Olivier Blin's research while affiliated with Aix-Marseille Université and other places

Publications (262)

Article
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Medical use of cannabis has been receiving growing attention over the last few decades in modern medicine. As we know that the endocannabinoid system is largely involved in neurological disorders, we focused on the scientific rationale of medical cannabis in three neurological disorders: amyotrophic lateral sclerosis, Parkinson’s disease, and Alzhe...
Article
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Background: Local anesthetic systemic toxicity (LAST) has been reported as a serious complication of local anesthetic (LA) peripheral injection. The signs and symptoms of LAST are highly variable, and the challenge remains to confirm its diagnosis. In this context, the determination of LA plasma concentration appears as a valuable tool to confirm...
Article
Full-text available
Alzheimer’s disease (AD) is the most frequent neurodegenerative disease with an increasing prevalence in industrialized, aging populations. AD susceptibility has an established genetic basis which has been the focus of a large number of genomewide association studies (GWAS) published over the last decade. Most of these GWAS used dichotomized clinic...
Article
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The BDNF Val66Met gene polymorphism is a relevant factor explaining inter-individual differences to TMS responses in studies of the motor system. However, whether this variant also contributes to TMS-induced memory effects, as well as their underlying brain mechanisms, remains unexplored. In this investigation, we applied rTMS during encoding of a...
Preprint
Full-text available
Alzheimer's disease (AD) is the most frequent neurodegenerative disease with an increasing prevalence in industrialized, ageing populations. AD susceptibility has an established genetic basis which has been the focus of a large number of genome-wide association studies (GWAS) published over the last decade. Most of these GWAS used dichotomized clin...
Article
Full-text available
Background: physiological differences between males and females could contribute to the development of Alzheimer's Disease (AD). Here, we examined metabolic pathways that may lead to precision medicine initiatives. Methods: We explored whether sex modifies the association of 540 plasma metabolites with AD endophenotypes including diagnosis, cere...
Article
Background: Previous studies reported default mode network (DMN) and limbic network (LIN) brain perfusion deficits in patients with amnestic mild cognitive impairment (aMCI), frequently a prodromal stage of Alzheimer's disease (AD). However, the validity of these measures as AD markers has not yet been tested using MRI arterial spin labeling (ASL)...
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Introduction: Neurofilament light (NfL), chitinase-3-like protein 1 (YKL-40), and neurogranin (Ng) are biomarkers for Alzheimer's disease (AD) to monitor axonal damage, astroglial activation, and synaptic degeneration, respectively. Methods: We performed genome-wide association studies (GWAS) using DNA and cerebrospinal fluid (CSF) samples from...
Article
Introduction Mood disorders are severe yet frequent psychiatric disorders worldwide, comprising major depressive disorder (MDD) and bipolar disorders (BD). Their treatment remains poorly effective. For the past decades, various pathophysiological processes have been explored and growing evidence for epigenetic mechanisms has emerged. Consequently,...
Preprint
BACKGROUND: Physiological differences between males and females could contribute to the development of AD. Here, we examined metabolic pathways that may lead to precision medicine initiatives. METHODS: We explored whether sex modifies the association of 540 plasma metabolites with AD endophenotypes including diagnosis, CSF biomarkers, brain imaging...
Article
Full-text available
Introduction: This study sought to discover and replicate plasma proteomic biomarkers relating to Alzheimer's disease (AD) including both the "ATN" (amyloid/tau/neurodegeneration) diagnostic framework and clinical diagnosis. Methods: Plasma proteins from 972 subjects (372 controls, 409 mild cognitive impairment [MCI], and 191 AD) were measured u...
Article
Brain vascular damage accumulate in aging and often manifest as white matter hyperintensities (WMHs) on MRI. Despite increased interest in automated methods to segment WMHs, a gold standard has not been achieved and their longitudinal reproducibility has been poorly investigated. The aim of present work is to evaluate accuracy and reproducibility o...
