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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]

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]

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]

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]

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: 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]

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: 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]

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]

Background/aim: Assessment of cognitive function in people with neurosychiatric disorders can be challenging, due to behavioural and psychiatric symptomatology. The Behavioural Assesment Tool for Cognition and Higher Functioning (BATCH) is a validated observational tool that complements formal cognitive testing in this patient population. This study aimed to determine the capacity of the BATCH as a predictive tool for discharge planning. Method: BATCH scores for 330 consecutive admissions for assessment to a specialist neuropsychiatry unit between 2007 and 2015 were analysed. The variables of interest included discharge destination, diagnosis, length of stay, age at discharge and BATCH scores (both subdomain and total). Significant predictors of discharge destination were identified using logistic regression analysis. Results: After adjusting for age at discharge, three variables were found to be significant predictors of discharge destination – length of stay, diagnosis, and BATCH total score. The odds of being discharged to a destination other than home decreased by 3% for each additional BATCH total score unit. The length of stay remained a significant predictor of discharge destination when adjusting for BATCH total score, age at admission and diagnosis. Conclusion: BATCH total scores, but not subdomain scores, were predictive of discharge destination, along with the patients' length of stay and diagnosis. Knowledge of this relationship may guide clinical discharge planning, when working with the complex needs of this group of patients. A larger study is indicated to determine the range and cut‐off scores for discharge destinations other than home. [ABSTRACT FROM AUTHOR]

Abstract: Behavioral variant frontotemporal dementia (bvFTD) has been predominantly considered as a frontotemporal cortical disease, with limited direct investigation of frontal–subcortical connections. We aim to characterize the grey and white matter components of frontal–thalamic and frontal–striatal circuits in bvFTD. Twenty‐four patients with bvFTD and 24 healthy controls underwent morphological and diffusion imaging. Subcortical structures were manually segmented according to published protocols. Probabilistic pathways were reconstructed separately from the dorsolateral, orbitofrontal and medial prefrontal cortex to the striatum and thalamus. Patients with bvFTD had smaller cortical and subcortical volumes, lower fractional anisotropy, and higher mean diffusivity metrics, which is consistent with disruptions in frontal–striatal–thalamic pathways. Unexpectedly, regional volumes of the striatum and thalamus connected to the medial prefrontal cortex were significantly larger in bvFTD (by 135% in the striatum, p = .032, and 217% in the thalamus, p = .004), despite smaller dorsolateral prefrontal cortex connected regional volumes (by 67% in the striatum, p = .002, and 65% in the thalamus, p = .020), and inconsistent changes in orbitofrontal cortex connected regions. These unanticipated findings may represent compensatory or maladaptive remodeling in bvFTD networks. Comparisons are made to other neuropsychiatric disorders suggesting a common mechanism of changes in frontal–subcortical networks; however, longitudinal studies are necessary to test this hypothesis. [ABSTRACT FROM AUTHOR]

Objective: Improving and minimizing challenging behaviors seen in psychiatric conditions, including behavioral and psychological symptoms of dementia are important in the care of people with these conditions. Yet there is a lack of systematic evaluation of these as a part of routine clinical care. The Neuropsychiatric Inventory is a validated and reliable tool for rating the severity and disruptiveness of challenging behaviors. We report on the evaluation of a Web-based symptom assessment manager (SAM), designed to address the limitation of previous tools using some of the Neuropsychiatric Inventory functions, to monitor behaviors by staff caring for people with dementia and other psychiatric conditions in inpatient and residential care settings.Methods: The SAM was piloted in an 8-bed inpatient neuropsychiatry unit over 5 months. Eleven nurses and 4 clinicians were trained in usage of SAM. Primary outcomes were usage of SAM and perceived usability, utility, and acceptance of SAM. Secondary outcomes were the frequencies of documented behavior. Usage data were analyzed using chi-square and logistic regression analyses.Results: The SAM was used for all admitted patients regardless of diagnosis, with a usage rate of 64% for nurses regularly employed in the unit. Staff provided positive feedback regarding the utility of SAM.Conclusions: The SAM appeared to offer individualized behavior assessment by providing a quick, structured, and standardized platform for assessing behavior in a real-world setting. Further research would involve trialing SAM with more staff in alternative settings such as in home or residential care settings. [ABSTRACT FROM AUTHOR]

Background: It is common for patients presenting with neuropsychiatric symptoms to endure significant diagnostic odyssey. Neurofilament light chain (NfL) has shown promise in being able to differentiate between neurodegenerative and psychiatric disorders. This study aimed to assess the clinical utility of NfL in avoiding misdiagnosis. Method: In this retrospective study, we conducted file review of patients assessed at Neuropsychiatry, Royal Melbourne Hospital between 2009 to 2020. We included all patients (n = 212) who had a CSF NfL level at their baseline assessment. Investigators blinded to NfL levels extracted clinical information including diagnoses from the initial and follow‐up assessments using documentation available. In addition, we collected follow‐up data from external services where available. Initial and follow‐up/final diagnoses were categorised as neurodegenerative disorder (ND), psychiatric disorder (PSY), mild cognitive impairment (MCI), unclear, and not‐neurodegenerative (Not‐ND). Not‐ND were individuals who did not meet the diagnosis for PSY or MCI, and did not have worsening symptoms. Based on our previous findings, we defined an NfL>582pg/mL as a positive test result for ND. Result: So far, we have collected information from 135 patients. Of these, 14/89 (16%) patients initially diagnosed with ND were re‐diagnosed as PSY or Not‐ND. 2/30 (7%) patients initially diagnosed with PSY were re‐diagnosed as having ND. Including MCI and unclear, 32/135 (24%) had a delayed diagnosis, which could have been reduced to 14% based on baseline CSF NfL predicting ND or Not‐ND/MC/PSY. Data analysis is ongoing and full results will be presented at the conference. Conclusion: Baseline CSF NfL could have aided clinicians in a real‐world clinical setting, to reduce misdiagnosis, and increase diagnostic accuracy from 76% to 86%. An elevated level could prompt assertive investigations for neurological and neurodegenerative causes. Conversely, a low NfL, could reassure against a neurodegenerative disorder, preventing unnecessary assessments. Timely and accurate diagnosis will improve outcomes and precision care for patients and families. [ABSTRACT FROM AUTHOR]

