Younger people with dementia registered to public mental health services in Victoria, Australia.

ObjectivesIndividuals 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.MethodsTriage 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.ResultsOf 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.ConclusionFindings 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.

Peer Support for Caregivers of People Living with Posterior Cortical Atrophy in Melbourne, Australia: A Feasibility Study.

Posterior Cortical Atrophy (PCA) is a rare form of young-onset dementia that causes early visuospatial and visuoperceptual deficits. The symptom profile of Posterior Cortical Atrophy leads to very specific care needs for those affected, who often rely on informal caregivers (including friends and family). Rare dementia support groups can be useful for both patients and their caregivers to assist with knowledge sharing, psychoeducation, and the provision of psychosocial support. Despite this, few such support groups exist. The purpose of this study was to examine a PCA support group for caregivers of individuals living with PCA. We held a structured psychoeducation support group comprised of four sessions with the aim being to provide education, strategies for the management of the disease, and peer support. Caregivers' mental health and quality of life were assessed. The results of our study showed that support group participation was a positive experience and assisted with increasing the knowledge of caregivers and fostering social connections. We suggest that peer support groups may be beneficial for both people living with PCA and their caregivers. We recommend that future quantitative and qualitative research is conducted to further assess health-promotion benefits to people living with PCA and their caregivers, and to assess their development and implementation in different contexts.

Plasma neurofilament light chain is increased in Niemann-Pick Type C but glial fibrillary acidic protein remains normal.

OBJECTIVE: Niemann-Pick Type C (NPC) is a genetic neurodegenerative lysosomal storage disorder commonly associated with psychiatric symptoms and delays to accurate diagnosis and treatment. This study investigated biomarker levels and diagnostic utility of plasma neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) in NPC compared to healthy controls. METHODS: Patients with NPC were recruited from a specialist assessment and management service. Data was available from an age and sex-matched healthy control group. NfL and GFAP were measured on Quanterix Simoa HD-X analysers and groups compared using generalised linear models. NfL levels were compared to, and percentiles derived from, recently developed NfL reference ranges. RESULTS: Plasma NfL was significantly elevated in 11 patients with NPC compared to 25 controls (mean 17.1 vs. 7.4 pg/ml, p < 0.001), and reference ranges (all >98th percentile). NfL distinguished NPC from controls with high accuracy. GFAP levels were not elevated in NPC (66.6 vs. 75.1 pg/ml). DISCUSSION: The study adds important evidence on the potential diagnostic utility of plasma NfL in NPC, extends the literature of NfL as a diagnostic tool to differentiate neurodegenerative from primary psychiatric disorders, and adds support to the pathology in NPC primarily involving neuronal, particularly axonal, degeneration.

Investigating Equivalence of In-Person and Telehealth-Based Neuropsychological Assessment Performance for Individuals Being Investigated for Younger Onset Dementia.

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 (Mage = 60.26, SDage = 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.

Effects of physical activity on depressive symptoms in older caregivers: The IMPACCT randomized controlled trial.

OBJECTIVES: Physical activity (PA) can reduce depressive symptoms but has not been tested amongst depressed older caregivers and their care-recipients. The aim of this single-blind randomized controlled trial was to investigate the effect of a 6-month tailored PA program on depressive symptoms in older caregivers. METHOD: Caregivers were included if they had scores of ≥5 on the 15-item geriatric depression scale (GDS-15). Care-recipients could have any type of physical, mental or cognitive condition requiring support. The PA intervention group completed an individualized program based on the Otago-Plus Exercise Program. The primary outcome was improvement in depressive symptoms in caregivers measured at six and 12 months. RESULTS: Two hundred and twelve participants (91 dyads and 30 caregivers only) were randomized using a 3:3:1 ratio to PA intervention, social-control, and usual-care control groups. There were no significant differences in depressive symptoms of the caregivers between the three groups at 6 months or 12 months. However, more than 50% of caregivers in all three groups no longer had a GDS-15 score ≥5 at 6 months. Further analysis revealed that caregivers in the PA group caring for someone with a standardised mini-mental state examination (SMMSE) score ≥24 had significantly less depressive symptoms than those caring for someone with a SMMSE score <24 compared with social-control (p < 0.02) and usual-care groups (p < 0.02). CONCLUSIONS: A PA intervention may be beneficial for some caregivers in reducing symptoms of depression but may not be as beneficial to caregivers of people living with cognitive impairment.

