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Primary progressive aphasia (PPA) describes a group of language-led dementias. PPAs are complex, diverse and difficult to diagnose, and therefore conventional models of aphasia and dementia treatment do not meet their needs. The research evidence on intervention for PPA is developing, but to date there are only a few case studies exploring the experiences of people with PPA (PwPPA) themselves.To explore the experiences and opinions of PwPPA and their communication partners (CPs) to understand how speech and language therapy (SLT) services can better meet their needs.A qualitative research approach was used whereby PwPPA and their friends or family members were recruited to participate in focus groups, via advertisements in the Rare Dementia Support PPA group newsletters. Consenting participants were allocated to attend one of four focus groups hosted on an online video conferencing platform. Participants were asked about their communication difficulties, and how SLT could address these needs. All meetings were transcribed, and data were examined using reflexive thematic analysis.Six PwPPA and 14 CPs representing all three PPA variants and mixed PPA participated in the focus groups. Four main themes were identified during the analysis of the focus group discussions: (1) CPs' burden, (2) adjusting to the diagnosis, (3) communication abilities and difficulties and (4) beyond language. A further 10 subthemes were identified.This study provides a greater understanding of the experiences and needs of PwPPA and their families in relation to SLT. This work underlines the importance of a person-centred approach that considers the broader needs of both the PwPPA and the people around them. This will enable service providers to deliver SLT that meets the needs of PwPPA and their families and will also inform future research in this field.What is already known on this subject We know that PwPPA can maintain or even make improvements in word retrieval and speech fluency with SLT exercises. There is also developing evidence of the benefits of interventions such as CP training, communication aid support and other functional interventions. What this paper adds to existing knowledge This study provides an understanding of the experiences and opinions of people living with PPA and their families in relation to SLT. Results demonstrate that PwPPA and their families have to navigate a complex journey, identifying strategies to support communication but also the influence of personality and other cognitive symptoms. SLT was useful, but not always available. What are the potential or actual clinical implications of this work? This study will enable service providers to better plan, justify funding for and delivery of SLT that will meet the needs of PwPPA and their families. Most importantly this work underlines the importance of a person-centred approach, incorporating the broader needs of the person with PPA and those around them.

The early and accurate diagnosis of dementia is more important than ever before but remains challenging. Dementia is increasingly the business of neurologists and, with ageing populations worldwide, will become even more so in future. Here we outline a practical, symptom-led, bedside approach to suspecting dementia and its likely diagnosis, inspired by clinical experience and based on recognition of characteristic syndromic patterns. We show how clinical intuition reflects underlying signature profiles of brain involvement by the diseases that cause dementia and suggest next steps that can be taken to define the diagnosis. We propose ‘canaries’ that provide an early warning signal of emerging dementia and highlight the ‘chameleons’ that disguise or mimic this, as well as the ‘zebras’ that herald a rare (and sometimes curable) diagnostic opportunity.

The association between hearing impairment and dementia has emerged as a major public health challenge, with significant opportunities for earlier diagnosis, treatment and prevention. However, the nature of this association has not been defined. We hear with our brains, particularly within the complex soundscapes of everyday life: neurodegenerative pathologies target the auditory brain, and are therefore predicted to damage hearing function early and profoundly. Here we present evidence for this proposition, based on structural and functional features of auditory brain organization that confer vulnerability to neurodegeneration, the extensive, reciprocal interplay between ‘peripheral’ and ‘central’ hearing dysfunction, and recently characterized auditory signatures of canonical neurodegenerative dementias (Alzheimer’s disease, Lewy body disease and frontotemporal dementia). Moving beyond any simple dichotomy of ear and brain, we argue for a reappraisal of the role of auditory cognitive dysfunction and the critical coupling of brain to peripheral organs of hearing in the dementias. We call for a clinical assessment of real-world hearing in these diseases that moves beyond pure tone perception to the development of novel auditory ‘cognitive stress tests’ and proximity markers for the early diagnosis of dementia and management strategies that harness retained auditory plasticity., Epidemiological data indicate that mid-life hearing loss is a modifiable risk factor for dementia, with potentially major diagnostic and therapeutic implications. Johnson et al. explore why realising this potential requires understanding hearing as a complex brain function that is especially vulnerable to neurodegeneration.

