Olivier Piguet

The University of Sydney · School of Psychology; Brain & Mind Centre

Neuroinflammation is a hallmark of frontotemporal dementia (FTD), a heterogeneous group of proteinopathies characterized by the progressive degeneration of the frontal and temporal lobes. It is marked by microglial activation and subsequent cytokine release. Although cytokine levels in FTD brain and CSF have been examined, the number of cytokines m...

Introduction: Accurate prediction of the underlying neuropathology in behavioural variant frontotemporal dementia (bvFTD) is challenging but essential for future targeted therapy trials and prognostication. Alzheimer’s disease (AD) pathology has been reported in a significant proportion of patients with clinical bvFTD. We sought to determine whethe...

Objectives: To identify the patterns of errors in facial emotion recognition in frontotemporal dementia (FTD) subtypes compared with Alzheimer's disease (AD) and healthy controls. Design: Retrospective analysis. Setting: Participants were recruited from FRONTIER, the frontotemporal dementia research group at the University of Sydney, Australia...

Background and objectives Early-stage behavioural variant frontotemporal dementia (bvFTD) is often misdiagnosed, highlighting the need for new diagnostic instruments. Based on the revised diagnostic criteria for bvFTD, we developed the Behavioural Dysfunction Questionnaire (BDQ). In this explorative study, we aimed to determine the best scoring and...

Disease-specific mechanisms underlying emotion recognition difficulties in behavioural-variant frontotemporal dementia (bvFTD), Alzheimer's disease (AD), and Parkinson's disease (PD) are unknown. Interoceptive accuracy, accurately detecting internal cues (e.g., one's heart beating), and cognitive abilities are candidate mechanisms underlying emotio...

Two common clinical variants of frontotemporal dementia are the behavioural variant frontotemporal dementia presenting with behavioural and personality changes attributable to prefrontal atrophy, and semantic dementia displaying early semantic dysfunction primarily due to anterior temporal degeneration. Despite representing independent diagnostic e...

Amyotrophic lateral sclerosis is a rapidly progressing neurodegenerative disease characterised by degeneration of motor neurons and loss of various muscular functions. Dyslipidaemia is prevalent in amyotrophic lateral sclerosis with aberrant changes mainly in cholesterol ester and triglyceride. Despite this, little is known about global lipid chang...

Recent allostatic‐interoceptive predictive coding theories propose that efficient regulation of the internal milieu is necessary to correctly anticipate the needs required to overcome environmental challenges before they arise. These theories are based on neurocognitive models of allostatic load and interoceptive processes, dimensions convergently...

Primary progressive aphasias are rare younger-onset dementias. As the label denotes, these dementias are characterised clinically by marked changes in language skills. Evidence over the years has shown that individuals with primary progressive aphasia experience widespread cognitive and behavioural changes that extend beyond language. This evidence...

Background Hypothalamic dysregulation plays an established role in eating abnormalities in behavioural variant frontotemporal dementia (bvFTD) and amyotrophic lateral sclerosis (ALS). Its contribution to cognitive and behavioural impairments, however, remains unexplored. Methods Correlation between hypothalamic subregion atrophy and cognitive and...

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...

Purpose: Speed and accuracy of lexical access change with healthy ageing and neurodegeneration. While a word's immediate phonological neighbourhood density (i.e. words differing by a single phoneme) influences access, connectivity to all words in the phonological network (i.e. closeness centrality) may influence processing. This study aimed to inve...

Introduction While apathy is broadly defined as a loss of motivation, it is increasingly recognised as a multidimensional syndrome spanning executive, emotional, and initiation domains. Emotional apathy is purportedly driven by deficits in using socioemotional rewards to guide behaviour, yet the link between these symptoms and reward processing, an...

Recent allostatic–interoceptive explanations using predictive coding models propose that efficient regulation of the body’s internal milieu is necessary to correctly anticipate environmental needs. We review this framework applied to understanding behavioral variant frontotemporal dementia (bvFTD) considering both allostatic overload and interocept...

Impairments of Theory of Mind (ToM) abilities occur in a wide range of brain disorders. Therefore, reliable and ecologically valid examination of these abilities is a crucial part of any comprehensive neuropsychological assessment. An established and ecologically valid, English‐language test identifying deficits in ToM abilities is “The Awareness o...

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 Psychiatric presentations similar to that observed in primary psychiatric disorders are well described across the amyotrophic lateral sclerosis–frontotemporal dementia (ALS–FTD) spectrum. Despite this, schizotypal personality traits associated with increased risks of clinical psychosis development and poor psychosocial outcomes have neve...

