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Objectives: Mental health triage services are the first contact for people wanting support for their mental health and provide access to public mental health services in Victoria, Australia. People living with young-onset dementia and their families may contact triage services seeking assistance for behaviour changes and pathways to care as there are few alternative services available. Methods: The authors reviewed the minimum triage dataset from one of the largest mental health services in Victoria, Australia from 2018 to 2021 investigating reasons for referral for people with young-onset dementia. Results: Of the 1766 referrals for 'dementia', 145 were for young-onset dementia. Of these, 69% were referred for behaviour changes. About half of the referrals for behaviour changes were triaged as 'advice only'. One-third of referrals were from general practitioners. Conclusions: The availability of dementia-specific support services that could provide advice on dementia as well as advice for behaviour changes related to the disease could potentially ease the burden of phone calls received by mental health triage services. What is known about the topic? Young-onset dementia refers to a dementia with onset at less than 65 years of age. People with young-onset dementia may contact mental health services for support but the reasons for contact are unknown. What does this paper add? The reasons for contacting one Victorian mental health service included behaviour changes such as agitation or aggression and psychotic symptoms (74%) and general advice, including about dementia pathways (14%). General practitioners made up one-third of referral sources. What are the implications for practitioners? Victorian mental health services are generally overloaded and complex. There is a need to promote alternative dementia support organisations in order to provide an alternative contact for people affected by young-onset dementia. [ABSTRACT FROM AUTHOR]

Objectives: Individuals living with young-onset dementia fall through the gaps of adult and geriatric services. Given that non-cognitive symptoms of dementia in younger people are often psychiatric and behavioural in nature, these people may contact mental health services. There is sparse information investigating the frequency of people with young-onset dementia who contact mental health triage in Victoria. Methods: Triage data were obtained from the Victorian Agency for Health Information. The data contained demographics for people registered with Victorian mental health services. Consumers who had an International Classification for Diseases code for dementia and were aged less than 65 years were identified as people with young-onset dementia. Using information of the frequency of people with young-onset dementia who were registered with each area-based mental health service, population census statistics were used to make estimates of the frequency of young-onset dementia. Results: Of the 6172 people who had a dementia diagnosis, 1020 of them were aged less than 65 years and had young-onset dementia. There were proportionally more men who had young-onset dementia compared to women. There were more people with young-onset dementia registered to rural mental health services compared to metropolitan services. Conclusion: Findings provide important information for service planning in Victoria. Recommendations include upskilling and education for the assessment of dementia for those clinicians who work in mental health services, particularly in rural regions. What is known about the topic? Young-onset dementia refers to a dementia with onset at an age less than 65 years. Accessing age-appropriate services for these people is difficult as they fall through the gaps of adult and aged services due to their age. What does this paper add? Due to the behavioural and psychiatric manifestations related to young-onset dementia, data is provided about mental health service involvement for these people. What are the implications for practitioners? There is a need to upskill mental health clinicians, especially in rural areas, as younger people with dementia are accessing these services. [ABSTRACT FROM AUTHOR]

Objective Given the rapid shift to in-home teleneuropsychology models, more research is needed to investigate the equivalence of non-facilitator models of teleneuropsychology delivery for people with younger onset dementia (YOD). This study aimed to determine whether equivalent performances were observed on neuropsychological measures administered in-person and via teleneuropsychology in a sample of people being investigated for YOD. Method Using a randomized counterbalanced cross-over design, 43 participants (M age = 60.26, SD age = 7.19) with a possible or probable YOD diagnosis completed 14 neuropsychological tests in-person and via teleneuropsychology, with a 2-week interval. Repeated measures t -tests, intraclass correlation coefficients (ICC), and Bland Altman analyses were used to investigate equivalence across the administration conditions. Results No statistical differences were found between in-person and teleneuropsychology conditions, except for the Hospital Anxiety and Depression Scale Anxiety subtest. Small to negligible effect sizes were observed (ranging from.01 to.20). ICC estimates ranged from.71 to.97 across the neuropsychological measures. Bland Altman analyses revealed that the Wechsler Adult Intelligence Scale—Fourth Edition Block Design subtest had slightly better overall performance in the in-person condition and participants reported higher levels of anxiety symptoms during the teleneuropsychology condition; however, average anxiety symptoms remained within the clinically normal range. Participants reported a high level of acceptability for teleneuropsychology assessments. Conclusions These results suggest that performances are comparable between in-person and teleneuropsychology assessment modalities. Our findings support teleneuropsychology as a feasible alternative to in-person neuropsychological services for people under investigation of YOD, who face significant barriers in accessing timely diagnoses and treatment options. [ABSTRACT FROM AUTHOR]

Most suspected Creutzfeldt‐Jakob disease (CJD) cases are eventually diagnosed with other disorders. We assessed the utility of investigating Alzheimer's disease (AD) biomarkers and neurofilament light (NfL) in patients when CJD is suspected. The study cohort consisted of cerebrospinal fluid (CSF) samples referred for CJD biomarker screening wherein amyloid beta 1‐42 (Aβ1‐42), phosphorylated tau 181 (p‐tau181), and total tau (t‐tau) could be assessed via Elecsys immunoassays (n = 419) and NfL via enzyme‐linked immunosorbent assay (ELISA; n = 161). In the non‐CJD sub cohort (n = 371), 59% (219/371) had A+T– (abnormal Aβ1‐42 only) and 21% (79/371) returned A+T+ (abnormal Aβ1‐42 and p‐tau181). In the 48 CJD subjects, a similar AD biomarker profile distribution was observed. To partially address the prevalence of likely pre‐symptomatic AD, NfL was utilized to assess for neuronal damage. NfL was abnormal in 76% (25/33) of A+T– subjects 40 to 69 years of age, 80% (20/25) of whom had normal t‐tau. This study reinforces AD as an important differential diagnosis of suspected CJD, highlighting that incorporating AD biomarkers and NfL at initial testing is worthwhile. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to compare Greek Australian and English language normative data with regard to impairment rates yielded within a healthy Greek Australian older adult sample. We also examined whether optimal cut scores could be identified and capable of sensitively and specifically distinguishing between healthy Greek Australians from those with a diagnosis of Alzheimer's disease (AD). Method: Ninety healthy Greek Australian older adults and 20 demographically matched individuals with a diagnosis of AD completed a range of neuropsychological measures, including the Wechsler Adult Intelligence Scale-Fourth Edition, Greek Adaptation (WAIS-IV GR), verbal and visual memory, language and naming, and executive functions. Impairment rates derived from the use of either Greek Australian or English language normative data were calculated and compared, using a 1.5 standard deviation criterion to denote impairment. Receiver operating characteristics curve analysis was used to investigate the sensitivity and specificity of alternate cut scores. Results: Impairment rates derived from the Greek Australian normative data showed that rates of impairment generally fell within the expected 7% range. In contrast, impairment rates for all tests derived using English language normative data were significantly higher and ranged from 11%–66%. Comparisons between healthy and AD participants with moderate dementia showed significant differences across all measures. Area under the curve results ranged from.721 to.999 across all measures, with most tests displaying excellent sensitivity and specificity. Conclusions: English language normative data were found to be inappropriate for use with Greek Australian elders, potentially leading to erroneous diagnostic outcomes. The use of minority group specific normative data and associated cut points appear to partially ameliorate this issue. Clinical implications are discussed alongside future research directions. [ABSTRACT FROM AUTHOR]

Patients diagnosed with functional (psychogenic nonepileptic) seizures have similar or greater levels of disability, morbidity and mortality than people with epilepsy, but there are far fewer treatment services. In contrast to epilepsy, the current understanding of pathophysiological mechanisms and the development of evidence-based treatments for functional seizures is rudimentary. This leads to high direct healthcare costs and high indirect costs to the patient, family and wider society. There are many patient, clinician and system-level barriers to improving outcomes for functional seizures. At a patient level, these include the heterogeneity of symptoms, diagnostic uncertainty, family factors and difficulty in perceiving psychological aspects of illness and potential benefits of treatment. Clinician-level barriers include sub-specialism, poor knowledge, skills and attitudes and stigma. System-level barriers include the siloed nature of healthcare, the high prevalence of functional seizures and funding models relying on individual medical practitioners. Through the examination of international examples and expert recommendations, several themes emerge that may address some of these barriers. These include (1) stepped care with low-level, brief generalised interventions, proceeding to higher level, extended and individualised treatments; (2) active triage of complexity, acuity and treatment readiness; (3) integrated interdisciplinary teams that individualise formulation, triage, and treatment planning and (4) shared care with primary, emergency and community providers and secondary consultation. Consideration of the application of these principles to the Australian and New Zealand context is proposed as a significant opportunity to meet an urgent need. [ABSTRACT FROM AUTHOR]

