Examining the propensity and nature of criminal risk behaviours in frontotemporal dementia syndromes and Alzheimer's disease.

INTRODUCTION: Some people with dementia develop changes in behaviour and cognition that may lead to interactions with police or the legal system. However, large, prospective case-control studies examining these behaviours are lacking. METHODS: One hundred and forty-four people with dementia and 53 controls completed the Misdemeanours and Transgressions Screener. RESULTS: Criminal risk behaviours were reported in: 65.6% of behavioural-variant frontotemporal dementia, 46.2% of right-lateralised semantic dementia, and 27.0% of Alzheimer's disease patients. In 19.1% of patients these behaviours led to contact with police or authority figures. Compared to controls, people with dementia showed higher rates of physical assault (p = 0.024), financial/professional recklessness (p = 0.009), and inappropriate behaviours (p  = 0.052). DISCUSSION: Criminal risk behaviours are common across dementia subtypes and may be one of the first clinical signs of frontotemporal dementia. Further research to understand how to balance risk minimisation with an individual's liberties as well as the inappropriate criminalisation of people with dementia is needed. Highlights: The Misdemeanours and Transgressions Screener is a new tool to assess criminal risk behaviours.Forty-seven percent of patients with dementia show criminal risk behaviour after dementia onset.Behaviours included verbal abuse, traffic violations, physical assault.New onset of criminal risk behaviours >50 years is a clinical sign for frontotemporal dementia.

"It's Opened My Eyes to a Whole New World": Positive Behaviour Support Training for Staff and Family Members Supporting Residents With Dementia in Aged Care Settings.

OBJECTIVES: This study examined the acceptability and usefulness of Positive Behaviour Support (PBS) training in enhancing the capabilities of support staff and family members providing behaviour support to residents with dementia in residential aged care (RAC). METHODS: A mixed-methods pilot study was conducted across 3 RAC organisations, involving pre- and post-training questionnaire assessments for clinical leaders (n = 8), support staff (n = 37) and family members (n = 18). RESULTS: Findings indicated increased confidence among support staff and family members in providing behaviour support, with 96% indicating it would support their practices across settings. Key training benefits included identifying and addressing underlying causes of challenging behaviours. A majority (89%) expressed the need for further behaviour support training. CONCLUSION: Recommendations focus on developing systems to enable effective and collaborative behaviour support practices. Further research is needed to examine application of PBS principles and planning for residents living with dementia.

Disrupted social perception in frontotemporal dementia and Alzheimer's disease - Associated cognitive processes and clinical implications.

BACKGROUND: Social perception refers to the ability to adapt and update one's behaviour in accordance with the current context and provides the foundation for many complex social and emotional interactions. Alterations in social cognition are a hallmark of the behavioural variant of frontotemporal dementia (bvFTD), yet the capacity for social perception in this syndrome remains unclear. METHODS: We examined social perception in 18 bvFTD and 13 Alzheimer's disease (AD) patients, in comparison with 17 healthy older controls, using a social perception task derived from the Dewey Story Test. Participants also completed a comprehensive neuropsychological battery and carers provided ratings of behavioural and neuropsychiatric changes. RESULTS: Overall, bvFTD and AD performance diverged significantly from control ratings on the social perception task, however, no significant difference was found between patient groups. Standardised values relative to the mean control rating revealed considerable variability within the patient groups in terms of the direction of deviation, i.e., over- or under-rating the vignettes relative to healthy controls (range z-scores = -1.79 to +1.63). Greater deviation from control ratings was associated with more pronounced memory (p = .007) and behavioural (p = .009) disturbances in bvFTD; whilst social perception performance correlated exclusively with verbal fluency in AD (p = .003). CONCLUSIONS: Social perception is comparably disrupted in bvFTD and AD, yet likely reflects the differential breakdown of distinct cognitive processes in each dementia syndrome. Our findings have important clinical implications for the development of targeted interventions to manage disease-specific changes in social perception in dementia.

Dementia in Australia: Clinical recommendations post-diagnosis.

