Rose Bruffaerts

• MD PhD
• Tenure-track professor at University of Antwerp

Cross-linguistic studies with healthy individuals are vital, as they can reveal typologically common and different patterns while providing tailored benchmarks for patient studies. Nevertheless, cross-linguistic differences in narrative speech production, particularly among speakers of languages belonging to distinct language families, have been in...

Background An early and accurate diagnosis is crucial to provide optimal patient care in neurodegenerative diseases. Although an EEG shows advantages in availability and cost compared to the current diagnostic tools, it is not routinely used in clinical practice. Previous reviews have either focused on single disease populations and/or solely on re...

Objectives To highlight the worldwide presence of CSF1R-related disorder (CSF1R-RD), discuss its penetrance, and provide the first haplotype analysis. Methods Data on patients worldwide were collected, including demographics, genotype, family history, and clinical status. For haplotype analysis, polymorphisms of short tandem repeats in 3 distinct...

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: CSF1R-related disorder (CSF1R-RD) is a rare hereditary neurodegenerative disease manifesting with neurological symptoms, congenital and acquired brain abnormalities, and skeletal dysplasia. CSF1R-RD may be caused by mono- and bi-allelic CSF1R mutations, and depending on the age of symptomatic onset (AOO), is subdivided into early- (<18...

Frontotemporal dementia (FTD) is a neurodegenerative disease spectrum with an urgent need for reliable biomarkers for early diagnosis and monitoring. Speech and language changes occur in the early stages of FTD and offer a potential non-invasive, early, and accessible diagnostic tool. The use of speech and language markers in this disease spectrum...

Purpose Metabolic network analysis of FDG-PET utilizes an index of inter-regional correlation of resting state glucose metabolism and has been proven to provide complementary information regarding the disease process in parkinsonian syndromes. The goals of this study were (i) to evaluate pattern similarities of glucose metabolism and network connec...

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...

Although neuropsychiatric symptoms are a hallmark of the behavioral variant of frontotemporal degeneration (FTD), there is limited evidence on the optimal therapeutic management of these symptoms. In this issue, Katisko et al. report real-world multicentric data on the use of psychopharmacological medication in newly diagnosed patients with FTD. Su...

Introduction: Artificial intelligence (AI) and neuroimaging offer new opportunities for diagnosis and prognosis of dementia. Methods: We systematically reviewed studies reporting AI for neuroimaging in diagnosis and/or prognosis of cognitive neurodegenerative diseases. Results: A total of 255 studies were identified. Most studies relied on the...

Advances in artificial intelligence have cultivated a strong interest in developing and validating the clinical utilities of computer-aided diagnostic models. Machine learning for diagnostic neuroimaging has often been applied to detect psychological and neurological disorders, typically on small-scale datasets or data collected in a research setti...

Making meaningful inferences about the functional architecture of the language system requires the ability to refer to the same neural units across individuals and studies. Traditional brain imaging approaches align and average brains together in a common space. However, lateral frontal and temporal cortex, where the language system resides, is cha...

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...

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 In recent years, neuroimaging with deep learning (DL) algorithms have made remarkable advances in the diagnosis of neurodegenerative disorders. However, applying DL in different medical domains is usually challenged by lack of labeled data. To address this challenge, transfer learning (TL) has been applied to use state-of-the-art convolu...

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...

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...

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...

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...

Blood-based (BB) biomarkers for Aβ and tau can indicate pathological processes in the brain, in the early pathological, even pre-symptomatic stages in Alzheimer’s disease. However, the relation between BB biomarkers and AD-related processes in the brain in the earliest pre-pathology stage before amyloid pathology develops, and their relation with t...

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...

Background and purposeThe Oxford Cognitive Screen is a stroke-specific screen to evaluate attention, executive functions, memory, praxis, language, and numeric cognition. It was originally validated in England for acute stroke patients. In this study, we examined the psychometric properties of the Dutch OCS (OCS-NL).MethodsA total of 193 (99 acute...

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...

Recent mechanistic models argue for a key role of rhythm processing in both speech production and speech perception. Patients with the non-fluent variant (NFV) of primary progressive aphasia (PPA) with apraxia of speech (AOS) represent a specific study population in which this link can be examined. Previously, we observed impaired rhythm processing...