Behaviour changes (BCs) are common in young-onset dementia (YOD). Access to knowledgeable and age-appropriate support services is needed to assist with the appropriate management of BCs. We sought to investigate the types of YOD-related BCs that most commonly require support, the formal services being accessed for support, and the experiences of those seeking support in Australia. We employed a cross-sectional online questionnaire for individuals living with YOD as well as individuals providing informal or formal care for someone with YOD. Thirty-six questionnaire responses were recorded. Of the total sample, 83% reported YOD-related BCs requiring support, the most common being appetite/eating changes, followed by agitation/aggression and apathy/indifference. Seventy-six percent of these individuals had attempted to seek support from a formal service, with Dementia Australia, Dementia Support Australia, and general practitioners most commonly approached. Responses suggested that the support access pathway is suboptimal, with a lack of clarity about what services to approach for support and long wait times. Furthermore, 28% of participants had not gained access to support utilizing non-pharmacological strategies. Individuals who need support for YOD-related BCs demonstrated a high rate of help-seeking from formal support services; however, the support access pathway is slow, is difficult to navigate, and does not result in the best-practice management of BCs. Formal services resourced to provide efficient support with the implementation of behavioural strategies are needed, along with clear, accessible guidelines on the pathway to access them. [ABSTRACT FROM AUTHOR]

Introduction: While individuals with Huntington disease (HD) show memory impairment that indicates hippocampal dysfunction, the available literature does not consistently identify structural evidence for involvement of the whole hippocampus but rather suggests that hippocampal atrophy may be confined to certain hippocampal subregions. Methods: We processed T1‐weighted MRI from IMAGE‐HD study using FreeSurfer 7.0 and compared the volumes of the hippocampal subfields among 36 early motor symptomatic (symp‐HD), 40 pre‐symptomatic (pre‐HD), and 36 healthy control individuals across three timepoints over 36 months. Results: Mixed‐model analyses revealed significantly lower subfield volumes in symp‐HD, compared with pre‐HD and control groups, in the subicular regions of the perforant‐pathway: presubiculum, subiculum, dentate gyrus, tail, and right molecular layer. These adjoining subfields aggregated into a single principal component, which demonstrated an accelerated rate of atrophy in the symp‐HD. Volumes between pre‐HD and controls did not show any significant difference. In the combined HD groups, CAG repeat length and disease burden score were associated with presubiculum, molecular layer, tail, and perforant‐pathway subfield volumes. Hippocampal left tail and perforant‐pathway subfields were associated with motor onset in the pre‐HD group. Conclusions: Hippocampal subfields atrophy in early symptomatic HD affects key regions of the perforant‐pathway, which may implicate the distinctive memory impairment at this stage of illness. Their volumetric associations with genetic and clinical markers suggest the selective susceptibility of these subfields to mutant Huntingtin and disease progression. [ABSTRACT FROM AUTHOR]

Objectives: Vascular dementia (VD) is one of the more common types of dementia. Much is known about VD in older adults in terms of survival and associated risk factors, but comparatively less is known about VD in a younger population. This study aimed to investigate survival in people with young-onset VD (YO-VD) compared to those with late-onset VD (LO-VD) and to investigate predictors of mortality. Design: Retrospective file review from 1992 to 2014. Setting: The inpatient unit of a tertiary neuropsychiatry service in Victoria, Australia. Participants: Inpatients with a diagnosis of VD. Measurements and methods: Mortality information was obtained from the Australian Institute of Health and Welfare. Clinical variables included age of onset, sex, vascular risk factors, structural neuroimaging, and Hachinksi scores. Statistical analyses used were Kaplan–Meier curves for median survival and Cox regression for predictors of mortality. Results: Eighty-four participants were included with few clinical differences between the LO-VD and YO-VD groups. Sixty-eight (81%) had died. Median survival was 9.9 years (95% confidence interval 7.9, 11.7), with those with LO-VD having significantly shorter survival compared to those with YO-VD (6.1 years and 12.8 years, respectively) and proportionally more with LO-VD had died (94.6%) compared to those with YO-VD (67.5%), χ2(1) = 9.16, p = 0.002. The only significant predictor of mortality was increasing age (p = 0.001). Conclusion: While there were few clinical differences, and older age was the only factor associated with survival, further research into the effects of managing cardiovascular risk factors and their impact on survival are recommended. [ABSTRACT FROM AUTHOR]

Background and Aims: Neurodegeneration underpins the pathological processes of younger‐onset dementia (YOD) and has been implicated in primary psychiatric disorders (PSYs). Cerebrospinal fluid (CSF) neurofilament light (NfL) has been used to investigate neurodegeneration severity through correlation with structural brain changes in various conditions, but has seldom been evaluated in YOD and PSYs. Methods: This retrospective study included patients with YOD or PSYs with magnetic resonance imaging (MRI) of the brain and CSF NfL analysis. Findings from brain MRI were analysed using automated volumetry (volBrain) to measure white matter (WM), grey matter (GM) and whole brain (WB) volumes expressed as percentages of total intracranial volume. Correlations between NfL and brain volume measurements were computed whilst adjusting for age. Results: Seventy patients (47 with YOD and 23 with PSY) were identified. YOD types included Alzheimer disease and behavioural variant frontotemporal dementia. PSY included schizophrenia and major depressive disorder. MRI brain sequences were either fast spoiler gradient‐echo (FSPGR) or magnetization‐prepared rapid acquisition gradient‐echo (MPRAGE). In the total cohort, higher NfL was associated with reduced WB in the FSPGR and MPRAGE sequences (r = −0.402 [95% confidence interval (CI), −0.593 to −0.147], P = 0.008 and r = −0.625 [95% CI, −0.828 to −0.395], P < 0.001, respectively). Higher NfL was related to reduced GM in FSPGR (r = 0.385 [95% CI, −0.649 to −0.014], P = 0.017) and reduced WM in MPRAGE (r = −0.650 [95% CI, −0.777 to −0.307], P < 0.001). Similar relationships were seen in YOD, but not in PSY. Conclusion: Higher CSF NfL is related to brain atrophy in YOD, further supporting its use as a nonspecific marker of neurodegeneration severity. [ABSTRACT FROM AUTHOR]

Background: Anorexia nervosa (AN) is a potentially fatal psychiatric condition, associated with structural brain changes such as gray matter volume loss. The pathophysiological mechanisms for these changes are not yet fully understood. Iron is a crucial element in the development and function of the brain. Considering the systemic alterations in iron homeostasis in AN, we hypothesized that brain iron would be altered as a possible factor associated with structural brain changes in AN. Methods: In this study, we used quantitative susceptibility mapping (QSM) magnetic resonance imaging to investigate brain iron in current AN (c-AN) and weight-restored AN compared with healthy individuals. Whole-brain voxel wise comparison was used to probe areas with possible group differences. Further, the thalamus, caudate nucleus, putamen, nucleus accumbens, hippocampus, and amygdala were selected as the regions of interest (ROIs) for ROI-based comparison of mean QSM values. Results: Whole-brain voxel-wise and ROI-based comparison of QSM did not reveal any differences between groups. Exploratory analyses revealed a correlation between higher regional QSM (higher iron) and lower body mass index, higher illness severity, longer illness duration, and younger age at onset in the c-AN group. Conclusions: This study did not find evidence of altered brain iron in AN compared to healthy individuals. However, the correlations between clinical variables and QSM suggest a link between brain iron and weight status or biological processes in AN, which warrants further investigation. [ABSTRACT FROM AUTHOR]

The successful implementation of telehealth services depends largely on clinician acceptance of telehealth as a viable healthcare option and their adoption of telehealth methods into their clinical practice. While growing research supports the feasibility of telehealth services, no research has evaluated clinicians' experiences during the implementation of a younger onset dementia telehealth service. Semi-structured group interviews were conducted with 7 metropolitan (hub) clinicians and 16 rural (spoke) clinicians during the pre-and post-implementation phases of a novel Younger onset dementia (YOD) telehealth service. Reflexive thematic analysis identified five themes at pre-implementation: clinical need, previous experiences and views, potential telehealth barriers, solutions to potential telehealth barriers, and potential clinical outcomes. At post-implementation, nine themes were identified: clinical need, clinical relationships, concerns about the future of rural healthcare, clinical practice and resourcing factors, patient suitability, difficulties with technology, service quality, the way forward, and the impact of COVID-19. Most clinicians held positive views regarding the service, particularly the ability to provide more options to rural-dwelling patients. However, some concerns about threats to rural healthcare and the validity of telehealth assessments remained. Overall, this study has identified service implementation barriers and facilitators and contributes to the long-term sustainability of current and future telehealth YOD services. [ABSTRACT FROM AUTHOR]