The delivery of a dementia diagnosis, the information provided, and the practical advice and support arranged can have a long-lasting impact on patients and their families and deserves attention equal to that given to the assessment and investigation process. Patients and their families need a constructive yet sensitive conversation about the nature and cause of their difficulties, communicated in plain language, and tailored to their main concerns and needs. This conversation should lead to the provision of high-quality, easily accessible information. Following this, clinicians may wish to consider broaching the following dementia topics: (1) pharmacological and non-pharmacological interventions, (2) connection and integration with relevant organisations, (3, 4) application for formal support services and engagement with support teams, (5) safety in the home, (6, 7) financial planning, guardianship and legal matters, (8) driving eligibility, (9) support and education resources to family carers and (10) research initiatives and genetic information. Addressing these topics will contribute to improved disease management, which is likely to improve the dementia journey for the patient, their carer(s), and family.

Exploring graded profiles of hippocampal atrophy along the anterior-posterior axis in semantic dementia and Alzheimer's disease.

Mounting evidence indicates marked hippocampal degeneration in semantic dementia (SD) however, the spatial distribution of hippocampal atrophy profiles in this syndrome remains unclear. Using a recently developed parcellation approach, we extracted hippocampal volumes from four distinct subregions running from anterior to posterior along the longitudinal axis (anterior, intermediate rostral, intermediate caudal, and posterior). Volumetric differences in hippocampal subregions were compared between 21 SD, 24 matched Alzheimer's disease (AD), and 27 healthy older Control participants. Despite comparable overall hippocampal volume loss, SD and AD groups diverged in terms of the magnitude of atrophy along the anterior-posterior axis of the hippocampus. Global hippocampal atrophy was observed in AD, with no discernible gradation or lateralisation. In contrast, SD patients displayed graded bilateral hippocampal atrophy, most pronounced on the left-hand side, and concentrated in anterior relative to posterior subregions. Finally, we found preliminary evidence that disease-specific vulnerability along the anterior-posterior axis of the hippocampus was associated with canonical clinical features of these syndromes.

Clinical and cortical trajectories in non-fluent primary progressive aphasia and Alzheimer's disease: A role for emotion processing.

OBJECTIVES: To examine the clinical trajectories and neural correlates of cognitive and emotion processing changes in the non-fluent/agrammatic (nfvPPA) and the logopenic (lvPPA) variants of primary progressive aphasia (PPA). DESIGN: Observational case-control longitudinal cohort study. SETTING: Research clinic of frontotemporal dementia. PARTICIPANTS: This study recruited 29 non-semantic PPA patients (15 nfvPPA and 14 lvPPA) and compared them with 15 Alzheimer's disease (AD) patients and 14 healthy controls. MEASUREMENTS: Participants completed an annual assessment (median = 2 years; range = 1-5 years) of general cognition, emotion processing and structural MRI. Linear mixed effects models investigated clinical and imaging trajectories between groups. RESULTS: Over time, lvPPA showed the greatest cognitive deterioration. In contrast, nfvPPA showed significant decline in emotion recognition, whereas AD showed preserved emotion recognition, even with disease progression. Importantly, lvPPA also developed emotion processing impairments, with disease progression. Both nfvPPA and lvPPA showed continuing cortical atrophy in hallmark language-processing regions associated with these syndromes, together with progressive involvement of the right hemisphere regions, mirroring left hemisphere atrophy patterns at presentation. Decline in emotion processing was associated with bilateral frontal atrophy in nfvPPA and right temporal atrophy in lvPPA. CONCLUSIONS: Our results show divergent clinical courses in nfvPPA and lvPPA, with rapid cognitive and neural deterioration in lvPPA and emotion processing decline in both groups and support the concurrent assessment of cognition and emotion processing in the clinic to inform diagnosis and monitoring in the non-semantic variants of PPA.

Longitudinal volumetric changes in amygdala subregions in frontotemporal dementia.