Background: Distinguishing behavioural variant frontotemporal dementia (bvFTD) from non‐neurodegenerative 'non‐progressor', 'phenocopy' mimics of frontal lobe dysfunction, can be one of the most challenging clinical dilemmas. A biomarker of neuronal injury, neurofilament light chain (NfL), could reduce misdiagnosis and delay. Method: Cerebrospinal fluid (CSF) NfL, amyloid beta 1‐42 (AB42), total and phosphorylated tau (T‐tau, P‐tau) levels were examined in patients with an initial diagnosis of bvFTD. Based on follow up information, patients were categorised as Progressors. Non‐Progressors were subtyped in to Phenocopy Non‐Progressors (non‐neurological/neurodegenerative final diagnosis), and Static Non‐Progressors (static deficits, not fully explained by non‐neurological/neurodegenerative causes). Result: Forty‐three patients were included: 20 Progressors, 23 Non‐Progressors (15 Phenocopy, 8 Static), 20 controls. NfL concentrations were lower in Non‐Progressors (Non‐Progressors Mean, M=554pg/mL, 95%CI:[461, 675], Phenocopy Non‐Progressors M=459pg/mL, 95%CI:[385, 539], Static Non‐Progressors M=730pg/mL, 95%CI:[516, 940]), compared to bvFTD Progressors (M=2397pg/mL, 95%CI:[1607, 3332]). NfL distinguished Progressors from Non‐Progressors with the highest accuracy (area under the curve 0.92, 90%/87% sensitivity/specificity, 86%/91% positive/negative predictive value, 88% accuracy). Static Non‐Progressors tended to have higher T‐tau and P‐tau levels compared to Phenocopy Non‐Progressors. Conclusion: This study demonstrated strong diagnostic utility of CSF NfL in distinguishing bvFTD from phenocopy non‐progressor variants, at baseline, with high accuracy, in a real‐world clinical setting. This has important clinical implications to improve outcomes for patients and clinicians facing this challenging clinical dilemma, as well as for healthcare services, and clinical trials. Further research is required to investigate heterogeneity within the non‐progressor group and potential diagnostic algorithms, and prospective studies are underway assessing plasma NfL. [ABSTRACT FROM AUTHOR]

Purpose: To investigate whether there are any white matter changes in a 6-month follow-up of mild-moderate Alzheimer's patients using diffusion tensor imaging (DTI). Materials and Methods: We recruited 18 mild-moderate Alzheimer's disease patients and they underwent magnetic resonance imaging (MRI) at recruitment and at 6-month follow-up. Diffusion MRI images were processed using DTI-ToolKit to create a population-based tensor template. This template was integrated with a voxel-wise and atlas-based analysis in FSL to determine the magnitude and location of change in diffusion metrics over the 6-month follow-up period. Results: There were significant widespread changes in diffusion metrics across the entire white matter skeleton (P < 0.001), 95% confidence interval (CI) difference in fractional anisotropy: -0.007 (-0.011, -0.002), mean diffusivity: 0.040 (0.023, 0.058), axial diffusivity: 0.015 (0.008, 0.022), radial diffusivity: 0.012 (0.006, 0.019), as well as regions of interest in the splenium and superior longitudinal fasciculus. Conclusion: Our findings show that diffusion metrics are altered in a 6-month follow-up period of mild-moderate Alzheimer's patients, supporting the potential of DTI metrics to act as sensitive biomarkers for disease progression even over a relatively short time interval, and the potential utility to be applied to clinical trials of putative disease-modifying therapies. [ABSTRACT FROM AUTHOR]

Background: Hyperphosphorylated tau is a pathological hallmark of ∼45% of behavioural variant frontotemporal dementia (bvFTD). For this reason, hyperphosphorylated tau represents a promising treatment target for this population. Sodium selenate stimulates the PP2A enzyme, which directly dephosphorylates hyperphosphorylated tau. This Phase 1b, open‐labelled, study investigated sodium selenate as a disease‐modifying treatment for patients with bvFTD. Method: Twelve patients with bvFTD were treated with sodium selenate (15mg tds) for twelve months. Participants underwent a cognitive and behavioural battery, MRI, lumbar puncture and safety assessments at screening, baseline, and at regular intervals following treatment commencement. Adverse events were monitored via diary cards between clinic visits. Result: All 12 patients completed the study. Safety analysis found that sodium selenate was safe and well tolerated, with no study withdrawals. Commonly reported mild‐moderate adverse events were nail changes (n=6), muscles aches (n=4), headache, fatigue, hair loss and fall (n=3). Five patients reduced their dose to 10mg tds due to adverse events. No treatment‐related serious adverse events occurred. Analyses of efficacy data are ongoing. A mixed‐effects analysis showed an overall small but significant decline on cognition and behaviour, including total NUCOG score (b=‐0.18, 95% CI=‐0.28–0.08) Cambridge Behavioural Index (b=0.32, 95% CI=0.18‐0.46) and Carer Burden Scale score (b=0.1, 95% CI = 0.02‐0.18). Percentage change in whole‐brain volume from baseline to week 52 ranged from ‐0.26% to ‐6.51% (n=7 >‐1.8%, n=4 <‐1.8%). Plasma tau levels (n=6) did not change from baseline (3.73±0.26pg/mL) to week 52 (4.66±0.24pg/mL). CSF tau also showed no change from baseline (167.8±11.2pg/mL) to week 52 (156.1±2.49pg/mL). Although not significant, the directional changes are in line with the proposed mechanism of sodium selenate. Exploratory analyses of "responders" (brain volume change >‐1.8%, n=7) found no change in NUCOG total score (b=‐0.03, 95% CI ‐0.14‐0.07) or CBS score (b=‐0.05, 95% CI ‐0.04‐0.13) over time. Conclusion: Sodium selenate is safe and well tolerated in patients with bvFTD. Exploratory analyses indicate it may reduce atrophy and halt cognitive decline in a subset of bvFTD patients. Sodium selenate should be further investigated as a potential treatment for bvFTD, and biomarkers to identify the subset of "responder" patients explored. [ABSTRACT FROM AUTHOR]

