Search

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]

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]

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]

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]