trial satisfaction is increasingly important for future trial designs and is associated with treatment adherence and willingness to enroll in future research studies or to recommend trial participation. In this post-trial survey, we examined participant satisfaction and attitudes toward future clinical trials in the Dominantly Inherited Al...
Résumé
Le dosage des biomarqueurs du liquide cérébrospinal (LCS) a intégré depuis maintenant plusieurs années la démarche diagnostique en cas de suspicion de maladie d’Alzheimer (MA). En France, où l’imagerie moléculaire n’est pas accessible en soin courant, ils sont le seul outil disponible pour poser un diagnostic biologique de MA selon les critè...
Introduction: We aimed to assess episodic memory in genetic frontotemporal dementia (FTD) with the Free and Cued Selective Reminding Test (FCSRT). Methods: The FCSRT was administered in 417 presymptomatic and symptomatic mutation carriers (181 chromosome 9 open reading frame 72 [C9orf72], 163 progranulin [GRN], and 73 microtubule-associated protein...
Objective:
In this study, we assessed a support program based on acceptance, role transition, and couple dynamics for spouses of people with young-onset dementia. The qualitative feedback from the caregivers' experience is analyzed. The goal was to explore how this home-based support program is perceived and to appraise the impact of the different...
Humans have developed specific abilities to interact efficiently with their conspecifics (social cognition). Despite abundant behavioral and neuroscientific research, the influence of cultural factors on these skills remains poorly understood. This issue is of particular importance as most cognitive tasks are developed in highly specific contexts,...
Purpose
This study aims at assessing whether EANM harmonisation strategy combined with EQ·PET methodology could be successfully applied to harmonize brain 2-deoxy-2[18F]fluoro-D-glucose ([18F]FDG) positron emission tomography (PET) images.
Methods
The NEMA NU 2 body phantom was prepared according to the EANM guidelines with an [18F]FDG solution. R...
Background
Pathogenic variants in the autosomal dominant genes PSEN1, PSEN2, or APP, APOE4 alleles, and rare variants within TREM2, SORL1, and ABCA7 contribute to early-onset Alzheimer’s disease (EOAD). However, sporadic EOAD patients have been insufficiently studied to define the probability of being a carrier of one of these variants.
Objective...
Although several ADAMs (A disintegrin-like and metalloproteases) have been shown to contribute to the amy-loid precursor protein (APP) metabolism, the full spectrum of metalloproteases involved in this metabolism remains to be established. Transcriptomic analyses centred on metalloprotease genes unraveled a 50% decrease in ADAM30 expression that in...
Objective
We 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.
Settings
We analysed two large complementary databases to study the incidence and characteristics of this population on a nationwide scope in France from 2014 to 2...
BACKGROUND: Hypertension is common among patients with Alzheimer disease. Because this group has been excluded from hypertension trials, evidence regarding safety of treatment is lacking. This secondary analysis of a randomized controlled trial assessed whether antihypertensive treatment increases the prevalence of orthostatic hypotension (OH) in p...
Objectives
New diagnostic criteria for Alzheimer’s disease (AD) include cerebrospinal fluid (CSF) biomarkers that allow diagnosis at the stage of mild cognitive impairment (MCI). However, the impact of CSF biomarkers in MCI populations in clinical practice has been poorly evaluated. The objective of this study is to assess the use and impact in cli...
Objective: The aim of this study is to test the effects of a customized intervention on distress among caregivers of persons with dementia (PWD) using a quasi-experimental design. Method: Fifty-one spouse caregivers in the experimental group and 51 in the control group participated in the study. The effects of the intervention were examined by comp...
Les troubles du langage peuvent être inauguraux et pré-dominants dans certaines pathologies neurodégénératives. Déterminer s'ils proviennent d'une atteinte de la production du mot ou de sa compréhension due à des troubles lexicosémantiques peut aider à caractériser le phénotype clinique notam-ment entre une aphasie primaire progressive non fluente...
Les troubles du langage peuvent être inauguraux et pré-dominants dans certaines pathologies neurodégénératives. Déterminer s'ils proviennent d'une atteinte de la production du mot ou de sa compréhension due à des troubles lexicosémantiques peut aider à caractériser le phénotype clinique notam-ment entre une aphasie primaire progressive non fluente...
[This corrects the article DOI: 10.3389/fnagi.2018.00297.].
Introduction
Patients with positive tauopathy but negative Aβ42 (A−T+) in the cerebrospinal fluid (CSF) represent a diagnostic challenge. The Aβ42/40 ratio supersedes Aβ42 and reintegrates “false” A−T+ patients into the Alzheimer's disease spectrum. However, the biomarker and clinical characteristics of “true” and “false” A−T+ patients remain elusi...
