An attentional and working memory theory of hallucination vulnerability in frontotemporal dementia.

The rate and prevalence of hallucinations in behavioural variant frontotemporal dementia is well established. The mechanisms for underlying vulnerability however are the least well described in FTD compared with other neuropsychiatric conditions, despite the presence of these features significantly complicating the diagnostic process. As such, this present study aimed to provide a detailed characterization of the neural, cognitive and behavioural profile associated with a predisposition to hallucinatory experiences in behavioural variant frontotemporal dementia. In total, 153 patients with behavioural variant frontotemporal dementia were recruited sequentially for this study. A group of patients with well characterized hallucinations and good-quality volumetric MRI scans (n = 23) were genetically and demographically matched to a group without hallucinations (n = 23) and a healthy control cohort (n = 23). All patients were assessed at their initial visit by means of a detailed clinical interview, a comprehensive battery of neuropsychological tests and MRI. Data were analysed according to three levels: (i) the relationship between neural structures, cognition, behaviour and hallucinations in behavioural variant frontotemporal dementia; (ii) the impact of the C9orf72 expansion; and (iii) hallucination subtype on expression of hallucinations. Basic and complex attentional (including divided attention and working memory) and visual function measures differed between groups (all P < 0.001) with hallucinators demonstrating poorer performance, along with evidence of structural changes centred on the prefrontal cortex, caudate and cerebellum (corrected for False Discovery Rate at P < 0.05 with a cluster threshold of 100 contiguous voxels). Attentional processes were also implicated in C9orf72 carriers with hallucinations with structural changes selectively involving the thalamus. Patients with visual hallucinations in isolation showed a similar pattern with emphasis on cerebellar atrophy. Our findings provided novel insights that attentional and visual function subsystems and related distributed brain structures are implicated in the generation of hallucinations in behavioural variant frontotemporal dementia, that dissociate across C9orf72, sporadic behavioural variant frontotemporal dementia and for the visual subtype of hallucinations. This loading on attentional and working memory measures is in line with current mechanistic models of hallucinations that frequently suggest a failure of integration of cognitive and perceptual processes. We therefore propose a novel cognitive and neural model for hallucination predisposition in behavioural variant frontotemporal dementia that aligns with a transdiagnostic model for hallucinations across neurodegeneration and psychiatry.

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.

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.

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.

Reduced Sensitivity to Background Reward Underlies Apathy After Traumatic Brain Injury: Insights From an Ecological Foraging Framework.

BACKGROUND: Altered reward processing is increasingly recognised as a crucial mechanism underpinning apathy in many brain disorders. However despite its clinical relevance, little is known about the mechanisms of apathy following moderate-to-severe traumatic brain injury (TBI). In real-life situations, reward representations encompass both foreground (gains from current activity) and background (potential gains from the broader environment) elements. This latter variable provides a crucial set-point for switching behaviour in many naturalistic settings. We hypothesised apathy post-TBI would be associated with disrupted background reward sensitivity. METHODS: We administered a computer-based foraging task to 45 people with moderate-to-severe TBI (20 with apathy, 39 males) and 37 matched controls. Participants decided when to leave locations (patches) where foreground reward rates depleted at differing rates, to pursue greater rewards from other patches in the environment, which had either a high or low background reward rate. Primary analysis was performed using linear mixed effects models, with patch leaving time the dependent variable. RESULTS: Findings showed a significant interaction between apathy and background reward sensitivity, driven by apathetic TBI participants not altering patch-leaving decisions as environmental reward rate changed. In contrast, although TBI was associated with reduced sensitivity to changing foreground rewards, this did not vary as a function of apathy. CONCLUSIONS: These results provide the first evidence directly linking disrupted background reward processing to apathy in any brain disorder. They identify a novel mechanism for apathy following moderate-to-severe TBI, and point towards novel interventions to improve this debilitating complication of head injury.

Gaps in clinical research in frontotemporal dementia: A call for diversity and disparities-focused research.

Frontotemporal dementia (FTD) is one of the leading causes of dementia before age 65 and often manifests as abnormal behavior (in behavioral variant FTD) or language impairment (in primary progressive aphasia). FTD's exact clinical presentation varies by culture, language, education, social norms, and other socioeconomic factors; current research and clinical practice, however, is mainly based on studies conducted in North America and Western Europe. Changes in diagnostic criteria and procedures as well as new or adapted cognitive tests are likely needed to take into consideration global diversity. This perspective paper by two professional interest areas of the Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment examines how increasing global diversity impacts the clinical presentation, screening, assessment, and diagnosis of FTD and its treatment and care. It subsequently provides recommendations to address immediate needs to advance global FTD research and clinical practice.

