13th ForeFront Scientific Meeting

Thank you

On behalf of the ForeFront group leaders, thank you to all who could be part of our 13th and Final Annual ForeFront Scientific Meeting. It was last but certainly not least! I would like to say a special thank you to all the presenters, chairs, ForeFront admin team and to all the people that submitted posters and took the digital challenge. These scientific meetings have provided a forum over the years for our research groups to discuss how the basic and clinical sciences can work together to improve knowledge of the mechanisms underlying of brain disorders, and have been integral in collaborative research within and beyond our research group.

Invited Speakers

Tthank you to all our invited international and national speakers, for taking the time to travel and be part of this year’s ForeFront scientific meeting. We were very fortunate to be able to showcase international specialists in the fields of MND, Movement disorders, FTD and other dementias. Your talks were fantastic!

Dr Angela Genge

Day 1: ForeFront Scientific Meeting – Motor neuron disease plenary (Monday 9:05am)

Dr. Angela Genge has been the Director of the Clinical Research Unit at the Montreal Neurological Institute since 2004. Since 2020, she has also served as Chief Medical Officer for QurAlis and Scientific Director of CATALIS. Her expertise and ground-breaking work in the introduction of innovative therapies in the rare disease space has led her to be a sought-after member of numerous advisory boards for companies developing therapies for these diseases. Clinically, she is the Director of the Neuro ALS clinical program and multidisciplinary clinic, and a neuromuscular neurologist. Throughout her career she has received numerous awards, most recently the 2018 Forbes Norris Award, the DIVA of Distinction Award, and the Governor General Diamond Jubilee Award.

This presentation will cover all current considerations in clinical trial design in ALS/MND from Phase 1 FIH to Phase 3 pivotal. The use of biomarkers in various programs including biological e.g. neurofilament light, electrophysiological e.g. CMAP, SDTC, imaging will be included. Also the effective use of adaptive designs to shorten the development period will be reviewed. Finally a number of current programs will be discussed to illustrate each of these points

Professor Eneida Mioshi

Day 1: ForeFront Scientific Meeting – Motor neuron disease plenary (Monday 9:45am)

Eneida trained as an occupational therapist (BSc Hons; MSc OT, Sao Paulo, Brazil), and has a PhD in Applied Cognitive Psychology (Cambridge, UK). Her first postdoctoral role was at Frontier. Eneida’s research programme investigates the interactions of brain changes, disability, and family context in dementia and motor neurone disease, with a view to developing clinical assessments and novel non-pharmacological interventions to support those affected by these conditions. When not at work or trying to keep up with her teenagers’ schedules, Eneida can be found swimming. She is not very particular and will happily swim in pools, lakes, rivers, and seas.

Cognitive and behavioural symptoms in MND have been well recognised, with various clinical assessments available for detection in clinical and research settings. Many of these symptoms overlap with those observed in FTD, such as apathy, disinhibition, rigidity, deficits in social cognition and lack of insight. As such, people with MND and/or FTD may not be fully aware of the behavioural changes they are presenting with, leading to challenging situations for family members, as well as issues in clinical decision making. Despite recognition of such difficult symptoms, no standardised approaches in managing these exist in MND. Not surprisingly, questions about ‘what should I do?’ constantly arise from families and healthcare professionals. MiNDToolkit, a novel psychoeducational intervention for carers, is currently being tested in a randomised feasibility trial in the UK. MiNDToolkit is hybrid; the intervention is delivered via the online platform as well as through trained healthcare professionals. For this reason, MiNDToolkit has its own bespoke online platform that brings together carers, healthcare professionals and researchers. In this talk you will hear about the development, content, and preliminary findings of the MiNDToolkit randomised feasibility trial.

