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.

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.

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.

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.

Young-onset dementia diagnosis, management and care: a narrative review.

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).

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.

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.

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.

Cerebrospinal fluid neurofilament light and cerebral atrophy in younger-onset dementia and primary psychiatric disorders.

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.

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.

Australian older persons mental health inpatient and ambulatory services in 2015-2020 - A descriptive analysis and commentary.

OBJECTIVE: To provide a commentary on Australian state/territory older persons mental health service (OPMHS) expenditure, inpatient and outpatient services and key performance indicators (KPIs). METHOD: Descriptive analysis of data from the Australian Institute of Health and Welfare (AIHW), the Australian Bureau of Statistics and the World Health Organisation. RESULTS: Between 2015-16 and 2019-20, annual expenditure on OPMHS in Australia increased by an average of only 2.3%, compared to 2.9% for all population groups, despite an increase in the number of over 65 year olds. Per capita recurrent expenditure on OPMHS decreased by an average of 1% annually. Australia's total mental health beds increased, whereas OPMHS beds decreased, mainly due to a reduction in non-acute beds. Outcomes for OPMHS admissions were similar to other age groups, except for a longer length of stay and reduced readmission rate. Older Australians accessed ambulatory mental health care at a lower rate and had a lower rate of improvement after a completed episode. CONCLUSIONS: OPMHS expenditure has not increased at commensurate levels compared to other populations. The mental health of people aged over 65 appears to be a neglected policy priority in Australia. The Royal Commission into Aged Care Quality and Safety may herald service and expenditure changes.

Clinical impact of whole-genome sequencing in patients with early-onset dementia.

BACKGROUND: In the clinical setting, identification of the genetic cause in patients with early-onset dementia (EOD) is challenging due to multiple types of genetic tests required to arrive at a diagnosis. Whole-genome sequencing (WGS) has the potential to serve as a single diagnostic platform, due to its superior ability to detect common, rare and structural genetic variation. METHODS: WGS analysis was performed in 50 patients with EOD. Point mutations, small insertions/deletions, as well as structural variants (SVs) and short tandem repeats (STRs), were analysed. An Alzheimer's disease (AD)-related polygenic risk score (PRS) was calculated in patients with AD. RESULTS: Clinical genetic diagnosis was achieved in 7 of 50 (14%) of the patients, with a further 8 patients (16%) found to have established risk factors which may have contributed to their EOD. Two pathogenic variants were identified through SV analysis. No expanded STRs were found in this study cohort, but a blinded analysis with a positive control identified a C9orf72 expansion accurately. Approximately 37% (7 of 19) of patients with AD had a PRS equivalent to >90th percentile risk. DISCUSSION: WGS acts as a single genetic test to identify different types of clinically relevant genetic variations in patients with EOD. WGS, if used as a first-line clinical diagnostic test, has the potential to increase the diagnostic yield and reduce time to diagnosis for EOD.

The Diagnostic Challenge of Young-Onset Dementia Syndromes and Primary Psychiatric Diseases: Results From a Retrospective 20-Year Cross-Sectional Study.

OBJECTIVE: Distinguishing a dementia syndrome from a primary psychiatric disease in younger patients can be challenging and may lead to diagnostic change over time. The investigators aimed to examine diagnostic stability in a cohort of patients with younger-onset neurocognitive disorders. METHODS: A retrospective review of records was conducted for patients who were admitted to an inpatient neuropsychiatry service unit between 2000 and 2019, who were followed up for at least 12 months, and who received a diagnosis of young-onset dementia at any time point. Initial diagnosis included Alzheimer's disease-type dementia (N=30), frontotemporal dementia (FTD) syndromes (N=44), vascular dementia (N=7), mild cognitive impairment (N=10), primary psychiatric diseases (N=6), and other conditions, such as Lewy body dementia (N=30). RESULTS: Among 127 patients, 49 (39%) had a change in their initial diagnoses during the follow-up period. Behavioral variant FTD (bvFTD) was the least stable diagnosis, followed by dementia not otherwise specified and mild cognitive impairment. Compared with patients with a stable diagnosis, those who changed exhibited a higher cognitive score at baseline, a longer follow-up period, greater delay to final diagnosis, and no family history of dementia. Patients whose diagnosis changed from a neurodegenerative to a psychiatric diagnosis were more likely to have a long psychiatric history, while those whose diagnosis changed from a psychiatric to a neurodegenerative one had a recent manifestation of psychiatric symptoms. CONCLUSIONS: Misdiagnosis of younger patients with neurocognitive disorders is not uncommon, especially in cases of bvFTD. Late-onset psychiatric symptoms may be the harbinger to a neurodegenerative disease. Close follow-up and monitoring of these patients are necessary.