Background: Distinguishing a dementia syndrome from a primary psychiatric disease in younger patients can be challenging and may lead to diagnostic change over time. The aim of this study was to examine diagnostic stability in a cohort of patients with younger‐onset neurocognitive disorders. Method: We retrospectively reviewed records of patients that were admitted to our unit between 2000 and 2019, were followed‐up for ≥12 months and received a diagnosis of young onset dementia at any time point. Initial diagnosis included Alzheimer disease (AD)‐type dementia (n= 30), frontotemporal dementia (FTD) syndromes (n=44), vascular dementia (VaD, n=7), mild cognitive impairment (MCI, n= 10), primary psychiatric diseases (n=6) and other conditions such as Lewy Body Dementia (n=30). Result: In a total of n=127 patients, 49 (39%) changed their initial diagnoses during follow‐up. Behavioural variant FTD (bvFTD) was the least stable diagnosis, followed by dementia not otherwise specified and MCI. Compared to 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 switching from a neurodegenerative to a psychiatric diagnosis more likely had a long psychiatric history, while those changing from a psychiatric to a neurodegenerative diagnosis had a recent manifestation of psychiatric symptoms. Conclusion: Misdiagnosis in younger patients with neurocognitive disorders is not uncommon, especially in cases of behavioural variant FTD. Late‐onset psychiatric symptoms may be the harbinger to a neurodegenerative disease. Close follow‐up and monitoring of these patients are necessary. [ABSTRACT FROM AUTHOR]

Background: Patients presenting with neuropsychiatric symptoms often face significant diagnostic odyssey. Our recent research (Eratne et al, ANZJP, 2020) found neurofilament light (NfL) differentiated between neurodegenerative and psychiatric disorders, with high accuracy. Yet the clinical utility of NfL, as to whether it can aid clinicians in avoiding misdiagnosis in a real‐world clinical setting, is unknown. Our primary aim was to measure the rates of diagnostic change in patients with neuropsychiatric symptoms assessed at a tertiary multidisciplinary service, and determine whether baseline cerebrospinal (CSF) NfL level could have prevented misdiagnoses, by predicting the final diagnosis after follow up. Methods: We conducted a retrospective file review of patients assessed at an Australian neuropsychiatry and young‐onset dementia service between 2009‐2020. NfL levels were measured from CSF collected at their baseline assessment. Blinded investigators (MK, HD, DE) extracted clinical data including diagnoses from discharge summaries and outpatient letters from the initial assessment and re‐assessment. Baseline and final diagnoses were categorised as neurodegenerative disorder [ND], or, other non‐neurodegenerative conditions including primary psychiatric disorder [Other/PPD]. We also obtained follow‐up information on patients that were subsequently seen at external services where available. Results: From a preliminary analysis of those with follow‐up information for at least a year (N=32), six patients' diagnostic categories (19%) were revised (ND to Other/PPD=5; Other/PPD to ND=1). In all six cases (figure 2), baseline CSF NfL levels, using our previously established cut‐off, would have predicted the final revised diagnosis. As this study is underway, findings for over 200 patients will be presented for the Conference. Conclusions: In a real‐world tertiary clinical setting, baseline CSF NfL would have accurately predicted diagnostic change, showing promise to aid clinicians assessing patients with neuropsychiatric symptoms, and reduce misdiagnosis. An elevated level could help exclude primary psychiatric provisional or differential diagnoses, and prompt assertive investigations for neurological and neurodegenerative causes. Conversely, a low NfL, could reassure against a neurodegenerative disorder, preventing unnecessary assessments. Timely and accurate diagnosis will reduce uncertainty, enable early care planning, reduce patient and carer burden, thus improving outcomes and the diagnostic odyssey faced by patients and families. [ABSTRACT FROM AUTHOR]