The selective destruction of large-scale brain networks by pathogenic protein spread is a ubiquitous theme in neurodegenerative disease. Characterising the circuit architecture of these diseases could illuminate both their pathophysiology and the computational architecture of the cognitive processes they target. However, this is challenging using standard neuroimaging techniques. Here we addressed this issue using a novel technique—spectral dynamic causal modelling—that estimates the effective connectivity between brain regions from resting-state fMRI data. We studied patients with semantic dementia—the paradigmatic disorder of the brain system mediating world knowledge—relative to healthy older individuals. We assessed how the effective connectivity of the semantic appraisal network targeted by this disease was modulated by pathogenic protein deposition and by two key phenotypic factors, semantic impairment and behavioural disinhibition. The presence of pathogenic protein in SD weakened the normal inhibitory self-coupling of network hubs in both antero-mesial temporal lobes, with development of an abnormal excitatory fronto-temporal projection in the left cerebral hemisphere. Semantic impairment and social disinhibition were linked to a similar but more extensive profile of abnormally attenuated inhibitory self-coupling within temporal lobe regions and excitatory projections between temporal and inferior frontal regions. Our findings demonstrate that population-level dynamic causal modelling can disclose a core pathophysiological feature of proteinopathic network architecture—attenuation of inhibitory connectivity—and the key elements of distributed neuronal processing that underwrite semantic memory.

Introduction Abnormal behavioural and physiological reactivity to emotional stimuli is a hallmark of frontotemporal dementia (FTD), particularly the behavioural variant (bvFTD). As part of this repertoire, altered phobic responses have been reported in some patients with FTD but are poorly characterised. Methods We collected data (based on caregiver reports) concerning the prevalence and nature of any behavioural changes related to specific phobias in a cohort of patients representing canonical syndromes of FTD and Alzheimer's disease (AD), relative to healthy older controls. Neuroanatomical correlates of altered phobic reactivity were assessed using voxel-based morphometry. Results 46 patients with bvFTD, 20 with semantic variant primary progressive aphasia, 25 with non-fluent variant primary progressive aphasia, 29 with AD and 55 healthy age-matched individuals participated. Changes in specific phobia were significantly more prevalent in the combined FTD cohort (15.4% of cases) and in the bvFTD group (17.4%) compared both to healthy controls (3.6%) and patients with AD (3.5%). Attenuation of phobic reactivity was reported for individuals in all participant groups, however new phobias developed only in the FTD cohort. Altered phobic reactivity was significantly associated with relative preservation of grey matter in left posterior middle temporal gyrus, right temporo-occipital junction and right anterior cingulate gyrus, brain regions previously implicated in contextual decoding, salience processing and reward valuation. Conclusion Altered phobic reactivity is a relatively common issue in patients with FTD, particularly bvFTD. This novel paradigm of strong fear experience has broad implications: clinically, for diagnosis and patient well-being; and neurobiologically, for our understanding of the pathophysiology of aversive sensory signal processing in FTD and the neural mechanisms of fear more generally.

Logopenic variant primary progressive aphasia (lvPPA) is the least well defined of the major primary progressive aphasia (PPA) syndromes. We assessed phoneme discrimination in patients with PPA (semantic, nonfluent/agrammatic, and logopenic variants) and typical Alzheimer’s disease, relative to healthy age‐matched participants. The lvPPA group performed significantly worse than all other groups apart from tAD, after adjusting for auditory verbal working memory. In the combined PPA cohort, voxel‐based morphometry correlated phonemic discrimination score with grey matter in left angular gyrus. Our findings suggest that impaired phonemic discrimination may help differentiate lvPPA from other PPA subtypes, with important diagnostic and management implications.

