Simon Ducharme

Simon Ducharme
McGill University | McGill · Department of Psychiatry

MD, MSc, FRCPC

About

171
Publications
26,871
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Introduction
I'm an Associate-Professor in the Department of Psychiatry and an Associate Member of the Department of Neurology & Neurosurgery at McGill University. I'm a board certified Psychiatrist and hold a UCNS certification in Behavioral Neurology & Neuropsychiatry. I work at the Douglas Mental Health University Institute and the Montreal Neurological Institute. I'm a Faculty of the McConnell Brain Imaging Centre where I do neuroimaging research on brain development, aging and frontotemporal dementia.
Additional affiliations
July 2012 - June 2014
Harvard University
Position
  • Harvard Medical School
January 2011 - December 2012
McGill University
Education
July 2012 - June 2014
Harvard Medical School
Field of study
  • Behaviora Neurology & Neuropsychiatry
June 2009 - November 2011
McGill University
Field of study
  • Neuroimaging
July 2007 - June 2012
McGill University
Field of study
  • Psychiatry

Publications

Publications (171)
Article
Full-text available
Background Clinical endpoints for upcoming therapeutic trials in frontotemporal dementia (FTD) are increasingly urgent. Cognitive composite scores are often used as endpoints but are lacking in genetic FTD. We aimed to create cognitive composite scores for genetic frontotemporal dementia (FTD) as well as recommendations for recruitment and duration...
Article
Full-text available
Background Neuroinflammation is emerging as an important pathological process in frontotemporal dementia (FTD), but biomarkers are lacking. We aimed to determine the value of complement proteins, which are key components of innate immunity, as biomarkers in cerebrospinal fluid (CSF) and plasma of presymptomatic and symptomatic genetic FTD mutation...
Article
Unlike familial Alzheimer’s disease, we have been unable to accurately predict symptom onset in presymptomatic familial frontotemporal dementia (f-FTD) mutation carriers, which is a major hurdle to designing disease prevention trials. We developed multimodal models for f-FTD disease progression and estimated clinical trial sample sizes in C9orf72,...
Article
Full-text available
Background Approximately a third of frontotemporal dementia (FTD) is genetic with mutations in three genes accounting for most of the inheritance: C9orf72 , GRN , and MAPT . Impaired synaptic health is a common mechanism in all three genetic variants, so developing fluid biomarkers of this process could be useful as a readout of cellular dysfunctio...
Article
Full-text available
Dodich and colleagues recently reviewed the evidence supporting clinical use of social cognition assessment in behavioral variant frontotemporal dementia (Dodich et al., 2021). Here, we comment on their methods and present an initiative to address some of the limitations that emerged from their study. In particular, we established the social cognit...
Article
Full-text available
Background and Objectives Frontotemporal dementia (FTD) is a highly heritable disorder. The majority of genetic cases are caused by autosomal dominant pathogenic variants in the c9orf72 , GRN and MAPT gene. As motor disorders are increasingly recognized as part of the clinical spectrum the current study aimed to describe motor phenotypes caused by...
Article
Full-text available
Traditional methods for detecting asymptomatic brain changes in neurodegenerative diseases such as Alzheimer’s disease or frontotemporal degeneration (FTD) typically evaluate changes in volume at a predefined level of granularity, e.g. voxel-wise or in a priori defined cortical volumes of interest. Here we apply a method based on hierarchical spect...
Article
Background Onset of neuropsychiatric symptoms in older adults may represent prodromal manifestations of neurodegenerative disorders. The association between the onset of somatic symptom and related disorders (SSRD) and the subsequent development of neurodegenerative disorders remains unclear. Objectives To critically review studies describing the...
Article
The postacute sequelae of COVID-19 infection (PASC), also known as post-COVID condition or "long COVID," refers to symptoms that persist after the initial acute phase of the infection. PASC symptoms may occur in patients who had mild acute disease. On the basis of current data, commonly reported neurological and psychiatric symptoms in PASC include...
Poster
Frontotemporal dementia (FTD) is a neurodegenerative disease impacting 50% of people with dementia under the age of 60. A core feature of FTD is a deficit in social cognition. The salience network, a functionally connected assembly of brain regions including the anterior insula (aINS) and anterior cingulate, is impacted by FTD. The Genetic FTD Init...
