Simon Ducharme

• MD, MSc, FRCPC
• Professor at McGill University

INTRODUCTION We assessed the prognostic accuracy of plasma p‐tau217 in predicting the progression to mild cognitive impairment (MCI) in cognitively unimpaired (CU) individuals over a mean follow‐up of 5.65 years after plasma collection (range 1.01–10.47). METHODS We included 215 participants from the PREVENT−AD cohort with plasma Aβ42/40 and p‐tau...

Frontotemporal dementia (FTD) shows autosomal dominant transmission in up to a third of families, enabling the study of presymptomatic and prodromal phases. Despite self-reported well-being and normal daily cognitive functioning, brain structural changes are evident a decade or more before the expected onset of disease. This divergence between cogn...

Frontotemporal Dementia (FTD) is a prevalent form of early-onset dementia characterized by progressive neurodegeneration and encompasses a group of heterogeneous disorders. Due to overlapping symptoms, diagnosis of FTD and its subtypes still poses a challenge. Magnetic-resonance imaging (MRI) is commonly used to support the diagnosis of FTD. Using...

We used an untargeted mass spectrometric approach, tandem mass tag proteomics, for the identification of proteomic signatures in genetic frontotemporal dementia (FTD). A total of 238 cerebrospinal fluid (CSF) samples from the Genetic FTD Initiative were analyzed, including samples from 107 presymptomatic (44 C9orf72 , 38 GRN , and 25 MAPT ) and 55...

Lecanemab and donanemab are monoclonal antibody therapies that remove amyloid-beta from the brain. They are the first therapies that alter a fundamental mechanism, amyloid-beta deposition, in Alzheimer disease (AD). To inform Canadian decisions on approval and use of these drugs, the Canadian Consortium on Neurodegeneration in Aging commissioned Wo...

INTRODUCTION The phase 3 trial CLARITY AD found lecanemab slowed cognitive decline by 27%. However, subgroup analyses indicated a significant 31% sex difference in the effect and suggested no or limited effectiveness in females. We used simulations constrained by the trial design to determine whether that difference reflects a pre‐existing sex diff...

Background Mivelsiran (ALN‐APP) is an investigational, intrathecally administered RNA interference therapeutic designed to lower levels of amyloid‐β (Aβ) peptide, a key driver of Alzheimer’s disease (AD) and cerebral amyloid angiopathy (CAA) pathogenesis, by reducing upstream production of amyloid precursor protein (APP). We report additional safet...

Background There is a critical need for minimally‐invasive robust peripheral markers of neurodegenerative conditions. Peripheral RNA may be a powerful tool for in‐depth tracking of biological processes in AD and related disorders. Here, we combine whole‐blood microarray data from Alzheimer's Disease Neuroimaging Initiative (ADNI; N=743) and RNA‐Seq...

Background Sporadic bvFTD is often misdiagnosed as a primary psychiatric disorder (PPD) due to overlapping clinical features and lack of reliable biomarkers. The multi‐centre study DIPPA‐FTD aims to develop diagnostic‐ and prognostic‐algorithms that can distinguish sporadic bvFTD from late‐onset PPD. The aim of the retrospective DIPPA‐FTD study was...

The Canadian Consortium on Neurodegeneration in Aging (CCNA) was created by the Canadian federal government through its health research funding agency, the Canadian Institutes for Health Research (CIHR), in 2014, as a response to the G7 initiative to fight dementia. Two five-year funding cycles (2014–2019; 2019–2024) have occurred following peer re...

Background and purpose Behavioral variant frontotemporal dementia (bvFTD) is essentially characterized by progressive changes in personality and cognition. Clinically, bvFTD presents with often profound behavioral symptomatology. Despite the high burden of these symptoms for both patients and caregivers, there is no general consensus on an effectiv...

Background and objectives: Sleep dysfunction is common in patients with neurodegenerative disorders; however, its neural underpinnings remain poorly characterized in genetic frontotemporal dementia (FTD). Hypothalamic nuclei important for sleep regulation may be related to this dysfunction. Thus, we examined changes in hypothalamic structure acros...

