Your search for: 'author:("Martinaud, Olivier")' has returned 9 results. (0.012s) Save search

Authors: Godefroy, Olivier | Martinaud, Olivier | Verny, Marc | Mosca, Chrystèle | Lenoir, Hermine | Bretault, Eric | Roussel, Martine | GREFEX Study Group

Article Type: Research Article

Abstract: Background: Dysexecutive disorders are common in early-stage Alzheimer’s disease (AD) but have yet to be characterized in detail. Objective: The objectives of the present study based on validated diagnostic criteria were to determine the frequency and characterize the profile of behavioral and cognitive dysexecutive disorders in AD. Methods: 102 patients with AD (mild: n = 92; moderate: n = 10; mean MMSE score: 23.2) were examined with the GREFEX battery. Neuropsychological data were interpreted within a validated framework based on the performance levels of 780 control participants from the GREFEX study. Results: Dysexecutive syndrome was observed in 87.5% (95%CI: 79–96) …of the AD patients (p = 0.0001). The dysexecutive disorder profile was characterized by prominent impairments of planning, inhibition flexibility and generation in the cognitive domain (p = 0.0001 as compared to controls for all) and global hypoactivity in the behavioral domain (p = 0.0001 as compared to controls). Conclusions: Dysexecutive syndrome is observed in over 80% of AD patients and has a distinct profile. Show more

Keywords: Alzheimer disease, attention, dementia, executive function, mild cognitive impairment

DOI: 10.3233/JAD-140585

Citation: Journal of Alzheimer's Disease, vol. 42, no. 4, pp. 1203-1208, 2014

Authors: Nicolas, Gaël | Beherec, Laurène | Hannequin, Didier | Opolczynski, Gaëlle | Rothärmel, Maud | Wallon, David | Véra, Pierre | Martinaud, Olivier | Guillin, Olivier | Campion, Dominique

Article Type: Research Article

Abstract: Background: Although numerous studies have assessed cognitive dysfunction in patients with schizophrenia, very few have focused on the diagnosis of dementia. Objective: Our objectives were to accurately diagnose dementia in a cohort of middle-aged patients with schizophrenia and to assess the type of dementia. Methods: 96 patients with schizophrenia (46 inpatients and 50 outpatients), aged 50 to 70 years, underwent a psychiatric, neurological, and neuropsychological evaluation at baseline and after a 20-month follow-up. We established a 3-step procedure: 1) diagnose dementia according to the DSM-IV criteria, using the Mattis Dementia Rating and Activities of Daily Living scales; 2) characterize dementia …using brain imaging, perfusion by 99m Tc-ECD-SPECT and laboratory tests including Alzheimer’s disease cerebrospinal fluid biomarkers; and 3) search for genetic determinants. Results: Fourteen patients fulfilled the diagnostic criteria of dementia. Four were diagnosed with possible or probable behavioral-variant frontotemporal dementia (bvFTD), two with probable Alzheimer’s disease, two with probable vascular dementia (including one due to CADASIL), one with CNS inflammatory disease, and six could not be fully characterized. Conclusions: The diagnosis of dementia in middle-aged patients with schizophrenia is challenging but possible, using a multistep procedure. The most frequent condition, bvFTD, could reflect the presence of an evolutive neurodegenerative process in some patients. Show more

Keywords: Alzheimer's disease, dementia, frontotemporal lobar degeneration, Mattis Dementia Rating Scale, schizophrenia, vascular dementia

DOI: 10.3233/JAD-131688

Citation: Journal of Alzheimer's Disease, vol. 39, no. 4, pp. 809-822, 2014

Authors: Grangeon, Lou | Paquet, Claire | Guey, Stéphanie | Zarea, Aline | Martinaud, Olivier | Rotharmel, Maud | Maltête, David | Quillard-Muraine, Muriel | Nicolas, Gael | Charbonnier, Camille | Chabriat, Hugues | Wallon, David