Purpose
One can reasonably suppose that cerebrospinal spinal fluid (CSF) biomarkers can identify distinct subgroups of Alzheimer’s disease (AD) patients. In order to better understand differences in CSF biomarker patterns, we used FDG PET to assess cerebral metabolism in CSF-based subgroups of AD patients.
Methods
Eighty-five patients fulfilling t...
Objective
To assess the added value of neurite orientation dispersion and density imaging (NODDI) compared with conventional diffusion tensor imaging (DTI) and anatomical MRI to detect changes in presymptomatic carriers of chromosome 9 open reading frame 72 ( C9orf72 ) mutation.
Methods
The PREV-DEMALS (Predict to Prevent Frontotemporal Lobar Dege...
A combination of low cerebrospinal fluid (CSF) Amyloid β1–42 (Aβ1–42) and high Total-Tau (T-Tau) and Phosphorylated-Tau (P-Tau) occurs at a prodromal stage of Alzheimer’s disease (AD) and recent findings suggest that network abnormalities and interneurons dysfunction contribute to cognitive deficits. Somatostatin (SOM) and Neuropeptide Y (NPY) are...
Objective
To estimate the prevalence of amyloid‐positivity, defined by PET/CSF biomarkers and/or neuropathological examination, in primary progressive aphasia (PPA) variants.
Methods
We conducted a meta‐analysis with individual participant data from 1,251 patients diagnosed with PPA (including logopenic [lvPPA, n=443], non‐fluent [nfvPPA, n=333],...
The G4C2-repeat expansion in C9orf72 is the most common known cause of amyotrophic lateral sclerosis and frontotemporal dementia. The high phenotypic heterogeneity of C9orf72 patients includes a wide range in age of onset, modifiers of which are largely unknown. Age of onset could be influenced by environmental and genetic factors both of which may...
Detailed statistical methods.
(DOCX)
Study design and treatment.
(DOCX)
Personal correspondence.
(DOCX)
ADAS-Cog 12 sex subgroup analysis results.
ADAS-Cog 12, Alzheimer's Disease Assessment Scale Cognitive-12.
(DOCX)
Trial-associated boards.
(DOCX)
Distribution of treatment arms recruited in each site.
(DOCX)
ADAS-Cog 12 severity subgroup analysis results.
ADAS-Cog 12, Alzheimer's Disease Assessment Scale Cognitive-12.
(DOCX)
Clinical chemistry and haematology findings at screening visit and week 78.
(DOCX)
ADAS-Cog 12 APOE ε4 subgroup analysis results.
ε4, epsilon 4 allele; ADAS-Cog 12, Alzheimer's Disease Assessment Scale Cognitive-12; APOE, Apolipoprotein E gene.
(DOCX)
MedDRA coded adverse events per group.
MedDRA, Medical Dictionary for Regulatory Activities.
(XLSX)
Neuroimaging studies have described the brain alterations in primary progressive aphasia (PPA) variants (semantic, logopenic, nonfluent/agrammatic). However, few studies combined T1, FDG-PET, and diffusion MRI techniques to study atrophy, hypometabolism, and tract alterations across the three PPA main variants. We therefore explored a large early-s...
Areas of significant hypometabolism in sv-PPA, lv-PPA and nfv-PPA, compared to healthy controls. The maps display p-values, corrected for multiple comparisons using cluster correction and a FWHM (Full Width at Half Maximum) at 8 mm.
Repartition of participants across centers for the T1-PET the T1-DWI cohorts.
A (GGGGCC)n repeat expansion in C9orf72 gene is the major cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). The relations between the repeats size and the age at disease onset (AO) or the clinical phenotype (FTD vs. ALS) were investigated in 125 FTD, ALS, and presymptomatic carriers. Positive correlations were found be...
Aims The main aim of the present work was to assess if sex influences the occurrence of major clinical events in elderly people with type 2 diabetes followed up in the primary care.
Methods 983 subjects aged ≥65years with type 2 diabetes were included by 213 general practitioners and followed up prospectively for three years. Major clinical events...
Background: There is an unmet need for an accurate, non-invasive and non-costly biomarker test for the diagnosis of Alzheimer’s disease (AD). The objectives of the ADDIA study are a) the proof-of-performance of two cellular biomarkers, β-amyloid peptide and a kinase, detected in blood cells using specific fluorescent probes, and b) the validation o...
Aim:
Object/background association is critical to understand the context of visual scenes but also in daily life tasks like object search. Patients with Alzheimer disease (AD) exhibit impairment in scene processing at different levels: perception, recognition, memory and spatial navigation. We explored whether patients with AD make use of contextu...