Background and objectives: Pathogenic variants in the GRN gene cause frontotemporal dementia (FTD-GRN) with marked brain asymmetry. This study aims to assess whether the disease progression of FTD-GRN depends on the initial side of the atrophy. We also investigated the potential use of brain asymmetry as a biomarker of the disease. Methods: Retr...

A diagnosis of behavioral variant frontotemporal dementia (bvFTD) often relies on informant reports of significant behavioral changes. "BvFTD-by-proxy" describes situations of neuropsychiatric changes reported solely by an informant under circumstances that may raise questions regarding their objectivity. We present three cases of bvFTD-like sympto...

Accurate diagnosis of frontotemporal dementia (FTD) with right anterior temporal lobe (RATL) predominance remains challenging due to lack of clinical characterization, and standardized terminology. The recent research of the International Working Group (IWG) identified common symptoms but also unveiled broad terminologies lacking precision and oper...

INTRODUCTION Genetic mutation carriers of frontotemporal dementia can remain cognitively well despite neurodegeneration. A better understanding of brain structural, perfusion, and functional patterns in the pre‐symptomatic stage could inform accurate staging and potential mechanisms. METHODS We included 207 pre‐symptomatic genetic mutation carrier...

In this study, we propose a novel approach to uncover subgroup-specific and subgroup-common latent factors addressing the challenges posed by the heterogeneity of neurological and mental disorders, which hinder disease understanding, treatment development, and outcome prediction. The proposed approach, sparse Group Factor Analysis (GFA) with regula...

Background and Objective: 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. Behavioural and neuropsychiatric symptoms are frequent in genetic FTD. We aimed to describe behavioural and neuropsychiatric phenotypes in genet...

Background Long non-coding RNAs (lncRNAs) play crucial roles in gene regulation and are implicated in neurodegenerative diseases, including frontotemporal dementia (FTD). However, their expression patterns and potential as biomarkers in genetic FTD involving Chromosome 9 Open Reading Frame (C9ORF72), Microtubule Associated Protein Tau (MAPT), and P...

INTRODUCTION: The Phase 3 trial CLARITY AD found that lecanemab slowed cognitive decline by a statistically significant 27% vs. placebo. However, the subgroup analysis indicated a significant sex difference in the effect, and recent work has implied that lecanemab has either no or limited effectiveness in females. To resolve this ambiguity, we used...

INTRODUCTION Although frontotemporal dementia (FTD) with right anterior temporal lobe (RATL) predominance has been recognized, a uniform description of the syndrome is still missing. This multicenter study aims to establish a cohesive clinical phenotype. METHODS Retrospective clinical data from 18 centers across 12 countries yielded 360 FTD patien...

Frontotemporal Dementia (FTD) is a prevalent form of early-onset dementia characterized by progressive neurodegeneration. It encompasses a group of heterogeneous disorders, including behavioral variant frontotemporal dementia (bvFTD), nonfluent variant primary progressive aphasia (nfvPPA), and semantic variant primary progressive aphasia (svPPA). D...

The glymphatic system is an emerging target in neurodegenerative disorders. Here, we investigated the activity of the glymphatic system in genetic frontotemporal dementia with a diffusion-based technique called diffusion tensor image analysis along the perivascular space. We investigated 291 subjects with symptomatic or presymptomatic frontotempora...

Background Executive dysfunction is a core feature of frontotemporal dementia (FTD). Whilst there has been extensive research into such impairments in sporadic FTD, there has been little research in the familial forms. Methods 752 individuals were recruited in total: 214 C9orf72 , 205 GRN and 86 MAPT mutation carriers, stratified into asymptomatic...

Studying the oculomotor system provides a unique window to assess brain health and function in various clinical populations. Although the use of detailed oculomotor parameters in clinical research has been limited due to the scalability of the required equipment, the development of novel tablet-based technologies has created opportunities for fast,...