Article Type: Research Article

Abstract: Background: There is no consensus regarding the diagnostic value of cerebrospinal fluid (CSF) Alzheimer’s disease (AD) biomarkers in cerebral amyloid angiopathy (CAA). Objective: To describe the CSF levels of Aβ42 , Aβ40 , total protein Tau, and phosphorylated-Tau (p-Tau) in a large series of probable CAA patients and to compare with AD patients in order to identify a specific pattern in CAA but also to look for correlations with the neuroimaging profile. Methods: We retrospectively included from 2 French centers probable CAA patients according to modified Boston criteria who underwent lumbar puncture (LP) with CSF AD biomarker quantifications. Two neurologists …independently analyzed all MRI sequences. A logistic regression and Spearman’s correlation coefficient were used to identify correlation between MRI and CSF biomarkers in CAA. Results: We included 63 probable CAA and 27 AD patients. Among CAA 50.8% presented with decreased Aβ42 level associated with elevated p-Tau and/or Tau, 34.9% with isolated decreased Aβ42 level and 14.3% patients with normal Aβ42 level. Compared to AD, CAA showed lower levels of Tau (p  = 0.008), p-Tau (p  = 0.004), and Aβ40 (p  = 0.001) but similar Aβ42 level (p  = 0.07). No correlation between Aβ42 or Aβ40 levels and neuroimaging was found. Conclusion: CSF biomarkers may improve the accuracy of the modified Boston criteria with altered profile in 85% of the patients fulfilling revised Boston criteria for probable CAA. Aβ40 appears as an interesting selective biomarker in differential diagnosis. Show more

Keywords: Aβ42, Aβ40, cerebral amyloid angiopathy, cerebrospinal fluid biomarker, intracerebral hemorrhage

DOI: 10.3233/JAD-215208

Citation: Journal of Alzheimer's Disease, vol. 87, no. 2, pp. 791-802, 2022

Authors: Boscher, Emmanuelle | Husson, Thomas | Quenez, Olivier | Laquerrière, Annie | Marguet, Florent | Cassinari, Kevin | Wallon, David | Martinaud, Olivier | Charbonnier, Camille | Nicolas, Gaël | Deleuze, Jean-François | Boland, Anne | Lathrop, Mark | Frébourg, Thierry | FREX Consortium | Campion, Dominique | Hébert, Sébastien S. | Rovelet-Lecrux, Anne

Article Type: Research Article

Abstract: Early-onset Alzheimer’s disease (EOAD) accounts for 5-10% of all AD cases, with a heritability ranging between 92% to 100%. With the exception of rare mutations in APP , PSEN1, and PSEN2 genes causing autosomal dominant EOAD, little is known about the genetic factors underlying most of the EOAD cases. In this study, we hypothesized that copy number variations (CNVs) in microRNA (miR) genes could contribute to risk for EOAD. miRs are short non-coding RNAs previously implicated in the regulation of AD-related genes and phenotypes. Using whole exome sequencing, we screened a series of 546 EOAD patients negative for autosomal dominant …EOAD mutations and 597 controls. We identified 86 CNVs in miR genes of which 31 were exclusive to EOAD cases, including a duplication of the MIR138-2 locus. In functional studies in human cultured cells, we could demonstrate that miR-138 overexpression leads to higher Aβ production as well as tau phosphorylation, both implicated in AD pathophysiology. These changes were mediated in part by GSK-3β and FERMT2, a potential risk factor for AD. Additional disease-related genes were also prone to miR-138 regulation including APP and BACE1 . This study suggests that increased gene dosage of MIR138-2 could contribute to risk for EOAD by regulating different biological pathways implicated in amyloid and tau metabolism. Additional studies are now required to better understand the role of miR-CNVs in EOAD. Show more

Keywords: Copy number variants, early-onset Alzheimer’s disease, microRNA, miR-138

DOI: 10.3233/JAD-180940

Citation: Journal of Alzheimer's Disease, vol. 68, no. 3, pp. 1243-1255, 2019

Authors: Morin, Alexandre | Pressat-Laffouilhere, Thibaut | Sarazin, Marie | Lagarde, Julien | Roue-Jagot, Carole | Olivieri, Pauline | Paquet, Claire | Cognat, Emmanuel | Dumurgier, Julien | Pasquier, Florence | Lebouvier, Thibaut | Ceccaldi, Matthieu | Godefroy, Olivier | Martinaud, Olivier | Grosjean, Julien | Zarea, Aline | Maltête, David | Wallon, David

Article Type: Short Communication

Abstract: This multicenter study was conducted in French memory clinics during the first COVID-2019 lockdown (March–May 2020). The objective was to evaluate the effect of a telemedicine consultation on treatment modification in dementia care. Among 874 patients who had a telemedicine consultation, 103 (10.7%) had treatment modifications, in particular those living with a relative or diagnosed with Alzheimer’s disease. A control group of patients referred March–May 2019 was also included. Treatment modification rate was similar between periods with an adjusted percentage difference of –4% (p  = 0.27). Telemedicine consultations allowed treatment modifications with only a minor short-term negative impact on therapeutic strategies.