Background: Accurate, timely diagnosis of neurodegenerative disorders, in particular distinguishing primary psychiatric from neurological disorders and in younger people, can be challenging. There is a need for biomarkers to reduce the diagnostic odyssey and improve outcomes. Neurofilament light (NfL) has shown promise as a diagnostic biomarker in a wide range of disorders. Our Markers in Neuropsychiatric Disorders (MiND) Study builds on our pilot (Eratne et al, ANZJP, 2020), to explore the diagnostic and broader utility of plasma and cerebrospinal fluid (CSF) NfL and other novel markers such as phosphorylated tau 181 (p‐tau181), in a broad range of psychiatric and neurodegenerative/neurological disorders, with a view of translation into routine clinical practice. Methods: We assessed plasma and/or CSF NfL and p‐tau181 concentrations in broad cohorts, including: patients assessed for neurocognitive/psychiatric symptoms at Neuropsychiatry and Melbourne Young‐Onset Dementia services and other services, in a wide range of disorders including Alzheimer disease, frontotemporal dementia, schizophrenia, bipolar disorder, depression, Niemann‐Pick Type C, epilepsy, functional neurological disorders. The most recent primary consensus diagnosis informed by established diagnostic criteria was categorised: primary psychiatric disorder (PPD), neurodegenerative/neurological disorder (ND), or healthy controls (HC). Results: Findings from over 500 patients/participants will be presented, which indicate that CSF and plasma NfL levels are significantly elevated in a broad range of ND compared to a broad range of PPD, and HC, and bvFTD progressors from phenocopy syndromes, differentiating with areas under the curve of >0.90, sensitivity and specificity >90%. Plasma P‐tau181 levels distinguished Alzheimer disease (mainly younger sporadic), compared to other neurodegenerative disorders, with AUC 0.90, 90% sensitivity and specificity. As recruitment, sample analysis, data collection is ongoing, the most up to date results will be presented. Conclusions: NfL shows great promise as a diagnostic test to assist with the common, challenging diagnostic dilemma of distinguishing neurodegenerative from non‐neurodegenerative and primary psychiatric disorders. Plasma p‐tau181 shows strong diagnostic utility in younger‐onset Alzheimer disease. A significantly elevated NfL in someone with a psychiatric diagnosis should prompt consideration of neurodegenerative differentials. Plasma NfL could dramatically alter clinical care of patients with neuropsychiatric and neurological symptoms, improving outcomes for patients, their families, the healthcare system, and clinical trials. [ABSTRACT FROM AUTHOR]

Background: There are currently 28000 people in Australia with younger‐onset dementia (YOD). A recent review of younger‐onset dementia cohorts (Loi SM et al. submitted) suggested that there needs to be more detailed study in this heterogenous group in order to glean more clinically relevant information. For example, our group (Eratne D et al. 2020) investigated the utility of cerebrospinal fluid (CSF) neurofilament light (NfL) chain in a group of people with a range of psychiatric and neurodegenerative disorders and reported that NfL could distinguish between these two broad disorders, demonstrating the benefits in studying a large range of YODs. BeYOND (Biomarkers in younger‐onset neurocognitive disorders) was established as a longitudinal cohort of younger people presenting with neurocognitive symptoms to a clinical diagnostic service, with the aim of identifying clinical and investigational biomarkers which can inform diagnostic and psychosocial outcomes in a clinically heterogenous population. Method: Patients are prospectively recruited during their index presentation to Neuropsychiatry, Royal Melbourne Hospital, Australia. Neuropsychiatry is a tertiary specialist service which provides diagnostic work‐up for patients with cognitive, psychiatric and neurological symptoms. The diagnostic process includes baseline and 18 month assessments of clinical and diagnostic outcomes including CSF and blood biomarkers, cognition, neuroimaging and psychosocial (including caregiver). Results: To date, 50 participants have been recruited (17 females, mean age 55). Thirty of had a dementia diagnosis (including Alzheimer's dementia, frontotemporal dementia and Huntington's disease), with the remainder having a psychiatric disorder (including depression and schizophrenia) as principle diagnosis. All participants have had clinical, neuropsychology and imaging. Eleven have had a lumbar puncture. Twenty participants have had a research blood panel for genetic analysis)and 12 had quantitative susceptibility mapping imaging. Conclusion: The diagnosis of neurodegenerative disorders in younger people can be difficult and is often associated with diagnostic delays (Draper B et al. 2016). The BeYOND study aims to longitudinally assess younger patients with suspected neurodegenerative disease in order to improve diagnostic and psychosocial outcomes for this population. References: Loi SM et al. J Neuropsychiatry Clin Neuroscience. Submitted 23/1/2020. Eratne D et al. ANZJP. 54 (1): 57‐67. 2020. Draper B et al. Int J Geriatr Psychiatry. 31 (11): 1217‐1224. 2016. [ABSTRACT FROM AUTHOR]

Background: Distinguishing primary psychiatric disorders (PPD) from neurological/neurodegenerative disorders (NND) is a common diagnostic dilemma in clinical practice. Numerous studies have focused on whether cognitive, neuroimaging or blood/ cerebrospinal fluid (CSF) are of assistance in this clinical scenario. Olfactory impairment has not however been systematically examined as a clinical tool for this purpose. The aim of this study was to identify whether performance in olfactory identification can distinguish NND and PPD. Method: This was a cross‐sectional retrospective study of inpatients assessed in Neuropsychiatry, Royal Melbourne Hospital (RMH) over the period 2015‐2019. Neuropsychiatry is a tertiary / quaternary service which provides diagnostic work up for patients with cognitive, psychiatric and neurological symptoms. Data extracted from the admission records included: demographics, tobacco use, medical comorbidities, cognitive function using the Neuropsychiatry Unit Cognitive Assessment Tool (NUCOG), and odour identification assessed using the Sniffin' Sticks Screening 12 Test (SS12). The final discharge diagnosis for all patients was informed by established diagnostic criteria. Result: 121 patients were identified who had valid Sniffin Stick testing over this period. 88 patients (72.7%) were diagnosed with NND (mean age‐ 60, including Alzheimer's dementia, frontotemporal dementia, Lewy body parkinsonian‐related dementias [Parkinson's disease, Multiple Systematic Atrophy, Dementia with Lewy bodies] and other neurological causes of dementia), 33 patients (27.3%) were diagnosed with PPD (mean age=57 years, including mood and psychotic disorders). Patients who scored ≤8 in SS12 were more likely to have NND than PPD, even after adjustment for age, gender and tobacco use [(p=0.005, unadjusted OR=3.51, 95% CI=1.463,8.410), (p=0.009, adjusted OR=3.848, 95% CI=1.395,10.617)]. Receiver Operating Curve (ROC) analyses demonstrated that a score of ≤8 differentiated NND from PSY with sensitivity of 56.8% and specificity of 72.7% (ROC area under the curve of 0.672, p=0.004). Conclusion: Patients presenting with diagnostically complex neurocognitive / neuropsychiatric difficulties who score 8 or less on Sniffin' Sticks are more likely to have a neurodegenerative illness. A cut‐off score of 8 is potentially a "red‐flag" for clinicians faced with the diagnostic question of PPD versus NND. [ABSTRACT FROM AUTHOR]