INTRODUCTION Effective longitudinal biomarkers that track disease progression are needed to characterize the presymptomatic phase of genetic frontotemporal dementia (FTD). We investigate the utility of cerebral perfusion as one such biomarker in presymptomatic FTD mutation carriers. METHODS We investigated longitudinal profiles of cerebral perfusi...

INTRODUCTION We aimed to expand the range of the frontotemporal dementia (FTD) phenotypes assessed by the Clinical Dementia Rating Dementia Staging Instrument plus National Alzheimer's Coordinating Center Behavior and Language Domains (CDR plus NACC FTLD). METHODS Neuropsychiatric and motor domains were added to the standard CDR plus NACC FTLD gen...

BACKGROUND AND AIMS: A robust feature characterizing frontotemporal dementia from other dementias are early deficits in social cognition. The salience and default networks, comprising groups of brain regions studied using resting-state functional connectivity (RSFC), are linked to the processing of emotionally salient stimuli and inferring others’...

INTRODUCTION: Cerebrovascular reactivity (CVR) is an indicator of cerebrovascular health and its signature in hereditary frontotemporal dementia (FTD) remains unknown. We investigated CVR in genetic FTD and its relationship to cognition. METHODS: CVR differences were assessed between 284 pre-symptomatic and 124 symptomatic mutation carriers, and 26...

INTRODUCTION: Gene carriers of frontotemporal dementia can remain cognitively well despite neurodegeneration. A better understanding of brain structural, perfusion and functional patterns in pre-symptomatic stage could inform accurate staging and potential mechanisms. METHODS: We included 207 pre-symptomatic carriers and 188 relatives without mutat...

The volume of the lateral ventricles is a reliable and sensitive indicator of brain atrophy and disease progression in behavioural variant frontotemporal dementia. In this study, we validate our previously developed automated tool using ventricular features (known as VentRa) for the classification of behavioural variant frontotemporal dementia vers...

Background Blood neurofilament light chain (NfL) is increasingly considered as a key trial biomarker in genetic frontotemporal dementia (gFTD). We aimed to facilitate the use of NfL in gFTD multicentre trials by testing its (1) reliability across labs; (2) reliability to stratify gFTD disease stages; (3) comparability between blood matrices and (4)...

Background The Genetic Frontotemporal Initiative Staging Group has proposed clinical criteria for the diagnosis of prodromal frontotemporal dementia (FTD), termed mild cognitive and/or behavioral and/or motor impairment (MCBMI). The objective of the study was to validate the proposed research criteria for MCBMI-FTD in a cohort of genetically confir...

Studying the oculomotor system provides a unique opportunity and window to assess brain health and function in various clinical populations. Although the use of detailed oculomotor parameters in clinical research has been limited due to the scalability of the required equipment, the development of novel tablet-based eye-tracking technologies has cr...

Background Frontotemporal dementia (FTD) is a neurodegenerative disorder characterized by heterogeneous clinical, pathological, and genetic features. Mutations in three genes account for the majority of autosomal dominant FTD: GRN , MAPT , and C9orf72 . We tested whether gene‐based aggregate burden of genome‐wide low frequency variants contribute t...

Background The CDR®+NACC FTLD Sum of Boxes (SB) score is a well‐established measure of disease severity in frontotemporal dementia (FTD), however, few studies have assessed longitudinal changes in score within familial forms of FTD. Method 343 participants from the Genetic FTD Initiative (77 mutation‐negative controls, 109 C9orf72 expansion carrie...

Background Frontotemporal dementia (FTD) is a neurodegenerative condition characterized by heterogeneous clinical, pathological, and genetic features. Mutations in three genes account for the majority of autosomal dominant FTD: GRN , MAPT , and C9orf72 . We tested whether gene‐based aggregate burden of genome‐wide low‐frequency variants contribute...

Background A novel panel of 14 proteins measured in the CSF could separate individuals with genetic frontotemporal dementia (FTD) from controls, with most significant findings observed for neurofilament medium (NEFM), neuronal pentraxin 2 (NPTX2), neurosecretory protein VGF (VGF) and aquaporin 4 (AQP4) [1]. However, it is currently unknown whether...