Keywords: Alzheimer’s disease, COVID-19, psychoactive drugs, telemedicine, treatments in dementia

DOI: 10.3233/JAD-215459

Citation: Journal of Alzheimer's Disease, vol. 86, no. 2, pp. 525-530, 2022

Authors: Grangeon, Lou | Paquet, Claire | Bombois, Stephanie | Quillard-Muraine, Muriel | Martinaud, Olivier | Bourre, Bertrand | Lefaucheur, Romain | Nicolas, Gaël | Dumurgier, Julien | Gerardin, Emmanuel | Jan, Mary | Laplanche, Jean-Louis | Peoc’h, Katell | Hugon, Jacques | Pasquier, Florence | Maltête, David | Hannequin, Didier | Wallon, David | the collaborators of the ePLM.fr group

Article Type: Research Article

Abstract: Background: Total Tau concentration in cerebrospinal fluid (CSF) is widely used as a biomarker in the diagnosis of neurodegenerative process primarily in Alzheimer’s disease (AD). A particularly high Tau level may indicate AD but may also be associated with Creutzfeldt-Jakob disease (CJD). In such situations little is known about the distribution of differential diagnoses. Objective: Our study aimed to describe the different diagnoses encountered in clinical practice for patients with dementia and CSF Tau levels over 1000 pg/ml. We studied the p-Tau/Tau ratio to specify its ability to distinguish AD from CJD. Methods: Patients (n  = 202) with CSF Tau levels …over 1000 pg/ml were recruited in three memory clinics in France. All diagnoses were made using the same diagnostic procedure and criteria. Results: Patients were diagnosed with AD (n  = 148, 73.2%), mixed dementia (n  = 38, 18.8%), CJD, vascular dementia (n  = 4, 2.0% for each), Lewy body dementia, and frontotemporal dementia (n  = 3, 1.5% for each). Dispersion of CSF Tau levels clearly showed an overlap between all diagnoses. Using the p-Tau/Tau ratio suggestive of CJD (<0.075), all CJD patients were correctly categorized and only two AD patients were miscategorized. This ratio was highly associated with CJD compared to AD (p  < 0.0001). Conclusion: Our study showed that in clinical practice, extremely high CSF Tau levels are mainly related to diagnosis of AD. CJD patients represent a minority. Our results support a sequential interpretation algorithm for CSF biomarkers in dementia. High CSF Tau levels should alert clinicians to check the p-Tau/Tau ratio to consider a probable diagnosis of CJD. Show more

Keywords: Alzheimer’s disease, cerebrospinal fluid biomarker, Creutzfeldt-Jakob disease, dementia, tau

DOI: 10.3233/JAD-151111

Citation: Journal of Alzheimer's Disease, vol. 51, no. 3, pp. 905-913, 2016

Authors: 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 | Sauvée, Mathilde | Laquerrière, Annie | Duyckaerts, Charles | Delisle, Marie-Bernadette | Streichenberger, Nathalie | Lannes, Béatrice | Frebourg, Thierry | Hannequin, Didier | Campion, Dominique | The collaborators of the GMAJ project

Article Type: Research Article

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. Show more

Keywords: Alzheimer's disease, AβPP, CSF biomarkers, early-onset, genetics, PSEN1, PSEN2

DOI: 10.3233/JAD-2012-120172

Citation: Journal of Alzheimer's Disease, vol. 30, no. 4, pp. 847-856, 2012

Authors: Lacour, Morgane | Quenez, Olivier | Rovelet-Lecrux, Anne | Salomon, Bruno | Rousseau, Stephane | Richard, Anne-Claire | Quillard-Muraine, Muriel | Pasquier, Florence | Rollin-Sillaire, Adeline | Martinaud, Olivier | Zarea, Aline | de la Sayette, Vincent | Boutoleau-Bretonniere, Claire | Etcharry-Bouyx, Frédérique | Chauviré, Valérie | Sarazin, Marie | le Ber, Isabelle | Epelbaum, Stéphane | Jonveaux, Thérèse | Rouaud, Olivier | Ceccaldi, Mathieu | Godefroy, Olivier | Formaglio, Maite | Croisile, Bernard | Auriacombe, Sophie | Magnin, Eloi | Sauvée, Mathilde | Marelli, Cecilia | Gabelle, Audrey | Pariente, Jeremie | Paquet, Claire | Boland, Anne | Deleuze, Jean-François | Campion, Dominique | Hannequin, Didier | Nicolas, Gael | Wallon, David | The collaborators of the CNR-MAJ