Background: Laughter is a fundamental communicative signal in our relations with other people and is used to convey a diverse repertoire of social and emotional information. It is therefore potentially a useful probe of impaired socio-emotional signal processing in neurodegenerative diseases. Here we investigated the cognitive and affective processing of laughter systematically in patients representing all major syndromes of frontotemporal dementia, a disease spectrum characterised by severe socio-emotional dysfunction, as well as typical amnestic Alzheimer’s disease in relation to healthy age-matched individuals. Methods: We assessed cognitive labelling and valence rating of samples of spontaneous (mirthful and hostile) and volitional (posed) laughter versus two auditory control conditions (a synthetic laughter-like stimulus and spoken numbers) in 47 patients with frontotemporal dementia (22 with behavioural variant frontotemporal dementia, 12 with semantic variant primary progressive aphasia and 13 with nonfluent-agrammatic primary progressive aphasia), 15 patients with typical amnestic Alzheimer’s disease and 20 healthy age-matched individuals. Neuroanatomical associations of laughter processing were assessed using voxel-based morphometry of patients’ brain MR images. Results: While all dementia syndromes were associated with impaired identification of laughter subtypes relative to healthy controls, this was significantly more severe overall in frontotemporal dementia than in Alzheimer’s disease and particularly in the behavioural and semantic variants, which also showed abnormal affective evaluation of laughter. Certain striking syndromic signatures emerged, including enhanced liking for hostile laughter in behavioural variant frontotemporal dementia, impaired processing of synthetic laughter in the nonfluent-agrammatic variant (consistent with a generic complex auditory perceptual deficit) and ‘numerophilia’ in the semantic variant. Across the patient cohort, overall laughter identification accuracy correlated with regional grey matter in a core network encompassing inferior frontal and cingulo-insular cortices; and more specific correlates of laughter identification accuracy were delineated in cortical regions mediating affective disambiguation (identification of hostile and posed laughter in orbitofrontal cortex) and authenticity (social intent) decoding (identification of mirthful and posed laughter in anteromedial prefrontal cortex).Conclusions: These findings reveal a rich diversity of cognitive and affective laughter phenotypes in canonical dementia syndromes and suggest that laughter is an informative probe of neural mechanisms underpinning socio-emotional dysfunction in neurodegenerative disease.

Making predictions about the world and responding appropriately to unexpected events are essential functions of the healthy brain. In neurodegenerative disorders, such as frontotemporal dementia and Alzheimer’s disease, impaired processing of ‘surprise’ may underpin a diverse array of symptoms, particularly abnormalities of social and emotional behaviour, but is challenging to characterize. Here, we addressed this issue using a novel paradigm: music. We studied 62 patients (24 female; aged 53–88) representing major syndromes of frontotemporal dementia (behavioural variant, semantic variant primary progressive aphasia, non-fluent-agrammatic variant primary progressive aphasia) and typical amnestic Alzheimer’s disease, in relation to 33 healthy controls (18 female; aged 54–78). Participants heard famous melodies containing no deviants or one of three types of deviant note—acoustic (white-noise burst), syntactic (key-violating pitch change) or semantic (key-preserving pitch change). Using a regression model that took elementary perceptual, executive and musical competence into account, we assessed accuracy detecting melodic deviants and simultaneously recorded pupillary responses and related these to deviant surprise value (information-content) and carrier melody predictability (entropy), calculated using an unsupervised machine learning model of music. Neuroanatomical associations of deviant detection accuracy and coupling of detection to deviant surprise value were assessed using voxel-based morphometry of patients’ brain MRI. Whereas Alzheimer’s disease was associated with normal deviant detection accuracy, behavioural and semantic variant frontotemporal dementia syndromes were associated with strikingly similar profiles of impaired syntactic and semantic deviant detection accuracy and impaired behavioural and autonomic sensitivity to deviant information-content (all P, Benhamou et al. report that major dementias have distinct behavioural, autonomic and neuroanatomical profiles of musical ‘surprise’ processing. While Alzheimer’s disease patients showed normal reactivity to deviants in familiar melodies, frontotemporal dementia patients had specific impairments, suggesting that musical ‘tools’ could measure complex behavioural changes in these diseases., Graphical Abstract Graphical Abstract