A number of metabolic disorders that affect the central nervous system can present in childhood, adolescence or adulthood as a phenocopy of a major psychiatric syndrome such as psychosis, depression, anxiety or mania. An understanding and awareness of secondary syndromes in metabolic disorders is of great importance as it can lead to the early diagnosis of such disorders. Many of these metabolic disorders are progressive and may have illness-modifying treatments available. Earlier diagnosis may prevent or delay damage to the central nervous system and allow for the institution of appropriate treatment and family and genetic counselling. Metabolic disorders appear to result in neuropsychiatric illness either through disruption of late neurodevelopmental processes (metachromatic leukodystrophy, adrenoleukodystrophy, GM2 gangliosidosis, Niemann-Pick type C, cerebrotendinous xanthomatosis, neuronal ceroid lipofuscinosis, and alpha mannosidosis) or via chronic or acute disruption of excitatory/inhibitory or monoaminergic neurotransmitter systems (acute intermittent porphyria, maple syrup urine disease, urea cycle disorders, phenylketonuria and disorders of homocysteine metabolism). In this manuscript we review the evidence for neuropsychiatric illness in major metabolic disorders and discuss the possible models for how these disorders result in psychiatric symptoms. Treatment considerations are discussed, including treatment resistance, the increased propensity for side-effects and the possibility of some treatments worsening the underlying disorder. [ABSTRACT FROM AUTHOR]

Peduncular hallucinations are generally associated with lesions in the midbrain. They have rarely been associated with central pontine myelinolysis, a condition associated with rapid alterations in serum sodium and chronic alcoholism. Described herein is the case of a 46-year-old man who developed typical peduncular hallucinations, whose imaging demonstrated central pontine myelinolysis. After alcohol cessation and neuroimaging resolution, the patient's hallucinatory phenomena abated. [ABSTRACT FROM AUTHOR]

Purpose: A lifetime psychiatric history has been reported to be associated with poorer seizure outcome following temporal lobectomy for drug-resistant focal epilepsy, but it remains unclear whether this is confounded by the nature of the epileptogenic pathology. Here we examined this association in a pathologically homogeneous group of patients with mesial temporal sclerosis (MTS). Methods: The study population included 72 consecutive patients who underwent a temporal lobectomy for drug resistant temporal lobe epilepsy (TLE) and had histopathologically proven MTS. All patients were assessed preoperatively by a neuropsychiatrist. Chi-square analysis was undertaken to look for demographic, clinical, psychiatric, or neurologic factors associated with seizure outcome at 1 year. The relationship between having a psychiatric disorder and seizure outcome was examined by generating Kaplan-Meier curves and comparing between groups the log rank test as well as generating Cox regression models to estimate hazard ratios. Key Findings: There were no significant associations between postsurgery seizure outcome and a current or lifetime history of any psychiatric disorder. Significance: A history of psychiatric disorder, in particular depression and psychosis, is not associated with a poorer surgical outcome in patients with MTS. These findings have implications for the clinical management of patients under consideration for temporal lobectomy. [ABSTRACT FROM AUTHOR]

The corpus callosum facilitates communication between the cerebral hemispheres. Morphological abnormalities of the corpus callosum have been identified in numerous psychiatric and neurological disorders. To quantitatively analyze the thickness profile of the corpus callosum, we adapted an automatic thickness measurement method, which was originally used on magnetic resonance (MR) images of the cerebral cortex (Hutton et al. []: NeuroImage 40:1701-10; Jones et al. []: Hum Brain Mapp 11:12-32; Schmitt and Böhme []: NeuroImage 16:1103-9; Yezzi and Prince []: IEEE Trans Med Imaging 22:1332-9), to MR images of the corpus callosum. The thickness model was derived by computing a solution to Laplace's equation evaluated on callosal voxels. The streamlines from this solution form non-overlapping, cross-sectional contours the lengths of which are modeled as the callosal thickness. Apart from the semi-automated segmentation and endpoint selection procedures, the method is fully automated, robust, and reproducible. We compared the Laplace method with the orthogonal projection technique previously published (Walterfang et al. []: Psych Res Neuroimaging 173:77-82; Walterfang et al. []: Br J Psychiatry 192:429-34; Walterfang et al. []: Schizophr Res 103:1-10) on a cohort of 296 subjects, composed of 86 patients with chronic schizophrenia (CSZ), 110 individuals with first-episode psychosis, 100 individuals at ultra-high risk for psychosis (UHR; 27 of whom later developed psychosis, UHR-P, and 73 who did not, UHR-NP), and 55 control subjects (CTL). We report similar patterns of statistically significant differences in regional callosal thickness with respect to the comparisons CSZ vs. CTL, UHR vs. CTL, UHR-P vs. UHR-NP, and UHR vs. CTL. Hum Brain Mapp, 2011. © 2011 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