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.

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.

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.

The influence of culture and cognitive reserve on the clinical presentation of behavioural-variant frontotemporal dementia.

Characterisation of the clinical profile of behavioural-variant frontotemporal dementia (bvFTD) has predominantly been based on Western samples. Some small studies have suggested that the clinical profile may differ in culturally and linguistically diverse populations. Additionally, there is evidence that patients from non-English speaking backgrounds may have more cognitive reserve, allowing them to tolerate more disease pathology before clinical symptoms emerge. This study aims to characterise the clinical profiles of patients with bvFTD from culturally diverse backgrounds. BvFTD patients were classified as Australian-born (Australian) or Culturally and Linguistically Diverse-English-speaking (CALD-English) and Culturally and Linguistically Diverse-Language Other Than English (CALD-LOTE). Clinical features, cognitive test performance and cognitive reserve were compared between groups. Voxel-based morphometry was used to examine the neural correlates of cognitive reserve. 107 patients with bvFTD (53 Australian, 36 CALD-English, 18 CALD-LOTE) and 51 controls were included. Analysis of neuropsychiatric features revealed more elation in Australian patients compared to CALD-English patients, with trends for CALD-LOTE patients to report more irritability. CALD-LOTE patients also had higher cognitive reserve and showed relatively greater verbal than non-verbal cognitive impairment. Neuroimaging analyses revealed that higher cognitive reserve was associated with lower integrity in the frontal-temporal regions associated with typical disease pathology in bvFTD. Our findings support the hypothesis that cognitive reserve may delay early cognitive decline in culturally and linguistically diverse patients, although these patients may still show poor verbal performance due to cultural testing biases. Clinically, these results highlight the need to consider cultural and linguistic background to inform the assessment of dementia.

Altered reward processing underpins emotional apathy in dementia.

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, and their common neural correlates, has not been directly examined. METHODS: Sixty-four patients (33 behavioural-variant frontotemporal dementia, 14 Alzheimer's disease, 8 semantic dementia, 6 progressive nonfluent aphasia, 3 logopenic progressive aphasia) were classified into high (HEA; n = 36) and low (LEA; n = 28) emotional apathy groups based on emotional apathy subscale scores on the Dimensional Apathy Scale. Patients and age-matched healthy controls (n = 27) performed an instrumental reward learning task where they learned to associate cues with either social or monetary outcomes. RESULTS: HEA patients showed impaired learning on both the social and monetary reward conditions, relative to LEA patients (p = 0.016) and controls (p = 0.005). Conversely, the LEA group did not differ from controls (p = 0.925). Importantly, multiple regression analyses indicated that social reward learning significantly predicted emotional apathy. Voxel-based morphometry analyses revealed that emotional apathy and social reward learning were both associated with orbitofrontal cortex, ventral striatum, and insula atrophy. DISCUSSION: Our results demonstrate a unique link between impaired social reward learning and emotional apathy in dementia and reveal a shared neurobiological basis. Greater understanding of these neurocognitive mechanisms of reward processing will help improve the identification of emotional apathy in dementia and inform the development of novel interventions to address these symptoms.

Neural compensation in manifest neurodegeneration: systems neuroscience evidence from social cognition in frontotemporal dementia.

BACKGROUND: It has been argued that symptom onset in neurodegeneration reflects the overload of compensatory mechanisms. The present study aimed to investigate whether neural functional compensation can be observed in the manifest neurodegenerative disease stage, by focusing on a core deficit in frontotemporal dementia, i.e. social cognition, and by combining psychophysical assessment, structural MRI and functional MRI with multidimensional neural markers that allow quantification of neural computations. METHODS: Nineteen patients with clinically manifest behavioral variant frontotemporal dementia (bvFTD) and 20 controls performed facial expression recognition tasks in the MRI-scanner and offline. Group differences in grey matter volume, neural response amplitude and neural patterns were assessed via a combination of voxel-wise whole-brain, searchlight, and ROI-analyses and these measures were correlated with psychophysical measures of emotion, valence and arousal ratings. RESULTS: Significant group effects were observed only outside task-relevant regions, converging in the caudate nucleus. This area showed a diagnostic neural pattern as well as hyperactivation and stronger neural representation of facial expressions in the bvFTD sample. Furthermore, response amplitude was associated with behavioral arousal ratings. CONCLUSIONS: The combined findings reveal converging support for compensatory processes in clinically manifest neurodegeneration, complementing accounts that clinical onset synchronizes with the breakdown of compensatory processes. Furthermore, active compensation may proceed along nodes in intrinsically connected networks, rather than along the more task-specific networks. The findings underscore the potential of distributed multidimensional functional neural characteristics that may provide a novel class of biomarkers with both diagnostic and therapeutic implications, including biomarkers for clinical trials.