Article
Full-text available
Background and objectives: Disease-modifying therapeutic trials for genetic frontotemporal dementia (FTD) are underway, but sensitive cognitive outcome measures are lacking. The aim of this study was to identify such cognitive tests in early stage FTD by investigating firstly, cognitive decline in a large cohort of genetic FTD pathogenic variant c...
Article
Full-text available
Objective A GGGGCC repeat expansion in the C9orf72 gene is the most common cause of genetic frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). As potential therapies targeting the repeat expansion are now entering clinical trials, sensitive biomarker assays of target engagement are urgently required. Our objective was to develop...
Preprint
Full-text available
Introduction Lateral ventricles are reliable and sensitive indicators of brain atrophy and disease progression in behavioral variant frontotemporal dementia (bvFTD). Here we validate our previously developed automated tool using ventricular features (known as VentRa) for the classification of bvFTD vs a mixed cohort of neurodegenerative, vascular,...
Article
Full-text available
Introduction A third of frontotemporal dementia (FTD) is caused by an autosomal-dominant genetic mutation in one of three genes: microtubule-associated protein tau ( MAPT ), chromosome 9 open reading frame 72 ( C9orf72 ) and progranulin ( GRN ). Prior studies of prodromal FTD have identified impaired executive function and social cognition early in...
Article
INTRODUCTION: A third of frontotemporal dementia (FTD) is caused by an autosomal-dominant genetic mutation in one of three genes: microtubule-associated protein tau (MAPT), chromosome 9 open reading frame 72 (C9orf72) and progranulin (GRN). Prior studies of prodromal FTD have identified impaired executive function and social cognition early in the...
Preprint
Background Behavioural variant frontotemporal dementia (bvFTD) is characterised by a progressive change in personality in association with atrophy of the frontal and temporal lobes. Whilst language impairment has been described in people with bvFTD, little is currently known about the extent or type of linguistic difficulties that occur, particular...
Article
Full-text available
Introduction: Behavioural dysfunction is a key feature of genetic frontotemporal dementia (FTD) but validated clinical scales measuring behaviour are lacking at present. Methods: We assessed behaviour using the revised version of the Cambridge Behavioural Inventory (CBI-R) in 733 participants from the Genetic FTD Initiative study: 466 mutation c...
Article
Connections among brain regions allow pathological perturbations to spread from a single source region to multiple regions. Patterns of neurodegeneration in multiple diseases, including behavioral variant of frontotemporal dementia (bvFTD), resemble the large-scale functional systems, but how bvFTD-related atrophy patterns relate to structural netw...
Article
Full-text available
Frontotemporal dementia in genetic forms is highly heterogeneous and begins many years to prior symptom onset, complicating disease understanding and treatment development. Unifying methods to stage the disease during both the presymptomatic and symptomatic phases are needed for the development of clinical trials outcomes. Here we used the contrast...
Article
Full-text available
Background Reduced empathy is a common symptom in frontotemporal dementia (FTD). Although empathy deficits have been extensively researched in sporadic cases, few studies have explored the differences in familial forms of FTD. Methods Empathy was examined using a modified version of the Interpersonal Reactivity Index (mIRI) in 676 participants fro...
Article
Frontotemporal dementia (FTD) associated with granulin (GRN) mutations presents asymmetric brain atrophy. We applied a Minimum Spanning Tree plus an Efficiency Cost Optimization (MST+ ECO) approach to cortical thickness data in order to test whether graph theory measures could identify global or local impairment of connectivity in the presymptomati...
Article
Full-text available
Introduction Lateral ventricles are reliable and sensitive indicators of brain atrophy and disease progression in behavioral variant frontotemporal dementia (bvFTD). We aimed to investigate whether an automated tool using ventricular features could improve diagnostic accuracy in bvFTD across neurodegenerative diseases. Methods Using 678 subjects -...
Article
Background: Magnetic resonance imaging (MRI) measures may be used as outcome markers in frontotemporal dementia (FTD). Objectives: To predict MRI cortical thickness (CT) at follow-up at the single subject level, using brain MRI acquired at baseline in preclinical FTD. Methods: 84 presymptomatic subjects carrying Granulin mutations underwent MR...