In transgenic mouse models of Huntington disease (HD) environmental enrichment significantly delays disease onset. A questionnaire-based survey of 154 adults with diagnosed HD (mean 4.2 years postdiagnosis) and a known IT15 CAG repeat length, explored whether premorbid lifestyle may relate to age-at-onset (AO). Participants were drawn from HD outpatient clinics in Australia and New Zealand. Premorbid physical, intellectual, and passive activity levels were used to generate scores in the categories of leisure, nonleisure (education, occupation and domestic duties) and total lifestyle. AO was associated with increased CAG repeat length as expected (r = −0.72, P < 0.001), but also with a lifestyle that included higher levels of passive activity (r = −0.38, P < 0.001). Multiple linear regression modeling showed lifestyle passivity to be a variable independent of CAG repeat length in predicting AO (R2 = 0.54, b = −0.22, P = 0.005). Comparison of the mean AO across tertiles of lifestyle passivity scores showed onset 4.6 years (95% CI = 1.3-7.9) later in the least compared with the most passive tertile. CAG repeat length was also shown to predict lifestyle passivity (R2 = 0.12, b = 1.08, P < 0.0005). Neither intellectual nor physical activity showed significant relationships to AO or CAG repeat length in this cohort. Our study leads to two conclusions: that a passive lifestyle may be a preclinical expression of HD, and that it actually contributes to the earlier onset of symptoms. Overcoming the tendency to be passive may substantially delay onset of HD. © 2010 Movement Disorder Society [ABSTRACT FROM AUTHOR]

This study aims to establish psychometric properties of the Malay Neuropsychiatry Unit Cognitive Assessment Tool ( Malay NuCOG) in Alzheimer's disease. NuCOG was translated to Malay language and compared with Montreal Cognitive Assessment Tool on 80 individuals. The Malay NuCOG showed good internal consistency and reliability ( Cronbach's alpha = 0.895). It demonstrated 100% sensitivity and 87.5% specificity at the cutoff score of 78.50/100. The Malay NuCOG is a valid and reliable cognitive instrument that is sensitive and specific for the detection of dementia and has clinical advantages in its ability to examine individual cognitive domains. [ABSTRACT FROM AUTHOR]

The article analyzes the impact of neuroimaging studies on the risk of developing psychosis. It states that those studies that have been cross-sectional can determine and assess the period of transition from the at-risk mental state to the illness itself. Findings of the study show progressive brain changes that are not seen in at-risk individuals who do not develop the disorder. The studies also challenge the traditional models of schizophrenia.

THEME: Clinical manifestations TOPIC: Neuropsychiatry & beh neurology SUBTOPIC: Neuropsychiatry Background: Survival duration in frontotemporal dementia (FTD) remains inconsistent, depending on the clinical phenotype with different risk factors identified. Risk factors to mortality include the FTD‐MND presentation, a genetic predisposition (Agarwal S et al. 2019), deficits in neuropsychological tests, imaging changes (Agarwal et al. 2019; Hodges et al. 2003) and non‐tau pathology (Roberson et al. 2005; Hodges et al. 2003). We aimed to identify survival duration and cause of death in this group. Method: All inpatients admitted to Neuropsychiatry, based at the Royal Melbourne Hospital, in metropolitan Australia from 1992 – 2014, who were diagnosed with probably FTD of any subtype were included. Linkage data was obtained by the Australian Institute of Health and Welfare (AIHW). We reviewed their clinical information including demographics, age of symptom onset, type of presenting symptom, neuroimaging and diagnosis. Result: Of the 528 individual inpatients identified with a dementia, there were n=100 who had a diagnosis of probable FTD. There were n=76 who had a behavioural‐variant FTD (bv‐FTD), n=14 who had a language‐variant FTD (lang‐FTD) and n=10 who had FTD‐MND. 67% of the group had died. Overall median duration of survival was 10.5 years (95% CI 7.9, 12.2). There were no differences in age of death nor age onset between the three FTD‐subtypes (p=0.479, p=0.289, respectively). As expected, there were significant differences in the median survival duration of the three FTD subtypes, with FTD‐MND having the shortest duration (p=0.004). Causes of death based on ICD‐10 were predominantly dementia‐related (26.3% Other degenerative diseases of nervous system; 17.5% unspecified dementia) but also included acute myocardial infarction (7%) and alcohol‐related (7%). Standardised mortality ratios (SMRs) revealed that compared to population norms, people with FTD had 8x mortality rate. Conclusion: Not unsurprisingly, FTD‐MND had the shortest duration compared to the other subtypes of FTD. The duration of survival was comparable to other studies. Causes of death revealed that a dementia was identified in almost half of cases. High SMRs suggest that FTD is a particularly "fatal" type of dementia in younger people. Investigation into risk factors to death is required. [ABSTRACT FROM AUTHOR]

Background: There is limited information about survival and mortality in younger‐onset dementia (YOD), including the role of sex differences. In older‐onset Alzheimer's disease (AD), the risk of AD appears to be higher in women, despite longer life expectancy, and a recent mortality study suggested that women's older age at death may explain sex‐related differences in death rates from AD and dementia (1). There have also been reports that women have more atrophy and amyloid burden in YOD (2). We sought to further explore this in YOD. Method: Neuropsychiatry inpatients with a diagnosis of dementia or cognitive impairment (excluding those who had a diagnosis of Huntington's disease) between 1992‐2014 were submitted to the Australian National Death Index. Kaplan Meier curves were used to estimate median survival and standardized mortality ratios (SMRs) were used to compare deaths in people with YOD with population norms. Results: 468 inpatients were included in the study, of whom n=330 of them (74.5%) had a YOD. 65% of them (n=215) had died. The mean age of death was 64 years old (SD=10.4). Median survival for the different dementias were: AD – 11.2 years, frontotemporal dementia (FTD) – 10.7 years, "other dementia" – 14.8 years and vascular dementia – 12.3 years. There were no differences in the proportions of people who had died according to dementia type, p=0.438 but median survival for men and women was significant, with men – 13.6 years, compared to women 10.9 years, p=0.02. SMRs were also higher for FTD (SMR=8.1) and for women, compared to men, particularly with women+FTD (SMR=12.2). Conclusion: This study highlights that sex differences also exist in YOD. Differences such as increased cognitive reserve in men and sex‐related bias in identifying dementia in younger people are possible explanations but further investigation is warranted. References: 1. Buckley R. et al. 2019. To what extent does age at death account for sex differences in rates of mortality from AD? Am J Epidemiology. 188: 1213‐1223. 2. Groh J. et al. 2020. Sex‐associated differences in pathology burden in early‐onset AD. Alzheimer's Dement. 16 (supp. 5): e046532 [ABSTRACT FROM AUTHOR]