Article Type: Research Article

Abstract: Background: Pathogenic variants in the autosomal dominant genes PSEN1 , PSEN2 , or APP , APOE4 alleles, and rare variants within TREM2 , SORL1 , and ABCA7 contribute to early-onset Alzheimer’s disease (EOAD). However, sporadic EOAD patients have been insufficiently studied to define the probability of being a carrier of one of these variants. Objective: To describe the proportion of each genetic variation among patients with very young-onset sporadic AD. Methods: We first screened PSEN1 , PSEN2 , and APP in 154 EOAD patients with an onset before 51 years and a negative family history. Among 99 patients with no …mutation (NMC), whole exome sequencing (WES) was performed. We analyzed the APOE genotype and rare protein-truncating or missense predicted damaging variants of TREM2 , SORL1 , and ABCA7 . Neurological examination and cerebrospinal fluid (CSF) biomarkers were systematically retrieved. Results: Nineteen (12.3%) mutation carriers (MC) harbored an APP or PSEN1 pathogenic or likely pathogenic variant. Among the NMC, 54/99 carried at least one genetic risk factor, including 9 APOE4/E4 homozygous, 37 APOE4 heterozygous, and 14 with a rare variant in another risk factor gene: 3 SORL1 , 4 TREM2 , and 9 ABCA7. MC presented an earlier disease onset (p  < 0.0001) and associated neurologic symptoms more frequently (p  < 0.002). All but one patient had at least 2 CSF biomarkers in abnormal ranges. Conclusion: The genetic component of very early sporadic EOAD gathers a substantial proportion of pathogenic variants in autosomal dominant genes and an even higher proportion of patients carrying genetic risk factors, suggesting an oligogenic determinism, even at this range of ages. Show more

DOI: 10.3233/JAD-190193

Citation: Journal of Alzheimer's Disease, vol. 71, no. 1, pp. 227-243, 2019

Authors: Le Ber, Isabelle | Camuzat, Agnès | Guillot-Noel, Lena | Hannequin, Didier | Lacomblez, Lucette | Golfier, Véronique | Puel, Michèle | Martinaud, Olivier | Deramecourt, Vincent | Rivaud-Pechoux, Sophie | Millecamps, Stéphanie | Vercelletto, Martine | Couratier, Philippe | Sellal, François | Pasquier, Florence | Salachas, François | Thomas-Antérion, Catherine | Didic, Mira | Pariente, Jérémie | Seilhean, Danielle | Ruberg, Merle | Wargon, Isabelle | Blanc, Frédéric | Camu, William | Michel, Bernard-François | Berger, Eric | Sauvée, Mathilde | Thauvin-Robinet, Christel | Mondon, Karl | Tournier-Lasserve, Elisabeth | Goizet, Cyril | Fleury, Marie | Viennet, Gabriel | Verpillat, Patrice | Meininger, Vincent | Duyckaerts, Charles | Dubois, Bruno | Brice, Alexis | the French research network on FTLD/FTLD-ALS

Article Type: Research Article

Abstract: Frontotemporal dementia (FTD) refers to a disease spectrum including the behavioral variant FTD (bvFTD), primary progressive aphasia (PPA), progressive supranuclear palsy/corticobasal degeneration syndrome (PSP/CBDS), and FTD with amyotrophic lateral sclerosis (FTD-ALS). A GGGGCC expansion in C9ORF72 is a major cause of FTD and ALS. C9ORF72 was analyzed in 833 bvFTD, FTD-ALS, PPA, and PSP/CBDS probands; 202 patients from 151 families carried an expansion. C9ORF72 expansions were much more frequent in the large subgroup of patients with familial FTD-ALS (65.9%) than in those with pure FTD (12.8%); they were even more frequent than in familial pure ALS, according to estimated frequencies …in the literature (23–50%). The frequency of carriers in non-familial FTD-ALS (12.7%) indicates that C9ORF72 should be analyzed even when family history is negative. Mutations were detected in 6.8% of PPA patients, and in 3.2% of patients with a clinical phenotype of PSP, thus enlarging the phenotype spectrum of C9ORF72. Onset was later in C9ORF72 (57.4 years, 95%CI: 55.9–56.1) than in MAPT patients (46.8, 95%CI: 43.0–50.6; p = 0.00001) and the same as in PGRN patients (59.6 years; 95%CI: 57.6–61.7; p = 0.4). ALS was more frequent in C9ORF72 than in MAPT and PGRN patients; onset before age 50 and parkinsonism were indicative of MAPT mutations, whereas hallucinations were indicative of PGRN mutations; prioritization of genetic testing is thus possible. Penetrance was age- and gender-dependent: by age 50, 78% of male carriers were symptomatic, but only 52% of females. This can also guide genetic testing and counseling. A flowchart for genetic testing is thus proposed. Show more

Keywords: Amyotrophic lateral sclerosis, C9ORF72, frontotemporal dementia, frontotemporal lobar degeneration, protein TDP43

DOI: 10.3233/JAD-121456

Citation: Journal of Alzheimer's Disease, vol. 34, no. 2, pp. 485-499, 2013