Aims Visuospatial skills are frequently assessed with drawing tests. Research has suggested that the use of drawing tasks in low educated groups may lack the ability to discriminate healthy individuals from clinical populations. The aims of this study were to investigate the validity of visuoconstructional tests in a sample of older Greek Australian immigrants and compare their performances to a matched sample of patients with Alzheimer's disease (ad). Method We assessed visuoconstructional performances in a sample of 90 healthy older Greek Australians, with a primary school level of education, and compared performances to a demographically matched sample of 20 Greek Australians with a diagnosis of ad on four visuoconstructional drawing tests: Greek cross, four-pointed star, intersecting pentagons, and the Necker Cube. Results While healthy participants tended to outperform the ad group on most copy tasks, high fail rates within the healthy sample were observed for the intersecting pentagons and Necker cube (78% and 73% fail rates, respectively) when using established clinical cut-off scores. High rates of curved angle, omission, distorted relation between elements, spatial disorganization and three-dimensional design errors were found across the four-pointed star, intersecting pentagons, and the Necker cube in both healthy participants and those with ad. Exploratory receiver operating characteristic curve analysis revealed that, with perhaps the exception of the Greek cross, meaningful sensitivity and specificity could not be reached for the four-pointed star, intersecting pentagons, and Necker cube. Conclusion Cognitively healthy immigrants with low education appear to be at a disadvantage when completing visuoconstructional drawing tests, as their performance may be misinterpreted as indicating cognitive impairment. Future research is needed to identify alternative approaches to assess visuoconstructional ability in culturally and linguistically diverse older cohorts with limited education. [ABSTRACT FROM AUTHOR]

Objectives: To compare survival and risk factors associated with mortality in common young‐onset dementias (YOD) including Huntington's disease. Methods: This retrospective cohort study included inpatients from an Australian specialist neuropsychiatry service, over 20 years. Dementia diagnoses were based on consensus criteria and Huntington's disease (HD) was confirmed genetically. Mortality and cause of death were determined using linkage to the Australian Institute of Health and Welfare National Death Index. Results: There were 386 individuals with YOD included. The dementia types included frontotemporal dementia (FTD) (24.5%), HD (21.2%) and Alzheimer's disease (AD) (20.5%). 63% (n = 243) individuals had died. The longest median survival was for those who had HD, 18.8 years from symptom onset and with a reduced mortality risk compared to AD and FTD (hazard ratio 0.5). Overall, people with YOD had significantly increased mortality, of 5–8 times, compared to the general population. Females with a YOD had higher standardised mortality ratio compared to males (9.3 vs. 4.9) overall. The most frequent cause of death in those with HD was reported as HD, with other causes of death in the other YOD‐subtypes related to dementia and mental/behavioural disorders. Discussion: This is the first Australian study to investigate survival and risk factors of mortality in people with YOD. YOD has a significant risk of death compared to the general population. Our findings provide useful clinical information for people affected by YOD as well as future planning and service provision. Key points: Dementia is a leading cause of death in Australia and the leading cause of death in females. There is limited mortality information pertaining to younger people with dementia.We investigated mortality and risk factors in young‐onset dementia, including Huntington's disease. Huntington's disease had the longest survival ‐ 18.8 years, with Alzheimer's disease, frontotemporal and vascular dementias having 11 and 13 years median survival. Young‐onset dementia conferred between 5 and 8 times increased risk of death compared to the general population.Young‐onset dementia is a fatal disease with shortened lifespan. Early identification and timely age‐appropriate services are necessary for these individuals. [ABSTRACT FROM AUTHOR]

Summary: Young‐onset dementia comprises a heterogeneous range of dementias, with onset at less than 65 years of age. These include primary dementias such as Alzheimer disease, frontotemporal and vascular dementias; genetic/familial dementias; metabolic disorders; and secondary dementias such as those that result from alcohol use disorder, traumatic brain injury, and infections.The presentation of young‐onset dementia is varied and may include cognitive, psychiatric and neurological symptoms. Diagnostic delay is common, with a frequent diagnostic conundrum being, "Is this young‐onset dementia or is this psychiatric?".For assessment and accurate diagnosis, a thorough screen is recommended, such as collateral history and investigations such as neuroimaging, lumbar puncture, neuropsychology, and genetic testing.The management of young‐onset dementia needs to be age‐appropriate and multidisciplinary, with timely access to services and consideration of the family (including children). [ABSTRACT FROM AUTHOR]

Objective: Childhood trauma has been implicated as a risk factor for the etiology of psychogenic nonepileptic seizures (PNES). Relatively little attention has been paid to whether profiles of specific trauma types differ between patients with epilepsy and PNES. Investigating childhood trauma profiles in these patient groups may identify psychological vulnerabilities that predispose to developing PNES, and aid early diagnoses, prevention, and treatment. Methods: Data were collected from two cohorts (nRetrospective = 203; nProspective = 209) admitted to video–electroencephalography (EEG) monitoring units in Melbourne Australia. The differences in Childhood Trauma Questionnaire domain score between patient groups were investigated using standardized effect sizes and general linear mixed‐effects models (GLMMs). Receiver‐operating characteristic curves were used to investigate classification accuracy. Results: In the retrospective cohort, patients diagnosed with PNES reported greater childhood emotional abuse, emotional neglect, physical abuse, sexual abuse, and physical neglect relative to patients with epilepsy. These differences were replicated in the prospective cohort, except for physical abuse. GLMMs revealed significant main effects for group in both cohorts, but no evidence for any group by domain interactions. Reported sexual abuse showed the best screening performance of PNES, although no psychometric scores were adequate as isolated measures. Significance: Patients with PNES report a greater frequency of childhood trauma than patients with epilepsy. This effect appears to hold across all trauma types, with no strong evidence emerging for a particular trauma type that is more prevalent in PNES. From a practical perspective, inquiry regarding a history of sexual abuse shows the most promise as a screening measure. [ABSTRACT FROM AUTHOR]

Objective: Younger-onset dementia accounts for about 5–10% of all dementias in Australia. Little data is available on neuropsychiatric symptoms in people with younger-onset dementia compared to those with older-onset dementia. This study aims to compare the types of neuropsychiatric symptoms and their clinico-demographic characteristics of people with younger-onset dementia and older-onset dementia who are referred to a specific dementia support service. Methods: A 2-year retrospective observational cross-sectional analysis was undertaken on referrals with neuropsychiatric symptoms from Dementia Support Australia programmes. Neuropsychiatric symptoms were measured using the Neuropsychiatric Inventory total severity scores and distress scores. Contributing factors to neuropsychiatric symptoms for dementia groups were examined. Logistic regression was used to examine the relationship between individual neuropsychiatric symptoms and having older-onset dementia vs younger-onset dementia. Results: Of the 15,952 referrals, about 5% (n = 729, mean age: 60.7 years, standard deviation = 5.4) were individuals with younger-onset dementia. Referrals with older-onset dementia were more likely to be female (56%), whereas referrals with younger-onset dementia were more likely to be male (54%). There was a four times greater rate of frontotemporal dementia for those with younger-onset dementia (16.0%, n = 117) compared to those with older-onset dementia (2.8%, n = 427), χ2 (1) = 366.2, p < 0.001. Referrals with younger-onset dementia were more likely to be referred from community settings and those with older-onset dementia were more likely to be from residential aged care. Overall, there was no difference in the severity and distress of neuropsychiatric symptoms between the two groups. Contributing factors to neuropsychiatric symptoms were different between the groups, with pain being more frequently endorsed for individuals with older-onset dementia whereas communication difficulties were more commonly identified for those with younger-onset dementia. Conclusion: Clinico-demographics of referrals with younger-onset dementia differ from those with older-onset dementia. There were some differences in the characteristics of neuropsychiatric symptoms between younger-onset dementia and older-onset dementia. Our findings have implications for service provision and support for people with dementia at different ages. [ABSTRACT FROM AUTHOR]