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...

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...

Purpose The purpose of this study is to develop and validate a 3D deep learning model that predicts the final clinical diagnosis of Alzheimer’s disease (AD), dementia with Lewy bodies (DLB), mild cognitive impairment due to Alzheimer’s disease (MCI-AD), and cognitively normal (CN) using fluorine 18 fluorodeoxyglucose PET (18F-FDG PET) and compare m...

Conscious processing of word meaning can be guided by attention. In this event-related functional magnetic resonance imaging study in 22 healthy young volunteers, we examined in which regions orienting attention to two fundamental and generic dimensions of word meaning, concreteness versus valence, alters the semantic representations coded in activ...

Introduction

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...

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...

Background and purpose The optimal management of post-stroke cognitive impairment (PSCI) remains controversial. These joint European Stroke Organisation (ESO) and European Academy of Neurology (EAN) guidelines provide evidence-based recommendations to assist clinicians in decision making regarding prevention, diagnosis, treatment and prognosis. Me...

Introduction The optimal management of post stroke cognitive impairment remains controversial. These joint European Stroke Organisation (ESO) and European Academy of Neurology (EAN) guidelines provide evidence-based recommendations to assist clinicians in decision making around prevention, diagnosis, treatment, and prognosis. Methods Guidelines we...

Introduction: The optimal management of post stroke cognitive impairment remains controversial. These joint European Stroke Organisation (ESO) and European Academy of Neurology (EAN) guidelines provide evidence-based recommendations to assist clinicians in decision making around prevention, diagnosis, treatment, and prognosis. Methods: These guidel...

Evidence from model organisms and clinical genetics suggests coordination between the developing brain and face, but the role of this link in common genetic variation remains unknown. We performed a multivariate genome-wide association study of cortical surface morphology in 19,644 individuals of European ancestry, identifying 472 genomic loci infl...

Purpose The purpose of this study is to develop and validate a 3D deep learning model that predicts the final clinical diagnosis of Alzheimer’s disease (AD), Dementia with Lewy Bodies (DLB), Mild Cognitive Impairment due to Alzheimer’s disease (MCI-AD), and cognitively normal (CN) using fluorine 18 fluorodeoxyglucose PET (¹⁸F-FDG PET) and compare m...

Amyotrophic lateral sclerosis (ALS) has long been considered to be a purely motor disorder. However, it has become apparent that many ALS patients develop cognitive and behavioral manifestations similar to frontotemporal dementia and the term amyotrophic lateral sclerosis-frontotemporal spectrum disorder (ALS-FTSD) is now used in these circumstance...

Introduction: We assessed the influence of education as a proxy of cognitive reserve and age on the dementia with Lewy bodies (DLB) metabolic pattern. Methods: Brain 18F-fluorodeoxyglucose positron emission tomography and clinical/demographic information were available in 169 probable DLB patients included in the European DLB-consortium database. P...

Abstract Background Blood-based amyloid biomarkers may provide a non-invasive, cost-effective and scalable manner for detecting cerebral amyloidosis in early disease stages. Methods In this prospective cross-sectional study, we quantified plasma Aβ1–42/Aβ1–40 ratios with both routinely available ELISAs and novel SIMOA Amyblood assays, and provided...

Background Formation of amyloid plaques and fibrillary tau tangles in brain are key pathological hallmarks in Alzheimer’s disease (AD). Surrogate biomarkers of these hallmarks have been established in CSF. However, a less invasive sample source would simplify the recruitment and the follow‐up of response in clinical trials targeting the pathologica...

Background In patients with apraxia of speech (AOS), we observed impaired perceptual timing abilities, which lead us to propose a shared mechanism of impaired timing processing underlying both impaired perceptual processing and motor speech output [1]. Given that white matter damage is often observed in AOS, we here investigate whether white matter...

Introduction The eye offers potential for the diagnosis of Alzheimer’s disease (AD) with retinal imaging techniques being explored to quantify amyloid accumulation and aspects of neurodegeneration. To assess these changes, this proof-of-concept study combined hyperspectral imaging and optical coherence tomography to build a classification model to...

