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Summary: Isolated rapid eye movement (REM) sleep behaviour disorder (iRBD) is a sleep disorder that is characterised by dream enactment episodes during REM sleep. It is the strongest known predictor of α‐synuclein‐related neurodegenerative disease (αNDD), such that >80% of people with iRBD will eventually develop Parkinson's disease, dementia with Lewy bodies, or multiple system atrophy in later life. More research is needed to understand the trajectory of phenoconversion to each αNDD. Only five 'gold standard' prevalence studies of iRBD in older adults have been undertaken previously, with estimates ranging from 0.74% to 2.01%. The diagnostic recommendations for video‐polysomnography (vPSG) to confirm iRBD makes prevalence studies challenging, as vPSG is often unavailable to large cohorts. In Australia, there have been no iRBD prevalence studies, and little is known about the cognitive and motor profiles of Australian people with iRBD. The Island Study Linking Ageing and Neurodegenerative Disease (ISLAND) Sleep Study will investigate the prevalence of iRBD in Tasmania, an island state of Australia, using validated questionnaires and home‐based vPSG. It will also explore several cognitive, motor, olfactory, autonomic, visual, tactile, and sleep profiles in people with iRBD to better understand which characteristics influence the progression of iRBD to αNDD. This paper details the ISLAND Sleep Study protocol and presents preliminary baseline results. [ABSTRACT FROM AUTHOR]

Issue Addressed: Gender and bilingualism are reported to influence the risk of dementia. This study examined the prevalence of self‐reported modifiable dementia risk factors by gender in two samples: one that speaks at least one language other than English (LoE) and one that speaks only English. Methods: A descriptive cross‐sectional study was conducted on a sample of Australian residents aged 50 years or over (n = 4339). Participant characteristics and dementia risk behaviours were inspected using descriptive statistics in data collected via online surveys between October 2020 and November 2021. Results: In both samples, men had a higher rate than women of being overweight and were classified more frequently as being at risk of dementia due to alcohol consumption, lower cognitive activity, and non‐adherence to the Mediterranean‐style diet. Men reported better management of their cardiometabolic health than women across both groups. Non‐significant trends showed men were more often smokers but more physically active than women in the LoE group, and less often smokers but less physically active than women in the English‐only group. Conclusion: This study found men and women reported similar patterns of dementia risk behaviours regardless of LoE or English‐only status. So What?: Gender differences in risk behaviours prevail regardless of language‐speaking status. The results can be used to guide future research aiming to understand and reduce modifiable dementia risk in Australia and beyond. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Low‐cost simple tests for preclinical Alzheimer's disease are a research priority. We evaluated whether remote unsupervised webcam recordings of finger‐tapping were associated with cognitive performance in older adults. METHODS: A total of 404 cognitively‐asymptomatic participants (64.6 [6.77] years; 70.8% female) completed 10‐second finger‐tapping tests (Tasmanian [TAS] Test) and cognitive tests (Cambridge Neuropsychological Test Automated Battery [CANTAB]) online at home. Regression models including hand movement features were compared with null models (comprising age, sex, and education level); change in Akaike Information Criterion greater than 2 (ΔAIC > 2) denoted statistical difference. RESULTS: Hand movement features improved prediction of episodic memory, executive function, and working memory scores (ΔAIC > 2). Dominant hand features outperformed nondominant hand features for episodic memory (ΔAIC = 2.5), executive function (ΔAIC = 4.8), and working memory (ΔAIC = 2.2). DISCUSSION: This brief webcam test improved prediction of cognitive performance compared to age, sex, and education. Finger‐tapping holds potential as a remote language‐agnostic screening tool to stratify community cohorts at risk for cognitive decline. [ABSTRACT FROM AUTHOR]