Inter-individual variations in the sulco-gyral pattern of Heschl's gyrus (HG) might contribute to emotional processing. However, it remains largely unknown whether borderline personality disorder (BPD) patients exhibit an altered HG gyrification pattern, compared with healthy individuals, and whether such a brain morphological feature, if present, might contribute to their clinical characteristics. The present study used magnetic resonance imaging to investigate the distribution of HG gyrification patterns (single or duplicated) and their relationship to clinical characteristics in teenage BPD patients with minimal treatment exposure. No significant difference was noted for the prevalence of HG patterns between 20 BPD and 20 healthy participants. However, the BPD participants with left duplicated HG were characterized by higher prevalence of comorbid disruptive behavior disorders, with higher externalizing score compared with those with left single HG. Our preliminary results suggest that neurodevelopmental pathology associated with gyral formation might be implicated in the neurobiology of early BPD, especially for emotional and behavioral control. [ABSTRACT FROM AUTHOR]

Objective: Schizophrenia, a complex psychiatric disorder, is often associated with cognitive, neurological and neuroimaging abnormalities. The processes underlying these abnormalities, and whether a subset of people with schizophrenia have a neuroprogressive or neurodegenerative component to schizophrenia, remain largely unknown. Examining fluid biomarkers of diverse types of neuronal damage could increase our understanding of these processes, as well as potentially provide clinically useful biomarkers, for example with assisting with differentiation from progressive neurodegenerative disorders such as Alzheimer and frontotemporal dementias. Methods: This study measured plasma neurofilament light chain protein (NfL) using ultrasensitive Simoa technology, to investigate the degree of neuronal injury in a well-characterised cohort of people with treatment-resistant schizophrenia on clozapine (n = 82), compared to first-degree relatives (an at-risk group, n = 37), people with schizophrenia not treated with clozapine (n = 13), and age- and sex-matched controls (n = 59). Results: We found no differences in NfL levels between treatment-resistant schizophrenia (mean NfL, M = 6.3 pg/mL, 95% confidence interval: [5.5, 7.2]), first-degree relatives (siblings, M = 6.7 pg/mL, 95% confidence interval: [5.2, 8.2]; parents, M after adjusting for age = 6.7 pg/mL, 95% confidence interval: [4.7, 8.8]), controls (M = 5.8 pg/mL, 95% confidence interval: [5.3, 6.3]) and not treated with clozapine (M = 4.9 pg/mL, 95% confidence interval: [4.0, 5.8]). Exploratory, hypothesis-generating analyses found weak correlations in treatment-resistant schizophrenia, between NfL and clozapine levels (Spearman's r = 0.258, 95% confidence interval: [0.034, 0.457]), dyslipidaemia (r = 0.280, 95% confidence interval: [0.064, 0.470]) and a negative correlation with weight (r = −0.305, 95% confidence interval: [−0.504, −0.076]). Conclusion: Treatment-resistant schizophrenia does not appear to be associated with neuronal, particularly axonal degeneration. Further studies are warranted to investigate the utility of NfL to differentiate treatment-resistant schizophrenia from neurodegenerative disorders such as behavioural variant frontotemporal dementia, and to explore NfL in other stages of schizophrenia such as the prodome and first episode. [ABSTRACT FROM AUTHOR]

Importance: The behavioral and cognitive symptoms of severe psychotic disorders overlap with those seen in dementia. However, shared brain alterations remain disputed, and their relevance for patients in at-risk disease stages has not been explored so far.Objective: To use machine learning to compare the expression of structural magnetic resonance imaging (MRI) patterns of behavioral-variant frontotemporal dementia (bvFTD), Alzheimer disease (AD), and schizophrenia; estimate predictability in patients with bvFTD and schizophrenia based on sociodemographic, clinical, and biological data; and examine prognostic value, genetic underpinnings, and progression in patients with clinical high-risk (CHR) states for psychosis or recent-onset depression (ROD).Design, Setting, and Participants: This study included 1870 individuals from 5 cohorts, including (1) patients with bvFTD (n = 108), established AD (n = 44), mild cognitive impairment or early-stage AD (n = 96), schizophrenia (n = 157), or major depression (n = 102) to derive and compare diagnostic patterns and (2) patients with CHR (n = 160) or ROD (n = 161) to test patterns' prognostic relevance and progression. Healthy individuals (n = 1042) were used for age-related and cohort-related data calibration. Data were collected from January 1996 to July 2019 and analyzed between April 2020 and April 2022.Main Outcomes and Measures: Case assignments based on diagnostic patterns; sociodemographic, clinical, and biological data; 2-year functional outcomes and genetic separability of patients with CHR and ROD with high vs low pattern expression; and pattern progression from baseline to follow-up MRI scans in patients with nonrecovery vs preserved recovery.Results: Of 1870 included patients, 902 (48.2%) were female, and the mean (SD) age was 38.0 (19.3) years. The bvFTD pattern comprising prefrontal, insular, and limbic volume reductions was more expressed in patients with schizophrenia (65 of 157 [41.2%]) and major depression (22 of 102 [21.6%]) than the temporo-limbic AD patterns (28 of 157 [17.8%] and 3 of 102 [2.9%], respectively). bvFTD expression was predicted by high body mass index, psychomotor slowing, affective disinhibition, and paranoid ideation (R2 = 0.11). The schizophrenia pattern was expressed in 92 of 108 patients (85.5%) with bvFTD and was linked to the C9orf72 variant, oligoclonal banding in the cerebrospinal fluid, cognitive impairment, and younger age (R2 = 0.29). bvFTD and schizophrenia pattern expressions forecasted 2-year psychosocial impairments in patients with CHR and were predicted by polygenic risk scores for frontotemporal dementia, AD, and schizophrenia. Findings were not associated with AD or accelerated brain aging. Finally, 1-year bvFTD/schizophrenia pattern progression distinguished patients with nonrecovery from those with preserved recovery.Conclusions and Relevance: Neurobiological links may exist between bvFTD and psychosis focusing on prefrontal and salience system alterations. Further transdiagnostic investigations are needed to identify shared pathophysiological processes underlying the neuroanatomical interface between the 2 disease spectra. [ABSTRACT FROM AUTHOR]

In a large proportion of individuals with fronto-temporal lobar degeneration (FTLD), the underlying pathology is associated with the misfolding and aggregation of the microtubule associated protein tau (FTLD-tau). With disease progression, widespread protein accumulation throughout cortical and subcortical brain regions may be responsible for neurodegeneration. One of the syndromes of FTLD is the behavioral variant of frontotemporal dementia (bvFTD), in which the underlying pathology is heterogenous, with half of the cases being related to FTLD-tau. Currently, there are no approved disease-modifying treatments for FTLD-tau, therefore representing a major unmet therapeutic need. These descriptive, preliminary findings of the phase 1 open-label trial provide data to support the potential of sodium selenate to halt the cognitive and behavioral decline, as well as to reduce tau levels in a small group of participants with bvFTD (N = 11). All participants were treated with sodium selenate over a period of 52 weeks. Cognition was assessed with the Neuropsychiatry Unit Cognitive Assessment Tool (NUCOG, total scores), social cognition with the Revised Self-Monitoring Scale (RSMS, total scores), behavior with the Cambridge Behavioral Inventory (CBI), and carer burden with the Caregiver Buden Scale (CBS). Fluid biomarker measures include cerebrospinal fluid of total tau (t-tau), phosphorylated tau (p-tau181), NfL, p-tau181/t-tau, t-tau/Aβ1-42, and p-tau181/Aβ1-42 levels. After treatment at follow-up, cognition and behavior showed further negative change (based on a reliable change criterion cut-off of annual NUCOG decline) in the "progressors," but not in the "non-progressors." "Non-progressors" also showed elevated baseline CSF tau levels and no increase after treatment, indicating underlying tau pathology and a positive response to sodium selenate treatment. Significant changes in MRI were not observed. The findings provide useful information for future clinical trials to systematically assess the disease-modifying treatment effects of sodium selenate in randomized controlled designs for bvFTD and FTLD-tau pathologies. [ABSTRACT FROM AUTHOR]