Background
Studies have shown the frequent coexistence of Lewy pathology (LP) in Alzheimer’s Disease (AD).
Objective
The aim of this study was to determine the influence of LP on the clinical and cognitive phenotype in a cohort of patients with a neuropathological diagnosis of AD.
Methods
We reviewed neuropathologically proven AD cases, reaching...
Introduction
L’analyse dans le liquide cérébro-spinal (LCS) des 3 principaux biomarqueurs biologiques (A?42, T-Tau et P-Tau) est un élément contributif du diagnostic de maladie d’Alzheimer (MA), qui pourrait également permettre d’identifier des sous-groupes de patients distincts. Notre objectif était de rechercher si le métabolisme cérébral, évalué...
Introduction:
The free and cued selective reminding test is used to identify memory deficits in mild cognitive impairment and demented patients. It allows assessing three processes: encoding, storage, and recollection of verbal episodic memory.
Methods:
We investigated the neural correlates of these three memory processes in a large cohort study...
Background:
Loss-of-function mutations in GRN cause frontotemporal lobar degeneration (FTLD). Patients with GRN mutations present with a uniform subtype of TAR DNA-binding protein 43 (TDP-43) pathology at autopsy (FTLD-TDP type A); however, age at onset and clinical presentation are variable, even within families. We aimed to identify potential ge...
Introduction:
Progress in understanding and management of vascular cognitive impairment (VCI) has been hampered by lack of consensus on diagnosis, reflecting the use of multiple different assessment protocols. A large multinational group of clinicians and researchers participated in a two-phase Vascular Impairment of Cognition Classification Conse...
Introduction
La maladie d’Alzheimer à début précoce (early-onset Alzheimer's disease ou EOAD), dont les symptômes apparaissent avant 65 ans, est caractérisée par une fréquence élevée de présentations cliniques atypiques non mnésiques associant une atteinte anatomopathologique plus sévère et une évolution clinique plus agressive que les présentation...
Objective:
To 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.
Methods:
We used a cross-s...
INTRODUCTION: Progress in understanding and management of vascular cognitive impairment (VCI) has been hampered by lack of consensus on diagnosis, reflecting the use of multiple different assessment protocols. A large multinational group of clinicians and researchers participated in a two-phase Vascular Impairment of Cognition Classification Consen...
![Figure 4. In vivo [ 18 F]FDG-PET cerebral metabolic measurement six...](profile/Yaohua-Chen-3/publication/322516150/figure/fig2/AS:631957641773056@1527681851283/n-vivo-18-FFDG-PET-cerebral-metabolic-measurement-six-weeks-after-surgery-a-Bars_Q320.jpg)
Cerebral microbleeds (CMBs) could contribute to cognitive impairment in the general population and in patients with dementia. We designed a study to (i) develop a murine model of CMBs, (ii) assess whether CMBs affect cognition in this model and (iii) assess whether this model is sensitive to pharmacological modulation. Male C57Bl6/J mice were stere...
Background:
Few patients with a normal cerebrospinal fluid (CSF) biomarker profile fulfill the clinical criteria for Alzheimer disease (AD).
Objective:
The aim of this study was to test the hypothesis of misdiagnoses for these patients.
Method:
Patients from the e-PLM centers fulfilling the core clinical criteria for probable AD dementia or mi...
Introduction: The prevalence of dementia is increasing in our aging population. Because of the complexity of disease pathology, dementia classifications remain controversial. The present post-mortem study investigates whether there are age differences between dementia brains with a single pure neurodegenerative or cerebrovascular disease and those...
Importance:
Presymptomatic carriers of chromosome 9 open reading frame 72 (C9orf72) mutation, the most frequent genetic cause of frontotemporal lobar degeneration and amyotrophic lateral sclerosis, represent the optimal target population for the development of disease-modifying drugs. Preclinical biomarkers are needed to monitor the effect of ther...
Objective
To quantify the effect of genetic factors and generations influencing the age at onset (AAO) in families with frontotemporal lobar dementia (FTD) due to C9ORF72 hexanucleotide repeat expansions and GRN mutations.
Methods
We studied 504 affected individuals from 133 families with C9ORF72 repeat expansions and 90 FTD families with mutation...
Frontotemporal lobar degeneration (FTLD) includes the behavioral variant of frontotemporal lobar degeneration (bvFTD), also called frontotemporal dementia (FTD), and two language variants, namely, semantic dementia (SD) and primary progressive agrammatic aphasia (PPA). There is a large degree of overlap between the three FTLD variants, as well as b...
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 memo...
Objective:
The aim of this study was to estimate the association between gender and control of diabetes and other cardiovascular risk factors in elderly patients with type 2 diabetes mellitus.
