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1. Statin Use and Incidence of Parkinson's Disease in Women from the French <scp>E3N</scp> Cohort Study

Author

Thi Thu Ha Nguyen, Agnès Fournier, Émeline Courtois, Fanny Artaud, Sylvie Escolano, Pascale Tubert‐Bitter, Marie‐Christine Boutron‐Ruault, Isabelle Degaey, Emmanuel Roze, Marianne Canonico, Ismaïl Ahmed, Anne C.M. Thiébaut, Alexis Elbaz, HAL UVSQ, Équipe, APPEL À PROJETS GÉNÉRIQUE 2018 - Facteurs de risque de la Maladie de Parkinson chez les femmes de la cohorte E3N - - PARKIN-WOMEN2018 - ANR-18-CE36-0006 - AAPG2018 - VALID, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Sorbonne Université (SU), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), 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), T.T.H.N. was supported by post‐doctoral grants from the Michael J Fox foundation and the France Parkinson association. E.C. was supported by post‐doctoral grants from the Michael J Fox foundation. F.A. reports no disclosures. S.E. reports no disclosures. P.T.‐B. reports no disclosures. M.‐C.B.‐R. received speaker fees in 2020 from MAYOLI‐SPINDLER and GILEAD outside the field of the present paper. I.D. reports no disclosures. E.R. received honorarium for speech from Orkyn Aguettant, Elivie and for participating in an advisory board from Allergan and has received research support from Merz‐Pharma, Orkyn, Aguettant, Elivie, Ipsen, Allergan, Everpharma, Fondation Desmarest, AMADYS, ADCY5.org , ANR, Societé Française de Médecine Esthétique, and Dystonia Medical Research Foundation. M.C. has obtained research grant from French National Research Agency (ANR). I.A. reports no disclosures. A.C.M.T. reports no disclosures. A.E. has obtained research grants from Plan Ecophyto (French ministry of agriculture) and France Parkinson., T.T.H.N. was supported by postdoctoral grants from The Michael J. Fox Foundation and the France Parkinson Association. E.C. was supported by postdoctoral grants from The Michael J. Fox foundation. F.A., S.E., P.T.‐B., I.A., and A.C.M.T. report no disclosures. M.‐C.B.‐R. received speaker fees in 2020 from Mayoli‐Spindler and Gilead outside the field of the present article. I.D. reports no disclosures. E.R. received honorarium for speeches from Orkyn Aguettant and Elivie and for participating in an advisory board from Allergan and has received research support from Merz‐Pharma, Orkyn, Aguettant, Elivie, Ipsen, Allergan, Everpharma, Fondation Desmarest, AMADYS, ADCY5.org , French National Research Agency (ANR), Societé Française de Médecine Esthétique, and the Dystonia Medical Research Foundation. M.C. obtained a research grant from the ANR. A.E. has obtained research grants from Plan Ecophyto (French Ministry of Agriculture) and France Parkinson Association. The work reported in this article was performed during A.F.'s term as a visiting scientist at the International Agency for Research on Cancer. The authors declare no other relationships or activities that could appear to have influenced the submitted work. Relevant conflicts of interest/financial disclosures, This work was realized with data of the E3N cohort (INSERM) and supported by the Mutuelle Générale de l'Education Nationale (MGEN), Gustave Roussy Institute, and French League against Cancer for the constitution and maintenance of the cohort. This work has benefited from State aid managed by the National Research Agency (ANR) under the program 'Investment in the future' bearing the reference ANR‐10‐COHO‐0006 and under the program 'Young researcher' bearing the reference ANR‐18‐CE36‐0006‐01, as well as a subsidy from the Ministry of Higher Education, Research and Innovation for public service charges bearing the reference N°2102918823, 2103236497, and 2103586016, and from IRESP (Institut de Recherche En Santé Publique). The authors acknowledge all women enrolled in the E3N cohort for their continued participation. They are also grateful to all members of the E3N study group., This project was funded by the Michael J. Fox Foundation for Parkinson's Research and the France Parkinson Association. Funding agencies., and ANR-18-CE36-0006,PARKIN-WOMEN,Facteurs de risque de la Maladie de Parkinson chez les femmes de la cohorte E3N(2018)

Subjects
[SDV] Life Sciences [q-bio], pharmacoepidemiology, cohort studies, drug repurposing, Neurology, Parkinson's disease, [SDV]Life Sciences [q-bio], Neurology (clinical), statins
Abstract