Social and emotional changes are key features of frontotemporal dementia but remain challenging to characterise and measure. Marshall et al. report the functional neuroanatomy of aberrant emotion processing across the spectrum of frontotemporal dementia, demonstrating abnormalities at multiple hierarchical levels including sensory processing, emotion categorisation and autonomic reactivity., Impaired processing of emotional signals is a core feature of frontotemporal dementia syndromes, but the underlying neural mechanisms have proved challenging to characterize and measure. Progress in this field may depend on detecting functional changes in the working brain, and disentangling components of emotion processing that include sensory decoding, emotion categorization and emotional contagion. We addressed this using functional MRI of naturalistic, dynamic facial emotion processing with concurrent indices of autonomic arousal, in a cohort of patients representing all major frontotemporal dementia syndromes relative to healthy age-matched individuals. Seventeen patients with behavioural variant frontotemporal dementia [four female; mean (standard deviation) age 64.8 (6.8) years], 12 with semantic variant primary progressive aphasia [four female; 66.9 (7.0) years], nine with non-fluent variant primary progressive aphasia [five female; 67.4 (8.1) years] and 22 healthy controls [12 female; 68.6 (6.8) years] passively viewed videos of universal facial expressions during functional MRI acquisition, with simultaneous heart rate and pupillometric recordings; emotion identification accuracy was assessed in a post-scan behavioural task. Relative to healthy controls, patient groups showed significant impairments (analysis of variance models, all P < 0.05) of facial emotion identification (all syndromes) and cardiac (all syndromes) and pupillary (non-fluent variant only) reactivity. Group-level functional neuroanatomical changes were assessed using statistical parametric mapping, thresholded at P < 0.05 after correction for multiple comparisons over the whole brain or within pre-specified regions of interest. In response to viewing facial expressions, all participant groups showed comparable activation of primary visual cortex while patient groups showed differential hypo-activation of fusiform and posterior temporo-occipital junctional cortices. Bi-hemispheric, syndrome-specific activations predicting facial emotion identification performance were identified (behavioural variant, anterior insula and caudate; semantic variant, anterior temporal cortex; non-fluent variant, frontal operculum). The semantic and non-fluent variant groups additionally showed complex profiles of central parasympathetic and sympathetic autonomic involvement that overlapped signatures of emotional visual and categorization processing and extended (in the non-fluent group) to brainstem effector pathways. These findings open a window on the functional cerebral mechanisms underpinning complex socio-emotional phenotypes of frontotemporal dementia, with implications for novel physiological biomarker development.

Frontotemporal dementias are a clinically, neuroanatomically, and pathologically diverse group of diseases that collectively constitute an important cause of young-onset dementia. Clinically, frontotemporal dementias characteristically strike capacities that define us as individuals, presenting broadly as disorders of social behavior or language. Neurobiologically, these diseases can be regarded as “molecular nexopathies,” a paradigm for selective targeting and destruction of brain networks by pathogenic proteins. Mutations in three major genes collectively account for a substantial proportion of behavioral presentations, with far-reaching implications for the lives of families but also potential opportunities for presymptomatic diagnosis and intervention. Predicting molecular pathology from clinical and radiological phenotypes remains challenging; however, certain patterns have been identified, and genetically mediated forms of frontotemporal dementia have spearheaded this enterprise. Here we present a clinical roadmap for diagnosis and assessment of the frontotemporal dementias, motivated by our emerging understanding of the mechanisms by which pathogenic protein effects at the cellular level translate to abnormal neural network physiology and ultimately, complex clinical symptoms. We conclude by outlining principles of management and prospects for disease modification.