Background: The aetiology of neuropsychiatric symptoms (NPS) in dementia remains unclear, and currently, it is challenging to distinguish neuropsychiatric manifestations related to younger‐onset neurodegenerative diseases from those of primary psychiatric disorders. Neurofilament light chain (NfL) is a promising biomarker for axonal injury and has been found to differentiate between neurodegenerative diseases and primary psychiatric disorders. The aim was to investigate cerebrospinal fluid (CSF) NfL and its relationship with NPS and compare it with traditional biomarkers, namely Aβ and tau. Methods: Retrospective data for 54 patients with younger‐onset dementia was collated (mean age ± SD, 57.9 ± 7.1, females n = 15 [28%], co‐morbid psychiatric diagnoses n = 17 [31%]). Of these, 23 had Alzheimer's disease (AD), 14 had frontotemporal dementia (FTD), 9 had mild cognitive impairment (MCI), and 8 were diagnosed with other types of dementia. Neuropsychiatric measures were extracted from the Neuropsychiatry Unit Cognitive Assessment Tool (NUCOG), the Depression Anxiety and Stress Scale 21 (DASS‐21), and the revised Cambridge Behavioural Inventory (CBI‐R). CSF biomarkers included NfL, Ab‐42, p‐tau and t‐tau. Results: No significant associations between NPS and NfL was seen in patients with AD, FTD, MCI or other diagnoses. In the combined cohort, a positive correlation was found between the overall cognitive functioning and Ab‐42 levels (r = 0.47, p = 0.01), and visuoconstruction, a specific domain of cognitive functioning, was found to be positively correlated with Ab‐42 levels (r = 0.44, p = 0.03) and negatively correlated with t‐tau levels (r = ‐0.43, p = 0.03). In FTD, a positive correlation was found between stress and p‐tau levels (n = 8, r = 0.89, p = 0.04), and this correlation was stronger in patients without co‐morbid psychiatric diagnoses (n = 7, r = 0.93, p = 0.03). Conclusion: The results suggest that levels of CSF biomarkers, especially Ab‐42, are linked to deficits in cognitive functioning in patients with younger‐onset dementia, and levels of p‐tau are strongly related to stress particularly in the absence of co‐morbid psychiatric diagnoses. Therefore, these biomarkers may assist in the identification of patients who are at an increased risk of developing cognitive impairment and stress. [ABSTRACT FROM AUTHOR]

The anterior cingulate cortex (ACC) appears to be critically involved in the pathophysiology of schizophrenia, but past attempts at characterizing pathological changes in the region using magnetic resonance imaging have been restricted by a limited appreciation of its functional and anatomical diversity and a reliance on relatively coarse metrics (e.g., volume) to index anatomical change. In this study, we applied a novel, surface-based protocol to T1-weighted scans acquired from 40 first episode schizophrenia patients and 40 healthy controls individually matched for age, sex, and morphology of the paracingulate sulcus, a major anatomical variation that has been shown to affect morphometric estimates in the region. The surface-based approach enabled calculation of regional grey matter volume, surface area and curvature, cortical thickness, and depth of the cingulate sulcus, with sub-millimeter precision. Relative to controls, schizophrenia patients displayed a bilateral reduction in thickness of paralimbic regions of the ACC, along with a concomitant increase in surface area of both the limbic and paralimbic ACC. No differences were identified for regional grey matter volume, surface curvature, or CS depth. These findings illustrate the advantages of moving beyond traditional volume-based approaches when investigating cortical morphometry, and indicate that the early stages of schizophrenia are associated with a specific pattern of ACC abnormalities that cannot be attributed to variations in sulcal and gyral morphology. Hum Brain Mapp, 2008. © 2007 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

We describe one male and one female patient who each developed childhood/adolescent obsessive-compulsive disorder as a prelude to the development of a typical picture of chorea-acanthocytosis (ChAc). In each patient, the caudate nucleus showed dramatic atrophy. The role of the caudate in compulsive phenomena, and the predilection for neurological disorders with onset in adolescence to present as major mental illness, is discussed. On the basis of the current evidence and previous findings, we suggest that ChAc can be understood as a disorder whose clinical presentation reflects an interaction between the disease process and the individual's neurodevelopmental stage with both initial interrupted neurodevelopment, and supervening neurodegeneration. © 2007 Movement Disorder Society [ABSTRACT FROM AUTHOR]