Dr Emma Devenney

Day 1: ForeFront Scientific Meeting – Motor neuron disease plenary (Monday 10:25am)

Emma is a neurologist and NHMRC post-doctoral fellow at the Brain and Mind Centre and senior lecturer in the Faculty of Medicine and Health at the University of Sydney. She completed her neurology training (UK) in 2018 and a PhD at the University of New South Wales in 2016. She was awarded a MNDRA post-doctoral fellowship on completion of her PhD and more recently an NHMRC investigator grant (2020). She has expertise in cognitive and behavioural neurology, clinical genetics and neuropsychiatric disorders. Her research incorporates clinical, cognitive, genetic and neuroimaging advances to address the critical need for biomarkers to improve diagnosis and serve as targets for patient stratification, treatment and intervention.

Hallucinations in non–Parkinson’s disease neurodegeneration - evidence from cognition, genetics and neuroimaging Emma M Devenney, Nga Tse Tan, Rebekah M Ahmed, Jashelle Caga, James Carrick, Claire O’Callaghan, Olivier Piguet, Matthew C Kiernan, John R Hodges Objective: To explore the rate and underlying cognitive, behavioural and neural associations of hallucination development in non-Parkinson’s neurodegeneration Methods: Patients were recruited sequentially to this study and underwent a clinical examination to determine the presence of hallucinations, a battery of neuropsychological tests and MRI. A well-characterised homogenous group of patients with MND-FTD and well characterized hallucinations were genetically and demographically matched to a group without hallucinations and a healthy control cohort. Data was analysed according to 3 levels; 1) the relationship between neural structures, cognition, behaviour and hallucinations and 2) the impact of the C9orf72 expansion and 3) hallucination subtype on expression of hallucinations. Results: From a transdiagnostic perspective, hallucinations were present in 55 of 449 patients (12.2%) across the spectrum of disorders. Of these, 60% were visual in nature only, 40% were auditory with 40% a combination of both. Specifically within the diagnostic categories, hallucinations were present in 22% of MND-FTD cases, 7% of SD cases, 11% of CBS cases, 14% of AD cases, 11% of lvPPA cases and 9% of PCA cases. There were no hallucinations in any of 35 cases of nfv PPA or in 21 cases of PSP. Attentional and working memory measures differed between groups (all p less than0.02) with hallucinators making more frequent attentional and processing speed errors with evidence of structural changes centred on the prefrontal cortex, caudate and cerebellum (p less than 0.001). Attentional processes were also implicated in C9orf72 carriers with hallucinations as well as visual functions (p less than 0.05) while structural changes were focused on the thalamus (p less than 0.001). Patients with visual hallucinations in isolation showed a similar pattern with emphasis on cerebellar atrophy. A predictive model suggested that attention and working memory deficits were the best predictors of hallucination status (pless than 0.05) Conclusion: Attentional and working memory subsystems and related distributed brain structures are implicated in the generation of hallucinations in MND-FTD that dissociate across C9orf72, sporadic MND-FTD and for the visual subtype of hallucinations.

Professor Michele Hu

Day 1: ForeFront Scientific Meeting – Movement disorders plenary (Monday 11:15am)

Michele is a Consultant Neurologist at Oxford University Hospitals, and Professor of Clinical Neuroscience at the Nuffield Department of Clinical Neurosciences, University of Oxford. Her clinical work focuses on Parkinson's disease and related movement disorders. Her research within the Oxford Parkinson's Disease Centre (website:www.opdc.ox.ac.uk) looks at longitudinal cohort studies and biomarkers for early and prodromal Parkinson’s disease, with particular focus on REM sleep behaviour disorder (RBD) and how sleep affects neurodegeneration. Interests include the delivery of tractable, low cost, wearable technology that has a real impact on patient’s daily lives, and imaging the human brain from prodromal to established Parkinson’s.