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.

Action control and selection in social disinhibition following severe TBI: a pavlovian-to-instrumental transfer and outcome devaluation study.

INTRODUCTION: Social disinhibition is a significant sequela of severe traumatic brain injury (TBI). Some research suggests that it could reflect a deficiency in goal-directed behavior. The current study aimed to test whether these inappropriate behaviors tend to be deficient in goal-directed control, that is, triggered more by environmental stimuli than by the known consequences of their actions. METHOD: We used a between-group design with 25 adult participants with severe TBI, and 27 control participants. Social disinhibition was measured using Frontal Systems Behavior Scale and Social Disinhibition Interview. Changes in reward-related goal-directed behavior were evaluated using a computer-based task in which we assessed the influence of cues predicting reward and of reward devaluation on choice performance. RESULTS: We found no difference in the levels of social disinhibition between the TBI and control groups and, using mixed two-way ANCOVAs, no overall effect of the stimuli or outcome devaluation. However, after combing these groups and splitting them based on their disinhibition levels, a significant interaction between group (High vs Low disinhibition) and reward type (Valued vs Devalued) in sensitivity to outcome devaluation test (F = 5.99, p = .01, ηp2 = .13) appeared. Comparing with the baseline rate of responding, the Low disinhibition group decreased their responding to devalued and increased their responding to still-valued outcomes. In contrast, the High disinhibition group showed the opposite pattern of choice performance. CONCLUSIONS: It appears that people with clinical levels of social disinhibition are both prone to outcome-response priming effects and insensitive to changes in the value of the consequences of their actions, that is, despite evidence they were aware of the reduction in the value of their actions's outcomes, people with high-level disinhibition kept performing those actions. This pattern has the hallmarks of a habit suggesting their disinhibition reflects a loss of executive control.

Phase I trial of the MuSic to CONnect (MuSiCON) protocol: feasibility and effect of choir participation for individuals with cognitive impairment.

BACKGROUND: Individuals living in residential aged care facilities with cognitive decline are at risk of social isolation and decreased wellbeing. These risks may be exacerbated by decline in communication skills. There is growing awareness that group singing may improve sense of wellbeing for individuals with dementia. However, to date few studies have examined broader rehabilitative effects on skills such as communication of individuals with dementia. AIMS: To determine the feasibility and acceptability of the MuSic to Connect (MuSiCON) choir and language/communication assessment protocol in people with cognitive impairment living in non-high-care wards of a residential facility. METHODS: Six individuals with mild-moderate cognitive impairment participated (age range 55-91 years, five female, one male). A mixed method approach was used. Quantitative outcomes included attendance rates, quality of life and communication measures. The qualitative measure was a brief survey of experience completed by participants and carers post-intervention. RESULTS: Overall, MuSiCON was perceived as positive and beneficial, with high attendance, perception of improved daily functioning and high therapeutic benefit without harmful effects. While there was no reliable change in communication skills over the course of the six-week intervention, most participants successfully engaged in the conversational task, suggesting it is a suitable and ecologically valid method for data collection. CONCLUSIONS: The MuSiCON protocol demonstrated feasibility and was well received by participants and staff at the residential facility. A co-design approach is recommended to improve upon feasibility, acceptability and validity of the assessment protocol prior to Phase II testing.

Contributions of intrinsic and extrinsic reward sensitivity to apathy: Evidence from traumatic brain injury.