The speech we hear every day is typically “degraded” by competing sounds and the idiosyncratic vocal characteristics of individual speakers. While the comprehension of “degraded” speech is normally automatic, it depends on dynamic and adaptive processing across distributed neural networks. This presents the brain with an immense computational challenge, making degraded speech processing vulnerable to a range of brain disorders. Therefore, it is likely to be a sensitive marker of neural circuit dysfunction and an index of retained neural plasticity. Considering experimental methods for studying degraded speech and factors that affect its processing in healthy individuals, we review the evidence for altered degraded speech processing in major neurodegenerative diseases, traumatic brain injury and stroke. We develop a predictive coding framework for understanding deficits of degraded speech processing in these disorders, focussing on the “language-led dementias”—the primary progressive aphasias. We conclude by considering prospects for using degraded speech as a probe of language network pathophysiology, a diagnostic tool and a target for therapeutic intervention.

Purpose of ReviewThe term primary progressive aphasia (PPA) refers to a diverse group of dementias that present with prominent and early problems with speech and language. They present considerable challenges to clinicians and researchers.Recent FindingsHere, we review critical issues around diagnosis of the three major PPA variants (semantic variant PPA, nonfluent/agrammatic variant PPA, logopenic variant PPA), as well as considering ‘fragmentary’ syndromes. We next consider issues around assessing disease stage, before discussing physiological phenotyping of proteinopathies across the PPA spectrum. We also review evidence for core central auditory impairments in PPA, outline critical challenges associated with treatment, discuss pathophysiological features of each major PPA variant, and conclude with thoughts on key challenges that remain to be addressed.SummaryNew findings elucidating the pathophysiology of PPA represent a major step forward in our understanding of these diseases, with implications for diagnosis, care, management, and therapies.

Background Patients with dementia commonly have problems processing speech in the presence of competing background speech or noise. This difficulty can be present from the very early stages of dementia, and may be a preclinical feature of Alzheimer's disease.Purpose This study investigates whether people with dementia perform worse on the dichotic digit test (DDT), an experimental probe of speech processing in the presence of competing speech, and whether test performance may predict dementia onset.Research Design Systematic review and meta-analysis.Data Collection and Analysis A literature search was conducted in Medline, Embase, Scopus, and Psycinfo. We included (1) studies that included people with a diagnosis of dementia and a healthy control group with no cognitive impairment; (2) studies that reported results from a DDT in a free-recall response task; and (3) studies that had the dichotic digit mean correct percentage score or right-ear advantage, as outcome measurements.Results People with dementia had a lower DDT total score, with a pooled mean difference of 18.6% (95% confidence interval [CI]: 21.2–15.9). Patients with dementia had an increased right-ear advantage relative to controls with a pooled difference of 24.4% (95% CI: 21.8–27.0).Conclusion The DDT total scores are lower and the right-ear advantage increased in cognitively impaired versus normal control participants. The findings also suggest that the reduction of dichotic digit total score and increase of right-ear advantage progress as cognitive impairment increases. Whether abnormalities in dichotic digit scores could predict subsequent dementia onset should be examined in further longitudinal studies.

International audience; Language production provides important markers of neurological health. One feature of impairments of language and cognition, such as those that occur in stroke aphasia or Alzheimer's disease, is an overuse of high frequency, “familiar” expressions. We used computerized analysis to profile narrative speech samples from speakers with variants of frontotemporal dementia (FTD), including subtypes of primary progressive aphasia (PPA). Analysis was performed on language samples from 29 speakers with semantic variant PPA (svPPA), 25 speakers with logopenic variant PPA (lvPPA), 34 speakers with non-fluent variant PPA (nfvPPA), 14 speakers with behavioral variant FTD (bvFTD) and 20 older normal controls (NCs). We used frequency and collocation strength measures to determine use of familiar words and word combinations. We also computed word counts, content word ratio and a combination ratio, a measure of the degree to which the individual produces connected language. All dementia subtypes differed significantly from NCs. The most discriminating variables were word count, combination ratio, and content word ratio, each of which distinguished at least one dementia group from NCs. All participants with PPA, but not participants with bvFTD, produced significantly more frequent forms at the level of content words, word combinations, or both. Each dementia group differed from the others on at least one variable, and language production variables correlated with established behavioral measures of disease progression. A machine learning classifier, using narrative speech variables, achieved 90% accuracy when classifying samples as NC or dementia, and 59.4% accuracy when matching samples to their diagnostic group. Automated quantification of spontaneous speech in both language-led and non-language led dementias, is feasible. It allows extraction of syndromic profiles that complement those derived from standardized tests, warranting further evaluation as candidate biomarkers. Inclusion of frequency-based language variables benefits profiling and classification.