Objectives: Carer burden in dementia is associated with poor outcomes, including early nursing home placement for people with dementia and psychological distress for their carers. Carers of people with young-onset dementia (YOD) are particularly vulnerable to carer burden. Yet they are often overlooked by clinicians as dementia services are generally designed for older people. We sought to estimate the rate of burden and psychological distress in carers of YOD at a state-wide tertiary service based in Australia.Methods: We conducted a cross-sectional study examining 71 dyads from a Neuropsychiatry service. We collected patient demographic and clinical data including the Neuropsychiatry Unit Cognitive Assessment tool (NUCOG) and Mini-Mental State Examination (MMSE). Carer data, such as demographics and psychological distress, were obtained using Depression Anxiety Stress Scale 21 (DASS-21). Carer burden was rated using the Zarit Burden Inventory-short version (ZBI).Results: Higher carer burden, measured using ZBI, was associated with longer duration of dementia and greater severity of overall cognitive impairment. Carers who felt burdened reported higher levels of stress, depression, and anxiety measured using DASS-21. Multiple linear regression analysis found carer burden was independently predicted by duration of dementia, total cognition score and carers experiencing psychological stress.Discussion: We found that patient variables of dementia duration and cognitive impairment and carer variable of carer stress to be associated with carer burden. Poor executive function was associated with carer stress. Early identification and management of carer burden and psychological distress is important for outcomes. Ideally, this should be provided by a specialist YOD service. [ABSTRACT FROM AUTHOR]

Objectives: Survival information in dementia is important for future planning and service provision. There have been limited Australian data investigating survival duration and risk factors associated with mortality in younger-onset dementia. Methods: This was a cross-sectional retrospective study investigating survival in inpatients with a diagnosis of dementia admitted to a tertiary neuropsychiatry service from 1991 to 2014. The Australian Institute of Health and Welfare National Death Index was used to obtain mortality information. Results: A total of 468 inpatients were identified, of which 75% had symptom onset at ⩽65 years of age (defined as younger-onset dementia). Dementia was categorised into four subtypes, Alzheimer's dementia, frontotemporal dementia, vascular dementia and other dementias; 72% of the patients had died. Overall median survival duration was 10.6 years with no significant differences in duration within the dementia subtypes (p = 0.174). Survival in older-onset dementia (symptom onset at >65 years of age) was about half of that in younger-onset dementia (median survival 6.3 years compared to 12.7 years, respectively). Independent predictors of mortality were having older-onset dementia (hazard ratio: 3.2) and having initial presenting symptoms being cognitive in nature (hazard ratio: 1.5). Females with an older-onset dementia had longer survival compared to males with an older-onset dementia, and this was reversed for younger-onset dementia. Older-onset dementia and younger-onset dementia conferred 3 and 6 times, respectively, increased risk of death compared to the general population. Conclusion: This is the largest Australian study to date investigating survival and risk factors to mortality in dementia. We report important clinical information to patients with dementia and their families about prognosis which will assist with future planning. Our findings suggest that for both older-onset dementia and younger-onset dementia, 'new onset' psychiatric symptoms precede the cognitive symptoms of a neurodegenerative process. This, and sex differences in survival depending on the age of onset of the dementia warrant further investigation. [ABSTRACT FROM AUTHOR]

Deep brain stimulation has shown promise for the treatment of severe, treatment-refractory obsessive-compulsive disorder. With the recent publication of the first Australian, randomised, sham-controlled trial of deep brain stimulation for obsessive-compulsive disorder, there are now four placebo-controlled trials demonstrating the efficacy of this therapy. Together with recent data identifying a biological substrate of effective stimulation that can predict response and that has been successfully reproduced, studies comparing and finding equivalent efficacy among different targets, as well as recent, large, open trials supporting the long-term effectiveness of deep brain stimulation, we argue that this should now be considered an accepted therapy for a select group of patients in the Australasian setting. We call on the Royal Australian and New Zealand College of Psychiatrists to revise their memorandum describing deep brain stimulation for obsessive-compulsive disorder as an ' experimental ' treatment and recognise that it has proven efficacy. We stress that this should remain a therapy offered only to those with high treatment-refractory illnesses and only at specialised centres where there is an experienced multidisciplinary team involved in work-up, implantation and follow-up and also where frameworks are in place to provide careful clinical governance and ensure appropriate fully informed consent. [ABSTRACT FROM AUTHOR]

Objectives: While early diagnosis of younger-onset dementia (YOD) is crucial in terms of accessing appropriate services and future planning, diagnostic delays are common. This study aims to identify predictors of delay to diagnosis in a large sample of people with YOD and to investigate the impact of a specialist YOD service on this time to diagnosis.Design: A retrospective cross-sectional study.Setting: The inpatient unit of a tertiary neuropsychiatry service in metropolitan Victoria, Australia.Participants: People diagnosed with a YOD.Measurements and Methods: We investigated the following predictors using general linear modeling: demographics including sex and location, age at onset, dementia type, cognition, psychiatric diagnosis, and number of services consulted with prior to diagnosis.Results: A total of 242 inpatients were included. The mean time to diagnosis was 3.4 years. Significant predictors of delay included younger age at onset, dementia type other than Alzheimer's disease (AD) and behavioral-variant frontotemporal dementia (bvFTD), and increased number of services consulted. These predictors individually led to an increased diagnostic delay of approximately 19 days, 5 months, and 6 months, respectively. A specialized YOD service reduced time to diagnosis by 12 months.Conclusion: We found that younger age at onset, having a dementia which was not the most commonly occurring AD or bvFTD, and increasing number of services were significant predictors of diagnostic delay. A novel result was that a specialist YOD service may decrease diagnostic delay, highlighting the importance of such as service in reducing time to diagnosis as well as providing post-diagnostic support. [ABSTRACT FROM AUTHOR]

Objectives: This narrative paper describes the influences behind the development of, and key components of a specialist younger-onset dementia service located in metropolitan Victoria, Australia.Conclusion: The Melbourne Young-Onset Dementia Service was established in 2013 and provides diagnosis and ongoing care for people with younger-onset dementia and their families, through collaboration with other medical units, allied health and community services. It is potentially a model for other younger-onset dementia services nationally and internationally. [ABSTRACT FROM AUTHOR]

Objectives: Frontotemporal dementia (FTD) is a common cause of dementia in younger people. There is less information known about risk factors to mortality such as the type of symptom onset and cause of death in this group. Method: This was a retrospective file review of inpatients with FTD admitted to a tertiary neuropsychiatry unit located in Australia from 1992 to 2014. Mortality information including linkage of names and causes of death were obtained from the Australian Institute Health and Welfare National Death Index. Results: One hundred inpatients were diagnosed with FTD, including behavioural‐variant, language‐variant FTDs and FTD‐motor neuron disease (FTD‐MND). Mean age was 52.8 years (SD = 10, range 31–76 years). Sixty‐seven of them had died at linkage. Median survival of the sample was 10.5 years and FTD‐MND had the shortest survival, 3.5 years. Increasing age of onset and FTD‐MND were found to be significant predictors of association for mortality. Compared to the general population, having a FTD had an 8× increased risk of death. Females had double the standardised mortality ratio compared to males. Discussion: This study provides important prognostic information for people diagnosed with FTD living in Australia. It highlights the importance of obtaining a definitive diagnosis as early as possible for future planning. More investigation into the relationship of symptom onset type and sex differences in FTD is required. Key points: Frontotemporal dementia (FTD) is a common cause of dementia occurring in younger people.This study found that compared to Australian population norms, having a FTD had 8× risk of death, with females having a much higher standardised mortality ratio (SMR) compared to males (SMR 12.2 vs. SMR 6.8). Having an FTD yielded a SMR 11× compared to population norms of people aged 50–59 years old.Determining the subtype of FTD is important as this may provide clinically relevant prognostic information such as median survival, with FTD‐motor neuron disease having the shortest survival, 3.5 years, compared to the behavioural‐variant (10.6 years) and language‐variant FTDs (14.2 years). [ABSTRACT FROM AUTHOR]