Perhaps the primary health challenge of the 21st Century is achieving a cure for neurodegenerative disorders including Alzheimer’s and Parkinson’s disease. The numbers of people living with Parkinson’s globally are projected to double from 2015 to 2040, and we are already seeing effects of this worldwide expansion for which we are ill prepared. Since 1989 billions of dollars have been invested by the pharmaceutical industry in the search for a Parkinson’s cure, with 16 drug compounds all testing negative in completed large-scale trials. These studies focused on patients with an established diagnosis, based according to current criteria on the presence of clinical motor features. We need to take stock and consider the reasons for this failure, as it may be that efforts have been made too late in the neurodegenerative cascade. In the search for a cure or effective disease modification, focus has therefore increasingly shifted to studying earlier stages with calls for a new research framework encompassing clinical features, pathological findings, genetics and molecular mechanisms to redefine Parkinson’s. My talk focuses on iRBD, a prodromal form of both Parkinson’s and Dementia with Lewy Bodies, providing a much earlier disease phase for targeted intervention with higher densities of salvageable brain neurons, but without the confounding placebo/nocebo effects of symptomatic therapies. My vision is to help researchers improve stratified iRBD participant selection for clinical trials, and to provide an outcome measure that is sensitive to change, quick to administer and cost effective; allowing participants to be assessed in clinic and at home.

Dr Paula Loveland

Day 1: ForeFront Scientific Meeting – Movement disorders plenary (Monday 12pm)

Dr Paula Loveland is a Geriatrician at The Royal Melbourne Hospital and PhD candidate in the lab led by A/Profs Rosie Watson and Nawaf Yassi at the Walter and Eliza Hall Institute of Medical Research in Melbourne. Her PhD focuses on investigating longitudinal change in blood biomarkers in Lewy body dementia, which is supported by an NHMRC postgraduate research scholarship. Paula’s clinical appointments include the Cognitive Dementia and Memory Assessment Service (CDAMS) at The Royal Melbourne Hospital and she contributes to medical student education at the University of Melbourne.

Timely and accurate diagnosis of Lewy body dementia is challenging, and it remains an under-recognised and often misdiagnosed form of dementia. Therefore, biomarkers that provide objective evidence of pathological change early in the disease course are of considerable interest to patients and clinicians. Unfortunately, several of the currently recognised ‘supportive’ diagnostic biomarkers are not available in Australia or are only in highly resourced research settings.

Recent developments towards novel biomarkers for Lewy body dementia offer improved understanding of disease pathogenesis, identification of new therapeutic targets, and support for trials of disease-modifying therapies. Promising strategies include imaging and biofluid analysis, including peripheral blood. This talk will discuss current and emerging biomarkers for Lewy body dementia, and the challenges that must be addressed to translate candidate biomarkers into the clinic.

Associate Professor Patricia Lillo

Day 2: ForeFront Scientific Meeting – Frontotemporal Dementia plenary (Tuesday 9:20am)

Patricia is a Medical doctor and cognitive neurologist. She holds a Diploma in Neuropsychology and completed her PhD Program at University of New South Wales (Sydney, Australia) in 2012, under the supervision of Prof John Hodges and Prof Glenda Halliday. Since 2015, Dr. Lillo is an associated investigator of the Geroscience Center for Brain Health and Metabolism (GERO-FONDAP), Chile. Currently, she is appointed as associate professor of neurology and Head of the Neurology Department (south division), Faculty of Medicine, University of Chile. She has a long-standing interest in cognitive neurology, including clinical aspects of aging and neurodegenerative conditions such as frontotemporal dementia and amyotrophic lateral sclerosis

Frontotemporal dementia (FTD) is one of the most common causes of early-onset dementia, age under 65 years, however data regarding prevalence and incidence in Latin America and Caribbean (LAC) is scarce. FTD is a condition frequently underdiagnosed and is often confounded with psychiatric diseases. The diagnosis is based in the clinical features and complimentary studies such as neuropsychology testing and neuroimaging. Although the frequency of dementia is rapidly increasing in Latin America in the last years, currently there is a lack of standardized and validated instruments to evaluate these cases. Therefore, here we present a review of the different tests and batteries used in Latin America to evaluate patients with FTD, which have been reported in previous publications. Besides that, we highlight the need to propose a LAC consortium to address the challenges regarding diagnosis and management of this condition.

