Your search for: 'author:("Paquet, Claire")' has returned 18 results. (0.014s) Save search

Authors: Dumurgier, Julien | Dartigues, Jean-François | Gabelle, Audrey | Paquet, Claire | Prevot, Magali | Hugon, Jacques | Tzourio, Christophe

Article Type: Research Article

Abstract: Time disorientation is commonly observed in dementia, however very little is known about the pathological significance of minor time errors in community-dwelling population. Our objective was to investigate the relationship between time orientation and risk of dementia in a population of older adults. Analyses relies on 8611 dementia-free subjects from the Three-City Study, France. Participants were followed up for 10 years for incident dementia. Time orientation was assessed by asking for the date, the day of the week, the month, the season and the year. At baseline, 905 subjects made at least one error in time orientation. During 57,073 person-years …of follow-up, 827 participants developed dementia. After controlling for age, gender and education level, subjects with one error in time had a greater risk of dementia (hazard ratio [HR] 1.44 [1.18–1.77]), while those with at least 2 errors had a more than three-fold increased risk (HR 3.10 [1.98–4.83]). This association was particularly marked for the diagnosis of probable Alzheimer’s disease. Time disorientation was associated with an increased risk of dementia in a large population of cognitively normal older people followed during up to 10 years and should not be underestimated in clinical setting. Show more

Keywords: Epidemiology, dementia, time orientation, neuropsychology, aging

DOI: 10.3233/JAD-160295

Citation: Journal of Alzheimer's Disease, vol. 53, no. 4, pp. 1411-1418, 2016

Authors: Gourmaud, Sarah | Thomas, Priscilla | Thomasseau, Sylvie | Tible, Marion | Abadie, Claire | Paquet, Claire | Hugon, Jacques

Article Type: Research Article

Abstract: Alzheimer’s disease (AD) is characterized by accumulations of amyloid-β (Aβ42 ) and hyperphosphorylated tau proteins, associated with neuroinflammation, synaptic loss, and neuronal death. Several studies indicate that c-Jun N-terminal kinase (JNK) is implicated in the pathological features of AD. We have investigated in 5XFAD mice, the therapeutic effects of Brimapitide, a JNK-specific inhibitory peptide previously tested with higher concentrations in another AD model (TgCRND8). Three-month-old 5XFAD and wild-type littermate mice were treated by intravenous injections of low doses (10 mg/kg) of Brimapitide every 3 weeks, for 3 or 6 months (n  = 6–9 per group). Cognitive deficits and brain lesions were assessed …using Y-maze, fear-conditioning test, and histological and biochemical methods. Chronic treatment of Brimapitide for 3 months resulted in a reduction of Aβ plaque burden in the cortex of 5XFAD treated mice. After 6 months of treatment, cognitive deficits were reduced but also a significant reduction of cell death markers and the pro-inflammatory IL-1β cytokine in treated mice were detected. The Aβ plaque burden was not anymore modified by the 6 months of treatment. In addition to modulating cognition and amyloid plaque accumulation, depending on the treatment duration, Brimapitide seems experimentally to reduce neuronal stress in 5XFAD mice. Show more

Keywords: Alzheimer’s disease, cell death, JNK, memory, mice model peptide inhibitor, therapeutic

DOI: 10.3233/JAD-171099

Citation: Journal of Alzheimer's Disease, vol. 63, no. 2, pp. 665-674, 2018

Authors: Gourmaud, Sarah | Mouton-Liger, François | Abadie, Claire | Meurs, Eliane F. | Paquet, Claire | Hugon, Jacques