Introduction: Sodium selenate increases tau dephosphorylation through protein phosphatase 2 activation. Here we report an open-label Phase 1b study of sodium selenate as a disease-modifying treatment for behavioral variant frontotemporal dementia (bvFTD). Methods: Twelve participants with bvFTD received sodium selenate (15 mg, three times a day) for 52 weeks. Safety assessments were carried out throughout the trial. Primary outcomes were frequency of adverse events (AEs), serious adverse events (SAEs), and discontinuations. Secondary outcomes of potential efficacy included cognitive and behavioral assessments, magnetic resonance imaging (MRI)whole brain volume, and cerebrospinal fluid (CSF) and blood total tau (t-tau), phosphorylated tau (ptau), and neurofilament light (NfL) levels, which were measured at baseline and at week 52. Results: Sodium selenate was safe and well tolerated. All participants completed the study, and the majority (64.7%) of reported AEs were mild. One SAE occurred, which was not treatment related. Small declines in MRI and cognitive and behavioral measures were observed over the treatment period. There was no evidence for change in CSF protein levels (t-tau, p-tau, or NfL). Further analysis showed two distinct groups when measuring disease progression markers over the course of the study--one (n = 4) with substantial brain atrophy (2.5% to 6.5% reduction) and cognitive and behavioral decline over the 12-month treatment period, and the second group (n=7) with no detectable change in cognitive and behavioral measures and less brain atrophy (0.3% to 1.7% reduction). Conclusion: Sodium selenate is safe and well tolerated in patients with bvFTD. Randomized-controlled trials are warranted to investigate potential efficacy. [ABSTRACT FROM AUTHOR]

Increased severity of neurological soft signs (NSS) in schizophrenia have been associated with abnormal brain morphology in cerebello-thalamo-cortical structures, but it is unclear whether similar structures underlie NSS prior to the onset of psychosis. The present study investigated the relationship between severity of NSS and grey matter volume (GMV) in individuals at ultra-high risk for psychosis (UHR) stratified for later conversion to psychosis. Structural T1-weighted MRI scans were obtained from 56 antipsychotic-naïve UHR individuals and 35 healthy controls (HC). The UHR individuals had follow-up data (mean follow-up: 5.2 years) to ascertain clinical outcome. Using whole-brain voxel-based morphometry, the relationship between NSS and GMV at baseline was assessed in UHR, HC, as well as individuals who later transitioned (UHR-P, n = 25) and did not transition (UHR-NP, n = 31) to psychosis. NSS total and subscale scores except motor coordination were significantly higher in UHR compared to HC. Higher signs were also found in UHR-P, but not UHR-NP. Total NSS was not associated with GMV in the whole sample or in each group. However, in UHR-P individuals, greater deficits in sensory integration was associated with lower GMV in the left cerebellum, right insula, and right middle frontal gyrus. In conclusion, NSS are present in UHR individuals, particularly those who later transitioned to a psychotic disorder. While these signs show little overall variation with GMV, the association of sensory integration deficits with lower GMV in UHR-P suggests that certain brain areas may be implicated in the development of specific neurological abnormalities in the psychosis prodrome. [ABSTRACT FROM AUTHOR]

Objective: Niemann Pick disease type C (NPC) is a rare progressive neurovisceral lysosomal disorder caused by autosomal recessive mutations in the NPC1 or NPC2 genes. 18F-fluorodeoxyglucose (FDG) is a positron-emitting glucose analogue for non-invasive imaging of brain metabolism. FDG PET is commonly used for dementia imaging but its specific application to NPC is rarely described. Methods: This is a retrospective study of all baseline brain FDG PET performed for NPC patients. Images were assessed using a normal database statistical comparison of metabolic changes expressed in standard deviations and three-dimensional Stereotactic Surface Projection maps. Typical hypometabolic patterns in NPC were identified. We further investigated any correlation between the degree of regional brain hypometabolism and the Iturriaga clinical severity scale. Results: Brain FDG PET images of 14 adolescent–adult NPC patients were analysed, with mean age of 35 years. We found significant frontal lobe hypometabolism in 12 patients (86%), thalamic hypometabolism in eight patients (57%) and variable parietal lobe hypometabolism in 13 patients (93%). Hypometabolic changes were usually bilateral and symmetric. Ten out of 13 ataxic patients showed cerebellar or thalamic hypometabolism (sensitivity 77%, specificity 100%). Linear regression analysis showed frontal lobe hypometabolism to have the best correlation with the Iturriaga clinical scale (R2 = 0.439; p = 0.01). Conclusions: We found bilateral symmetric hypometabolism of the frontal lobes, thalami and parietal lobes (especially posterior cingulate gyrus) to be typical of adolescent–adult NPC. Ataxia was commonly associated with cerebellar or thalamic hypometabolism. Frontal lobe hypometabolism showed the best inverse correlation with clinical severity. [ABSTRACT FROM AUTHOR]

Hippocampal brain regions are strongly implicated in Niemann Pick type C disease (NPC), but little is known regarding distinct subregions of the hippocampal complex and whether these are equally or differentially affected. To address this gap, we compared volumes of five hippocampal subfields between NPC and healthy individuals using MRI. To this end, 9 adult-onset NPC cases and 9 age- and gender-matched controls underwent a 3 T T1-weighted MRI scan. Gray matter volumes of the cornu ammonis (CA1, CA2 and CA3), dentate gyrus (DG), subiculum, entorhinal cortex and hippocampal-amygdalar transition area were calculated by integrating MRI-based image intensities with microscopically defined cytoarchitectonic probabilities. Compared to healthy controls, NPC patients showed smaller volumes of the CA1-3 and DG regions bilaterally, with the greatest difference localized to the left DG (Cohen's d = 1.993, p = 0.008). No significant associations were shown between hippocampal subfield volumes and key clinical features of NPC, including disease duration, symptom severity and psychosis. The pattern of hippocampal subregional atrophy in NPC differs from those seen in other dementias, which may indicate unique cytoarchitectural vulnerabilities in this earlier-onset disorder. Future MRI studies of hippocampal subfields may clarify its potential as a biomarker of neurodegeneration in NPC. [ABSTRACT FROM AUTHOR]

Objective: Visuospatial skills are frequently assessed with drawing tests. Research has suggested that the use of drawing tasks in low educated groups may lack the ability to discriminate healthy individuals from clinical populations. The aims of this study were to investigate the validity of visuoconstructional tests in a sample of older Greek Australian immigrants and compare their performances to a matched sample of patients with Alzheimer's disease (AD). Participants and Methods: We assessed visuoconstructional performances in a sample of 90 healthy older Greek Australians, with a primary school level of education, and compared performances to a demographically matched sample of 20 Greek Australians with a diagnosis of AD on four visuoconstructional drawing tests: Greek cross, four-pointed star, intersecting pentagons, and the Necker Cube. Results: While healthy participants tended to outperform the AD group on most copy tasks, high fail rates within the healthy sample were observed for the intersecting pentagons and Necker cube (78% and 73% fail rates respectively) when using established clinical cutoff scores. High rates of curved angle, omission, distorted relation between elements, spatial disorganization and three-dimensional design errors were found across the four-pointed star, intersecting pentagons, and the Necker cube in both healthy participants and those with AD. Exploratory receiver operating characteristic curve analysis revealed that, with perhaps the exception of the Greek cross, meaningful sensitivity and specificity could not be reached for the four-pointed star, intersecting pentagons, and Necker cube. Conclusions: Cognitively healthy immigrants with low education appear to be at a disadvantage when completing visuoconstructional drawing tests, as their performance may be misinterpreted as indicating cognitive impairment. Future research is needed to identify alternative approaches to assess visuoconstructional ability in low education older cohorts. [ABSTRACT FROM AUTHOR]

The authors comment on the need for action to improve identification, diagnosis, treatment and care of patients with young onset dementia (YOD) in Australia. Topics discussed include the aetiology of YOD, the two Australian Royal Commissions affecting people with YOD, the need to improve professional understanding of YOD to reduce the time of diagnosis, and the need to improve diagnostic accuracy.