A key symptom of frontotemporal dementia (FTD) is difficulty interacting socially with others. Social cognition problems in FTD include impaired emotion processing and theory of mind difficulties, and whilst these have been studied extensively in sporadic FTD, few studies have investigated them in familial FTD. Facial Emotion Recognition (FER) and...

Evidence from both model organisms and clinical genetics suggests close coordination between the developing brain and face, but it remains unknown whether this developmental link extends to genetic variation that drives normal-range diversity of face and brain shape. Here, we performed a multivariate genome-wide association study of cortical surfac...

Previous surveys revealed that only a minority of clinicians routinely disclosed the diagnosis of Alzheimer’s disease (AD) to their patients. Many health professionals fear that the disclosure could be harmful to the patient. Recent advances in the development of biomarkers and new diagnostic criteria allow for an earlier diagnosis of AD at the mil...

The examination of semantic cognition has traditionally identified word concreteness as well as valence as two of the principal dimensions in the representation of conceptual knowledge. More recently, corpus-based vector space models as well as graph-theoretical analysis of large-scale task-related behavioural responses have revolutionized our insi...

Background Striatal dopamine deficiency and metabolic changes are well‐known phenomena in dementia with Lewy bodies and can be quantified in vivo by ¹²³ I‐Ioflupane brain single‐photon emission computed tomography of dopamine transporter and ¹⁸ F‐fluorodesoxyglucose PET. However, the linkage between both biomarkers is ill‐understood. Objective We...

Background There are few validated fluid biomarkers in frontotemporal dementia (FTD). Glial fibrillary acidic protein (GFAP) is a measure of astrogliosis, a known pathological process of FTD, but has yet to be explored as potential biomarker. Methods Plasma GFAP and neurofilament light chain (NfL) concentration were measured in 469 individuals enr...

Objective: In some patients with apraxia of speech (AOS), we observed impaired perceptual timing abilities, which lead us to propose a shared mechanism of impaired perceptual timing underlying impaired rhythm discrimination (perceptual processing) and AOS (motor speech output). Given that considerable white matter damage is often observed in these...

Background Frontotemporal dementia is a heterogenous neurodegenerative disorder, with about a third of cases being genetic. Most of this genetic component is accounted for by mutations in GRN, MAPT, and C9orf72. In this study, we aimed to complement previous phenotypic studies by doing an international study of age at symptom onset, age at death, a...

Background: Neurofilament light chain (NfL) is a promising blood biomarker in genetic frontotemporal dementia, with elevated concentrations in symptomatic carriers of mutations in GRN, C9orf72, and MAPT. A better understanding of NfL dynamics is essential for upcoming therapeutic trials. We aimed to study longitudinal NfL trajectories in people wi...

Background: Frontotemporal dementia is a heterogenous neurodegenerative disorder, with about a third of cases being genetic. Most of this genetic component is accounted for by mutations in GRN, MAPT, and C9orf72. In this study, we aimed to complement previous phenotypic studies by doing an international study of age at symptom onset, age at death,...

Primary progressive aphasia (PPA) is an overarching term for a heterogeneous group of neurodegenerative diseases which affect language processing. Impaired picture naming has been linked to atrophy of the anterior temporal lobe in the semantic variant of PPA. Although atrophy of the anterior temporal lobe proposedly impairs picture naming by underm...

Frontotemporal dementia (FTD) is a heterogeneous group of neurodegenerative disorders with both sporadic and genetic forms. Mutations in the progranulin gene (GRN) are a common cause of genetic FTD, causing either a behavioural presentation or, less commonly, language impairment. Presence on T2-weighted images of white matter hyperintensities (WMH)...

Making sense of the external world is vital for multiple domains of cognition, and so it is crucial that object recognition is maintained across the lifespan. We investigated age differences in perceptual and conceptual processing of visual objects in a population-derived sample of 85 healthy adults (24–87 years old) by relating measures of object...