Amygdala atrophy has been found in frontotemporal dementia (FTD), yet the specific changes of its subregions across different FTD phenotypes remain unclear. The aim of this study was to investigate the volumetric alterations of the amygdala subregions in FTD phenotypes and how they evolve with disease progression. Patients clinically diagnosed with behavioral variant FTD (bvFTD) (n = 20), semantic dementia (SD) (n = 20), primary nonfluent aphasia (PNFA) (n = 20), Alzheimer's disease (AD) (n = 20), and 20 matched healthy controls underwent whole brain structural MRI. The patient groups were followed up annually for up to 3.5 years. Amygdala nuclei were segmented using FreeSurfer, corrected by total intracranial volumes, and grouped into the basolateral, superficial, and centromedial subregions. Linear mixed effects models were applied to identify changes in amygdala subregional volumes over time. At baseline, bvFTD, SD, and AD displayed global amygdala volume reduction, whereas amygdala volume appeared to be preserved in PNFA. Asymmetrical amygdala atrophy (left > right) was most pronounced in SD. Longitudinally, SD and PNFA showed greater rates of annual decline in the right basolateral and superficial subregions compared to bvFTD and AD. The findings provide comprehensive insights into the differential impact of FTD pathology on amygdala subregions, revealing distinct atrophy patterns that evolve over disease progression. The characterization of amygdala subregional involvement in FTD and their potential role as biomarkers carry substantial clinical implications.

Establishing the link between motivational disturbances and behavioural rigidity in frontotemporal dementia.

BACKGROUND: Rigid and inflexible behaviours are common in frontotemporal dementia (FTD), manifesting in compulsive pursuit of specific interests, routines, and rituals. Paradoxically, these changes occur alongside profound motivational disturbances including apathy and anhedonia. While posited to be related, no study to date has explored the link between motivational changes and behavioural rigidity in FTD. METHODS: Carer ratings for 71 FTD participants (26 semantic dementia [SD], 45 behavioural variant [bvFTD]) were obtained on the Dimensional Apathy Scale (apathy), the Snaith-Hamilton Pleasure Scale (hedonic tone) and the Cambridge Behavioural Inventory-Revised (CBI-R; behavioural changes). A rigidity index was created from existing items on the CBI-R. Whole-brain voxel-based morphometry was used to explore associations between rigidity and grey matter intensity in the combined FTD group. RESULTS: Behavioural rigidity was significantly related to apathy severity (r = 0.57) and decreased hedonic tone (r = -0.36) in the combined FTD group. Multiple linear regression revealed a significant diagnosis × hedonic tone interaction (ß = -1.40), whereby lower hedonic tone predicted rigidity in SD (r = -0.65) but not in bvFTD (r = -0.18). In contrast, the relationship between rigidity and apathy did not differ between the groups (ß = -0.42). At the neural level, rigidity correlated with degeneration of predominantly right-sided frontostriatal structures including, notably, the nucleus accumbens. CONCLUSIONS: As the first study to demonstrate a link between motivational changes and behavioural rigidity in FTD, our findings have important clinical implications. By identifying candidate mechanisms of behavioural rigidity, our findings can inform targeted interventions to manage inflexible patterns of thought and behaviour in daily life.

Rationale and Design of the "DIagnostic and Prognostic Precision Algorithm for behavioral variant Frontotemporal Dementia" (DIPPA-FTD) Study: A Study Aiming to Distinguish Early Stage Sporadic FTD from Late-Onset Primary Psychiatric Disorders.

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 improve diagnostics are centered on the minority of genetic cases. OBJECTIVE: The multi-center study DIPPA-FTD aims to develop diagnostic and prognostic algorithms to help distinguish sporadic bvFTD from late-onset PPD in its earliest stages. METHODS: The prospective DIPPA-FTD study recruits participants with late-life behavioral changes, suspect for bvFTD or late-onset PPD diagnosis with a negative family history for FTD and/or amyotrophic lateral sclerosis. Subjects are invited to participate after diagnostic screening at participating memory clinics or recruited by referrals from psychiatric departments. At baseline visit, participants undergo neurological and psychiatric examination, questionnaires, neuropsychological tests, and brain imaging. Blood is obtained to investigate biomarkers. Patients are informed about brain donation programs. Follow-up takes place 10-14 months after baseline visit where all examinations are repeated. Results from the DIPPA-FTD study will be integrated in a data-driven approach to develop diagnostic and prognostic models. CONCLUSIONS: DIPPA-FTD will make an important contribution to early sporadic bvFTD identification. By recruiting subjects with ambiguous or prodromal diagnoses, our research strategy will allow the characterization of early disease stages that are not covered in current sporadic FTD research. Results will hopefully increase the ability to diagnose sporadic bvFTD in the early stage and predict progression rate, which is pivotal for patient stratification and trial design.