Dr Sharon Savage

Day 2: ForeFront Scientific Meeting – Frontotemporal Dementia plenary (Tuesday 9:55am)

Sharon is a registered Clinical Neuropsychologist and lecturer in the School of Psychological Sciences at the University of Newcastle. Over the last 10 years Sharon has led research regarding diagnosis and treatment of people with Primary Progressive Aphasia (PPA), which she commenced when doing her PhD studies with the FRONTIER group. She has created tools to differentiate forms of PPA and developed simple practices for people to complete at home to improve word retrieval. Since her PhD she has extended her intervention work to include eHealth approaches, and investigated language impairments in non-language lead dementia types. She is part of an international peer network focused on sharing best practice in PPA and is dedicated to improving public awareness regarding different types of dementia and around dementia risk reduction.

Language is a central function in our everyday lives and an area of cognition that is impacted in many neurodegenerative conditions. In frontotemporal dementia (FTD), language changes are prominent within the subtypes of semantic dementia (or semantic variant Primary Progressive Aphasia) and the non-fluent variant of Primary Progressive Aphasia. While some changes are also observed within the behavioural variant of FTD, these changes are not typically as severe and appear significantly influenced by executive dysfunction. Regardless of subtype, there are currently no pharmacological interventions to cure or slow the language changes, but a number of behavioural approaches have shown benefit. This talk will provide an overview of research from the last two decades regarding interventions to support language in people with FTD, including recommendations for clinical practice and future research. The talk will identify which therapies offer the best outcomes and discuss current knowledge regarding the maintenance and generalisation of language therapy gains. While approaches which specifically target language impairments may assist, discussion will also extend to include compensatory approaches designed to support activities of daily living and the provision of education and psychological support to propose a more integrative framework of treatment and care as best practice in FTD.

Professor Michael Hornberger

Day 2: ForeFront Scientific Meeting – Dementia plenary (Tuesday 11am)

Michael is the Professor of Applied Dementia Research at the Norwich Medical School, University of East Anglia, UK. His current research is particularly focused on spatial orientation and navigation deficits in dementia and how this has an impact on people's outdoor activities such as driving and walking safely. Michael did his PhD at University College London before working at Cambridge University. From Cambridge, he followed John to Sydney, where he was part of Frontier for nearly 6 years (2007-2013), before returning to Cambridge and then taking up his current position in Norwich in 2015.

In my talk I will give an overview of our Sea Hero Quest citizen science project. Sea Hero Quest has been to date the largest citizen science project to help dementia research, with over 4.3 million people worldwide contributing data to the project. Specifically, Sea Hero Quest was to establish the largest normative data set for spatial navigation/orientation to allow benchmarking people with presymptomatic Alzheimer’s disease against. Alzheimer’s disease pathophysiology affects brain regions involved in spatial navigation before episodic memory symptoms occur, however those spatial navigation symptoms are subtle. Therefore, a large normative data is required to allow a more personalised benchmarking of people at risk of Alzheimer’s disease. I will show how Sea Hero Quest has helped with this benchmarking and how future cognitive diagnostic approaches for presymptomatic Alzheimer’s disease are emerging. Finally, I will highlight how Sea Hero Quest also has real-life implications for people with dementia. By the end of the talk, I hope to have persuaded you that citizen science can be a very powerful approach for dementia research by generating large data, which in turn can provide more personalised diagnostic and management approaches for dementia.

Dr Claire O'Connor

Day 2: ForeFront Scientific Meeting – Dementia plenary (Tuesday 11:30am)

Claire is a Senior Research Fellow in the School of Psychology, UNSW, Senior Research Fellow (Honorary) with NeuRA, and Honorary Research Associate with HammondCare. She is also a registered occupational therapist (AHPRA). Claire is currently undertaking a Dementia Centre for Research Collaboration (DCRC) post-doctoral fellowship to understand how to bridge the implementation gap to maximise everyday functioning for people living with dementia. Combining her clinical training in occupational therapy and research skills, Claire is passionate about contributing to research that is meaningful to people impacted by dementia and the health workforce who support them.