Our awareness of time, specifically of longer intervals spanning hours, days, months, and years, is critical for ensuring our sense of self-continuity. Disrupted time awareness over such intervals is a clinical feature in a number of frontotemporal dementia syndromes and Alzheimer's disease, but has not been studied and compared systematically in these diseases. We used a semi-structured caregiver survey to capture time-related behavioral alterations in 71 patients representing all major sporadic and genetic syndromes of frontotemporal dementia, in comparison to 28 patients with typical Alzheimer's disease and nine with logopenic aphasia, and 32 healthy older individuals. Survey items pertained to apparent difficulties ordering past personal events or estimating time intervals between events, temporal rigidity and clockwatching, and propensity to relive past events. We used a logistic regression model including diagnosis, age, gender, and disease severity as regressors to compare the proportions of individuals exhibiting each temporal awareness symptom between diagnostic groups. Gray matter associations of altered time awareness were assessed using voxel-based morphometry. All patient groups were significantly more prone to exhibit temporal awareness symptoms than healthy older individuals. Clinical syndromic signatures were identified. While patients with typical and logopenic Alzheimer's disease most frequently exhibited disturbed event ordering or interval estimation, patients with semantic dementia were most prone to temporal rigidity and clockwatching and those with behavioral variant frontotemporal dementia commonly exhibited all these temporal symptoms as well as a propensity to relive past events. On voxel-based morphometry, the tendency to relive past events was associated with relative preservation of a distributed left-sided temporo-parietal gray matter network including hippocampus. These findings reveal a rich and complex picture of disturbed temporal awareness in major dementia syndromes, with stratification of frontotemporal dementia syndromes from Alzheimer's disease. This is the first study to assess symptoms of altered temporal awareness across frontotemporal dementia syndromes and provides a motivation for future work directed to the development of validated clinical questionnaires, analysis of underlying neurobiological mechanisms and design of interventions.

Although posterior cortical atrophy is often regarded as the canonical ‘visual dementia’, auditory symptoms may also be salient in this disorder. Patients often report particular difficulty hearing in busy environments; however, the core cognitive process—parsing of the auditory environment (‘auditory scene analysis’)—has been poorly characterized. In this cross-sectional study, we used customized perceptual tasks to assess two generic cognitive operations underpinning auditory scene analysis—sound source segregation and sound event grouping—in a cohort of 21 patients with posterior cortical atrophy, referenced to 15 healthy age-matched individuals and 21 patients with typical Alzheimer’s disease. After adjusting for peripheral hearing function and performance on control tasks assessing perceptual and executive response demands, patients with posterior cortical atrophy performed significantly worse on both auditory scene analysis tasks relative to healthy controls and patients with typical Alzheimer’s disease (all P

