A5043890316- Dementia and Cognitive Impairment Research
- Alzheimer's disease research and treatments
- Functional Brain Connectivity Studies
- Advanced Neuroimaging Techniques and Applications
- Medical Imaging Techniques and Applications
- Health, Environment, Cognitive Aging
- Neurological Disease Mechanisms and Treatments
- Neuroinflammation and Neurodegeneration Mechanisms
- Bioinformatics and Genomic Networks
- Advanced MRI Techniques and Applications
- S100 Proteins and Annexins
- Tryptophan and brain disorders
- Radiomics and Machine Learning in Medical Imaging
- Genetic Associations and Epidemiology
- Neurological Disorders and Treatments
- Retinal Imaging and Analysis
- Pharmacogenetics and Drug Metabolism
- Parkinson's Disease Mechanisms and Treatments
- Brain Tumor Detection and Classification
- Computational Drug Discovery Methods
- Bipolar Disorder and Treatment
- Histone Deacetylase Inhibitors Research
- Cerebrovascular and Carotid Artery Diseases
- Neurobiology of Language and Bilingualism
- Epigenetics and DNA Methylation
McGill University
2016-2025
Montreal Neurological Institute and Hospital
2016-2025
Douglas Mental Health University Institute
2015-2024
Centre Intégré Universitaire de Santé et de Services Sociaux du Centre-Sud-de-l'Île-de-Montréal
2020-2022
Centre Intégré Universitaire de Santé et de Services Sociaux du Saguenay–Lac-Saint-Jean
2020-2022
Alzheimer’s Disease Neuroimaging Initiative
2022
McGill University Health Centre
2017-2020
National Neuroscience Institute
2017-2018
Ministry of Education
2018
HEC Montréal
2018
18F-THK5351 is a quinoline-derived tau imaging agent with high affinity to paired helical filaments (PHF). However, levels of retention in brain regions thought contain negligible concentrations PHF raise questions about the interpretation positron emission tomography (PET) signals, particularly given previously described interactions between quinolone derivatives and monoamine oxidase B (MAO-B). Here, we tested effects MAO-B inhibition on uptake using PET autoradiography. Eight participants...
Studies of rodent models Alzheimer's disease (AD) and human tissues suggest that the retinal changes occur in AD, including accumulation amyloid beta (Aβ), may serve as surrogate markers brain Aβ levels. As has a wavelength-dependent effect on light scatter, we investigate potential for vivo hyperspectral imaging to biomarker Aβ. Significant differences reflectance spectra are found between individuals with high burden PET mild cognitive impairment (n = 15), age-matched PET-negative controls...
Braak stages of tau neurofibrillary tangle accumulation have been incorporated in the criteria for neuropathological diagnosis Alzheimer's disease. It is expected that staging using brain imaging can stratify living individuals according to their individual patterns deposition, which may prove crucial clinical trials and practice. However, previous studies first-generation PET agents shown a low sensitivity detect pathology areas corresponding early histopathological (∼20% cognitively...
<h3>Importance</h3> Apolipoprotein E ε4 (<i>APOEε4</i>) is the single most important genetic risk factor for Alzheimer disease. While<i>APOEε4</i>is associated with increased amyloid-β burden, its association cerebral tau pathology has been controversial. <h3>Objective</h3> To determine whether<i>APOEε4</i>is medial temporal independently of amyloid-β, sex, clinical status, and age. <h3>Design, Setting, Participants</h3> This a study 2 cross-sectional cohorts volunteers who were cognitively...
Imaging agents capable of quantifying the brain's tau aggregates will allow a more precise staging Alzheimer's disease (AD). The aim present study was to examine in vitro properties as well vivo kinetics, using gold standard methods, novel positron emission tomography (PET) imaging agent [18F]MK-6240.In [18F]MK-6240 were estimated with autoradiography postmortem brain tissues 14 subjects (seven AD patients and seven age-matched controls). In quantification binding performed 16 (four...
Abstract Introduction Mild behavioral impairment (MBI) is characterized by the emergence of neuropsychiatric symptoms in elderly persons. Here, we examine associations between MBI and Alzheimer's disease (AD) biomarkers asymptomatic individuals. Methods Ninety‐six cognitively normal individuals underwent MRI, [ 18 F]AZD4694 β‐amyloid‐PET, F]MK6240 tau‐PET. was assessed using Checklist (MBI‐C). Pearson's correlations voxel‐based regressions were used to evaluate relationship MBI‐C score...
This study was designed to test the interaction between amyloid-β and tau proteins as a determinant of metabolic decline in preclinical Alzheimer's disease (AD). We assessed 120 cognitively normal individuals with [18F]florbetapir positron emission tomography (PET) cerebrospinal fluid (CSF) measurements at baseline, well [18F]fluorodeoxyglucose ([18F]FDG) PET baseline 24 months. A voxel-based model built associations continuous CSF biomarkers, [18F]FDG standardized uptake value ratios...
Identifying individuals destined to develop Alzheimer's dementia within time frames acceptable for clinical trials constitutes an important challenge design studies test emerging disease-modifying therapies. Although amyloid-β protein is the core pathologic feature of disease, biomarkers neuronal degeneration are only ones believed provide satisfactory predictions progression short frames. Here, we propose a machine learning–based probabilistic method designed assess 24 months, based on...
Recent literature proposes that amyloid β (Aβ) and phosphorylated tau (p-tau) synergism accelerates biomarker abnormalities in controls. Yet, it remains to be answered whether this is the driving force behind Alzheimer disease (AD) dementia.We stratified 314 mild cognitive impairment individuals using [18F]florbetapir positron emission tomography Aβ imaging cerebrospinal fluid p-tau. Regression voxel-based logistic regression models with interaction terms evaluated 2-year changes cognition...