The impacts of dementia are broad, leading to changes in behaviour and everyday functioning for the person with dementia, and wellbeing for both the person with dementia and their family carers. While no cure exists, non-pharmacological interventions to support people living with dementia are a vital approach recommended in clinical practice guidelines. There are many non-pharmacological interventions described in the research, however, this is not reflected in the real-world options available to people living with dementia in the community. For example, our survey of n=68 families living with younger onset dementia identified a need for better access to behaviour support services. In response to this need, we have been investigating the use of Positive Behaviour Support (PBS) for families living with dementia. In parallel with this work to support behaviour change in dementia, work is being done to bring interventions aimed at promoting wellbeing and maximising everyday functioning from research into the real-world. Specifically, two separate projects are currently using implementation science to evaluate Arts on Prescription at Home (AoP@Home) and reablement for people living with dementia in the community. These projects focusing on various non-pharmacological approaches will be described, with future directions discussed.

Professor Amy Brodtmann

Day 2: ForeFront Scientific Meeting – Dementia plenary (Tuesday 12pm)

Amy is a stroke and cognitive neurologist at the Royal Melbourne Hospital and Eastern Health and holds honorary appointments at Austin Health, Alfred Health and the Florey Institute. She leads the Cognitive Health Initiative at the Central Clinical School, Monash University, and holds professorial appointments at both the University of Melbourne and Monash University. She is the recipient of many awards and grants for her work in stroke and dementia and is the chief investigator on a Dementia Research Team Grant. Her research focuses the contributions of vascular risk factors to late-life cognition and improving the diagnosis of dementia syndromes. She is on the editorial boards of Neurology and International Journal for Stroke. She is a founding member of the Australian Frontotemporal Dementia Association, the inaugural Chair of the Australian chapter of the Organization of Human Brain Mapping, the inaugural President of the Australian Cognitive Neurology Association and is a member of the Wicking Strategic Review Panel. Amy serves on the Board of the Dementia Australia Research Foundation and in 2020 became one of DA’s Honorary Medical Advisors.

The prevailing dementia research orthodoxy of the latter half of the twentieth century was that neurodegeneration must arise from toxic brain proteins. There is now compelling evidence that vascular health is the greatest determinant of late-life cognition, including from community-based post-mortem studies (Nun study) finding that vascular brain burden determines cognitive profiles. Brain atrophy precedes and predicts cognitive decline in many neurodegenerative syndromes, but the trajectories of brain volume loss and cognitive impairment in stroke survivors are poorly understood. Brodtmann has introduced the concept of vascular neurodegeneration via her findings from the Cognition And Neocortical Volume After Stroke (CANVAS) study. She has demonstrated that stroke survivors have greater predicted brain age, greater signs of structural brain aging, extensive white and grey matter degeneration, and accelerated brain volume loss associated with cognitive changes. The use of imaging biomarkers in dementia intervention trials has several advantages over more traditionally used cognitive assessments, as atrophy rates are not as dependent on language or post-code. Describing the trajectories of brain volume loss in people with vascular contributions to their cognitive profile has increased our mechanistic understanding of neurodegeneration in high-risk populations and informed trial design to prevent post-stroke and vascular cognitive impairment.

Our Program

The scientific meeting was held over 2 days, and featured plenaries from international collaborators as well as highlights from researchers from our Forefront group, in the fields of Motor neuron disease, movement disorders, Frontotemporal and other dementias.

    Day 1, 24th October - Motor neuron disease/Movement disorder sessions. Invited guest speakers include Dr Angela Genge (Montreal), Professor Eneida Mioshi (Norwich), Emma Devenney (Sydney), Michele Hu (Oxford) and Paula Loveland (Melbourne). Day 2, 25th October - Frontotemporal Dementia and other Dementia sessions Invited guest speakers include Associate Professor Patricia Lillo (Santiago), Dr Sharon Savage (Newcastle), Michael Hornberger (Norwich), Claire O'Connor (Sydney) and Amy Brodtmann (Melbourne).