BackgroundHearing loss has been identified as one of the most important risk factors for Alzheimer’s disease (AD). However, the causality of this association has not been established.MethodsWe used publicly available GWAS summary statistics to construct instrumental variables for age-related hearing difficulty. We tested these genetic instruments for association with the outcome of AD using AD GWAS summary statistics in a two-sample Mendelian randomisation analysis. We used inverse-variance weighted meta-analysis to estimate the causal effect of hearing-related traits on AD, followed by secondary sensitivity analyses including a mixture of experts approach.ResultsThere was no strong evidence for a causal relationship between genetically-determined hearing difficulty (ORFE-IVW 1.27, 95% CI 0.89 to 1.82, p=0.189) and AD risk. There was no evidence to suggest that unbalanced horizontal pleiotropy was biasing the result. Power calculations indicated our instruments were sufficiently powered to detect the magnitude of effect described in case-control and cohort settings.ConclusionsOur results suggest that the size of the observed relationship between hearing loss and AD cannot be completely accounted for by a direct causal influence. Hearing loss may have more utility as a risk marker for AD than as a modifiable risk factor.

Objective\ud To establish proof‐of‐principle for the use of heart rate responses as objective measures of degraded emotional reactivity across the frontotemporal dementia spectrum, and to demonstrate specific relationships between cardiac autonomic responses and anatomical patterns of neurodegeneration.\ud \ud Methods\ud Thirty‐two patients representing all major frontotemporal dementia syndromes and 19 healthy older controls performed an emotion recognition task, viewing dynamic, naturalistic videos of facial emotions while ECG was recorded. Cardiac reactivity was indexed as the increase in interbeat interval at the onset of facial emotions. Gray matter associations of emotional reactivity were assessed using voxel‐based morphometry of patients’ brain MR images.\ud \ud Results\ud Relative to healthy controls, all patient groups had impaired emotion identification, whereas cardiac reactivity was attenuated in those groups with predominant fronto‐insular atrophy (behavioral variant frontotemporal dementia and nonfluent primary progressive aphasia), but preserved in syndromes focused on the anterior temporal lobes (right temporal variant frontotemporal dementia and semantic variant primary progressive aphasia). Impaired cardiac reactivity correlated with gray matter atrophy in a fronto‐cingulo‐insular network that overlapped correlates of cognitive emotion processing.\ud \ud Interpretation\ud Autonomic indices of emotional reactivity dissociate from emotion categorization ability, stratifying frontotemporal dementia syndromes and showing promise as novel biomarkers. Attenuated cardiac responses to the emotions of others suggest a core pathophysiological mechanism for emotional blunting and degraded interpersonal reactivity in these diseases.

Paintings could offer insight into the varied experiences of people with different dementias. In this project, a single exercise - the painting of a group of objects in still-life - was used to capture artistic production in four artists with different diagnoses of dementia and four healthy artists. Whilst quantitative studies provide important insights into the neuroanatomical supports for artistic actions, autonomous art exercises may yield deeper understanding of the individual creative experience in the context of neurodegenerative disease.

Background: The language profile of behavioral variant frontotemporal dementia (bvFTD) remains to be fully defined. Objective: We aimed to quantify the extent of language deficits in this patient group. Methods: We assessed a cohort of patients with bvFTD (n = 24) in relation to patients with semantic variant primary progressive aphasia (svPPA; n = 14), nonfluent variant primary progressive aphasia (nfvPPA; n = 18), and healthy age-matched individuals (n = 24) cross-sectionally and longitudinally using a comprehensive battery of language and general neuropsychological tests. Neuroanatomical associations of language performance were assessed using voxel-based morphometry of patients’ brain magnetic resonance images. Results: Relative to healthy controls, and after accounting for nonverbal executive performance, patients with bvFTD showed deficits of noun and verb naming and single word comprehension, diminished spontaneous propositional speech, and deterioration in naming performance over time. Within the bvFTD group, patients with MAPT mutations had more severe impairments of noun naming and single word comprehension than patients with C9orf72 mutations. Overall the bvFTD group had less severe language deficits than patients with PPA, but showed a language profile that was qualitatively similar to svPPA. Neuroanatomical correlates of naming and word comprehension performance in bvFTD were identified predominantly in inferior frontal and antero-inferior temporal cortices within the dominant hemispheric language network. Conclusions: bvFTD is associated with a language profile including verbal semantic impairment that warrants further evaluation as a novel biomarker.