Preprint
Background: Approximately a third of frontotemporal dementia (FTD) is genetic with mutations in three genes accounting for most of the inheritance: C9orf72, GRN and MAPT . Impaired synaptic health is a common mechanism in all three genetic variants and so developing fluid biomarkers of this process could be useful as a readout of cellular dysfuncti...
Preprint
Full-text available
A GGGGCC repeat expansion in the C9orf72 gene is the most common cause of genetic frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). As potential therapies targeting the repeat expansion are now entering clinical trials, sensitive biomarker assays of target engagement are urgently required. We utilised the single molecule array...
Article
Full-text available
The presymptomatic stages of frontotemporal dementia (FTD) are still poorly defined and encompass a long accrual of progressive biological (preclinical) and then clinical (prodromal) changes, antedating the onset of dementia. The heterogeneity of clinical presentations and the different neuropathological phenotypes have prevented a prior clear desc...
Article
Full-text available
Background Although social cognitive dysfunction is a major feature of frontotemporal dementia (FTD), it has been poorly studied in familial forms. A key goal of studies is to detect early cognitive impairment using validated measures in large patient cohorts. Methods We used the Revised Self-Monitoring Scale (RSMS) as a measure of socioemotional...
Article
Full-text available
Background A detailed understanding of the pathological processes involved in genetic frontotemporal dementia is critical in order to provide the patients with an optimal future treatment. Protein levels in CSF have the potential to reflect different pathophysiological processes in the brain. We aimed to identify and evaluate panels of CSF proteins...
Article
White matter hyperintensities (WMHs) are commonly assumed to represent non-specific cerebrovascular disease comorbid to neurodegenerative processes, rather than playing a synergistic role. We compared the impact of WMHs on grey matter (GM) atrophy and cognition in normal aging (N=571), mild cognitive impairment (MCI, N=551), Alzheimer's dementia (A...
Article
Full-text available
Background The COVID-19 pandemic has put chronic pressure on worldwide healthcare systems. While the literature regarding the prevalence of psychological distress and associated risk factors among healthcare workers facing COVID-19 has exploded, biological variables have been mostly overlooked. Methods 467 healthcare workers from Quebec, Canada, a...
Article
Frontotemporal dementia (FTD) is a progressive neurodegenerative disorder associated with atrophy of the frontal and/or anterior temporal lobes, it is highly heterogeneous and represents about 5% of all cases of dementia and it is one of the most common causes of early‐onset dementia (Onyike and Diehl‐Schmid, 2013). FTD syndromes can be divided int...
Article
Development of endpoints for clinical trials in frontotemporal dementia (FTD) is increasingly urgent. In other neurodegenerative diseases composite scores are often used as outcome measures but are, as of yet, lacking in FTD. The aim of this study was to create gene‐specific cognitive composite scores for MAPT, GRN and C9orf72 mutation carriers and...
Article
Approximately a third of frontotemporal dementia (FTD) is genetic with mutations in three genes accounting for the majority of the inheritance: C9orf72, GRN and MAPT. Synaptic dysfunction is a common mechanism in all of them and the use of fluid biomarkers could be helpful to improve the diagnostic accuracy and useful as a readout of cellular dysfu...
Article
Genetic frontotemporal dementia is highly heterogeneous, with different progression patterns seen between individuals. Using in vivo MR images from the Genetic FTD Initiative (GENFI), we aimed to identify clinical progression in genetic mutation carriers from their brain volumes at baseline. Cortical and subcortical volumes of interest (VOIs) were...
Article
Genetic frontotemporal dementia (FTD) is highly heterogeneous, with carriers of mutations in the same gene manifesting different phenotypes. Using in vivo MR images from the Genetic FTD Initiative (GENFI), we aimed to identify subgroups within the same genetic group whose brains were affected differently. Cortical and subcortical volumes of interes...
Article
Several fluid biomarkers for genetic frontotemporal dementia (FTD) have been proposed, including those reflecting neuroaxonal loss (neurofilament light chain (NfL) and phosphorylated neurofilament heavy chain (pNfH)), synapse dysfunction (neuronal pentraxin 2 (NPTX2)), gliosis (glial fibrillary acidic protein (GFAP)) and complement activation (C3b,...