Carer burden and psychological distress in young-onset dementia: An Australian perspective.

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.

Time to diagnosis in younger-onset dementia and the impact of a specialist diagnostic service.

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.

What constitutes 'good' home care for people with dementia? An investigation of the views of home care service recipients and providers.

BACKGROUND: Our objective was to explore what people receiving and providing care consider to be 'good' in-home care for people living with dementia. METHODS: We conducted 36 in-depth interviews and two focus groups with key stakeholders in Australia in the first quarter of 2018. Participants included those receiving care (4 people living with dementia, 15 family carers) or providing care (9 case managers, 5 service managers, 10 home care workers). Qualitative thematic analysis was guided by Braun and Clarke's six-step approach. RESULTS: Consensus was reached across all groups on five themes considered as important for good in-home dementia care: 1) Home care workers' understanding of dementia and its impact; 2) Home care workers' demonstrating person-centred care and empathy in their care relationship with their client; 3) Good relationships and communication between care worker, person with dementia and family carers; 4) Home care workers' knowing positive practical strategies for changed behaviours; 5) Effective workplace policies and workforce culture. The results contributed to the co-design of a dementia specific training program for home care workers. CONCLUSIONS: It is crucial to consider the views and opinions of each stakeholder group involved in providing/receiving dementia care from home care workers, to inform workforce training, education program design and service design. Results can be used to inform and empower home care providers, policy, and related decision makers to guide the delivery of improved home care services. TRIAL REGISTRATION: ACTRN 12619000251123 .

Clinico-demographics of people with younger-onset dementia and neuropsychiatric symptoms referred to an Australian dementia support service: A comparison study with older-onset dementia.

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.

Mortality in dementia is predicted by older age of onset and cognitive presentation.

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.

Cerebrospinal fluid neurofilament light chain differentiates primary psychiatric disorders from rapidly progressive, Alzheimer's disease and frontotemporal disorders in clinical settings.

INTRODUCTION: Many patients with cognitive and neuropsychiatric symptoms face diagnostic delay and misdiagnosis. We investigated whether cerebrospinal fluid (CSF) neurofilament light (NfL) and total-tau (t-tau) could assist in the clinical scenario of differentiating neurodegenerative (ND) from psychiatric disorders (PSY), and rapidly progressive disorders. METHODS: Biomarkers were examined in patients from specialist services (ND and PSY) and a national Creutzfeldt-Jakob registry (Creutzfeldt-Jakob disease [CJD] and rapidly progressive dementias/atypically rapid variants of common ND, RapidND). RESULTS: A total of 498 participants were included: 197 ND, 67 PSY, 161 CJD, 48 RapidND, and 20 controls. NfL was elevated in ND compared to PSY and controls, with highest levels in CJD and RapidND. NfL distinguished ND from PSY with 95%/78% positive/negative predictive value, 92%/87% sensitivity/specificity, 91% accuracy. NfL outperformed t-tau in most real-life clinical diagnostic dilemma scenarios, except distinguishing CJD from RapidND. DISCUSSION: We demonstrated strong generalizable evidence for the diagnostic utility of CSF NfL in differentiating ND from psychiatric disorders, with high accuracy.