Background: The heterogeneity of cognitive and behavioural disturbances in frontotemporal dementia-motor neuron disease (FTD-MND), and clinical differences between FTD-MND and FTD subtypes, have been illustrated cross-sectionally. This study aimed to examine the FTD-MND disease trajectory by comparing clinical features of FTD-MND and the behaviour...

Background: Olfactory dysfunction is highly prevalent in dementia syndromes, including Alzheimer's disease (AD) and frontotemporal dementia (FTD). The structural integrity of the olfactory bulb (OB) is thought to play a critical role in odor detection and identification, but no MRI study has measured OB volume in FTD, or measured OB volume longitu...

The Addenbrooke’s Cognitive Examination III is a brief cognitive screening tool that is widely used for the detection and monitoring of dementia. Recent findings suggest that the three variants of primary progressive aphasia can be distinguished based on their distinct profiles on the five subdomain scores of this test. Here, we investigated the ut...

Introduction: Changes in social behavior and emotion processing are common in frontotemporal dementia (FTD) and semantic dementia (SD), and less so in Alzheimer's disease (AD). Recent research has investigated oxytocin as a potential treatment for these symptoms; however, whether plasma oxytocin is associated with social-emotional symptoms of deme...

Apathy is the most common and disabling non-cognitive feature of dementia, affecting up to 90% of individuals over the disease course. Despite its prevalence, the underlying mechanisms of apathy remain elusive. This study aimed to investigate whether cognitive apathy and executive functioning have a shared cognitive and neural basis, in behavioural...

Aim This pilot study investigated the acceptability and usefulness of 4 weekly Positive Behaviour Support (PBS) education sessions (delivered face-to-face and online) for family carers of individuals diagnosed with behavioural-variant frontotemporal dementia (bvFTD). These sessions were adapted from the Family-directed Approach to Brain injury (FAB...

The behavioural variant of frontotemporal dementia (bvFTD) is characterised by pronounced alterations in social functioning, including the understanding of others’ thoughts and feelings via theory of mind. The emergence of such impairments in other social disorders such as autism and schizophrenia is suggested to reflect an inability to imagine the...

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are part of the same disease spectrum. While thalamic–cerebellar degeneration has been observed in C9orf72 expansion carriers, the exact subregions involved across the clinical phenotypes of the ALS–FTD spectrum remain unclear. Using MRIs from 58 bvFTD, 41 ALS–FTD and 52 ALS pati...

Frontotemporal dementia refers to a group of neurodegenerative disorders characterised by behaviour and language alterations and focal brain atrophy. Amyotrophic lateral sclerosis is a rapidly progressing neurodegenerative disease characterised by loss of motor neurons resulting in muscle wasting and paralysis. Frontotemporal dementia and amyotroph...

Objectives: Abnormal beliefs and delusions have been reported in some people with dementia, however, the prevalence of delusions, and their neurocognitive basis has been underexplored. This study aimed to examine the presence, severity, content and neural correlates of delusions in a large, well-characterised cohort of dementia patients using a tr...

Background The GGGGCC hexanucleotide repeat expansion in the non-coding region of the chromosome 9 open reading frame 72 gene (C9orf72) is the most common genetic cause of familial frontotemporal dementia (FTD). This study aims to clarify the patterns of cerebellar atrophy in FTD patients with and without a C9orf72 repeat expansion compared with he...

Scene construction refers to the process by which humans generate richly detailed and spatially cohesive scenes in the mind’s eye. The cognitive processes that underwrite this capacity remain unclear, particularly when the envisaged scene calls for the integration of various types of contextual information. Here, we explored social and non-social f...

Caregivers of patients diagnosed with amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) often experience distressing symptoms related to their caregiving role. This review evaluates the existing literature on coping and their relationship to ALS and FTD caregiver psychological wellbeing. Published articles were identified via a...

Objective: Emotion recognition (ER) is commonly impaired in many brain disorders. Therefore, its reliable and ecologically valid examination is a crucial part of any comprehensive neuropsychological assessment. In this regard, an established English-language test identifying deficits in ER is "The Awareness of Social Inference Test-Emotion Evaluat...

Background Behavioral variant frontotemporal dementia (bvFTD) is a common form of younger-onset dementia with a proportion of cases overlapping pathologically and genetically with amyotrophic lateral sclerosis (ALS). Previous studies have identified that the human endogenous retrovirus K (HERV-K) is elevated in ALS serum and is associated with ALS...

Purpose The three variants of primary progressive aphasia (PPA) differ in clinical presentation, underlying brain pathology, and clinical course, which stresses the need for early differentiation. However, brief cognitive tests that validly distinguish between all PPA variants are lacking. The Sydney Language Battery (SYDBAT) is a promising screeni...