Background At present, there are limited fluid biomarkers which measure the underlying pathophysiology of frontotemporal dementia (FTD). Approximately a third of people with FTD have a genetic cause where the pathological basis is well understood. Studying fluid biomarkers in these genetic forms therefore allows greater insight into the relationshi...

Background Atrophy of thalamic subregions has been observed across the spectrum of frontotemporal dementia (FTD). To gain better insight into underlying tissue changes, we investigated how thalamic subregional fractional anisotropy (FA) and mean diffusivity (MD) derived from diffusion tensor imaging (DTI) are altered in genetic FTD. Method We used...

Background Randomized clinical trials of Alzheimer’s‐modifying drugs typically report a clinical effect as the final observation difference in means for a cognitive endpoint between treated and placebo groups. However, randomization of subjects naturally following different cognitive decline trajectories could produce a between‐group endpoint diffe...

Background Previous research in genetic frontotemporal dementia (FTD) has suggested that the FTD Rating Scale (FRS) may be a more sensitive measure of disease severity than the Clinical Dementia Rating scale plus National Alzheimer’s Coordinating Centre Frontotemporal Lobar Degeneration score (CDR+NACC FTLD). This study aims to assess the potential...

Background Adult‐onset behavioral changes and altered executive functioning are frequently caused by behavioural variant of Frontotemporal dementia (bvFTD) or primary psychiatric disorders (PPD) which overlap in terms of clinical presentations but differ in terms of treatment and prognosis. The multi‐centre study DIPPA‐FTD aims to develop diagnosti...

Background Genetic‐driven deregulation of the amyloid pathway and overproduction of downstream amyloid‐β are known to cause early‐onset Alzheimer’s disease (EOAD)¹. ALN‐APP is an investigational intrathecally (IT) administered RNAi therapeutic designed to reduce upstream intracellular and extracellular amyloid precursor protein (APP) levels by lowe...

Background Semantic and socioemotional knowledge, including person recognition, can be altered in frontotemporal dementia (FTD), and is often associated with the right temporal lobe variant. Using data from the Genetic FTD Initiative, we investigated person recognition deficits in genetic FTD. Method 901 GENFI participants (279 mutation negative c...

Background Pathogenic mutations in the progranulin gene ( GRN ) are a key cause of frontotemporal dementia (FTD), inducing a reduced biofluid concentration of the progranulin protein (PGRN). PGRN is a cysteine‐rich glycoprotein with essential roles in inflammation and lysosomal function, made up of 7 granulin peptides and 1 paragranulin. The role o...

Background Adult‐onset behavioral changes and altered executive functioning are frequently caused by behavioural variant of Frontotemporal dementia (bvFTD) or primary psychiatric disorders (PPD) which overlap in terms of clinical presentations but differ in terms of treatment and prognosis. The multi‐centre study DIPPA‐FTD aims to develop diagnosti...

Background The behavioral variant of frontotemporal dementia (bvFTD) is very heterogeneous in pathology, genetics, and disease course. Unlike Alzheimer’s disease, reliable biomarkers are lacking and sporadic bvFTD is often misdiagnosed as a primary psychiatric disorder (PPD) due to overlapping clinical features. Current efforts to characterize and...

Introduction: This study examined (1) whether measures of paternal anxious and depressive symptoms collected prenatally and during a follow-up assessment when the child was in middle childhood, predict child neuroendocrine outcomes, and (2) whether neuroendocrine outcomes are intermediate factors between paternal mental health and child cognitive/b...

Background Plasma biomarkers reflecting the pathology of frontotemporal dementia would add significant value to clinical practice, to the design and implementation of treatment trials as well as our understanding of disease mechanisms. The aim of this study was to explore the levels of multiple plasma proteins in individuals from families with gene...

Neuropsychiatrie symptoms (NPS) are common manifestations of neurodegenerative disorders and are often early signs of those diseases. Among those neurodegenerative diseases, TDP-43 proteinopathies are an increasingly recognized cause of early neuropsychiatrie manifestations. TDP-43-related diseases include frontotemporal dementia (FTD), amyotrophic...