Article Type: Research Article

Abstract: In Alzheimer’s disease (AD), the amyloid cascade hypothesis proposes that amyloid-beta (Aβ) neurotoxicity leads to neuroinflammation, synaptic loss, and neuronal degeneration. In AD patients, anti-amyloid immunotherapies did not succeed because they were possibly administered late in AD progression. Modulating new targets associated with Aβ toxicity, such as PKR (double-stranded RNA dependent kinase), and JNK (c-Jun N-terminal kinase) is a major goal for neuroprotection. These two pro-apoptotic kinases are activated in AD brains and involved in Aβ production, tau phosphorylation, neuroinflammation, and neuronal death. In HEK cells transfected with siRNA directed against PKR, and in PKR knockout (PKR–/– ) mice neurons, …we showed that PKR triggers JNK activation. Aβ-induced neuronal apoptosis, measured by cleaved PARP (Poly ADP-ribose polymerase) and cleaved caspase 3 levels, was reduced in PKR–/– neurons. Two selective JNK inhibitory peptides also produced a striking reduction of Aβ toxicity. Finally, the dual inhibition of PKR and JNK nearly abolished Aβ toxicity in primary cultured neurons. These results reveal that dual kinase inhibition can afford neuroprotection and this approach is worth being tested in in vivo AD and oxidative stress models. Show more

Keywords: Alzheimer’s disease, amyloid-beta, JNK, neuronal death, PKR, therapeutic strategy

DOI: 10.3233/JAD-160509

Citation: Journal of Alzheimer's Disease, vol. 54, no. 4, pp. 1659-1670, 2016

Authors: Dumurgier, Julien | Paquet, Claire | Peoc'h, Katell | Lapalus, Pauline | Mouton-Liger, François | Benisty, Sarah | Chasseigneaux, Stéphanie | Chabriat, Hughes | Hugon, Jacques

Article Type: Research Article

Abstract: Glucose dysmetabolism has been consistently associated with an increased risk of cognitive disorders, and brain insulin resistance could play a role in Alzheimer's disease (AD) pathogenesis. Recent evidence suggests that cerebrospinal fluid (CSF) biomarkers may reflect the brain pathology in AD. We have investigated the relationship between CSF concentrations of amyloid-β peptide 1-42 (Aβ1-42 ), total tau, and phosphorylated tau (ptau-181) and plasma and CSF glucose levels in a cohort of 94 newly diagnosed non-diabetics AD patients. We report that CSF Aβ1-42 level was inversely associated with CSF to plasma glucose ratio (Spearman's coefficient = −0.27, p = 0.008). This …relationship remained after adjustment for age, gender, body mass index, hypertension, and MMSE score (β [SE] of linear regression = −0.93 [0.37], p = 0.01). In stratified analysis, this relationship was observed only in patients who did not carry the apolipoprotein E4 allele. No significant relationship was found between glucose levels and total tau or phosphorylated tau 181. These results support the idea that a link between glucose dysmetabolism and the amyloid pathway may exist in the pathogenesis of AD. Show more

Keywords: Alzheimer's disease, amyloid-β peptide, biomarkers, CSF, glucose

DOI: 10.3233/JAD-2011-111007

Citation: Journal of Alzheimer's Disease, vol. 27, no. 4, pp. 845-851, 2011

Authors: Troussière, Anne Cécile | Wallon, David | Mouton-Liger, François | Yatimi, Rachida | Robert, Philippe | Hugon, Jacques | Hannequin, Didier | Pasquier, Florence | Paquet, Claire

Article Type: Short Communication

Abstract: Cerebrospinal fluid (CSF) biomarkers for Alzheimer's disease (AD) are well validated in clinical research but less in clinical practice. Using a questionnaire, we evaluated the reasons for prescriptions and clinician's expectations concerning CSF biomarkers. The results show that CSF AD biomarkers are mainly required in case of atypical dementia and diagnosis uncertainty that are different from indications in clinical research. In the future, clinicians wish to get new biomarkers that could improve differential diagnosis and could have a good pronostic value. Further studies in routine practice are necessary to precise the role of these biomarkers in the management of patients.