The primary progressive aphasias are a heterogeneous group of focal 'language-led' dementias that pose substantial challenges for diagnosis and management. Here we present a clinical approach to the progressive aphasias, based on our experience of these disorders and directed at non-specialists. We first outline a framework for assessing language, tailored to the common presentations of progressive aphasia. We then consider the defining features of the canonical progressive nonfluent, semantic and logopenic aphasic syndromes, including 'clinical pearls' that we have found diagnostically useful and neuroanatomical and other key associations of each syndrome. We review potential diagnostic pitfalls and problematic presentations not well captured by conventional classifications and propose a diagnostic 'roadmap'. After outlining principles of management, we conclude with a prospect for future progress in these diseases, emphasising generic information processing deficits and novel pathophysiological biomarkers.

Highlights • Sleep is a key concern in dementias but their sleep phenotypes are not well defined. • We addressed this issue in major FTD and AD syndromes versus healthy older controls. • We surveyed sleep duration, quality and disruptive events, and daytime somnolence. • Sleep symptoms were frequent in FTD and AD and distinguished these diseases. • Sleep disturbance is an important clinical issue across major FTD and AD syndromes., Sleep disruption is a key clinical issue in the dementias but the sleep phenotypes of these diseases remain poorly characterised. Here we addressed this issue in a proof-of-principle study of 67 patients representing major syndromes of frontotemporal dementia (FTD) and Alzheimer’s disease (AD), in relation to 25 healthy older individuals. We collected reports on clinically-relevant sleep characteristics - time spent overnight in bed, sleep quality, excessive daytime somnolence and disruptive sleep events. Difficulty falling or staying asleep at night and excessive daytime somnolence were significantly more frequently reported for patients with both FTD and AD than healthy controls. On average, patients with FTD and AD retired earlier and patients with AD spent significantly longer in bed overnight than did healthy controls. Excessive daytime somnolence was significantly more frequent in the FTD group than the AD group; AD syndromic subgroups showed similar sleep symptom profiles while FTD subgroups showed more variable profiles. Sleep disturbance is a significant clinical issue in major FTD and AD variant syndromes and may be even more salient in FTD than AD. These preliminary findings warrant further systematic investigation with electrophysiological and neuroanatomical correlation in major proteinopathies.

Hearing impairment has emerged as a potent association of cognitive decline in dementia and a promising treatment target. To realise this promise, we need to resolve fundamental questions concerning the roles of peripheral versus central auditory deficits in different dementias, which hearing measures best capture cognitive symptoms and disability and whether hearing measures predict clinical course and brain atrophy.Using pre-existing and novel stimuli, created at the Dementia Research Centre, University College London, we have designed a unique test battery to assess central auditory function. This will be used to ‘phenotype’ central auditory dysfunction in Alzheimer’s disease (AD) and the primary progressive aphasias (PPA) and compare them with controls as well as across disease groups.This will provide new tools to determine how auditory measures relate to clinical symptoms and daily-life disability and care burden. Using voxel-based morphometry (VBM) we also aim to correlate test measures with regional brain degeneration and measure how hearing deficits predict longitudinal clinical course.Here we present the make-up of the battery, explaining the motivation behind component tests and how they probe different stations of the auditory hierarchy. We also make predictions of likely group-specific outcomes, based on neuroanatomical disease predilection.

Hearing deficits associated with cognitive impairment have attracted much recent interest, motivated by emerging evidence that impaired hearing is a risk factor for cognitive decline. However, dementia and hearing impairment present immense challenges in their own right, and their intersection in the auditory brain remains poorly understood and difficult to assess. Here, we outline a clinically oriented, symptom-based approach to the assessment of hearing in dementias, informed by recent progress in the clinical auditory neuroscience of these diseases. We consider the significance and interpretation of hearing loss and symptoms that point to a disorder of auditory cognition in patients with dementia. We identify key auditory characteristics of some important dementias and conclude with a bedside approach to assessing and managing auditory dysfunction in dementia.