Objectives: Unequal access to cognitive assessments is a major barrier to timely diagnosis, especially for those living in rural or remote areas. 'One‐stop' cognitive clinic models are a proposed solution, but few such clinics exist. We evaluate the implementation of a new one‐stop State‐wide clinic model in Tasmania, Australia, where 27% of people live in rural/remote areas. Methods: A novel single‐visit protocol has been developed, comprising interdisciplinary medical and cognitive assessments, research participation, consensus diagnosis and management plan. A cross‐sectional evaluation was undertaken using the RE‐AIM (reach, effectiveness, adoption, implementation, maintenance) framework and results benchmarked against the national Australian Dementia Network Registry. Results: Over the first 52 consecutive weekly clinics: Reach: 130 adults were assessed (mean age [SD] 70.12 years [10.31]; 59.2% female) with 40 (36.8%) from rural/remote areas. Effectiveness: 98.5% (128/130) received a same‐day diagnosis: 30.1% (n = 40) Subjective Cognitive Decline, 35.4% (46) Mild Cognitive Impairment, 33.1% (43) dementia and one case inconclusive. Adoption: 22.9% (156) of General Practitioners referred patients. Implementation: Nearly all 'ideal' diagnostic clinical practices were met and >90% of surveyed patients reported 'good/very good' clinic experience. The wait from referral to diagnosis was 2 months shorter than other national Registry clinics (78 vs. 133 days). Conclusions: This 'one‐stop' model provides an interdisciplinary consensus cognitive diagnosis quickly and is well accepted; this may reduce health inequities especially for people living in rural/remote areas. This cognitive clinic model may be of relevance to other centres worldwide and also provides a rich data source for research studies. Key points: Access to cognitive assessments is unequal, especially for people living in rural areas.A 'one‐stop' cognitive clinic resulted in 98.5% same‐day diagnosis, 2 months earlier than the national averageOne‐third of people assessed were from rural/remote areas.This model may inform service design for centres worldwide and provides rich data for research. [ABSTRACT FROM AUTHOR]

Environmentally enriched housing conditions can increase performance on cognitive tasks in APP/PS1 mice; however, the potential effects of environmental enrichment (EE) on disease modification in terms of pathological change are inconclusive. We hypothesized that previous contrasting findings may be attributable to regional differences in susceptibility to amyloid beta (Aβ) plaque deposition in cortical regions that are functionally associated with EE. We characterized fibrillar plaque deposition in 6, 12, and 18–22 months old APP/PS1 mice in the prefrontal (PFC), somatosensory (SS2), and primary motor cortex (M1). We found a significant increase in plaque load between 6 and 12 months in all regions. In animals over 12 months, only the PFC region continued to significantly accumulate plaques. Additionally, 12 months old animals subjected to 6 months of EE showed improved spatial navigation and had significantly fewer plaques in M1 and SS2, but not in the PFC. These findings suggest that the PFC region is selectively susceptible to Aβ deposition and less responsive to the attenuating effects of EE. In contrast, M1 and SS2 regions plateau with respect to Aβ deposition by 12 months of age and are susceptible to amyloid pathology modification by midlife EE. [ABSTRACT FROM AUTHOR]

Introduction: Declining cognition in later life is associated with loss of independence and quality of life. This decline in cognition may potentially be reduced or reversed through engaging in cognitively stimulating activities. This study examined the potential for university attendance in later life to enhance cognitive function in older adults. Methods: Cognitively unimpaired adults (n = 485, 69% female, median age 60 years) were given the opportunity to undertake free university study. Repeated neurocognitive assessment was performed over 7 years. Results: Participants in the university education group (n = 383) improved z = .02 SD (.01, .03) per year of the study compared to controls (P = .001; averaged across a battery of cognitive tests). The largest improvements were observed on tests of language and verbal learning, memory, and episodic memory. Discussion: Later-life university study was associated with improved cognitive trajectories. Later-life education may preserve cognitive function, specifically for functions associated with communication, social interaction, and maintaining independence. [ABSTRACT FROM AUTHOR]

Introduction Containment measures implemented to minimize the spread of coronavirus disease 2019 (COVID-19) are reported to be negatively affecting mental health, diet, and alcohol consumption. These factors, as well as poor cardiometabolic health and insufficient physical and cognitive activity, are known to increase the risk of developing dementia. COVID-19 “lockdown” measures may have exacerbated these dementia risk factors among people in mid-to-later life. Methods We compared longitudinal data from before (October 2019) and during (April-June 2020) the first COVID-19 lockdown period in Tasmania, Australia. Participants (n = 1671) were 50+ years of age and engaged in a public health program targeting dementia risk reduction, with one-third participating in the Preventing Dementia Massive Open Online Course (PD-MOOC). Regression models were used to assess changes in smoking, alcohol use, body mass index (BMI), diet, physical exercise, cognitive and social activity, anxiety and depression, and management of cholesterol, diabetes, and blood pressure. Where significant changes were noted, the moderating influence of being in current employment, living with others, and completing the PD-MOOC was tested. Results Although friend networks contracted marginally during lockdown, no detrimental effects on modifiable dementia risk factors were noted. Anxiety levels and alcohol consumption decreased, there was no change in depression scores, and small but significant improvements were observed in cognitive and physical activity, smoking, diet, and BMI. Stronger improvements in cognitive activity were observed among people who were cohabiting (not living alone) and both cognitive activity and adherence to the MIND diet (Mediterranean-DASH diet Intervention for Neurological Delay) improved more for people who participated in the PD-MOOC. Discussion Longitudinal data did not show widespread negative effects of COVID-19 lockdown on modifiable dementia risk factors in this sample. The results counter the dominant narratives of universal pandemic-related distress and suggest that engaging at-risk populations in proactive health promotion and education campaigns during lockdown events could be a protective public health strategy. [ABSTRACT FROM AUTHOR]