Keywords: Alzheimer's disease, biomarkers, cerebrospinal fluid, clinical practice

DOI: 10.3233/JAD-132672

Citation: Journal of Alzheimer's Disease, vol. 40, no. 4, pp. 857-861, 2014

Authors: Vrillon, Agathe | Deramecourt, Vincent | Pasquier, Florence | Magnin, Éloi | Wallon, David | Lozeron, Pierre | Bouaziz-Amar, Élodie | Paquet, Claire

Article Type: Short Communication

Abstract: Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia have a strong clinical, genetic, and pathological connection but association of ALS with Alzheimer’s disease (AD) is seldom reported. We report a series of 5 cases of AD associated with ALS. Our patients presented with cognitive deterioration with episodic memory impairment meeting criteria for AD. ALS occurred subsequently in all cases and its phenotype was not homogenous. Amyloid process was confirmed in four cases with cerebrospinal fluid biomarkers. One case underwent postmortem exam, demonstrating hallmarks lesions of both diseases. This series highlights that ALS-AD phenotype could be a specific underexplored entity.

Keywords: Alzheimer’s disease, amyotrophic lateral sclerosis, cerebrospinal fluid biomarkers, neurodegenerative disorders, neuropathology

DOI: 10.3233/JAD-215226

Citation: Journal of Alzheimer's Disease, vol. 84, no. 4, pp. 1439-1446, 2021

Authors: Cressot, Coralie | Vrillon, Agathe | Lilamand, Matthieu | Francisque, Hélène | Méauzoone, Aurélie | Hourregue, Claire | Dumurgier, Julien | Marlinge, Emeline | Paquet, Claire | Cognat, Emmanuel

Article Type: Systematic Review

Abstract: Background: Psychosis, characterized by delusions and/or hallucinations, is frequently observed during the progression of Alzheimer’s disease (AD) and other neurodegenerative dementias (ND) (i.e., dementia with Lewy bodies (DLB), and frontotemporal dementia (FTD)) and cause diagnostic and management difficulties. Objective: This review aims at presenting a concise and up-to-date overview of psychotic symptoms that occur in patients with ND with a comparative approach. Methods: A systematic review was conducted following the PRISMA guidelines. 98 original studies investigating psychosis phenotypes in neurodegenerative dementias were identified (40 cohort studies, 57 case reports). Results: Psychosis is a frequently observed phenomenon during the course of …ND, with reported prevalence ranging from 22.5% to 54.1% in AD, 55.9% to 73.9% in DLB, and 18% to 42% in FTD. Throughout all stages of these diseases, noticeable patterns emerge depending on their underlying causes. Misidentification delusions (16.6–78.3%) and visual hallucinations (50–69.6%) are frequently observed in DLB, while paranoid ideas and somatic preoccupations seem to be particularly common in AD and FTD, (respectively 9.1–60.3% and 3.10–41.5%). Limited data were found regarding psychosis in the early stages of these disorders. Conclusions: Literature data suggest that different ND are associated with noticeable variations in psychotic phenotypes, reflecting disease-specific tendencies. Further studies focusing on the early stages of these disorders are necessary to enhance our understanding of early psychotic manifestations associated with ND and help in differential diagnosis issues. Show more

Keywords: Alzheimer’s disease, delusion, dementia, dementia with Lewy bodies, frontotemporal degeneration, hallucinations, neurodegenerative disease, psychosis

DOI: 10.3233/JAD-231363

Citation: Journal of Alzheimer's Disease, vol. 99, no. 1, pp. 85-99, 2024

Authors: Gabelle, Audrey | Dumurgier, Julien | Vercruysse, Olivier | Paquet, Claire | Bombois, Stéphanie | Laplanche, Jean-Louis | Peoc'h, Katell | Schraen, Susanna | Buée, Luc | Pasquier, Florence | Hugon, Jacques | Touchon, Jacques | Lehmann, Sylvain

