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Supplemental material, sj-docx-1-anp-10.1177_00048674231187312 for Plasma neurofilament light in behavioural variant frontotemporal dementia compared to mood and psychotic disorders by Dhamidhu Eratne, Matthew Kang, Charles Malpas, Steve Simpson-Yap, Courtney Lewis, Christa Dang, Jasleen Grewal, Amy Coe, Hannah Dobson, Michael Keem, Wei-Hsuan Chiu, Tomas Kalincik, Suyi Ooi, David Darby, Amy Brodtmann, Oskar Hansson, Shorena Janelidze, Kaj Blennow, Henrik Zetterberg, Adam Walker, Olivia Dean, Michael Berk, Cassandra Wannan, Christos Pantelis, Samantha M Loi, Mark Walterfang, Samuel F Berkovic, Alexander F Santillo and Dennis Velakoulis in Australian & New Zealand Journal of Psychiatry

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 (p-tau), 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.

Supplemental material, sj-docx-1-anp-10.1177_00048674221080709 for Clinico-demographics of people with younger-onset dementia and neuropsychiatric symptoms referred to an Australian dementia support service: A comparison study with older-onset dementia by Samantha M Loi, Mustafa Atee, Thomas Morris, Daniel Whiting, Stephen Macfarlane, Colm Cunningham and Dennis Velakoulis in Australian & New Zealand Journal of Psychiatry

Supplemental material, sj-pdf-1-anp-10.1177_00048674211058684 for Plasma neurofilament light chain protein is not increased in treatment-resistant schizophrenia and first-degree relatives by Dhamidhu Eratne, Shorena Janelidze, Charles B Malpas, Samantha Loi, Mark Walterfang, Antonia Merritt, Ibrahima Diouf, Kaj Blennow, Henrik Zetterberg, Brandon Cilia, Cassandra Wannan, Chad Bousman, Ian Everall, Andrew Zalesky, Mahesh Jayaram, Naveen Thomas, Samuel F Berkovic, Oskar Hansson, Dennis Velakoulis, Christos Pantelis and Alexander Santillo in Australian & New Zealand Journal of Psychiatry

Supplemental material, Supplementary_Material for Neurological, neuropsychiatric and neurodevelopmental complications of COVID-19 by Christos Pantelis, Mahesh Jayaram, Anthony J Hannan, Robb Wesselingh, Jess Nithianantharajah, Cassandra MJ Wannan, Warda Taqdees Syeda, KH Christopher Choy, Daniela Zantomio, Arthur Christopoulos, Dennis Velakoulis and Terence J O’Brien in Australian & New Zealand Journal of Psychiatry

Supplemental material, Online_Supp for A pilot study of the utility of cerebrospinal fluid neurofilament light chain in differentiating neurodegenerative from psychiatric disorders: A ‘C-reactive protein’ for psychiatrists and neurologists? by Dhamidhu Eratne, Samantha M Loi, Nirbaanjot Walia, Sarah Farrand, Qiao-Xin Li, Shiji Varghese, Mark Walterfang, Andrew Evans, Ramon Mocellin, Kunal Dhiman, Veer Gupta, Charles B Malpas, Steven Collins, Colin L Masters and Dennis Velakoulis in Australian & New Zealand Journal of Psychiatry

Objective Epilepsy and psychogenic nonepileptic seizures (PNES) are serious conditions, associated with substantial morbidity and mortality. Although prompt diagnosis is essential, these conditions are frequently misdiagnosed, delaying appropriate treatment. We developed and validated the Anxiety, Abuse, and Somatization Questionnaire (AASQ), a quick and clinically practical tool to differentiate PNES from epilepsy. Method We retrospectively identified psychological variables that differentiated epilepsy from PNES in a discovery cohort of patients admitted to a video-electroencephalography monitoring (VEM) unit from 2002 to 2017. From these findings, we developed the AASQ and prospectively validated it in an independent cohort of patients with gold-standard VEM diagnosis. Results One thousand two hundred ninety-one patients were included in the retrospective study; mean age was 39.5 years (range: 18–99), 58% were female, 67% had epilepsy, and 33% had PNES. Psychometric data for 192 instrument items were reviewed, receiver operating characteristic curves were computed, and a 20-item AASQ was created. Prospective validation in 74 patients showed that a one-point increase in the AASQ score was associated with 11 times increase in the odds of having PNES compared with epilepsy. Low scores on the AASQ were associated with a low probability of PNES with a negative predictive value of 95%. Significance The AASQ is quick, inexpensive, and clinically useful for workup of seizure disorders. The AASQ excludes PNES with a high degree of confidence and can predict PNES with significance when combined with basic clinicodemographic variables. Future research will investigate diagnostic performance of the AASQ in relevant clinical subgroups, such as patients with comorbid epilepsy and PNES.