The presymptomatic phase of neurodegenerative diseases are characterized by structural brain changes without significant clinical features. We set out to investigate the contribution of functional network resilience to preserved cognition in presymptomatic genetic frontotemporal dementia. We studied 172 people from families carrying genetic abnorma...

Traditional neuroanatomical models of written word processing have proposed multiple parallel routes from the visual word form area to lateral temporal, inferior parietal and inferior frontal cortex. Here we hypothesize the existence of an alternative ventromedial occipitotemporal route that culminates in the left perirhinal cortex which codes for...

The boundaries of our understanding of conceptual representation in the brain have been redrawn since the introduction of explicit models of semantics. These models are grounded in vast behavioural datasets acquired in healthy volunteers. Here, we review the most important techniques which have been applied to detect semantic information in neuroim...

The main pathophysiological alterations of Alzheimer's disease (AD) include loss of neuronal and synaptic integrity, amyloidogenic processing, and neuroinflammation. Similar alterations can, however, also be observed in cognitively intact older subjects and may prelude the clinical manifestation of AD. The objectives of this prospective cross‐secti...

Objective: To identify brain regions whose metabolic impairment contributes to DLB clinical core features expression and to assess the influence of severity of global cognitive impairment on the DLB-hypometabolic-pattern. Methods: Brain FDG-PET and information on core features were available in 171 patients belonging to the imaging repository of...

Frontotemporal Dementia (FTD) is preceded by a long period of subtle brain changes, occurring in the absence of overt cognitive symptoms, that need to be still fully characterized. Dynamic network analysis based on resting-state magnetic resonance imaging (rs-fMRI) is a potentially powerful tool for the study of preclinical FTD. In the present stud...

Knowledge of visual and nonvisual attributes of concrete entities is distributed over neocortical uni- and polymodal association cortex. Here we investigated the role of left perirhinal cortex in explicit knowledge retrieval from written words. We examined whether it extended across visual and nonvisual properties, animate and inanimate entities, h...

Purpose: To assess the binding of the PET tracer [18F]THK5351 in patients with different primary progressive aphasia (PPA) variants and its correlation with clinical deficits. The majority of patients with nonfluent variant (NFV) and logopenic variant (LV) PPA have underlying tauopathy of the frontotemporal lobar or Alzheimer disease type, respect...

Artificial intelligence is increasingly becoming a part of everyday life. This raises the question whether clinical neurology can benefit from these novel methods to increase diagnostic accuracy. Several recent studies have used machine learning classifiers to predict whether subjects suffer from a neurological disorder. This article discusses whet...

Background: A subset of patients with the nonfluent variant of primary progressive aphasia (PPA) exhibit concomitant single-word comprehension problems, constituting a 'mixed variant' phenotype. This phenotype is rare and currently not fully characterized. The aim of this study was twofold: to assess the prevalence and nature of single-word compre...

In the field of Alzheimer's disease research, the use of biomarkers such as amyloid positron emission tomography (PET) has become widespread over a relatively brief period of time. There is an increasing tendency in research studies and trials to switch from no disclosure under any condition toward a qualified disclosure of individual research resu...

Background Biomarkers such as amyloid imaging are increasingly used for diagnosis in the early stages of Alzheimer’s disease. Very few studies have examined this from the perspective of the patient. To date, there is only limited evidence about how patients experience and value disclosure in an early disease stage. Methods Semistructured interview...

According to a recent study, semantic similarity between concrete entities correlates with the similarity of activity patterns in left middle IPS during category naming. We examined the replicability of this effect under passive viewing conditions, the potential role of visuoperceptual similarity, where the effect is situated compared to regions th...

Primary progressive aphasia (PPA) is a heterogeneous syndrome with various neuropathological causes for which no medical treatment with proven efficacy exists. Basal forebrain (BF) volume loss has been reported in PPA but its relation to cholinergic depletion is still unclear. The primary objective of this study was to investigate whether cholinerg...

View largeDownload slide The extent to which deficits in non-verbal auditory processing contribute to the clinical phenotype of primary progressive aphasia (PPA) is unclear. Grube et al. reveal impairments in processing the timing of brief sequences of non-linguistic stimuli, particularly in the non-fluent variant, indicative of a core central aud...