INTRODUCTION. The salience network (SN) is central for processing salient stimuli and plays an interactive role with neurocognitive networks relevant to goal-oriented behaviour. A robust feature characterising frontotemporal dementia (FTD) from other dementias are early deficits in social cognition and atrophy in the anterior insula (aINS). Resting...

Background Sleep dysfunction is common in neurodegenerative disorders, however, its neural correlates, remain poorly characterized in genetic frontotemporal dementia (FTD). Atrophy in two hypothalamic nuclei, the suprachiasmatic nucleus and the lateral hypothalamic area, important for sleep regulation, may be related to this dysfunction. Thus, we e...

Background MRI has a central value in frontotemporal dementia (FTD) diagnostic workup. We set out to examine how MRI results impact FTD cases workup and clinician belief revision. Method Questionnaire to Neuropsychiatry International Consortium Frontotemporal Dementia (NIC‐FTD) members in February 2021 (n = 23) with follow‐up questionnaire in June...

Background Mutations in the C9orf72, GRN, or MAPT genes are the most prevalent genetic causes of familial frontotemporal dementia (FTD). In a cross‐sectional study of genetic FTD, lower CBF was observed in presymptomatic FTD mutation carriers vs. controls from the same families in 6 regions of interest: the bilateral anterior cingulate cortex, the...

The idea that eye movements can reflect certain aspects of brain function and inform on the presence of neurodegeneration is not a new one. Indeed, a growing body of research has shown that several neurodegenerative disorders, such as Alzheimer’s and Parkinson’s Disease, present characteristic eye movement anomalies and that specific gaze and eye m...

Objective: To identify whether language impairment exists presymptomatically in genetic frontotemporal dementia (FTD), and if so, the key differences between the main genetic mutation groups. Methods: 682 participants from the international multicentre Genetic FTD Initiative (GENFI) study were recruited: 290 asymptomatic and 82 prodromal mutatio...

(Awarded Best Poster at 5th Annual Healthy Brains, Healthy Lives 2023 Research Symposium). BACKGROUND AND AIM. The salience network (SN), comprising the anterior insula, dorsal anterior cingulate and other structures, is central in the processing of emotionally salient stimuli and directly influences other neurocognitive networks relevant to goal...

Tau plays a key role in Alzheimer’s disease (AD) pathophysiology, and accumulating evidence suggests that lowering tau may reduce this pathology. We sought to inhibit MAPT expression with a tau-targeting antisense oligonucleotide (MAPTRx) and reduce tau levels in patients with mild AD. A randomized, double-blind, placebo-controlled, multiple-ascend...

Biomarkers that can predict disease progression in individuals with genetic frontotemporal dementia are urgently needed. We aimed to identify whether baseline MRI-based grey and white matter abnormalities are associated with different clinical progression profiles in presymptomatic mutation carriers in the GENetic Frontotemporal dementia Initiative...

Recent studies have reported early cerebellar and subcortical impact 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 cerebello-subcortical circuitry in FTD has been understudied despite its essential...

Background: Neurotransmitters deficits in Frontotemporal Dementia (FTD) are still poorly understood. Better knowledge of neurotransmitters impairment, especially in prodromal disease stages, might tailor symptomatic treatment approaches. Methods: In the present study, we applied JuSpace toolbox, which allowed for cross-modal correlation of Magne...

Primary progressive aphasia is most commonly a sporadic disorder but in some cases it can be genetic. This study aimed to understand the clinical, cognitive and imaging phenotype of the genetic forms of primary progressive aphasia in comparison to the canonical nonfluent, semantic and logopenic subtypes seen in sporadic disease. Participants with g...

Objective: Sensitive cognitive markers are still needed for frontotemporal dementia (FTD). The Benson Complex Figure Test (BCFT) is an interesting candidate test, as it assesses visuospatial, visual memory, and executive abilities, allowing the detection of multiple mechanisms of cognitive impairment. To investigate differences in BCFT Copy, Recal...

