Predicting neurodegeneration from sleep related biofluid changes

Sleep-wake disturbances are common in neurodegenerative diseases and may occur years before the clinical diagnosis, potentially either representing an early stage of the disease itself or acting as a pathophysiological driver. Therefore, discovering biomarkers that identify individuals with sleep-wake disturbances who are at risk of developing neurodegenerative diseases will allow early diagnosis and intervention. Given the association between sleep and neurodegeneration, the most frequently analyzed fluid biomarkers in people with sleep-wake disturbances to date include those directly associated with neurodegeneration itself, such as neurofilament light chain, phosphorylated tau, amyloid-beta and alpha-synuclein. Abnormalities in these biomarkers in patients with sleep-wake disturbances are considered as evidence of an underlying neurodegenerative process. Levels of hormonal sleep-related biomarkers such as melatonin, cortisol and orexin are often abnormal in patients with clinical neurodegenerative diseases, but their relationships with the more standard neurodegenerative biomarkers remain unclear. Similarly, it is unclear whether other chronobiological/circadian biomarkers, such as disrupted clock gene expression, are causal factors or a consequence of neurodegeneration. Current data would suggest that a combination of fluid biomarkers may identify sleep-wake disturbances that are most predictive for the risk of developing neurodegenerative disease with more optimal sensitivity and specificity

Tackling dementia together via the Australian dementia network (ADNeT): A summary of initiatives, progress and plans

In 2018, the Australian Dementia Network (ADNeT) was established to bring together Australia\u27s leading dementia researchers, people with living experience and clinicians to transform research and clinical care in the field. To address dementia diagnosis, treatment, and care, ADNeT has established three core initiatives: the Clinical Quality Registry (CQR), Memory Clinics, and Screening for Trials. Collectively, the initiatives have developed an integrated clinical and research community, driving practice excellence in this field, leading to novel innovations in diagnostics, clinical care, professional development, quality and harmonization of healthcare, clinical trials, and translation of research into practice. Australia now has a national Registry for Mild Cognitive Impairment and dementia with 55 participating clinical sites, an extensive map of memory clinic services, national Memory and Cognition Clinic Guidelines and specialized screening for trials sites in five states. This paper provides an overview of ADNeT\u27s achievements to date and future directions. With the increase in dementia cases expected over coming decades, and with recent advances in plasma biomarkers and amyloid lowering therapies, the nationally coordinated initiatives and partnerships ADNeT has established are critical for increased national prevention efforts, co-ordinated implementation of emerging treatments for Alzheimer\u27s disease, innovation of early and accurate diagnosis, driving continuous improvements in clinical care and patient outcome and access to post-diagnostic support and clinical trials. For a heterogenous disorder such as dementia, which is now the second leading cause of death in Australia following cardiovascular disease, the case for adequate investment into research and development has grown even more compelling

Sleep spindle architecture associated with distinct clinical phenotypes in older adults at risk for dementia

Sleep spindles are a hallmark of non-REM sleep and play a fundamental role in memory consolidation. Alterations in these spindles are emerging as sensitive biomarkers for neurodegenerative diseases of ageing. Understanding the clinical presentations associated with spindle alterations may help to elucidate the functional role of these distinct electroencephalographic oscillations and the pathophysiology of sleep and neurodegenerative disorders. Here, we use a data-driven approach to examine the sleep, memory and default mode network connectivity phenotypes associated with sleep spindle architecture in older adults (mean age = 66 years). Participants were recruited from a specialist clinic for early diagnosis and intervention for cognitive decline, with a proportion showing mild cognitive deficits on neuropsychological testing. In a sample of 88 people who underwent memory assessment, overnight polysomnography and resting-state fMRI, a k-means cluster analysis was applied to spindle measures of interest: fast spindle density, spindle duration and spindle amplitude. This resulted in three clusters, characterised by preserved spindle architecture with higher fast spindle density and longer spindle duration (Cluster 1), and alterations in spindle architecture (Clusters 2 and 3). These clusters were further characterised by reduced memory (Clusters 2 and 3) and nocturnal hypoxemia, associated with sleep apnea (Cluster 3). Resting-state fMRI analysis confirmed that default mode connectivity was related to spindle architecture, although directionality of this relationship differed across the cluster groups. Together, these results confirm a diversity in spindle architecture in older adults, associated with clinically meaningful phenotypes, including memory function and sleep apnea. They suggest that resting-state default mode connectivity during the awake state can be associated with sleep spindle architecture; however, this is highly dependent on clinical phenotype. Establishing relationships between clinical and neuroimaging features and sleep spindle alterations will advance our understanding of the bidirectional relationships between sleep changes and neurodegenerative diseases of ageing

Characterising Australian memory clinics: current practice and service needs informing national service guidelines

Abstract Background Memory clinics (MCs) play a key role in accurate and timely diagnoses and treatment of dementia and mild cognitive impairment. However, within Australia, there are little data available on current practices in MCs, which hinder international comparisons for best practice, harmonisation efforts and national coordination. Here, we aimed to characterise current service profiles of Australian MCs. Methods The ‘Australian Dementia Network Survey of Expert Opinion on Best Practice and the Current Clinical Landscape’ was conducted between August-September 2020 as part of a larger-scale Delphi process deployed to develop national MC guidelines. In this study, we report on the subset of questions pertaining to current practice including wait-times and post-diagnostic care. Results Responses were received from 100 health professionals representing 60 separate clinics (45 public, 11 private, and 4 university/research clinics). The majority of participants were from clinics in metropolitan areas (79%) and in general were from high socioeconomic areas. While wait-times varied, only 28.3% of clinics were able to offer an appointment within 1-2 weeks for urgent referrals, with significantly more private clinics (58.3%) compared to public clinics (19.5%) being able to do so. Wait-times were less than 8 weeks for 34.5% of non-urgent referrals. Only 20.0 and 30.9% of clinics provided cognitive interventions or post-diagnostic support respectively, with 7.3% offering home-based reablement programs, and only 12.7% offering access to group-based education. Metropolitan clinics utilised neuropsychological assessments for a broader range of cases and were more likely to offer clinical trials and access to research opportunities. Conclusions In comparison to similar countries with comprehensive government-funded public healthcare systems (i.e., United Kingdom, Ireland and Canada), wait-times for Australian MCs are long, and post-diagnostic support or evidence-based strategies targeting cognition are not common practice. The timely and important results of this study highlight a need for Australian MCs to adopt a more holistic service of multidisciplinary assessment and post-diagnostic support, as well as the need for the number of Australian MCs to be increased to match the rising number of dementia cases