OBJECTIVE: Apathy is a key feature of traumatic brain injury (TBI). However, mechanisms underlying apathy are poorly understood. Evidence suggests that changes in reward may be a crucial factor. Rewards can come from two important sources: extrinsic reward (e.g., money) and intrinsic reward (e.g., enjoyment). Here, we used an experimental paradigm to examine the contributions of intrinsic-extrinsic reward sensitivity to apathy post-TBI and neurocognitive processes associated with these reward processing components. METHOD: Fifty-seven patients with TBI (TBI with clinical/severe apathy [TBI + sA], TBI with subclinical/moderate apathy [TBI + mA] and TBI without apathy [TBI-A] groups), and 30 healthy individuals completed the "birthday-gift task." In the "intrinsic reward" condition, participants chose to "go" to collect the gift or "wait" for the same gift to be delivered. In the "extrinsic reward" condition, the task was identical, however, participants received monetary incentives when choosing "going" instead of "waiting." The Montreal Cognitive Assessment was utilized for cognitive examination. RESULTS: A smaller proportion of people in the TBI + sA group had high sensitivity to both intrinsic and extrinsic rewards than the TBI + mA, TBI-A and healthy comparison groups. The TBI+sA group also perceived the "go" option on the intrinsic reward condition as more effortful and made fewer "go" decisions on the extrinsic condition. Attention was the only predictor of intrinsic reward sensitivity, whereas executive functioning, attention and group predicted extrinsic reward. CONCLUSION: This study demonstrates the relationship between intrinsic-extrinsic reward hyposensitivity and apathy post-TBI. These results may be integrated into future trials to improve apathy in clinical practice. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Olfactory Bulb Integrity in Frontotemporal Dementia and Alzheimer's Disease.

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 longitudinally in AD. OBJECTIVE: To measure OB volume in FTD and AD patients longitudinally using MRI. METHODS: This study measured OB volumes using MRI in patients diagnosed with behavioral-variant FTD (n = 55), semantic dementia (n = 34), progressive non-fluent aphasia (n = 30), AD (n = 50), and healthy age-matched controls (n = 55) at their first visit to a dementia research clinic ('baseline'). Imaging data in patients 12-months later were analyzed where available (n = 84) for longitudinal assessment. Volumes of subcortical and cortical olfactory regions ('olfactory network') were obtained via surface-based morphometry. RESULTS: Results revealed that in AD and FTD at baseline, OB volumes were similar to controls, whereas volumes of olfactory network regions were significantly reduced in all patient groups except in progressive non-fluent aphasia. Longitudinal data revealed that OB volume became significantly reduced (10-25% volume reduction) in all dementia groups with disease progression. CONCLUSION: Olfactory dysfunction is common in patients diagnosed with AD or FTD, but our results indicate that there is no detectable volume loss to the OBs upon first presentation to the clinic. Our findings indicate that the OBs become detectably atrophied later in the disease process. OB atrophy indicates the potential usefulness for OBs to be targeted in interventions to improve olfactory function.

A shared cognitive and neural basis underpinning cognitive apathy and planning in behavioural-variant frontotemporal dementia and Alzheimer's disease.

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-variant frontotemporal dementia (bvFTD) and Alzheimer's disease (AD). Seventy-one participants (31 bvFTD, 17 AD and 23 controls) were assessed on a neuropsychological battery of executive tasks including the Zoo Map Test, Modified Six Elements Test, Tower Test and verbal fluency. The Dimensional Apathy Scale (DAS) was used to quantify cognitive apathy. Principal components analysis identified a single component underpinning performance on the neuropsychological tests, with both bvFTD and AD showing significantly reduced "planning ability" compared to controls. On the DAS, 74% of bvFTD patients and 59% of AD patients showed clinically significant cognitive apathy. Importantly, linear regression revealed that lower planning ability significantly predicted increased cognitive apathy, even after controlling for cognitive impairment and disease duration. Voxel-based morphometry analyses revealed that planning ability and cognitive apathy were both associated with atrophy of the right frontal pole and orbitofrontal cortex, as well as the thalamus and putamen. From a theoretical perspective, our results reveal a shared mechanism underpinning both cognitive apathy and planning deficits in bvFTD and AD. Clinically, this knowledge will help to improve the identification of apathy in clinical syndromes and inform targeted interventions to improve independence and wellbeing for those living with dementia.

Plasma Oxytocin Is Not Associated with Social Cognition or Behavior in Frontotemporal Dementia and Alzheimer's Disease Syndromes.