Supplemental material, APY766123_Appendix for Alzheimer Disease: Non-pharmacological and pharmacological management of cognition and neuropsychiatric symptoms by Samantha M Loi, Dhamidhu Eratne, Wendy Kelso, Dennis Velakoulis and Jeffrey CL Looi in Australasian Psychiatry

Supplemental material, APY766120_Appendix for Huntington’s disease: Managing neuropsychiatric symptoms in Huntington’s disease by Samantha M Loi, Mark Walterfang, Dennis Velakoulis and Jeffrey CL Looi in Australasian Psychiatry

ObjectiveTo investigate partial volume correction (PVC) of 2-[F]-fluoro-2-deoxy-D-glucose positron emission tomography in Alzheimer disease in a longitudinal context.MethodsA total of 115 participants were included, including 55 controls, 53 patients with mild cognitive impairment, and 7 patients with dementia of the Alzheimer type. Imaging was performed at baseline and 24 months. Partial volume corrected vs uncorrected rates of longitudinal change were compared for mesial temporal and cortical regions of interest.ResultsPartial volume correction increased apparent uptake, and this effect was greater at 24 months compared with baseline. Partial volume correction decreased the rate of decline, causing an apparent increase in uptake at 24 months compared with baseline. This effect was correlated with the structural atrophy.ConclusionsThese findings suggest that applying PVC in a longitudinal context in Alzheimer disease might produce unpredictable results. Accordingly, both PVC corrected and uncorrected data should be reported to ensure that the results are physiologically plausible.

Alzheimer's disease (AD) is characterized by two primary pathologies: tau-related neurofibrillary tangles and the extracellular accumulation of amyloid-β (Aβ). The development of these pathologies is topologically distinct early in the disease, with Aβ beginning to accumulate as a diffuse, neocortical pathology, while tau-related pathology begins to form in mesial temporal regions. This study investigated the hypothesis that, by virtue of this distinction, there exist preferential associations between the primary pathologies and aspects of the cognitive phenotype. We investigated the relationship between cerebrospinal fluid (CSF) biomarkers for tau and Aβ pathologies with neurocognitive measures in 191 patients with mild cognitive impairment (MCI). Participants completed cognitive tests of new learning, information processing speed, and working memory. Separate regression models were computed and then followed up with mediation analyses to examine the predictive status of CSF biomarkers. The effect of Aβ on learning was mediated by phospho-tau (p = 0.008). In contrast, Aβ had a direct effect on information processing speed that was not mediated by phospho-tau (p = 0.59). No predictors were significant for working memory. This study provided evidence for a differential relationship of Aβ and phospho-tau pathologies on the neurocognitive phenotype of MCI. This supports the proposition that these primary AD pathologies maximally affect different aspects of cognition, and has potential implications for cognitive assessments and the use of biomarkers in disease-modifyingtherapeutic trials.

Topiramate is a sulfamate-substituted monosaccharide anticonvulsant that is associated with anorexia and weight loss and has been used to treat binge eating disorder and bulimia nervosa. This report describes a man with frontotemporal dementia, behavioural variant, associated with abnormal eating behaviour which appeared to respond to topiramate. We review the physiological basis of abnormal eating behaviour in frontotemporal dementia and explore possible mechanisms of action by which topiramate may modify eating behaviour in this condition.