International audience; Background: Statins represent candidates for drug repurposing in Parkinson's disease (PD). Few studies examined the role of reverse causation, statin subgroups, and dose–response relations based on time-varying exposures. Objectives: We examined whether statin use is associated with PD incidence while attempting to overcome the limitations described previously, especially reverse causation. Method: We used data from the E3N cohort study of French women (follow-up, 2004–2018). Incident PD was ascertained using multiple sources and validated by experts. New statin users were identified through linked drug claims. We set up a nested case-control study to describe trajectories of statin prescriptions and medical consultations before diagnosis. We used time-varying multivariable Cox proportional hazards regression models to examine the statins–PD association. Exposure indexes included ever use, cumulative duration/dose, and mean daily dose and were lagged by 5 years to address reverse causation. Results: The case-control study (693 cases, 13,784 controls) showed differences in case-control trajectories, with changes in the 5 years before diagnosis in cases. Of 73,925 women (aged 54–79 years), 524 developed PD and 11,552 started using statins in lagged analyses. Ever use of any statin was not associated with PD (hazard ratio [HR] = 0.87, 95% confidence interval [CI] = 0.67–1.11). Alternatively, ever use of lipophilic statins was significantly associated with lower PD incidence (HR = 0.70, 95% CI = 0.51–0.98), with a dose–response relation for the mean daily dose (P-linear trend = 0.02). There was no association for hydrophilic statins. Conclusion: Use of lipophilic statins at least 5 years earlier was associated with reduced PD incidence in women, with a dose–response relation for the mean daily dose. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

Published
2023

2. Long-term risk of stroke and its predictors in transient ischaemic attack patients in Germany

Author

Karel Kostev, Louis Jacob, Christian Tanislav, Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), and The authors have received no financial support for the research, authorship and/or publication of this paper.

Subjects
Male, associated predictors, Cohort Studies, 0302 clinical medicine, general practices, Germany, Atrial Fibrillation, 030212 general & internal medicine, Stroke, Aged, 80 and over, Incidence, Hazard ratio, Age Factors, Atrial fibrillation, Middle Aged, stroke, 3. Good health, Neurology, Ischemic Attack, Transient, Hypertension, Cohort, Platelet aggregation inhibitor, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Risk, medicine.medical_specialty, transient ischaemic attack, 03 medical and health sciences, Sex Factors, Diabetes mellitus, Internal medicine, parasitic diseases, medicine, Humans, long-term risk, In patient, cardiovascular diseases, Aged, Ischemic Stroke, business.industry, Anticoagulants, Protective Factors, medicine.disease, nervous system diseases, Long term risk, Neurology (clinical), business, Platelet Aggregation Inhibitors, 030217 neurology & neurosurgery
Abstract

International audience; Background and purpose: Little is known about the long-term association between transient ischaemic attack (TIA) and stroke. Therefore, the goal of this study was to analyze the long-term risk of stroke and associated predictors in a large cohort of TIA patients followed in general practices in Germany. Methods: This study included patients with an initial TIA diagnosis and subsequently followed up in one of 1262 general practices in Germany between January 2007 and December 2016 (N = 19 824 patients). The primary outcome of the study was the risk of ischaemic stroke within 10 years of the initial diagnosis of TIA. The secondary outcome was the identification of demographic, clinical and pharmaceutical variables significantly associated with stroke in TIA patients. Results: Within 10 years of the initial TIA diagnosis, 18.3% of individuals were diagnosed with stroke. Age was positively associated with stroke, with hazard ratios ranging from 1.88 in patients aged 51–60 years to 4.00 in those aged >80 years (reference group: patients aged ≤50 years). Furthermore, male sex, hypertension, diabetes mellitus, atrial fibrillation and ischaemic heart diseases had an additional impact on the risk of stroke. Finally, new oral anticoagulants, heparins, diuretics, angiotensin II receptor blockers and platelet aggregation inhibitors were identified as protective factors. Conclusions: In a cohort of almost 20 000 TIA patients, 18.3% were diagnosed with stroke within 10 years after the TIA index event. Several demographic, clinical and pharmaceutical variables significantly predicted the long-term risk of stroke in TIA patients.