Background Current clinical rating scales in frontotemporal dementia (FTD) often do not incorporate neuropsychiatric features and may therefore inadequately measure disease stage. Methods 832 participants from the Genetic FTD Initiative (GENFI) were recruited: 522 mutation carriers and 310 mutation-negative controls. The standardised GENFI clinica...

Clinical trials of new treatments in different progressive diseases use power analysis to determine the sample size needed for a trial to obtain a statistically significant estimate for an anticipated treatment effect. In trials with parallel designs, the standard power analysis approach is based on a two-sample t-test. For example, the standard t-...

Background Behavioural variant fronto-temporal 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, particula...

Background Long-term psychological impacts of the COVID-19 pandemic on healthcare workers remain unknown. We aimed to determine the one-year progression of burnout and mental health since pandemic onset, and verify if protective factors against psychological distress at the beginning of the COVID-19 pandemic (Cyr et al. in Front Psychiatry; 2021) r...

Frontotemporal dementia (FTD) is a complex disease that can initially present with subtle symptoms across several domains including behavior, cognitive/language, psychiatric and motor. This heterogenous prodromal phase is preceded by a slowly progressive presymptomatic accumulation of biological changes. With the emergence of new potential therapeu...

While frontotemporal dementia has been considered a neurodegenerative disease that starts in mid-life or later, it is now clearly established that cortical and subcortical volume loss is observed more than a decade prior to symptom onset and progresses with ageing. To test the hypothesis that genetic mutations causing frontotemporal dementia have n...

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...

Previous reported sex differences on disease duration (DD) of frontotemporal dementia (FTD) have been inconsistent and lack the comparison between genetic and sporadic FTD. Our aim was to study the difference in disease duration between males and females in genetic and sporadic FTD. Mortality data was obtained from 61 deceased patients with genetic...

Background and objectivesThe C9orf72 expansion is the most common genetic cause of frontotemporal dementia (FTD) and/or motor neuron disease (MND). Corticospinal degeneration has been described in post-mortem neuropathological studies in these patients, especially in those with MND. We used MRI to analyze white matter (WM) volumes in presymptomatic...

Increased age and cognitive impairment is associated with an increase in cerebrovascular pathology often measured as white matter hyperintensities (WMHs) on MRI. Whether WMH burden differs between cognitively unimpaired older adults with subjective cognitive decline (SCD +) and without subjective cognitive decline (SCD −) remains conflicting, and c...

Objective To investigate the optimal method of adding motor features to a clinical rating scale for frontotemporal dementia (FTD). Methods Eight hundred and thirty-two participants from the international multicentre Genetic FTD Initiative (GENFI) study were recruited: 522 mutation carriers (with C9orf72 , GRN and MAPT mutations) and 310 mutation-n...

OBJECTIVE: To investigate the optimal method of adding motor features to a clinical rating scale for frontotemporal dementia (FTD). METHODS: Eight hundred and thirty-two participants from the international multicentre Genetic FTD Initiative (GENFI) study were recruited: 522 mutation carriers (with C9orf72, GRN and MAPT mutations) and 310 mutation-n...

Alzheimer’s disease (AD) is a heterogeneous disorder with abnormalities in multiple biological domains. In an advanced machine learning analysis of postmortem brain and in vivo blood multi-omics molecular data ( N = 1863), we integrated epigenomic, transcriptomic, proteomic, and metabolomic profiles into a multilevel biological AD taxonomy. We obta...

Introduction: We tested whether changes in functional networks predict cognitive decline and conversion from the presymptomatic prodrome to symptomatic disease in familial frontotemporal dementia (FTD). Methods: For hypothesis generation, 36 participants with behavioral variant FTD (bvFTD) and 34 controls were recruited from one site. For hypoth...

Background: Neuroinflammation has been shown to be an important pathophysiological disease mechanism in frontotemporal dementia (FTD). This includes activation of microglia, a process that can be measured in life through assaying different glia-derived biomarkers in cerebrospinal fluid. However, only a few studies so far have taken place in FTD, a...

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...

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,...

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...

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...

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...

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...

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...

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...

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...