Sporadic Creutzfeldt-Jakob disease (sCJD) is the most common form of CJD and is believed to be caused by the misfolding and aggregation of endogenous prion protein. Several classification systems have been developed to correlate the molecular characteristics of these misfolded prions (PrPSc) to the heterogeneous clinical presentations of sCJD. A central component of these systems is glycotyping, which involves the interpretation of the results of western immunoblotting of the protease-resistant fragment of the misfolded prion protein (PrPres). The two main classification systems differ in their recognition of a unique banding pattern on electrophoretic gels correlating to a putative clinical subtype. The perpetuation of both classification systems within scientific literature is, in part, due to a paucity of high-level evidence that conclusively addresses the merit of recognising each unique banding pattern. Here, 110 post-mortem confirmed cases of sCJD collected at the Australian Creutzfeldt-Jakob Disease Registry (ANCJDR) between 1993 and 2018 were analysed and classified as per the London classification system. The data presented here demonstrated that sCJD cases with 'type 1′ and 'type 2′ PrPSc as defined by the London classification system differ in their disease duration. No other differences in clinical phenotype or biological characteristics were found to be statistically significant. These findings highlight the importance of sample size and replicability in analyses of this rare disease process. Recognising these glycotypes as phenotypically distinct may represent 'best practice' in the collection and processing of sCJD samples within international registries for research purposes. [ABSTRACT FROM AUTHOR]

Objectives: To describe and provide experiential reflections on a model of continuing professional development in psychiatry for development and maintenance of specialised skills. Conclusions: For clinical psychiatrists working in smaller population centres, clinical observer visits with peers may be a useful method to develop, improve and calibrate knowledge and skills. Such potential benefits may be even more marked for specialised fields of psychiatry, such as neuropsychiatry. [ABSTRACT FROM AUTHOR]

Objective: When a genetic cause is suspected in a person with dementia, it creates unique diagnostic and management challenges to the treating clinician. Many clinicians may be unaware of the practicalities surrounding genetic testing for their patients, such as when to test and what tests to use and how to counsel patients and their families. This review was conducted to provide guidance to clinicians caring for patients with dementia regarding clinically relevant genetics. Methods: We searched PubMed for studies that involved genetics of dementia up to March 2020. Patient file reviews were also conducted to create composite cases. Results: In addition to families where a strong Mendelian pattern of family history is seen, people with younger age of onset, especially before the age of 65 years were found to be at an increased risk of harbouring a genetic cause for their dementia. This review discusses some of the most common genetic syndromes, including Alzheimer disease, frontotemporal dementia, vascular dementia, Parkinson disease dementia/dementia with Lewy bodies and some rarer types of genetic dementias, along with illustrative clinical case studies. This is followed by a brief review of the current genetic technologies and a discussion on the unique genetic counselling issues in dementia. Conclusions: Inclusion of genetic testing in the diagnostic pathway in some patients with dementia could potentially reduce the time taken to diagnose the cause of their dementia. Although a definite advantage as an addition to the diagnostic repository, genetic testing has many pros and cons which need to be carefully considered first. [ABSTRACT FROM AUTHOR]

Objective: The volumes of various brain regions can be rapidly quantified using automated magnetic resonance imaging tools. While these appear to be useful at face value, their formal clinical utility is not yet understood, particularly for non-neuroradiologists and in patients presenting with suspected dementia. This study investigated the utility of an automated normative morphometry tool on determinations of brain atrophy by psychiatrists and radiologists in a tertiary hospital. Methods: Consecutive magnetic resonance scans (n = 110) of patients referred with suspected neurodegenerative disorders were obtained retrospectively and rated by two neuroradiologists, two general radiologists and four psychiatrists over two sessions. First, conventional magnetic resonance sequences were shown. Then, morphometry colour-coded maps, which segmented T1-weighted magnetisation prepared rapid gradient echo images into brain regions and visualised these regions in colour according to their volumetric standard deviation from a normative population, were added to the second reading which occurred ⩾6 weeks later. Presence and laterality of atrophy in frontal, parietal and temporal lobes and hippocampal regions were measured using a digital checklist. The primary outcome of inter-rater agreement on atrophy was measured with Fleiss' Kappa (κ). We also evaluated the accuracy of the atrophy ratings for differentiating post hoc diagnosis of subjective cognitive impairment, mild cognitive impairment and dementia. Results: Agreement among all raters was fair in frontal lobe and moderate in other regions with conventional method (κ = 0.362–0.555). With morphometry, higher agreement was seen in all regions (κ = 0.551–0.654), reaching significant improvement in the frontal and temporal lobes. No significant improvement was seen within the various disciplines, except in frontal lobes rated by psychiatrists. Accuracy of atrophy ratings on determining post hoc diagnosis was significantly improved for distinguishing subjective cognitive impairment versus dementia. Conclusion: In routine clinical assessment, automated normative morphometry complements the determination of regional atrophy and improves inter-rater agreement regardless of neuroradiology experience. [ABSTRACT FROM AUTHOR]

Although COVID-19 is predominantly a respiratory disease, it is known to affect multiple organ systems. In this article, we highlight the impact of SARS-CoV-2 (the coronavirus causing COVID-19) on the central nervous system as there is an urgent need to understand the longitudinal impacts of COVID-19 on brain function, behaviour and cognition. Furthermore, we address the possibility of intergenerational impacts of COVID-19 on the brain, potentially via both maternal and paternal routes. Evidence from preclinical models of earlier coronaviruses has shown direct viral infiltration across the blood–brain barrier and indirect secondary effects due to other organ pathology and inflammation. In the most severely ill patients with pneumonia requiring intensive care, there appears to be additional severe inflammatory response and associated thrombophilia with widespread organ damage, including the brain. Maternal viral (and other) infections during pregnancy can affect the offspring, with greater incidence of neurodevelopmental disorders, such as autism, schizophrenia and epilepsy. Available reports suggest possible vertical transmission of SARS-CoV-2, although longitudinal cohort studies of such offspring are needed. The impact of paternal infection on the offspring and intergenerational effects should also be considered. Research targeted at mechanistic insights into all aspects of pathogenesis, including neurological, neuropsychiatric and haematological systems alongside pulmonary pathology, will be critical in informing future therapeutic approaches. With these future challenges in mind, we highlight the importance of national and international collaborative efforts to gather the required clinical and preclinical data to effectively address the possible long-term sequelae of this global pandemic, particularly with respect to the brain and mental health. [ABSTRACT FROM AUTHOR]

Brain metabolic imaging using 18F-fluorodeoxyglucose (FDG) Positron Emission Tomography (PET) with contemporaneous low-dose CT may be used to assess neurodegenerative diseases. In contrast to oncology whole-body FDG PET, qualitative assessment alone in brain FDG PET is subjective and vulnerable to visual interference due to high physiologic background activity. Therefore, mild changes in brain metabolism may be visually undetectable by qualitative interpretation alone, resulting in diagnostic inaccuracy. To overcome this, some institutions may employ an objective comparison to a normal reference database. To date, there is limited literature describing brain metabolic changes in rare genetic neurodegenerative diseases such as Niemann-Pick disease Type C, spinocerebellar ataxia and Huntington disease. In this case series, we illustrate the typical FDG PET findings in the cortex and deep grey matter for these rare diseases, utilising normal database comparison including three dimensional Stereotactic Surface Projection (3D-SSP) mapping. These comparisons can generate 3D-SSP maps where metabolic changes may be expressed in standard deviations from normal (z-score) and visually depicted in a scale of colours to improve diagnostic accuracy. [ABSTRACT FROM AUTHOR]

Niemann-Pick disease type C (NPC) is a rare, autosomal recessive neurodegenerative disease, characterized by progressive psychiatric and neurological deficits. Neurological symptoms include cognitive decline and dysphagia. Aspiration pneumonia secondary to dysphagia is a leading cause of death in NPC. Miglustat is currently the only approved disease-specific treatment shown to be effective in stabilizing neurological symptoms. Miglustat has previously been reported to halt or improve early dysphagia and cognitive symptoms. Here we examine the characteristics of dysphagia, the relationship between dysphagia and the presence of cognitive impairment, and longitudinal changes in swallowing function during miglustat treatment in adult-and-adolescent-onset NPC. Retrospective analysis of videofluoroscopic swallow studies (VFSS) was completed for ten adults with NPC (mean age 28.44 years ± 9.34 years). Participants were recruited through the Royal Melbourne Hospital in Australia between 2008 and 2015. The Bethlehem Swallowing Scale and the Penetration-Aspiration Scale were used to quantify VFSS data. Dysphagia was present in 90% of participants at baseline with reduced lingual function and a delayed swallowing reflex as the most common symptoms. Swallow impairment appeared to stabilize during miglustat therapy for periods up to 66 months, with no significant changes in scores (p > 0.05). Data were in accordance with the literature and support the use of miglustat as an efficacious treatment for reducing swallowing impairment and stabilizing cognitive function. Findings provide detailed information on the impairments experienced by patients, give context to events leading to aspiration in NPC and, importantly, inform how management of dysphagia can complement pharmaceutical treatment. [ABSTRACT FROM AUTHOR]