Published
2020

3. Advantages and disadvantages of the use of the CSF Amyloid β (Aβ) 42/40 ratio in the diagnosis of Alzheimer’s Disease

Author

Markus Otto, Henrik Zetterberg, Piotr Lewczuk, Oskar Hansson, Sylvain Lehmann, Clinical Memory Research Unit [Malmö, Suède], Department of Clinical Sciences [Malmö, Suède], Lund University [Malmö, Suède]-Lund University [Malmö, Suède], Memory Clinic [Malmö, Suède], Skåne University Hospital [Malmö, Suède], Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Department of Neurology [Ulm, Allemagne], Universität Ulm - Ulm University [Ulm, Allemagne], Clinical Neurochemistry Laboratory [Göteborg, Suède], Department of Psychiatry and Neurochemistry [Goteborg], Institute of Neuroscience and Physiology [Göteborg]-Sahlgrenska Academy at University of Gothenburg [Göteborg]-Institute of Neuroscience and Physiology [Göteborg]-Sahlgrenska Academy at University of Gothenburg [Göteborg], Department of Neurodegenerative Disease [Londres, Royaume-Uni], Institute of Neurology [London], University College of London [London] (UCL)-University College of London [London] (UCL), UK Dementia Research Institute (UK DRI), University College of London [London] (UCL), Department of Psychiatry and Psychotherapy [Erlangen, Allemagne], Universitätsklinikum Erlangen [Erlangen, Allemagne], Friedrich-Alexander Universität Erlangen-Nürnberg (FAU)-Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), Department of Neurodegeneration Diagnostics [Bialystok, Pologne], Medical University of Bialystok [Bialystok, Pologne], Lab for Clinical Neurochemistry and Neurochemical Dementia Diagnostics [Erlangen, Allemagne], Friedrich-Alexander Universität Erlangen-Nürnberg (FAU)-Friedrich-Alexander Universität Erlangen-Nürnberg (FAU)-Universitätsklinikum Erlangen [Erlangen, Allemagne], Fujirebio Europe sponsored this paper, however, it had no influence on its factual content. PL was supported by the Innovative Medicines Initiative Joint Undertaking under EMIF grant agreement n° 115372, resources of which are composed of financial contribution from the European Union’s Seventh Framework Programme (FP7/2007-2013) and EFPIA companies’ in kind contribution. OH has acquired research support (for the institution) from Roche, GE Healthcare, Biogen, AVID Radiopharmaceuticals, Fujirebio and Euroimmun. HZ’s research is supported by the Swedish Research Council, the European Research Council, the Knut and Alice Wallenberg Foundation, the Olav Thon Foundation, the UK Dementia Research Institute at UCL and Swedish State Support for Clinical Research (ALFGBG)., Lund University [Lund]-Lund University [Lund], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Medical University of Białystok (MUB), and Bodescot, Myriam

Subjects
0301 basic medicine, Oncology, medicine.medical_specialty, Neurology, Amyloid β, Cognitive Neuroscience, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Diagnostic accuracy, Disease, Review, Aβ 42/40 ratio, Alzheimer's Disease, lcsh:RC346-429, lcsh:RC321-571, 03 medical and health sciences, 0302 clinical medicine, Cerebrospinal fluid, Medizinische Fakultät, Alzheimer Disease, Internal medicine, medicine, Dementia, Humans, ddc:610, Alzheimer’s Disease, Cognitive impairment, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, Biochemical markers, lcsh:Neurology. Diseases of the nervous system, Cerebrospinal Fluid, Amyloid beta-Peptides, [SDV.MHEP.GEG] Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, business.industry, [SDV.MHEP.GEG]Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, medicine.disease, Peptide Fragments, 030104 developmental biology, Aβ42/40 ratio, Neurology (clinical), business, 030217 neurology & neurosurgery, Amyloidβ Peptides, Biomarkers
Abstract

International audience; The cerebrospinal fluid (CSF) biochemical markers (biomarkers) Amyloidβ 42 (Aβ42), total Tau (T-tau) and Tau phosphorylated at threonine 181 (P-tau181) have proven diagnostic accuracy for mild cognitive impairment and dementia due to Alzheimer's Disease (AD). In an effort to improve the accuracy of an AD diagnosis, it is important to be able to distinguish between AD and other types of dementia (non-AD). The concentration ratio of Aβ42 to Aβ40 (Aβ42/40 Ratio) has been suggested to be superior to the concentration of Aβ42 alone when identifying patients with AD. This article reviews the available evidence on the use of the CSF Aβ42/40 ratio in the diagnosis of AD. Based on the body of evidence presented herein, it is the conclusion of the current working group that the CSF Aβ42/40 ratio, rather than the absolute value of CSF Aβ42, should be used when analysing CSF AD biomarkers to improve the percentage of appropriately diagnosed patients.