Article
Mutations in MAPT are associated with frontotemporal dementia (FTD), but little is known about the progression in its early stages. We aimed at identifying the presence of early brain changes in MAPT mutation carriers. We included 3T MRIs from 84 MAPT carriers [27 symptomatic: mean(SD) age 58(8) years; 57 presymptomatic: 40(11) years] from the Gene...
Article
The reported sex distribution differs between frontotemporal dementia (FTD) cohorts. Possible explanations are the evolving clinical criteria of FTD and its subtypes and the discovery of FTD causal genetic mutations that have resulted in variable findings. Our aim was to determine the sex distribution in a large international retrospective cohort o...
Article
Patients in the early stages of AD dementia experience decline in their cognitive abilities at different rates. Accurately predicting the progression rate would enable the enrichment of patient populations in clinical trials. Using the early AD‐related pattern of atrophy and cognitive scores from a baseline visit, we trained a model to predict cogn...
Article
In the absence of a pathologic genetic mutation, diagnostic certainty of the behavioral variant frontotemporal dementia (bvFTD) still relies on convergence of clinical criteria and imaging findings. Using deformation‐based morphometry (DBM), we recently showed that ventricular volume can discriminate bvFTD from cognitively normal controls (CN)1. He...
Article
Accurately predicting the progression rate in patients with mild cognitive impairment and mild dementia due to AD enables enrichment of trial populations. Here, we evaluate the potential use of our prognostic model (Abstract #54217) as a screening tool for enrichment in clinical trials in early AD. Data included 312 patients with mild AD from the A...
Article
Frontotemporal dementia is a highly heterogeneous disorder and neurodegeneration begins years prior to symptom onset, complicating disease understanding and treatment. Here we used an unsupervised machine learning algorithm to identify disease sub‐trajectories in genetic frontotemporal dementia. The contrastive trajectory inference (cTI, available...
Article
Connections among brain regions allow pathological perturbations to spread from a single source node to multiple nodes. Patterns of neurodegeneration in multiple diseases, including behavioral variant of frontotemporal dementia (bvFTD), resemble the network architecture (Seeley et al., 2009, Neuron), but how bvFTD‐related atrophy patterns relate to...
Preprint
Full-text available
Recent studies have suggested that cerebellar and subcortical structures are impacted early in the disease progression of genetic frontotemporal dementia (FTD) due to microtubule-associated protein tau (MAPT), progranulin (GRN) and chromosome 9 open reading frame 72 (C9orf72). However, the clinical contribution of the structures involved in the cer...
Article
Full-text available
Objective While the presymptomatic stages of frontotemporal dementia (FTD) provide a unique chance to delay or even prevent neurodegeneration by early intervention, they remain poorly defined. Leveraging a large multicentre cohort of genetic FTD mutation carriers, we provide a biomarker-based stratification and biomarker cascade of the likely most...
Article
Full-text available
Tau is one of several proteins associated with frontotemporal dementia (FTD). While knowing which protein is causing a patient’s disease is crucial, no biomarker currently exists for identifying tau in vivo in FTD. The objective of this study was to investigate the potential for the promising [18F]MK-6240 positron emission tomography (PET) tracer t...
Article
Full-text available
Several CSF and blood biomarkers for genetic frontotemporal dementia (FTD) have been proposed, including those reflecting neuroaxonal loss (neurofilament light chain (NfL) and phosphorylated neurofilament heavy chain (pNfH)), synapse dysfunction (neuronal pentraxin 2 (NPTX2)), astrogliosis (glial fibrillary acidic protein (GFAP)), and complement ac...
Article
Full-text available
Background: Reported sex distributions differ between frontotemporal dementia (FTD) cohorts. Possible explanations are the evolving clinical criteria of FTD and its subtypes and the discovery of FTD causal genetic mutations that has resulted in varying demographics. Objective: Our aim was to determine the sex distribution of sporadic and genetic...