Mounting evidence suggests that, in parallel with well-defined changes in language, primary progressive aphasia (PPA) syndromes display co-occurring social cognitive impairments. Here, we explored multidimensional profiles of carer-rated social communication using the La Trobe Communication Questionnaire (LCQ) in 11 semantic dementia (SD), 12 logop...

Primary progressive aphasia (PPA) is a neurodegenerative clinical syndrome characterised by a progressive decline in speech and language functions. Deficits in behaviour, mood, and functional capacity are reported in PPA but are less well understood. This study examined the PPA variants’ profiles on these domains at initial presentation and over ti...

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...

Dementia rates in Aboriginal Australians are 3‐5 times higher than in the broader Australian population, and among the highest rates reported globally. Existing evidence suggests that dementia types are similar to those found in non‐Indigenous Australian populations. Neuroimaging, however, has not been previously available in any study of dementia...

Objective: This study aimed to establish (1) the pattern and severity of neuropsychiatric symptoms and other non-motor symptoms of sleep and mood, across ALS phenotypes in comparison to bvFTD and (2) the contribution of non-modifiable factors including age, sex and disease state to the severity of symptoms experienced by ALS patients. Methods: Cons...

Objective: This study investigated the impact of the COVID-19 pandemic and the public-health measures aiming to reduce the spread of COVID-19 (i.e restrictions, social distancing, self-isolation) on neuropsychiatric symptoms of patients with different forms of dementia and the mental health of their caregivers in Germany. Method: An online-survey...

Rare, yet biologically critical, lipids that contain very long chain fatty acids (VLCFA-lipids) are synthesized in the brain by the enzyme ELOVL4. High levels of VLCFA-lipids are toxic to cells and excess VLCFA-lipids are actively removed by ABCD1 in an ATP-dependent manner. Virtually nothing is known about the impact of VLCFA-lipids in neurodegene...

Two common clinical variants of frontotemporal dementia (FTD) are the behavioural variant (bvFTD) presenting with behavioural and personality changes attributable to prefrontal atrophy, and semantic dementia (SD) displaying early semantic dysfunction primarily due to anterior temporal degeneration. Despite representing independent diagnostic entiti...

The disease syndromes of amyotrophic lateral sclerosis and frontotemporal dementia display considerable clinical, genetic and pathological overlap, yet mounting evidence indicates substantial differences in progression and survival. To date, there has been limited examination of how profiles of brain atrophy might differ between clinical phenotypes...

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...

Face processing relies on a network of occipito-temporal and frontal brain regions. Temporal regions are heavily involved in looking at and processing emotional faces; however, the contribution of each hemisphere to this process remains under debate. Semantic dementia (SD) is a rare neurodegenerative brain condition characterized by anterior tempor...

Behavioral variant frontotemporal dementia (bvFTD) is a younger onset form of neurodegeneration initiated in the frontal and/or temporal lobes with a slow clinical onset but rapid progression. bvFTD is highly complex biologically with different pathological signatures and genetic variants that can exhibit a spectrum of overlapping clinical manifest...

Although characterized primarily as a language disorder, mounting evidence indicates episodic amnesia in Logopenic Progressive Aphasia (LPA). Whether such memory disturbances extend to information encoded pre-disease onset remains unclear. To address this question, we examined autobiographical memory in 10 LPA patients, contrasted with 18 typical a...

Administration of intranasal oxytocin has been found to improve social cognition in a number of brain conditions, including autism spectrum disorder and schizophrenia. Whether this approach is relevant in dementias is currently unknown, particularly in frontotemporal dementia, a younger-onset dementia characterized clinically by marked changes in s...

Objectives: Almost 10% of people with dementia experience a younger-onset of disease (before 65 years). Changes in behaviour are common, as are delays in diagnosis and limited access to appropriate support and services. This study aimed to explore the specific behaviour support needs of families living with younger-onset dementia. Methods: Seventy-...

While traditional analyses of autobiographical construction tend to focus on the ‘internal’ or episodic details of the narrative, contemporary studies employing fine-grained scoring measures reveal the ‘external’ component to contain important information relevant to the individual’s life story. Here, we used the recently developed NExt scoring pro...

Impaired verbal ‘phonological’ short-term memory is considered a cardinal feature of the logopenic variant of primary progressive aphasia (lv-PPA) and is assumed to underpin most of the language deficits in this syndrome. Clinically, examination of verbal short-term memory in individuals presenting with PPA is common practice and serves two objecti...

The behavioural variant of frontotemporal dementia (bvFTD) is characterised by pronounced alterations in social functioning, including the understanding of others’ thoughts and feelings via theory of mind. The emergence of such impairments in other social disorders such as autism and schizophrenia is suggested to reflect an inability to imagine the...