Methods:
The sujets âgés cohort is an observational study whose main objective was to describe the real-life management of elderly patients with type 2 di...
Amyotrophic lateral sclerosis (ALS) is associated with frontotemporal lobar degeneration (FTLD) in 15% of the cases. A neuropathological continuity between ALS and FTLD-TDP is suspected. The present post-mortem 7.0-tesla magnetic resonance imaging (MRI) study compares the topographic distribution of iron (Fe) deposition and the incidence of small c...
Purpose of review:
The purpose of this review is to provide an update on the role of tau beyond the stabilization of microtubules and on the clinical, pathological, diagnostic and therapeutic aspects of tauopathies.
Recent findings:
Beyond its function as a microtubule-associated tau protein, tau is also involved in gene regulation, signal trans...
Introduction
Le diabète est associé à des modifications cognitives aggravées par les complications vasculaires, un déséquilibre glycémique, des hypoglycémies. L’objectif principal de cette étude était de déterminer la fréquence des troubles cognitifs dans une cohorte de patients diabétiques âgés de 50 ans et plus. L’objectif secondaire était d’éval...
We identified rare coding variants associated with Alzheimer's disease in a three-stage case-control study of 85,133 subjects. In stage 1, we genotyped 34,174 samples using a whole-exome microarray. In stage 2, we tested associated variants (P < 1 × 10-4) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, we u...
Background:
The natural history and disease mechanisms of Alzheimer's disease and related disorders (ADRD) are still poorly understood. Very few resources are available to scrutinise patients as early as needed and to use integrative approaches combining standardised, repeated clinical investigations and cutting-edge biomarker measurements.
Metho...
We identified rare coding variants associated with Alzheimer's disease in a three-stage case-control study of 85,133 subjects. In stage 1, we genotyped 34,174 samples using a whole-exome microarray. In stage 2, we tested associated variants (P < 1 × 10(-4)) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, we...
We performed whole-exome and whole-genome sequencing in 927 late-onset Alzheimer Disease (LOAD) cases, 852 early-onset AD (EOAD) cases and 1,273 controls from France. We assessed evidence for gene-based association of rare variants with AD in 6 genes for which an association with such variants was previously claimed. When aggregating protein trunca...
Objectives: To investigate the characteristics of the caregiving experience according to age at onset of dementia to adapt support programs.
Method: Fifty-seven spouse caregivers of persons with early-onset dementia (PEOD) and 93 spouse caregivers of persons with late-onset dementia (PLOD) participated. The characteristics of the caregiving experie...
Résumé
• L’étude S.AGES avait pour objectif principal de décrire les caractéristiques cliniques et les modalités de prise en charge des patients diabétiques de type 2 (DT2) âgés, suivis en France en médecine générale.
• Il s’agit d’une étude de suivi de cohorte, non interventionnelle, nationale et multicentrique, qui a inclus 959 patients DT2 âgés...
Background:
In elderly brains of demented patients, Alzheimer and Lewy body pathology (LBP) are frequently associated. Cortical microinfarcts (CoMIs) are more observed in Lewy body disease, even in the absence of cerebral amyloid angiopathy (CAA). The present neuropathological and 7.0-tesla MRI studies investigate whether CoMIs are also more frequ...
Introduction
La maladie d’Alzheimer (MA) est de diagnostic difficile, en particulier dans ses formes precoces et atypiques, ou cas de comorbidites. Dans ce contexte, l’analyse des biomarqueurs du Liquide Cephalo-Rachidien (LCR) est recommandee, mais reste non realisable ou non-conclusive chez certains patients. Cette etude s’est interessee a l’impa...
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 fi...
Analysis plan.
(DOCX)
Different PSEN1 (n = 78), PSEN2 (n = 4), and APP (n = 8) mutations identified in the French EOAD whole series, totalizing 188 occurrences.
Y = yes.
(XLSX)
Introduction
Le dosage plasmatique des oxysterols et des lysosphingolipides est devenu le test diagnostic de premiere intention en cas de suspicion de la maladie de Niemann-Pick de type C (NPC).
Observation
Une patiente de 69 ans, sans antecedents personnels et familiaux notables, est adressee au CMRR pour des troubles cognitifs severes evoluant pr...
Introduction
Meme avant 60 ans, la maladie d’Alzheimer (MA) est la premiere cause de demence. Les presentations atypiques sont plus frequentes dans la MA du sujet jeune (MAJ) que dans les MA a debut plus tardif. L’evolution de la MAJ semble plus rapide mais reste meconnue.
Objectifs
Decrire l’evolution clinique, neuropsychologique, medico-sociale,...