Poster
The amygdala and the hippocampus are two limbic structures that play a critical role in cognition and behaviour but their small size hampers their manual segmentation in multicenter datasets. Here, we assessed the reliability of the automated segmentation of amygdalar nuclei and hippocampal subfields across sites and vendors. We applied a new high‐...
Article
Clinical trials involving brain disorders are notoriously difficult to set up and run. Innovative ways to develop effective prevention and treatment strategies for central nervous system (CNS) diseases are urgently needed. New approaches that are likely to renew or at least modify the paradigms used so far have been recently proposed. Quantitative...
Article
Alzheimer’s disease is associated with increases in amyloid β and hyperphosphorylated tau which is thought to occur decades before the onset of clinical symptoms, leading to cell loss and inhibition. Finding biomarkers to detect these changes before neuronal loss and therefore permanent damage has occurred is integral. Current biomarkers using cere...
Article
Neurodegenerative, amyloid and vascular pathologies have all been associated with cognitive performance, but their interrelationship remains uncertain. We investigated the associations between cerebrospinal fluid (CSF) neurofilament light (NfL), a biomarker for neurodegeneration, with four different cognitive measures in individuals with mild cogni...
Article
The National Institute on Aging‐Alzheimer’s Association (NIA‐AA) proposed the ATN framework as a classification system for Alzheimer’s disease. The ATN framework helps to inform participant inclusion and potentially trial outcomes as clinical trials are increasingly targeting a range of pathologies. However, it is limited by biomarkers that are eit...
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•We have developed a framework to describe the dynamics of Functional Connectivity (dFC) estimated from brain activity time-series as a complex random walk in the space of possible functional networks. This conceptual and methodological framework considers dFC as a smooth reconfiguration process, combining "liquid" and "coordinated" aspects. Unlike...
Article
Full-text available
Alzheimer’s disease (AD) is the most prevalent neurodegenerative disorder and the most common form of dementia in the elderly. Susceptibility to AD is considerably determined by genetic factors which hitherto were primarily identified using case–control designs. Elucidating the genetic architecture of additional AD-related phenotypic traits, ideall...
Article
Therapeutic drug monitoring (TDM) of hydroxychloroquine has been recommended to optimize the treatment of COVID-19 patients. The authors describe an ultra-high-performance liquid chromatography tandem spectrometry ( UHPLC-MS/MS) method developed in a context of emergency, to analyze hydroxychloroquine (HCQ) in both human plasma and blood samples.Af...
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Dynamic Functional Connectivity (dFC) in the resting state (rs) is considered as a correlate of cognitive processing. Describing dFC as a flow across morphing connectivity configurations, our notion of dFC speed quantifies the rate at which FC networks evolve in time. Here we probe the hypothesis that variations of rs dFC speed and cognitive perfor...
Preprint
Full-text available
Background Neurofilament light (NF-L), chitinase-3-like protein 1 (YKL-40), and neurogranin (Ng) are utilized as biomarkers for Alzheimer’s disease (AD), to monitor axonal damage, astroglial activation, and synaptic degeneration, respectively. Here we performed genome-wide association study (GWAS) analyses using all three biomarkers as outcome. Me...
Article
Purpose/background: Alzheimer disease (AD) is a public health issue because of the low number of symptomatic drugs and the difficulty to diagnose it at the prodromal stage. The need to develop new treatments and to validate sensitive tests for early diagnosis could be met by developing a challenge model reproducing cognitive impairments of AD. The...
Article
Full-text available
Background The amygdala and the hippocampus are two limbic structures that play a critical role in cognition and behavior, however their manual segmentation and that of their smaller nuclei/subfields in multicenter datasets is time consuming and difficult due to the low contrast of standard MRI. Here, we assessed the reliability of the automated se...
Article
For management of osteoarticular infections (OAI), rifampicin appears to be the key antibiotic. We aimed to evaluate the actual rifampicin dosing regimens using a population pharmacokinetic model of rifampicin in patients with OAI. A Monte Carlo simulation study was performed to simulate steady‐state plasma concentrations for 1,000 randomly sampled...