Article Type: Research Article

Abstract: The French Alzheimer's Disease Plan aims, in an unprecedented national effort, to develop research, promote optimal diagnosis, and take better care of patients. In order to evaluate the clinical interest and use of cerebrospinal fluid (CSF) biomarkers, a data-sharing project, the PLM (Paris-North, Lille and Montpellier) study has emerged through collaboration between these memory centers, already involved in this field. The revised Alzheimer's disease (AD) diagnosis criteria include CSF biomarkers, but little is known about their use in routine clinical practice. To evaluate their interest and diagnostic accuracy in routine AD diagnosis, a cohort of 677 patients from Montpellier was …first analyzed. The results were then validated through the analysis of a second cohort of 638 patients from Lille and Paris-Nord. Diagnoses of AD and other dementias were established by multidisciplinary expert teams, based on neuropsychological exams and structural brain imaging, blinded from CSF results. CSF amyloid-β, tau, and p-tau concentrations were measured for all patients. Receiver-operating characteristic curves were used to define cut-offs and evaluate the ability of each biomarker to discriminate AD from other diagnoses. We showed that p-tau outperformed other biomarkers for discriminating AD from non-AD patients and presents a clear clinical interest. The other biomarkers also showed relevant variations especially when the differential AD diagnoses were taken into account. Altogether we could demonstrate in both mono-centric and multi-centric cohorts from memory clinics the capacity of CSF biomarkers to discriminate AD from non-AD patients in clinical routine with a high sensitivity and specificity. Show more

Keywords: Alzheimer's disease, amyloid-β peptides, cerebrospinal fluid biomarkers, cohort studies, dementia, p-tau

DOI: 10.3233/JAD-121549

Citation: Journal of Alzheimer's Disease, vol. 34, no. 1, pp. 297-305, 2013

Authors: Foucard, Cendrine | Palisson, Juliette | Belin, Catherine | Bereaux, Chloé | Dumurgier, Julien | Paquet, Claire | Degos, Bertrand | Bouaziz-Amar, Elodie | Maillet, Didier | Houot, Marion | Garcin, Béatrice

Article Type: Research Article

Abstract: Background: The TNI-93 is a quick memory test designed for all patients regardless of their education level. A significant proportion of patients with Alzheimer’s disease (AD) are illiterate or poorly educated, and only a few memory tests are adapted for these patients. Objective: In this study we aimed at assessing the diagnostic value of the TNI-93 for diagnosis of patients with biologically confirmed amyloid status. Methods: We included all patients who had an analysis of AD cerebrospinal fluid biomarkers, a neuropsychological assessment including a TNI-93 and an anatomical brain imaging at Avicenne Hospital between January 2009 and November 2019. We …compared the TNI-93 scores in patients with amyloid abnormalities (A+) and patients without amyloid abnormalities (A-) according to the AT(N) diagnostic criteria. Results: 108 patients were included (mean age: 66.9±8.5 years old, mean education level: 8.9±5.2 years). Patients from the A + group (N= 80) were significantly more impaired than patients from the A- group (N= 28) on immediate recall (A+: 5.9±2.8; A-: 7.4±2.6; p = 0.001), free recall (A+: 3.5±2.7; A-: 5.9±2.8; p ≤ 0.001), total recall (A+: 5.7±3.5; A-:7.8±2.8; p ≤ 0.001), and on number of intrusions during the recall phase (A+: 1±1.8; A-: 0.1±0.3; p = 0.002). ROC curves revealed that the best scores to discriminate A + from A- patients were immediate recall (Area under curve (AUC): 0.70), number of encoding trials (AUC: 0.73), free recall (AUC: 0.74), and total recall (AUC: 0.74). Conclusion: The TNI-93’s immediate, free, and total recalls are valuable tools for the 39 diagnosis of AD. Show more

Keywords: Alzheimer’s disease, AT(N), cerebrospinal fluid biomarkers, illiteracy, memory test, neuropsychology

DOI: 10.3233/JAD-210546

Citation: Journal of Alzheimer's Disease, vol. 84, no. 4, pp. 1461-1471, 2021

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