A Psychosocial Intervention for Carers of Individuals Diagnosed with Dementia in Social Isolation.

Introduction: Growing research has shown the negative impact of social isolation on the health and psychological well-being of individuals with dementia and their carers. This study investigated the effectiveness of a psychosocial intervention for dementia carers during a lockdown period of the COVID-19 pandemic. Methods: Twenty-three family carers of individuals diagnosed with dementia living in the community were recruited and provided with an online psychoeducation toolkit that aims to improve health literacy, management of social and behavioural symptoms in dementia, carer social engagement, and coping skills. Carers were divided into "mild" or "moderate" groups based on the disease severity of the person with dementia they cared for. Outcome measures including distress and severity of neuropsychiatric symptoms, carer self-efficacy and burden, social network, and feelings of loneliness were assessed at baseline and 2 weeks later. Results: Carers in the moderate group reported higher levels of distress (p = 0.001) and severity (p < 0.001) of neuropsychiatric symptoms and greater carer burden (p = 0.003) than carers in the mild group. Following the intervention, both groups reported increased social networks (p = 0.001). In addition, carers in the moderate group reported significantly reduced distress for neuropsychiatric symptoms (p = 0.013), enhanced carer self-efficacy for controlling upsetting thoughts (p = 0.040), and decreased loneliness (p = 0.023). Conclusions: This study demonstrated that psychosocial interventions improve outcomes for carers of individuals with dementia, particularly those caring for individuals with greater disease severity. Findings from this study will inform the development of support services that meet the evolving needs of individuals with dementia and their carers in social isolation, during and in a post-pandemic context.

Frontotemporal lobar degeneration.

Frontotemporal lobar degeneration (FTLD) is one of the most common causes of early-onset dementia and presents with early social-emotional-behavioural and/or language changes that can be accompanied by a pyramidal or extrapyramidal motor disorder. About 20-25% of individuals with FTLD are estimated to carry a mutation associated with a specific FTLD pathology. The discovery of these mutations has led to important advances in potentially disease-modifying treatments that aim to slow progression or delay disease onset and has improved understanding of brain functioning. In both mutation carriers and those with sporadic disease, the most common underlying diagnoses are linked to neuronal and glial inclusions containing tau (FTLD-tau) or TDP-43 (FTLD-TDP), although 5-10% of patients may have inclusions containing proteins from the FUS-Ewing sarcoma-TAF15 family (FTLD-FET). Biomarkers definitively identifying specific pathological entities in sporadic disease have been elusive, which has impeded development of disease-modifying treatments. Nevertheless, disease-monitoring biofluid and imaging biomarkers are becoming increasingly sophisticated and are likely to serve as useful measures of treatment response during trials of disease-modifying treatments. Symptomatic trials using novel approaches such as transcranial direct current stimulation are also beginning to show promise.

Elevated GRO-α and IL-18 in serum and brain implicate the NLRP3 inflammasome in frontotemporal dementia.

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 measured in each study is limited and knowledge on cytokine concentrations in FTD serum is scarce. Here, we assessed 48 cytokines in FTD serum and brain. The aim was to determine common cytokine dysregulation pathways in serum and brain in FTD. Blood samples and brain tissue samples from the superior frontal cortex (SFC) were collected from individuals diagnosed with behavioral variant FTD (bvFTD) and healthy controls, and 48 cytokines were measured using a multiplex immunological assay. The data were evaluated by principal component factor analysis to determine the contribution from different components of the variance in the cohort. Levels of a number of cytokines were altered in serum and SFC in bvFTD compared to controls, with increases in GRO-α and IL-18 in both serum and SFC. These changes could be associated with NLRP3 inflammasome activation or the NFκB pathway, which activates NLRP3. The results suggest the possible importance of the NLRP3 inflammasome in FTD. An improved understanding of the role of inflammasomes in FTD could provide valuable insights into the pathogenesis, diagnosis and treatment of FTD.