Objective: This study was undertaken to identify factors that predict discordance between the screening instruments Neurological Disorders Depression Inventory for Epilepsy (NDDI‐E) and Generalized Anxiety Disorder scale (GAD‐7), and diagnoses made by qualified psychiatrists among patients with seizure disorders. Importantly, this is not a validation study; rather, it investigates clinicodemographic predictors of discordance between screening tests and psychiatric assessment. Methods: Adult patients admitted for inpatient video‐electroencephalographic monitoring completed eight psychometric instruments, including the NDDI‐E and GAD‐7, and psychiatric assessment. Patients were grouped according to agreement between the screening instrument and psychiatrists' diagnoses. Screening was "discordant" if the outcome differed from the psychiatrist's diagnosis, including both false positive and false negative results. Bayesian statistical analyses were used to identify factors associated with discordance. Results: A total of 411 patients met inclusion criteria; mean age was 39.6 years, and 55.5% (n = 228) were female. Depression screening was discordant in 33% of cases (n = 136/411), driven by false positives (n = 76/136, 56%) rather than false negatives (n = 60/136, 44%). Likewise, anxiety screening was discordant in one third of cases (n = 121/411, 29%) due to false positives (n = 60/121, 50%) and false negatives (n = 61/121, 50%). Seven clinical factors were predictive of discordant screening for both depression and anxiety: greater dissociative symptoms, greater patient‐reported adverse events, subjective cognitive impairment, negative affect, detachment, disinhibition, and psychoticism. When the analyses were restricted to only patients with psychogenic nonepileptic seizures (PNES) or epilepsy, the rate of discordant depression screening was higher in the PNES group (n = 29, 47%) compared to the epilepsy group (n = 70, 30%, Bayes factor for the alternative hypothesis = 4.65). Significance: Patients with seizure disorders who self‐report a variety of psychiatric and other symptoms should be evaluated more thoroughly for depression and anxiety, regardless of screening test results, especially if they have PNES and not epilepsy. Clinical assessment by a qualified psychiatrist remains essential in diagnosing depressive and anxiety disorders among such patients. [ABSTRACT FROM AUTHOR]

BACKGROUND AND PURPOSE: Recently, there has been growing interest in the glymphatic system (the functional waste clearance pathway for the central nervous system and its role in flushing solutes (such as amyloid ß and tau), metabolic, and other cellular waste products in the brain. Herein, we investigate a recent potential biomarker for glymphatic activity (the diffusion tensor imaging along the perivascular space [DTI‐ALPS] parameter) using diffusion MRI imaging in an elderly cohort comprising 10 cognitively normal, 10 mild cognitive impairment (MCI), and 16 Alzheimer's disease (AD). METHODS: All 36 participants imaged on a Siemens 3.0T Tim Trio. Single‐SE diffusion weighted Echo‐planar imaging scans were acquired as well as T1 magnetization prepared rapid gradient echo, T2 axial, and susceptibility weighted imaging. Three millimeter regions of interest were drawn in the projection and association fibers adjacent to the medullary veins at the level of the lateral ventricle. The DTI‐ALPS parameter was calculated in these regions and correlated with cognitive status, Mini‐Mental State Examination (MMSE), and ADASCog11 measures. RESULTS: Significant correlations were found between DTI‐ALPS and MMSE and ADASCog11 in the right hemisphere adjusting for age, sex, and APoE ε4 status. Significant differences were also found in the right DTI‐ALPS indices between cognitively normal and AD groups (P <.026) and MCI groups (P <.025) in a univariate general linear model corrected for age, sex, and APoE ε4. Significant differences in apparent diffusion coefficient between cognitively normal and AD groups were found in the right projection fibers (P =.028). CONCLUSION: Further work is needed to determine the utility of DTI‐ALPS index in larger elderly cohorts and whether it measures glymphatic activity. [ABSTRACT FROM AUTHOR]

Objective: People with neurocognitive disorders (NCDs) have an increased risk of epilepsy. However, most studies investigating the risk of seizures in people with NCDs are limited to those with Alzheimer's disease (AD) and vascular dementia (VD), and those who developed dementia after age 65 years. A knowledge gap exists regarding factors associated with development of epilepsy in people with younger-onset NCD, and those with non-AD and non-VD dementia subtypes. In this study, we aimed to identify the factors associated with the development of epilepsy in people with younger-onset NCDs of varied etiologies, the majority of whom had symptom onset prior to age 65 years. Participants and Methods: This was a retrospective study reviewing the medical records of consecutive people admitted with cognitive impairment to a tertiary neuropsychiatry unit between 1 January 2004 and 30 April 2019. People diagnosed with primary NCDs were included in the analysis. The prevalence and characteristics of epilepsy were described. The factors associated with developing epilepsy were identified in a binary logistic regression model. Results: A total of 427 people were included. One hundred fourteen had Alzheimer's disease, 104 frontotemporal dementia, 51 vascular dementia, 69 movement disorder-associated dementia, and 89 unspecified NCD. The median age on admission was 59 years (range 33–86) and 75.2% (n = 321/427) had young-onset NCD with onset before 65 years of age. 40/427 (9.4%) people had epilepsy, and epilepsy onset clustered between 2 years before and 6 years after the onset of cognitive decline in 80% (n = 32/40). The most frequent seizure type was focal to bilateral tonic-clonic seizure (35%, n = 14/40). Most of the people (94.7%, n = 36/38) achieved seizure freedom with one or two antiseizure medications. People with unspecified NCD (compared to frontotemporal dementia and movement disorder-associated dementia, age of onset of NCDs ≤50 years, and current smoking status were independently associated with higher risk of developing epilepsy. Conclusion: Epilepsy is common in people with younger-onset NCDs, and a high index of suspicion is warranted particularly for those with unspecified subtype and smoking status. Smoking reduction or cessation should be further investigated as a potentially modifiable factor for risk reduction. [ABSTRACT FROM AUTHOR]

Iron has been increasingly implicated in the pathology of neurodegenerative diseases. In the past decade, development of the new magnetic resonance imaging technique, quantitative susceptibility mapping (QSM), has enabled for the more comprehensive investigation of iron distribution in the brain. The aim of this systematic review was to provide a synthesis of the findings from existing QSM studies in neurodegenerative diseases. We identified 80 records by searching MEDLINE, Embase, Scopus, and PsycInfo databases. The disorders investigated in these studies included Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Wilson's disease, Huntington's disease, Friedreich's ataxia, spinocerebellar ataxia, Fabry disease, myotonic dystrophy, pantothenate-kinase-associated neurodegeneration, and mitochondrial membrane protein-associated neurodegeneration. As a general pattern, QSM revealed increased magnetic susceptibility (suggestive of increased iron content) in the brain regions associated with the pathology of each disorder, such as the amygdala and caudate nucleus in Alzheimer's disease, the substantia nigra in Parkinson's disease, motor cortex in amyotrophic lateral sclerosis, basal ganglia in Huntington's disease, and cerebellar dentate nucleus in Friedreich's ataxia. Furthermore, the increased magnetic susceptibility correlated with disease duration and severity of clinical features in some disorders. Although the number of studies is still limited in most of the neurodegenerative diseases, the existing evidence suggests that QSM can be a promising tool in the investigation of neurodegeneration. [ABSTRACT FROM AUTHOR]

Objectives: Younger‐onset dementia (YOD) refers to a dementia where symptom onset occurs when the patient is less than 65 years of age. YOD is far less common than late‐onset dementia (occurring when patients are over 65 years old) and more challenging to diagnose due to its heterogeneous presentation. There have been relatively few studies describing demographic and diagnostic characteristics of patients with YOD in the community, particularly with follow‐up information. Methods: A retrospective cohort study was performed of inpatients admitted to a tertiary neuropsychiatry service, located in metropolitan Victoria, Australia, from 2009 to 2019. Inpatients with a YOD diagnosis were identified and data regarding diagnosis, demographics and investigations were obtained. Results: There were 849 individual inpatients who were admitted to the service in the 10‐year period and received comprehensive assessment. There were 306 individuals who received a YOD diagnosis, using contemporaneous diagnostic criteria (frequency 36%). The most common diagnoses were Alzheimer's disease (24.2%), frontotemporal dementia (23.1%), Huntington's disease (16.7%) and vascular dementia (7.8%). More than half of these inpatients were followed up and 6.5% had a diagnostic change when reviewed. Conclusions: This study reports on the largest cohort of YOD to date, with diagnostic breakdown similar to previous retrospective file reviews. The neuropsychiatry service is funded to follow‐up its patients, thus allowing re‐assessment and continuity of care. While there are limitations in this study such as the lack of neuropathological outcomes, the findings emphasise the strengths of follow‐up and appropriate service provision for these patients. [ABSTRACT FROM AUTHOR]