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 dementia remains underexplored. METHODS: Thirty behavioral-variant FTD (bvFTD), 28 SD, 39 AD, and 24 controls underwent blood sampling to measure oxytocin. Participants completed an emotion processing battery. Carers completed the Cambridge Behavioral Inventory and the Neuropsychiatric Inventory. RESULTS: Patients with bvFTD were severely impaired in emotion processing and behavioral ratings, with milder impairment in SD and AD. No difference in plasma oxytocin was observed between groups (p = 0.632). No significant associations were found between oxytocin and social behavior or emotion processing (r values between -0.241 and 0.227, all p values >0.099). CONCLUSION: Our results indicate that plasma oxytocin is not reduced in dementia and is unrelated to social, emotional, and behavioral features. We noted high interindividual variability in our data; hence, future investigations should consider methodological influences such as serum versus saliva and diurnal variation on oxytocin function. These results demonstrate that current measurement measures of plasma oxytocin have limited utility in determining the role of oxytocin in FTD. Alternative oxytocin measures may prove more sensitive and should be considered when conducting clinical trials.

Managing communication changes in persons with multiple sclerosis: Findings from qualitative focus groups.

BACKGROUND: There is growing recognition that communication can be affected in multiple sclerosis (MS) and can negatively impact relationships, employment and psychological well-being. Some persons with MS (PwMS) implement strategies to facilitate their communication; however, some do not. Most PwMS who report communication changes do not engage with speech-language pathology (SLP) services. This raises concerns that a large portion of communication changes associated with MS go under-recognized and unmanaged. Little is known about what PwMS want and need to facilitate effective communication. AIM: To explore what PwMS want and need to better manage their communication changes. METHODS & PROCEDURES: Three focus groups were conducted online using Zoom, with a total of 12 PwMS. Participants were an opportunistic sample of PwMS within Australia recruited via advertisements distributed to various MS organizations and clinics. Data were transcribed verbatim and analysed using thematic content analysis to provide a qualitative analysis of the data. OUTCOMES & RESULTS: Two main themes emerged: (1) accessible knowledge and a holistic approach; and (2) partnerships. Specifically, the identified wants and needs of participants included: (1) assessment; (2) information; (3) raising awareness; (4) support groups; (5) a whole-person approach to intervention; (6) geographically and economically accessible and navigable services; (7) effective patient-physician interactions; and (8) a multidisciplinary team-based approach (e.g., SLP, psychology, neuropsychology, occupational therapy). CONCLUSIONS & IMPLICATIONS: This study identified a wide range of unmet wants and needs of PwMS related to communication changes. Participants wanted improved collaborative partnerships with healthcare professionals to better manage their communication changes. For example, healthcare professionals could ask PwMS about potential communication changes, provide education and make appropriate referrals. Education and information provision could focus on communication changes in MS, factors that trigger or exacerbate communication changes, impacts, self-management strategies, and available supports and services. Specific implications for clinical practice and future research are suggested in this paper, including ideas for patient education materials and content, suggestions for communication-specific screening and information that could be shared in patient-physician interactions, the development of guidelines to systematically screen, assess, manage and monitor communication changes in MS, and the design of evidence-based communication interventions for this clinical population. The results from this study can be used to guide the design of supports and services to help PwMS better manage communication changes, with the aim to reduce the negative impacts. WHAT THIS PAPER ADDS: What is already known on this subject PwMS can experience communication changes across a range of domains, including speech, voice, fluency, expressive and receptive language, and cognitive-linguistic functions. These changes can have profound and far-reaching negative impacts on educational and vocational outcomes, social participation, relationships, psychological well-being, and quality of life. Most PwMS who report communication changes do not engage with SLP services. There has been little research exploring what PwMS want and need to help manage their communication changes. What this paper adds to the existing knowledge This research is the first study of its kind that sets out specifically to explore what PwMS want and need to better manage their communication changes. This study increases our understanding of, and provides valuable insights into, the specific types of supports and services PwMS desire to access, and the partnerships and kinds of interactions PwMS dream of having with healthcare professionals to manage these changes. This information can facilitate the development of future interventions to manage communication changes in MS. What are the potential or actual clinical implications of this work? PwMS wanted healthcare professionals to ask about potential communication changes, provide education and make appropriate referrals. When providing education and information on communication changes in MS, healthcare professionals should focus on covering symptoms, triggers, impacts, self-management strategies, and available supports and services. There is a timely need to develop guidelines and interventions to manage communication changes in MS to reduce their negative impacts.