Neurofilament light (NfL) is a marker of neuroaxonal injury, prominent feature Alzheimer's disease. It remains uncertain, however, how it relates to amyloid and tau pathology or neurodegeneration across the disease continuum. The aim this study was investigate plasma NfL PET MRI measures brain atrophy in participants with without cognitive impairment. We retrospectively examined association between grey/white matter volumes Disease Neuroimaging Initiative [ADNI: n = 1149; 382 cognitively...
Tracking longitudinal tau tangles accumulation across the Alzheimer's disease continuum is crucial to better understand natural history of pathology and for clinical trials. Although available first-generation PET tracers detect in symptomatic individuals, their nanomolar affinity offers limited sensitivity early asymptomatic subjects. Here, we hypothesized novel subnanomolar tracer 18F-MK-6240 can We studied 125 living individuals (65 cognitively unimpaired elderly amyloid-β-negative, 22...
APOEε4 is the most well-established genetic risk factor for sporadic Alzheimer's disease and associated with cerebral amyloid-β. However, association between tau pathology, other major proteinopathy of disease, has been controversial. Here, we sought to determine whether relationship pathology determined by local interactions We examined three independent samples cognitively unimpaired, mild cognitive impairment subjects: (1) 211 participants who underwent tau-PET [18F]MK6240 amyloid-PET...
Abstract INTRODUCTION Tau‐positron emission tomography (PET) outcome data of patients with Alzheimer's disease (AD) cannot currently be meaningfully compared or combined when different tracers are used due to differences in tracer properties, instrumentation, and methods analysis. METHODS Using head‐to‐head from five cohorts tau PET radiotracers designed target deposition AD, we tested a joint propagation model (JPM) harmonize quantification (units termed “CenTauR” [CTR]). JPM is statistical...
In healthy individuals, behavioral outcomes are highly associated with the variability on brain regional structure or neurochemical phenotypes. Similarly, in context of neurodegenerative conditions, neuroimaging reveals that cognitive decline is linked to magnitude atrophy, declines, concentrations abnormal protein aggregates across regions. However, modeling effects multiple abnormalities as determinants at voxel level remains largely unexplored by multimodal imaging research, given high...
<h3>Objective:</h3> To identify regional brain metabolic dysfunctions associated with neuropsychiatric symptoms (NPS) in preclinical Alzheimer disease (AD). <h3>Methods:</h3> We stratified 115 cognitively normal individuals into AD (both amyloid and tau pathologies present), asymptomatic at risk for (either or pathology healthy controls (no present) using [<sup>18</sup>F]florbetapir PET CSF phosphorylated biomarkers. Regression voxel-based regression models evaluated the relationships...
Abstract The link between brain amyloid-β (Aβ), metabolism, and dementia symptoms remains a pressing question in Alzheimer’s disease. Here, using positron emission tomography ([ 18 F]florbetapir tracer for Aβ [ F]FDG glucose metabolism) with novel analytical framework, we found that aggregation within the brain’s default mode network leads to regional hypometabolism distant but functionally connected regions. Moreover, an interaction this overlapping is associated subsequent cognitive...
To identify the pathophysiologic mechanisms and clinical significance of anosognosia for cognitive decline in mild impairment.We stratified 468 patients with amnestic impairment into intact impaired awareness groups, determined by discrepancy between patient informant score on Everyday Cognition questionnaire. Voxel-based linear regression models evaluated associations self-awareness status baseline β-amyloid load, measured [18F]florbetapir, relationships regional brain glucose metabolism...
Neurofilament light chain (NfL) is a promising blood biomarker to detect neurodegeneration in Alzheimer's disease (AD) and other brain disorders. However, there are limited reports of how longitudinal NfL relates imaging biomarkers. We herein investigated the relationship between metabolism AD.Voxelwise regression models tested cross-sectional association [18F]fluorodeoxyglucose ([18F]FDG) both plasma cerebrospinal fluid cognitively impaired unimpaired subjects. Linear mixed were also used...
Abstract Background To investigate the association of plasma pTau181, assessed with a new immunoassay, neurodegeneration white matter and gray cross-sectionally longitudinally, in aging Alzheimer’s disease. Methods Observational data was obtained from Disease Neuroimaging Initiative, which participants underwent assessment magnetic resonance imaging. Based on their clinical diagnosis, were classified as cognitively unimpaired impaired. Linear regressions linear mixed-effect models used to...
Abstract Background Neuropsychiatric symptoms (NPS) are frequent in aging and Alzheimer's disease (AD). Here we study the relationship between NPS AD pathologies vivo. Method Two hundred twenty‐one individuals from TRIAD cohort (143 cognitively unimpaired, 52 mild cognitive impairment, 26 AD) underwent [ 18 F]MK6240‐tau‐positron emission tomography (PET), F]AZD4694‐amyloid‐PET, magnetic resonance imaging, neuropsychological evaluations. Spearman correlations voxel‐based regression models...
Abstract Alzheimer’s disease is the leading cause of dementia worldwide and characterized by a long preclinical phase in which amyloid-β tau accumulate absence cognitive decline. In vivo biomarkers for are expensive, invasive inaccessible, yet critical accurate diagnosis patient management. Recent ultrasensitive methods to measure plasma phosphorylated 181 (p-tau181) display strong correlations with positron emission tomography, p-tau181 CSF, pathology at autopsy. The clinical utility...