Article
Full-text available
Background: While both cognitive and magnetic resonance imaging (MRI) data has been used to predict progression in Alzheimer's disease, heterogeneity between patients makes it challenging to predict the rate of cognitive and functional decline for individual subjects. Objective: To investigate prognostic power of MRI-based biomarkers of medial t...
Preprint
Full-text available
Background: Clinical endpoints for upcoming therapeutic trials in frontotemporal dementia (FTD) are increasingly urgent. Cognitive composite scores are often used as endpoints but are lacking in genetic FTD. We aimed to create cognitive composite scores for genetic frontotemporal dementia (FTD) and recommend on recruitment and duration in clinical...
Article
Background The presymptomatic brain changes of granulin (GRN) disease, preceding by years frontotemporal dementia (FTD), has not been fully characterized. New approaches focus on the spatial chronnectome can capture both spatial network configurations and their dynamic changes over time. Objective To investigate the spatial dynamics in 141 presymp...
Preprint
Full-text available
Connections among brain regions allow pathological perturbations to spread from a single source region to multiple regions. Patterns of neurodegeneration in multiple diseases, including behavioral variant of frontotemporal dementia (bvFTD), resemble the large-scale functional systems, but how bvFTD-related atrophy patterns relate to structural netw...
Article
Full-text available
Standard templates are widely used in human neuroimaging processing pipelines to facilitate group-level analyses and comparisons across subjects/populations. MNI-ICBM152 template is the most commonly used standard template, representing an average of 152 healthy young adult brains. However, in patients with neurodegenerative diseases such as fronto...
Article
Full-text available
Background Therapeutic trials are now underway in genetic forms of frontotemporal dementia (FTD) but clinical outcome measures are limited. The two most commonly used measures, the Clinical Dementia Rating (CDR)+National Alzheimer’s Disease Coordinating Center (NACC) Frontotemporal Lobar Degeneration (FTLD) and the FTD Rating Scale (FRS), have yet...
Article
Full-text available
Objective: This study examined how best to identify modifiable protective and risk factors for burnout in healthcare workers in the face of the COVID-19 pandemic. Individual, occupational, organizational and social factors were investigated. The study also assessed the impact of these factors on post-traumatic stress disorder (PTSD), anxiety, and d...
Article
Full-text available
Background and Objective Mutations in the MAPT gene cause frontotemporal dementia (FTD). Most previous studies investigating the neuroanatomical signature of MAPT mutations have grouped all different mutations together and shown an association with focal atrophy of the temporal lobe. However, the variability in atrophy patterns between each particu...
Article
Full-text available
Introduction: We aimed to assess episodic memory in genetic frontotemporal dementia (FTD) with the Free and Cued Selective Reminding Test (FCSRT). Methods: The FCSRT was administered in 417 presymptomatic and symptomatic mutation carriers (181 chromosome 9 open reading frame 72 [C9orf72], 163 progranulin [GRN], and 73 microtubule-associated prot...
Article
Full-text available
Objective We tested the hypothesis that plasma neurofilament light chain (NfL) identifies asymptomatic carriers of familial frontotemporal lobar degeneration (FTLD)-causing mutations at risk of disease progression. Methods Baseline plasma NfL concentrations were measured with Simoa in original (n = 277) and validation (n = 297) cohorts. C9orf72 ,...
Article
Introduction Structural brain imaging is paramount for the diagnosis of behavioural variant of frontotemporal dementia (bvFTD), but it has low sensitivity leading to erroneous or late diagnosis. Methods A total of 515 subjects from two different bvFTD cohorts (training and independent validation cohorts) were used to perform voxel-wise morphometri...
Preprint
Full-text available
INTRODUCTION: Lateral ventricles are reliable and sensitive indicators of brain atrophy and disease progression in behavioral variant frontotemporal dementia (bvFTD). We aimed to investigate whether an automated tool using ventricular features could improve diagnostic accuracy in bvFTD across neurodegenerative diseases. METHODS: Using 678 subjects...
Article
Full-text available
In the last few years, a significant amount of work has aimed to characterize maturational trajectories of cortical development. The role of pericortical microstructure putatively characterized as the gray-white matter contrast (GWC) at the pericortical gray-white matter boundary and its relationship to more traditional morphological measures of co...