Article
Objectif Les objectifs de cette étude était de tester les effets pharmacodynamiques du donépézil (inhibiteur de la cholinestérase) et de la mémantine (antagoniste des récepteurs NMDA) sur les troubles cognitifs induits par 24 heures de privation de sommeil (PS). Méthodes Vingt-deux volontaires sains de sexe masculin ont participé à l’étude. Tous o...
Article
Clinical development for orphan drugs is extremely demanding but fascinating. There is no single aspect that is really specific to it but instead it gathers most of the hurdles: design, outcomes, recruitment, Ethics, cost, probability and predictability for success. To overcome these difficulties, there has to be a great collaboration between acade...
Article
The research and drug development process in rare diseases is challenging in addition to those for common diseases. To stimulate its development, the orphan drug designation (ODD) was introduced in in European Union in 2000. In the present paper, we describe the main characteristics of ODD in European Union in particular the requested criteria for...
Article
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We have previously investigated, discovered, and replicated plasma protein biomarkers for use to triage potential trials participants for PET or cerebrospinal fluid measures of Alzheimer's disease (AD) pathology. This study sought to undertake validation of these candidate plasma biomarkers in a large, multi-center sample collection. Targeted plasm...
Preprint
Full-text available
Dynamic Functional Connectivity (dFC) in the resting state (rs) is considered as a correlate of cognitive processing. Describing dFC as a flow across morphing connectivity configurations, our notion of dFC speed quantifies the rate at which FC networks evolve in time. Here we probe the hypothesis that variations of rs dFC speed and cognitive perfor...
Article
Résumé Si la France dispose de nombreux atouts dans le domaine de la santé pour devenir un leader de l’innovation (l’excellence de ses équipes de recherche, la renommée de son système de santé et de nombreuses startups), force est de constater qu’elle cumule des freins culturels et réglementaires qui limitent une interaction agile et performante en...
Article
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Introduction: Machine learning (ML) may harbor the potential to capture the metabolic complexity in Alzheimer Disease (AD). Here we set out to test the performance of metabolites in blood to categorize AD when compared to CSF biomarkers. Methods: This study analyzed samples from 242 cognitively normal (CN) people and 115 with AD-type dementia ut...
Article
Although France has numerous assets in the realm of health care, such as the excellence of its research teams, the reputation of its healthcare system, and the presence of many startups, all of which are necessary to become a leader in innovation, it also has combined cultural and regulatory barriers that limit the flexibility and efficiency of int...
Article
Amyloid and tau pathological accumulation should be considered for Alzheimer's disease (AD) definition and before subjects' enrollment in disease-modifying trials. Although age, APOEε4, and sex influence cerebrospinal fluid (CSF) biomarker levels, none of these variables are considered by current normality/abnormality cutoffs. Using baseline CSF da...
Preprint
Full-text available
INTRODUCTION: Machine learning (ML) may harbor the potential to capture the metabolic complexity in Alzheimer's Disease (AD). Here we set out to test the performance of metabolites in blood to categorise AD when compared to CSF biomarkers. METHODS: This study analysed samples from 242 cognitively normal (CN) people and 115 with AD-type dementia uti...
Preprint
Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder and the most common form of dementia in the elderly. Susceptibility to AD is considerably determined by genetic factors which hitherto were primarily identified using case-control designs. Elucidating the genetic architecture of additional AD-related phenotypic traits, ideall...
Article
Introduction: Plasma proteins have been widely studied as candidate biomarkers to predict brain amyloid deposition to increase recruitment efficiency in secondary prevention clinical trials for Alzheimer's disease. Most such biomarker studies are targeted to specific proteins or are biased toward high abundant proteins. Methods: 4001 plasma prot...
Article
Background and Objective: Nasal carriage of Staphylococcus aureus (S. aureus) constitutes an important risk factor for subsequent infections in some types of patient populations. Decolonization of carriers using intranasal mupirocin is widely used as a preventive measure. However, resistance to this agent has been rising and causing failure in the...