Cerebrospinal fluid neurofilament light predicts longitudinal diagnostic change in patients with psychiatric and neurodegenerative disorders.

OBJECTIVE: People with neuropsychiatric symptoms often experience delay in accurate diagnosis. Although cerebrospinal fluid neurofilament light (CSF NfL) shows promise in distinguishing neurodegenerative disorders (ND) from psychiatric disorders (PSY), its accuracy in a diagnostically challenging cohort longitudinally is unknown. METHODS: We collected longitudinal diagnostic information (mean = 36 months) from patients assessed at a neuropsychiatry service, categorising diagnoses as ND/mild cognitive impairment/other neurological disorders (ND/MCI/other) and PSY. We pre-specified NfL > 582 pg/mL as indicative of ND/MCI/other. RESULTS: Diagnostic category changed from initial to final diagnosis for 23% (49/212) of patients. NfL predicted the final diagnostic category for 92% (22/24) of these and predicted final diagnostic category overall (ND/MCI/other vs. PSY) in 88% (187/212), compared to 77% (163/212) with clinical assessment alone. CONCLUSIONS: CSF NfL improved diagnostic accuracy, with potential to have led to earlier, accurate diagnosis in a real-world setting using a pre-specified cut-off, adding weight to translation of NfL into clinical practice.

Plasma neurofilament light in behavioural variant frontotemporal dementia compared to mood and psychotic disorders.

OBJECTIVE: Blood biomarkers of neuronal injury such as neurofilament light (NfL) show promise to improve diagnosis of neurodegenerative disorders and distinguish neurodegenerative from primary psychiatric disorders (PPD). This study investigated the diagnostic utility of plasma NfL to differentiate behavioural variant frontotemporal dementia (bvFTD, a neurodegenerative disorder commonly misdiagnosed initially as PPD), from PPD, and performance of large normative/reference data sets and models. METHODS: Plasma NfL was analysed in major depressive disorder (MDD, n = 42), bipolar affective disorder (BPAD, n = 121), treatment-resistant schizophrenia (TRS, n = 82), bvFTD (n = 22), and compared to the reference cohort (Control Group 2, n = 1926, using GAMLSS modelling), and age-matched controls (Control Group 1, n = 96, using general linear models). RESULTS: Large differences were seen between bvFTD (mean NfL 34.9 pg/mL) and all PPDs and controls (all < 11 pg/mL). NfL distinguished bvFTD from PPD with high accuracy, sensitivity (86%), and specificity (88%). GAMLSS models using reference Control Group 2 facilitated precision interpretation of individual levels, while performing equally to or outperforming models using local controls. Slightly higher NfL levels were found in BPAD, compared to controls and TRS. CONCLUSIONS: This study adds further evidence on the diagnostic utility of NfL to distinguish bvFTD from PPD of high clinical relevance to a bvFTD differential diagnosis, and includes the largest cohort of BPAD to date. Using large reference cohorts, GAMLSS modelling and the interactive Internet-based application we developed, may have important implications for future research and clinical translation. Studies are underway investigating utility of plasma NfL in diverse neurodegenerative and primary psychiatric conditions in real-world clinical settings.

Post-Diagnostic Support for Behaviour Changes in Young-Onset Dementia in Australia.

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.

The Associations Between Neuropsychiatric Symptoms and Cognition in People with Dementia: A Systematic Review and Meta-Analysis.