Hemispheric contributions toward interoception and emotion recognition in left-vs right-semantic dementia.

BACKGROUND: The hemispheric contributions toward interoception, the perception of internal bodily cues, and emotion recognition remains unclear. Semantic dementia cases with either left-dominant (i.e., left-SD) or right-dominant (i.e., right-SD) anterior temporal lobe atrophy experience emotion recognition difficulties, however, little is known about interoception in these syndromes. Here, we hypothesised that right-SD would show worse interoception and emotion recognition due to right-dominant atrophy. METHODS: Thirty-five participants (8 left-SD; 6 right-SD; 21 controls) completed a monitoring task. Participants pressed a button when they: (1) felt their heartbeat, without pulse measurement (Interoception); or (2) heard a recorded heartbeat (Exteroception-control). Simultaneous ECG was recorded. Accuracy was calculated by comparing the event frequency (i.e., heartbeat or sound) to response frequency. Emotion recognition was assessed via the Facial Affect Selection Task. Voxel-based morphometry analyses identified neural correlates of interoception and emotion recognition. RESULTS: Right-SD showed worse interoception than controls and left-SD (both p's < 0.001). Both patient groups showed worse emotion recognition than controls (right-SD: p < .001; left-SD: p = .018), and right-SD showed worse emotion recognition than left-SD (p = .003). Regression analyses revealed that worse emotion recognition was predicted by right-SD (p = .002), left-SD (p = .005), and impaired interoception (p = .004). Interoception and emotion were associated with the integrity of right-lateralised structures including the insula, temporal pole, thalamus, superior temporal gyrus, and hippocampus. CONCLUSION: Our study provides the first evidence for impaired interoception in right-SD, suggesting that impaired emotion recognition in this syndrome is driven by inaccurate internal monitoring. Further we identified a common neurobiological basis for interoception and emotion in the right hemisphere.

Error profiles of facial emotion recognition in frontotemporal dementia and Alzheimer's disease.

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. PARTICIPANTS: A total of 356 participants (behavioral-variant FTD (bvFTD): 62, semantic dementia (SD)-left: 29, SD-right: 14, progressive non-fluent aphasia (PNFA): 21, AD: 76, controls: 90) were included. MEASUREMENTS: Facial emotion recognition was assessed using the Facial Affect Selection Task, a word-face matching task measuring recognition of the six basic emotions (anger, disgust, fear, happiness, sadness, and surprise), as well as neutral emotion, portrayed by black and white faces. RESULTS: Overall, all clinical groups performed significantly worse than controls with the exception of the PNFA subgroup (p = .051). The SD-right group scored worse than all other clinical groups (all p values < .027) and the bvFTD subgroup performed worse than the PNFA group (p < .001). The most frequent errors were in response to the facial emotions disgust (26.1%) and fear (22.9%). The primary error response to each target emotion was identified; patterns of errors were similar across all clinical groups. CONCLUSIONS: Facial emotion recognition is impaired in FTD and AD compared to healthy controls. Within FTD, bvFTD and SD-right are particularly impaired. Dementia groups cannot be distinguished based on error responses alone. Implications for future clinical diagnosis and research are discussed.

Thinking versus feeling: How interoception and cognition influence emotion recognition in behavioural-variant frontotemporal dementia, Alzheimer's disease, and Parkinson's disease.