Article
Objective: It has been reported that sleep deprivation affects the neurophysiological mechanisms underpinning the vigilance. Here, we tested the following hypotheses in the PharmaCog project (www.pharmacog.org): (i) sleep deprivation may alter posterior cortical delta and alpha sources of resting state eyes-closed electroencephalographic (rsEEG) r...
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p>INTRODUCTION: Plasma biomarkers for Alzheimer's disease (AD) diagnosis/stratification are a "Holy Grail" of AD research and intensively sought; however, there are no well-established plasma markers. METHODS: A hypothesis-led plasma biomarker search was conducted in the context of international multicenter studies. The discovery phase measured 53...
Article
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Introduction: A critical and as-yet unmet need in Alzheimer's disease (AD) is the discovery of peripheral small molecule biomarkers. Given that brain pathology precedes clinical symptom onset, we set out to test whether metabolites in blood associated with pathology as indexed by cerebrospinal fluid (CSF) AD biomarkers. Methods: This study analy...
Article
Introduction: Staphylococcus aureus (S. aureus) infections are associated with increased morbidity, mortality and health-care costs. Persistent nasal carriage of S. aureus found in 10–30% of the general population, constitutes a risk factor for these infections. Nasal decolonization is one of the used strategies to prevent this risk in some situati...
Article
Background: Assessment of human brain atrophy in temporal regions using magnetic resonance imaging (MRI), resting state functional MRI connectivity in the left parietal cortex, and limbic electroencephalographic (rsEEG) rhythms as well as plasma amyloid peptide 42 (Aβ42) has shown that each is a promising biomarker of disease progression in amnest...
Article
Full-text available
Introduction: Plasma biomarkers for Alzheimer's disease (AD) diagnosis/stratification are a "Holy Grail" of AD research and intensively sought; however, there are no well-established plasma markers. Methods: A hypothesis-led plasma biomarker search was conducted in the context of international multicenter studies. The discovery phase measured 53...
Article
Introduction: We investigated relations between amyloid-β (Aβ) status, apolipoprotein E (APOE) ε4, and cognition, with cerebrospinal fluid markers of neurogranin (Ng), neurofilament light (NFL), YKL-40, and total tau (T-tau). Methods: We included 770 individuals with normal cognition, mild cognitive impairment, and Alzheimer's disease (AD)-type...
Article
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Auditory "oddball" event-related potentials (aoERPs), resting state functional magnetic resonance imaging (rsfMRI) connectivity, and electroencephalographic (rsEEG) rhythms were tested as longitudinal functional biomarkers of prodromal Alzheimer's disease (AD). Data were collected at baseline and four follow-ups at 6, 12, 18, and 24 months in amnes...
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Purpose: Tumescent lidocaine anesthesia (TLA) is an opportunity to perform mastectomy for breast cancer without general anesthesia in elderly women. Few reports are available on the pharmacokinetics of lidocaine in a context of TLA during a unilateral mastectomy. The aim of this study was to describe lidocaine pharmacokinetics in elderly women und...
Article
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Up to 30% of the human population are asymptomatically and permanently colonized with nasal Staphylococcus aureus. To successfully colonize human nares, S. aureus needs to establish solid interactions with human nasal epithelial cells and overcome host defense mechanisms. However, some factors like bacterial interactions in the human nose can influ...
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Background: With the shift of research focus towards the pre-dementia stage of Alzheimer's disease (AD), there is an urgent need for reliable, non-invasive biomarkers to predict amyloid pathology. The aim of this study was to assess whether easily obtainable measures from structural MRI, combined with demographic data, cognitive data and apolipopr...
Article
Full-text available
It is an open issue whether blood biomarkers serve to diagnose Alzheimer's disease (AD) or monitor its progression over time from prodromal stages. Here, we addressed this question starting from data of the European FP7 IMI-PharmaCog/E-ADNI longitudinal study in amnesic mild cognitive impairment (aMCI) patients including biological, clinical, neuro...