Most people with dementia experience neuropsychiatric symptoms (NPS), including anxiety, depression or disinhibition. There is growing interest in the relationship between NPS and cognitive impairment, but data is still limited. This study aimed to investigate the specific associations between NPS and cognition in people with dementia. MEDLINE, EMBASE and PsycINFO were searched for published, peer-reviewed studies of associations between at least one NPS and one cognitive ability in people with dementia. The quality of the studies was assessed with the NIH National Heart, Lung and Blood Institute's quality assessment tools. A meta-analysis was conducted using Robumeta package for R. Ninety studies were included. We found significant associations between NPS, global cognition and cognitive domains, e.g. apathy was associated with global cognitive and memory impairment; dysphoria was associated with worse attention; delusions with executive dysfunction. Increased NPS in people with dementia are associated with worse cognitive performance. There were few studies looking at associations between some neuropsychiatric clusters and cognitive abilities, and there was little research on causal relationships. Our review was limited by the inclusion of studies that reported associations in specific formats, and most included people with a diagnosis of Alzheimer's disease (AD). However, given the large number of studies, this is unlikely to have biased results. More research is needed that includes diverse people with different dementia syndromes. Registration: PROSPERO 2020 CRD42020165565.

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.

Global rural health disparities in Alzheimer's disease and related dementias: State of the science.

INTRODUCTION: Individuals living in rural communities are at heightened risk for Alzheimer's disease and related dementias (ADRD), which parallels other persistent place-based health disparities. Identifying multiple potentially modifiable risk factors specific to rural areas that contribute to ADRD is an essential first step in understanding the complex interplay between various barriers and facilitators. METHODS: An interdisciplinary, international group of ADRD researchers convened to address the overarching question of: "What can be done to begin minimizing the rural health disparities that contribute uniquely to ADRD?" In this state of the science appraisal, we explore what is known about the biological, behavioral, sociocultural, and environmental influences on ADRD disparities in rural settings. RESULTS: A range of individual, interpersonal, and community factors were identified, including strengths of rural residents in facilitating healthy aging lifestyle interventions. DISCUSSION: A location dynamics model and ADRD-focused future directions are offered for guiding rural practitioners, researchers, and policymakers in mitigating rural disparities. HIGHLIGHTS: Rural residents face heightened Alzheimer's disease and related dementia (ADRD) risks and burdens due to health disparities. Defining the unique rural barriers and facilitators to cognitive health yields insight. The strengths and resilience of rural residents can mitigate ADRD-related challenges. A novel "location dynamics" model guides assessment of rural-specific ADRD issues.

Survival in Huntington's disease and other young-onset dementias.

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.

Comparing survival and mortality in patients with late-onset and young-onset vascular dementia.

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.

Mania Following Traumatic Brain Injury: A Systematic Review.

OBJECTIVE: Traumatic brain injury (TBI) is a leading cause of mortality and morbidity worldwide. Mania is an uncommon, but debilitating, psychiatric occurrence following TBI. The literature on mania following TBI is largely limited to case reports and case series. In the present review, the investigators describe the clinical, diagnostic, and treatment characteristics of mania following TBI. METHODS: A systematic search of MEDLINE, EMBASE, and PsycINFO was conducted for English-language studies published from 1980 to July 15, 2021. The included studies provided the required individual primary data and sufficient information on clinical presentation or treatment of manic symptoms. Studies with patients who reported a history of mania or bipolar disorder prior to TBI and studies with patients who sustained TBI before adulthood were excluded. RESULTS: Forty-one studies were included, which reported information for 50 patients (the mean±SD age at mania onset was 39.1±14.3 years). Patients were more frequently male, aged <50 years, and without a personal or family history of psychiatric disorders. Although 74% of patients reported mania developing within 1 year following TBI, latencies of up to 31 years were observed. Illness trajectory varied from a single manic episode to recurrent mood episodes. Rapid cycling was reported in six patients. Mood stabilizers and antipsychotics were most frequently used to improve symptoms. CONCLUSIONS: Heterogeneity of lesion locations and coexisting vulnerabilities make causality difficult to establish. Valproate or a second-generation antipsychotic, such as olanzapine or quetiapine, may be considered first-line therapy in the absence of high-level evidence for a more preferred treatment. Early escalation to combined therapy (mood stabilizer and second-generation antipsychotic) is recommended to control symptoms and prevent recurrence. Larger prospective studies and randomized controlled trials are needed to refine diagnostic criteria and provide definitive treatment recommendations.