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 emotion recognition. One hundred and sixty-eight participants (52 bvFTD; 41 AD; 24 PD; 51 controls) were recruited. Emotion recognition was measured via the Facial Affect Selection Task or the Mini-Social and Emotional Assessment Emotion Recognition Task. Interoception was assessed with a heartbeat detection task. Participants pressed a button each time they: 1) felt their heartbeat (Interoception); or 2) heard a recorded heartbeat (Exteroception-control). Cognition was measured via the Addenbrooke's Cognitive Examination-III or the Montreal Cognitive Assessment. Voxel-based morphometry analyses identified neural correlates associated with emotion recognition and interoceptive accuracy. All patient groups showed worse emotion recognition and cognition than controls (all P's ≤ .008). Only the bvFTD showed worse interoceptive accuracy than controls (P < .001). Regression analyses revealed that in bvFTD worse interoceptive accuracy predicted worse emotion recognition (P = .008). Whereas worse cognition predicted worse emotion recognition overall (P < .001). Neuroimaging analyses revealed that the insula, orbitofrontal cortex, and amygdala were involved in emotion recognition and interoceptive accuracy in bvFTD. Here, we provide evidence for disease-specific mechanisms for emotion recognition difficulties. In bvFTD, emotion recognition impairment is driven by inaccurate perception of the internal milieu. Whereas, in AD and PD, cognitive impairment likely underlies emotion recognition deficits. The current study furthers our theoretical understanding of emotion and highlights the need for targeted interventions.

The Behavioural Dysfunction Questionnaire discriminates behavioural variant frontotemporal dementia from Alzheimer's disease dementia and major depressive disorder.

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 analytical method for the BDQ to discriminate between bvFTD and non-bvFTD patients. MATERIALS AND METHODS: 34 patients with early-stage bvFTD, 56 with early-stage Alzheimer's disease dementia (ADD) and 41 with major depressive disorder (MDD) were recruited. We calculated BDQ-items with or without inclusion of a time criterion: (a) without time criterion, (b) with 10 years' time criterion (symptom presence less than 10 years), and (c) with 3 years' time criterion (symptom presentation within the first 3 years). Using these three differently calculated items, we generated six variables, i.e. 3*2 [BDQ-Global Score (BDQ-GS; domains average score); BDQ-Global Domain Score (BDQ-GDS; domains categorical score)]. Then, we performed univariate and bivariate (BDQ-GS and BDQ-GDS combined) ROC analyses. RESULTS: Models including BDQ-GS, BDQ-GDS or both variables combined discriminated similarly between groups. In contrast, models without time criterion or with 10 years' time criterion discriminated better than models including variables with 3 years' time criterion. These models discriminated highly (AUC = 85.98-87.78) between bvFTD and MDD and bvFTD and ADD, respectively. CONCLUSION: BDQ-scores without any time criterion discriminated highly between early-stage bvFTD and non-bvFTD groups, which could improve the early diagnosis of bvFTD. With its standardised procedure, the BDQ is also appropriate for repeated assessments.

Mapping behavioural, cognitive and affective transdiagnostic dimensions in frontotemporal dementia.

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 entities, mounting evidence indicates overlapping cognitive-behavioural profiles in these syndromes, particularly with disease progression. Why such overlap occurs remains unclear. Understanding the nature of this overlap, however, is essential to improve early diagnosis, characterization and management of those affected. Here, we explored common cognitive-behavioural and neural mechanisms contributing to heterogeneous frontotemporal dementia presentations, irrespective of clinical diagnosis. This transdiagnostic approach allowed us to ascertain whether symptoms not currently considered core to these two syndromes are present in a significant proportion of cases and to explore the neural basis of clinical heterogeneity. Sixty-two frontotemporal dementia patients (31 behavioural variant frontotemporal dementia and 31 semantic dementia) underwent comprehensive neuropsychological, behavioural and structural neuroimaging assessments. Orthogonally rotated principal component analysis of neuropsychological and behavioural data uncovered eight statistically independent factors explaining the majority of cognitive-behavioural performance variation in behavioural variant frontotemporal dementia and semantic dementia. These factors included Behavioural changes, Semantic dysfunction, General Cognition, Executive function, Initiation, Disinhibition, Visuospatial function and Affective changes. Marked individual-level overlap between behavioural variant frontotemporal dementia and semantic dementia was evident on the Behavioural changes, General Cognition, Initiation, Disinhibition and Affective changes factors. Compared to behavioural variant frontotemporal dementia, semantic dementia patients displayed disproportionate impairment on the Semantic dysfunction factor, whereas greater impairment on Executive and Visuospatial function factors was noted in behavioural variant frontotemporal dementia. Both patient groups showed comparable magnitude of atrophy to frontal regions, whereas severe temporal lobe atrophy was characteristic of semantic dementia. Whole-brain voxel-based morphometry correlations with emergent factors revealed associations between fronto-insular and striatal grey matter changes with Behavioural, Executive and Initiation factor performance, bilateral temporal atrophy with Semantic dysfunction factor scores, parietal-subcortical regions with General Cognitive performance and ventral temporal atrophy associated with Visuospatial factor scores. Together, these findings indicate that cognitive-behavioural overlap (i) occurs systematically in frontotemporal dementia; (ii) varies in a graded manner between individuals and (iii) is associated with degeneration of different neural systems. Our findings suggest that phenotypic heterogeneity in frontotemporal dementia syndromes can be captured along continuous, multidimensional spectra of cognitive-behavioural changes. This has implications for the diagnosis of both syndromes amidst overlapping features as well as the design of symptomatic treatments applicable to multiple syndromes.