Semantic dementia (SD) is a younger-onset neurodegenerative disease characterised by progressive deterioration of the semantic knowledge base in the context of predominantly left-lateralised anterior temporal lobe (ATL) atrophy. Mounting evidence indicates the emergence of florid socioemotional changes in SD as atrophy encroaches into right tempora...

Clinical and pathological heterogeneity is common in patients with FTLD pathology. This investigated clinical or imaging characteristics that differentiate FTLD-TDP from FTLD-tau, FTLD-TDP subtypes from each other, or pathological stages of FTLD-TDP. Initial clinical, neuropsychological and neuroimaging characteristics were compared between patholo...

Objective Differentiating the primary progressive aphasia (PPA) variants in clinical settings remains complex and challenging, especially for the logopenic (lv-PPA) and non-fluent variants (nfv-PPA). Recent studies suggest that visuospatial memory is more compromised in lv-PPA than in nfv-PPA and is relatively spared in the semantic variant (sv-PPA...

Aquired apraxia of speech is a disorder that impairs speech production, despite intact peripheral neuromotor function. Its pathomechanism remains to be established. Neurodegenerative lesion models provide an unequalled opportunity to explore the neural correlates of apraxia of speech, which is present in a subset of patients diagnosed with non-sema...

Objective The aims of this study were to (i) explore psychotic experiences across the entire amyotrophic lateral sclerosis-frontotemporal dementia (ALS-FTD) spectrum from a clinical and genetic perspective, (ii) determine the rate of abnormal perceptual experiences across the five sensory modalities and (iii) explore the neurobiological factors tha...

Leveraging recent advances in automated language analysis and anovel statistical approach utilizing an independent control group, we explored changes in lexical output across two published works of a man diagnosed with semantic dementia. We found significant increase in adverb usage and decline in familiarity, meaningfulness, age of acquisition and...

Objective The variants of primary progressive aphasia (PPA) are predominantly diagnosed on the basis of specific profiles of language impairments. Deficits in other cognitive domains and their evolution over time are less well documented. This study examined the cognitive profiles of the PPA variants over time and determined the contribution of cog...

Objective Alterations in eating behaviour are one of the diagnostic features of behavioural variant frontotemporal dementia (bvFTD). It is hypothesised that underlying brain network disturbances and atrophy to key structures may affect macronutrient preference in bvFTD. We aimed to establish whether a preference for dietary fat exists in bvFTD, its...

Much of human behaviour is motivated by the drive to experience pleasure. The capacity to envisage pleasurable outcomes and to engage in goal-directed behaviour to secure these outcomes depends upon the integrity of frontostriatal circuits in the brain. Anhedonia refers to the diminished ability to experience, and to pursue, pleasurable outcomes, a...

Primary progressive aphasia (PPA) is characterised by predominant language and communication impairment. However, behavioural changes, such as apathy, are increasingly recognised. Apathy is defined as a reduction in motivation and goal-directed behaviour. Recent theoretical models have suggested that apathy can be delineated into multiple dimension...

Across Latin American and Caribbean countries (LACs), the fight against dementia faces pressing challenges, such as heterogeneity, diversity, political instability, and socioeconomic disparities. These can be addressed more effectively in a collaborative setting that fosters open exchange of knowledge. In this work, the Latin American and Caribbean...

Objective To comprehensively examine the clinical presentation of patients diagnosed with frontotemporal dementia–motor neuron disease (FTD–MND) compared to FTD subtypes. To clarify the heterogeneity of behavioural and language deficits in FTD–MND using a data-driven approach.Methods Patients with FTD–MND (n = 31), behavioural variant FTD (n = 119)...

Objective: To test the hypothesis that white matter hyperintensities (WMH) in behavioral-variant frontotemporal dementia (bvFTD) and Alzheimer disease (AD) are associated with disease variables such as disease severity, cortical atrophy and cognition, we conducted a cross-sectional brain MRI study with volumetric and voxel-wise analyses. Methods:...

From molecular mechanisms to global brain networks, atypical fluctuations are the hallmark of neurodegenera-tion. Yet, traditional fMRI research on resting-state networks (RSNs) has favored static and average connectivity methods, which by overlooking the fluctuation dynamics triggered by neurodegeneration, have yielded inconsistent results. The pr...

Frontotemporal dementia (FTD), particularly the behavioural variant (bvFTD) form, has fascinated researchers. Recent years have seen an increasing interest in aspects of bvFTD that extend beyond the initial focus on cognitive changes and frontal executive dysfunction. Changes have been identified in aspects including fundamental changes in physiolo...