Published
2019

4. Disentangling the attention network test: behavioral, event related potentials, and neural source analyses

Author

Guillermo Izquierdo, Manuel Vázquez-Marrufo, Alejandro Galvao-Carmona, Dolores Páramo, María Luisa Benítez, Javier J. Gonzalez-Rosa, Antonio R. Hidalgo-Muñoz, [Galvao-Carmona,A, Hidalgo-Muñoz,AR, Vázquez-Marrufo,M] Psychophysiology Unit (Lab B508), Department of Experimental Psychology, Faculty of Psychology, University of Seville, Seville, Spain. [González-Rosa,JJ] Laboratory for Clinical Neuroscience, Centre of Biomedical Technology (CTB), Technical University of Madrid (UPM), Madrid, Spain. [Páramo,D, Izquierdo,G] Multiple Sclerosis Unit, Virgen Macarena University Hospital, Seville, Spain. [Benítez,ML] Department of Physiotherapy, Faculty of Nursing, University of Seville, Seville, Spain., This study was supported by Plan Nacional I+D+i (Ministerio de Economía y Competitividad, Government of Spain, PSI2010- 16825), Asociación Neuroinvest and Asociación Sanitaria Virgen Macarena. which has greatly improved this paper, Universidad de Sevilla. Departamento de Psicología Experimental, Universidad de Sevilla. Departamento de Fisioterapia, and Ministerio de Economía y Competitividad (MINECO). España

Subjects
CNV, Neurociencias, Sensory system, source analysis, lcsh:RC321-571, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Behavioral Neuroscience, Psychiatry and Psychology::Psychological Phenomena and Processes::Mental Processes::Learning::Cues [Medical Subject Headings], Psychiatry and Psychology::Psychological Phenomena and Processes::Mental Processes [Medical Subject Headings], Disciplines and Occupations::Natural Science Disciplines::Biological Science Disciplines::Neurosciences [Medical Subject Headings], Event-related potential, Attention network, Ssource analysis, Psychiatry and Psychology::Psychological Phenomena and Processes::Psychophysiology::Arousal::Attention [Medical Subject Headings], Orienting, Phenomena and Processes::Physiological Phenomena::Electrophysiological Phenomena::Evoked Potentials [Medical Subject Headings], Attention, Original Research Article, P300, Source analysis, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, Biological Psychiatry, Expectancy theory, Artificial neural network, orienting, Information processing, Psychiatry and Psychology::Behavior and Behavior Mechanisms::Adaptation, Psychological::Orientation [Medical Subject Headings], neural networks, attention, Psychiatry and Mental health, Neuropsychology and Physiological Psychology, Neurology, Potenciales evocados, alerting, Procesos mentales, Basic level, ANT, Alerting, Psychology, Neuroscience, Neural networks
Abstract

Background: The study of the attentional system remains a challenge for current neuroscience. The “Attention Network Test” (ANT) was designed to study simultaneously three different attentional networks (alerting, orienting, and executive) based in subtraction of different experimental conditions. However, some studies recommend caution with these calculations due to the interactions between the attentional networks. In particular, it is highly relevant that several interpretations about attentional impairment have arisen from these calculations in diverse pathologies. Event related potentials (ERPs) and neural source analysis can be applied to disentangle the relationships between these attentional networks not specifically shown by behavioral measures. Results: This study shows that there is a basic level of alerting (tonic alerting) in the no cue (NC) condition, represented by a slow negative trend in the ERP trace prior to the onset of the target stimuli. A progressive increase in the CNV amplitude related to the amount of information provided by the cue conditions is also shown. Neural source analysis reveals specific modulations of the CNV related to a task-related expectancy presented in the NC condition; a late modulation triggered by the central cue (CC) condition and probably representing a generic motor preparation; and an early and late modulation for spatial cue (SC) condition suggesting specific motor and sensory preactivation. Finally, the first component in the information processing of the target stimuli modulated by the interaction between orienting network and the executive system can be represented by N1. Conclusions: The ANT is useful as a paradigm to study specific attentional mechanisms and their interactions. However, calculation of network effects is based in subtractions with non-comparable experimental conditions, as evidenced by the present data, which can induce misinterpretations in the study of the attentional capacity in human subjects. Ministerio de Economía y Competitividad PSI2010- 16825

Published
2014