Multiple pathways of lipid dysregulation in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis is a rapidly progressing neurodegenerative disease characterized by the 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 changes in amyotrophic lateral sclerosis or in relation to disease progression. The present study incorporated a longitudinal lipidomic analysis of amyotrophic lateral sclerosis serum with a comparison with healthy controls using advanced liquid chromatography-mass spectrometry. The results established that diglyceride, the precursor of triglyceride, was enriched the most, while ceramide was depleted the most in amyotrophic lateral sclerosis compared with controls, with the diglyceride species (18:1/18:1) correlating significantly to neurofilament light levels. The prenol lipid CoQ8 was also decreased in amyotrophic lateral sclerosis and correlated to neurofilament light levels. Most interestingly, the phospholipid phosphatidylethanolamine and its three derivatives decreased with disease progression, in contrast to changes with normal ageing. Unsaturated lipids that are prone to lipid peroxidation were elevated with disease progression with increases in the formation of toxic lipid products. Furthermore, in vitro studies revealed that phosphatidylethanolamine synthesis modulated TARDBP expression in SH-SY5Y neuronal cells. Finally, diglyceride, cholesterol ester and ceramide were identified as potential lipid biomarkers for amyotrophic lateral sclerosis diagnosis and monitoring disease progression. In summary, this study represents a longitudinal lipidomics analysis of amyotrophic lateral sclerosis serum and has provided new insights into multiple pathways of lipid dysregulation in amyotrophic lateral sclerosis.

The Acceptability and Usefulness of Positive Behaviour Support Education for Family Carers of People With Frontotemporal Dementia: A Pilot Study.

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)-PBS program to the FTD population. METHODS: A pre-test post-test mixed-methods design was utilized. Primary outcome measures included a Carer Confidence questionnaire and post-intervention Feedback Questionnaire. Assessments were conducted prior to the 4-week education program, immediately following the final session and a 3 months follow-up. RESULTS: Ten family carers completed the 4 PBS education sessions and indicated that the program was helpful in providing behaviour support. No significant changes in confidence ratings were found before and following the education sessions. A majority of participants, however, reported positive changes to their approach in providing behaviour support, with key themes including 'recognising the function of behaviour', 'changing their own behaviour' and 'promoting a calmer approach'. CONCLUSIONS: The FAB-PBS education sessions demonstrate to be an acceptable approach to increasing the capability of family carers in providing behaviour support to individuals with FTD, which will need to be confirmed in a larger feasibility study.

Current Potential for Clinical Optimization of Social Cognition Assessment for Frontotemporal Dementia and Primary Psychiatric Disorders.

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 cognition workgroup within the Neuropsychiatric International Consortium Frontotemporal dementia (scNIC-FTD), aiming to validate social cognition assessment for diagnostic purposes and tracking of change across clinical situations.