A thematic analysis of psychotic symptoms in young-onset dementia.

OBJECTIVES: Exploration of the themes and content of psychotic symptoms in young-onset dementia (YOD) is limited to case analysis. The primary objective of this study was to determine the themes of psychotic symptoms in individuals diagnosed with YOD. DESIGN: Comprehensive retrospective file review of discharge summaries. SETTING: Neuropsychiatry, a specialist mental health service located at the Royal Melbourne Hospital, Australia. PARTICIPANTS: Inpatients at Neuropsychiatry admitted between 2018 and 2020 (inclusive). MEASUREMENTS: Data extracted included descriptions and prevalence of psychotic symptoms as well as general demographic and clinical data. Data analysis was conducted using a thematic approach. RESULTS: Twenty-three inpatients had a diagnosis of YOD with psychotic symptoms. Themes were identified in the domains of delusions (six themes), auditory hallucinations (five themes), and visual hallucinations (two themes). Strong recurring themes across the modalities of hallucinations and delusions were beliefs and experiences relating to paranoia, suspicion, harm, and abuse. Themes did not clearly intersect across the modalities of hallucinations and delusions. A degree of thematic heterogeneity existed within individuals, and individuals experienced delusions or hallucinations of multiple themes. The themes of the psychotic symptoms did not clearly relate to diagnostic category, nor to time from diagnosis. CONCLUSION: This study is the first thematic analysis of psychotic symptoms in YOD and provides further understanding of patient phenomenology and experiences of psychosis in YOD.

Carer burden and behavioral disturbance is similar between younger-onset Alzheimer's disease and behavioral variant frontotemporal dementia.

OBJECTIVES: Carer burden is common in younger-onset dementia (YOD), often due to the difficulty of navigating services often designed for older people with dementia. Compared to Alzheimer's disease (AD), the burden is reported to be higher in behavioral variant frontotemporal dementia (bvFTD). However, there is little literature comparing carer burden specifically in YOD. This study hypothesized that carer burden in bvFTD would be higher than in AD. DESIGN: Retrospective cross-sectional study. SETTING: Tertiary neuropsychiatry service in Victoria, Australia. PARTICIPANTS: Patient-carer dyads with YOD. MEASUREMENTS: We collected patient data, including behaviors using the Cambridge Behavioral Inventory-Revised (CBI-R). Carer burden was rated using the Zarit Burden Inventory-short version (ZBI-12). Descriptive statistics and Mann-Whitney U tests were used to analyze the data. RESULTS: Carers reported high burden (ZBI-12 mean score = 17.2, SD = 10.5), with no significant difference in burden between younger-onset AD and bvFTD. CBI-R stereotypic and motor behaviors, CBI-R everyday skills, and total NUCOG scores differed between the two groups. There was no significant difference in the rest of the CBI-R subcategories, including the behavior-related domains. CONCLUSION: Carers of YOD face high burden and are managing significant challenging behaviors. We found no difference in carer burden between younger-onset AD and bvFTD. This could be due to similarities in the two subtypes in terms of abnormal behavior, motivation, and self-care as measured on CBI-R, contrary to previous literature. Clinicians should screen for carer burden and associated factors including behavioral symptoms in YOD syndromes, as they may contribute to carer burden regardless of the type.