The structural and functional consequences of interindividual variations in cortical morphology are poorly understood. In this study, we examined the relationship between one well-characterized variation of the medial frontal lobes, variability of the paracingulate sulcus (PCS), and grey matter volume, cortical thickness, surface area, and sulcal depth of the adjacent anterior cingulate cortex (ACC) and paracingulate cortex (PaC). Seventy-seven healthy individuals were assigned to one of four groups depending on PCS incidence in both hemispheres: left-present, right-absent; left-absent, right-present; both absent; or both present. Comparing these groups on each measure yielded four primary findings: (1) The presence of a PCS was associated with increased PaC and decreased ACC grey matter volume in the hemisphere in which it was apparent, with an almost identical pattern being observed for surface area; (2) there was a more complex relationship between PCS variability and regional thickness, such that a PCS in the left hemisphere was associated with increased left PaC and right ACC thickness, with no comparable effects being observed for the presence of a right PCS; (3) the depths of all major left hemisphere sulci in the region were strongly positively correlated, whereas no such associations were apparent in the right hemisphere; and (4) a leftward asymmetry in PaC thickness was specifically associated with better performance on a test of spatial working memory ability. These results provide evidence for a complex interhemispheric relationship between sulcal variability and cortical morphometry, and indicate that such relationships may be important for understanding individual differences in cognitive abilities. Hum Brain Mapp, 2008. © 2007 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Langerhan’s cell histiocytosis (LCH) has been described as a progressive neurological disorder marked by neurological and cognitive decline. The authors here report a case of a childhood LCH sufferer who made a significant recovery of neuropsychological function in the absence of motor recovery in late adolescence. This differential recovery of motor and cognitive functioning may relate to the interaction between LCH and childhood and adolescent neurodevelopmental processes. [ABSTRACT FROM AUTHOR]

Background: There are currently no approved disease‐modifying treatments of behavioural variant frontotemporal dementia (bvFTD), with the only treatments available providing symptomatic relief to secondary behavioural symptoms. Approximately 45% of bvFTD cases are tauopathies, with the main pathological hallmark and proposed pathogenic mechanism being the accumulation and aggregation of hyperphosphorylated tau. For this reason, hyperphosphorylated tau represents a promising target for a disease modifying treatment in this population. Sodium selenate stimulates the PP2A enzyme, which directly dephosphorylates hyperphosphorylated tau. This study investigated the use of sodium selenate as a disease‐modifying treatment for patients with bvFTD. Method: Fifteen patients with possible bvFTD were treated with sodium selenate (15mg tds) for twelve months. Participants underwent a battery of cognitive and behavioural tests, MRI, lumbar puncture and safety assessments at screening, baseline, and at regular intervals following the commencement of treatment. Adverse events were monitored via diary cards between clinic visits. Result: Fourteen patients are either on treatment or have completed the study. Interim safety analysis (9 completed patients, 5 on treatment) has shown that sodium selenate is safe and well tolerated, with no study withdrawals. Commonly reported adverse events are nail changes (n=5), fatigue (n=4) and nausea (n=4). No treatment related serious adverse events have occurred. An interim mixed‐effects analysis on all available neurocognitive data showed no statistically significant change in NUCOG total score (b=‐0.02, 95% CI = ‐0.18, 0.14]) or Carer Burden Scale (CBS) score (b =0.04, 95% CI = ‐0.05, 0.13]), CVLT total learning score (M diff = 5.80, 95% CI = ‐6.97, 18.57]), or NIH composite score (M diff = 4.72, 95%CI = ‐11.50, 14.70]). Percentage change in whole‐brain volume from baseline to 12 months ranged from ‐0.68% to ‐6.26% (n=5 <‐2%, n=2 ‐5‐6%). Conclusion: The interim results have shown that sodium selenate is safe and well tolerated in patients with bvFTD. Early indications show sodium selenate may be effective in reducing atrophy and halting cognitive decline in a subset of bvFTD patients. A larger phase 2 placebo controlled study is necessary to evaluate whether sodium selenate is efficacious as a disease modifying treatment of bvFTD. [ABSTRACT FROM AUTHOR]

Abstract: We describe the presentation of an adolescent with juvenile‐onset Niemann‐Pick disease type C (NPC) who presented with post‐ictal psychosis in the context of a developing seizure disorder. After demonstrating mild gait disturbance beginning at the age of 4 years, he was diagnosed with NPC at age 12 on the basis of 95% of cultured fibroblasts staining positive for filipin and a reduced fibroblast cholesterol esterification rate. He then developed a seizure disorder at age 15, where clusters of seizures produced typical psychotic symptoms, including hallucinations and delusions. His seizure disorder responded to valproate, which resulted in a settling of his psychotic symptoms. Whilst post‐ictal psychosis is rarely reported prior to the age of 16, NPC in adolescents and adults is particularly psychotogenic and may increase the risk for post‐ictal psychosis in the pediatric population. [ABSTRACT FROM AUTHOR]

A case of presumed Hashimoto’s encephalopathy (HE) is presented. The presentation included memory loss, delusions, functional decline and culminated in a generalized seizure. Anti-thyroid antibodies were detected and symptoms resolved with prednisolone. Patients with HE may present with prominent neuropsychiatric symptoms, attract psychiatric diagnoses and present to psychiatric services. Primarily a diagnosis of exclusion, HE should be considered in cases of encephalopathy in which standard investigations are negative. [ABSTRACT FROM AUTHOR]

This article presents comments of the authors on a study by researcher T. Reisch, where he discusses a case of a young man with hydrocephalus occlusus, who was initially treated for a bipolar illness. Whilst it is tempting to ascribe causality of the entire illness course to the identified organic brain pathology, it is equally valid to consider the cerebral lesion within the clinical context overall, and to understand the interaction between psychiatric illness and organic brain pathology. The prodromal history could thus be consistent with either a psychotic illness or the insidious evolution of the organic condition. Surgical treatment may have been expected to lead to improvement in the behavioral syndrome exhibited by the patient but interestingly, the patient continued to exhibit a motivation and adynamia, with normal neuropsychological function, after surgery.