Axon degeneration and axonal loss is a feature of neurodegenerative disease and injury and occurs via programmed pathways that are distinct from cell death pathways. While the pathways of axonal loss following axon severing are well described, less is known about axonal loss following other neurodegenerative insults. Here we use primary mouse cortical neuron cultures grown in compartmentalized chambers to investigate the role of calcium in the degeneration of axons that occurs following a somal insult by the excitotoxin kainic acid. Calcium influx has been implicated in both excitotoxicity and axon degeneration mechanisms, however the link between a somal insult and axonal calcium increase is unclear. Live imaging of axons demonstrated that pharmacologically preventing intracellular calcium increases through the endoplasmic reticulum or mitochondria significantly (p < 0.05) reduced axon degeneration. Live calcium‐imaging with the Ca2+ indicator Fluo‐4 demonstrated that kainic acid exposure to the soma resulted in a rapid, and transient, increase in calcium in the axon, which occured even at low kainic acid concentrations that do not cause axon degeneration within 24 h. However, this calcium transient was followed by a gradual increase in axonal calcium, which was associated with axonal loss. Furthermore, treatment with a range of doses of the microtubule stabilizing drug taxol, which protects against axon fragmentation in this model, prevented this gradual calcium increase, suggesting that the intra‐axonal calcium changes are downstream of microtubule associated events. Biochemical analysis of taxol treated neurons demonstrated a shift in microtubule post‐translational modifications, with a significant (p < 0.05) increase in acetylated tubulin and a significant (p < 0.05) decrease in tyrosinated tubulin, suggestive of a more stable microtubule pool. Together our results suggest that axonal degeneration following excitotoxicity is dependent on an increase in axonal calcium, which is downstream of a microtubule‐dependent event. [ABSTRACT FROM AUTHOR]

It is intuitive to suggest that reverse osmosis (RO), which is used for the removal of dissolved solutes (salts), can also be used to achieve the removal of virus, Giardia, and Cryptosporidium. The challenge is that the use of conductivity for water quality monitoring of the RO process lacks sufficient sensitivity, and a direct integrity test that translates water quality performance to regulatory compliance for pathogen removal has not been established or accepted as a practice. The basis of this article is as follows: It is proposed for a production‐level (e.g., 1 mgd or larger) RO system that the sensitivity can be increased by using the results of a conductivity profile, which is an existing diagnostic tool used to identify integrity defects within an RO unit. The proposed direct integrity test methodology uses the results of a conductivity profile to (1) determine that RO unit integrity exists within statistical limits, (2) isolate and differentiate between the conductivity associated with diffusion and with a defect, and (3) calculate the log removal value (LRV) that would be associated with an RO membrane defect. The resulting calculation approach significantly increases the sensitivity of the LRV calculation and is supported by full‐scale testing data using MS2 coliphage as the challenge organism. [ABSTRACT FROM AUTHOR]

Early-life cognitive enrichment may reduce the risk of experiencing cognitive deterioration and dementia in later-life. However, an intervention to prevent or delay dementia is likely to be taken up in mid to later-life. Hence, we investigated the effects of environmental enrichment in wildtype mice and in a mouse model of Aβ neuropathology (APPSWE/PS1dE9) from 6 months of age. After 6 months of housing in standard laboratory cages, APPSWE/PS1dE9 ( n = 27) and healthy wildtype ( n = 21) mice were randomly assigned to either enriched or standard housing. At 12 months of age, wildtype mice showed altered synaptic protein levels and relatively superior cognitive performance afforded by environmental enrichment. Environmental enrichment was not associated with alterations to Aβ plaque pathology in the neocortex or hippocampus of APPSWE/PS1dE9 mice. However, a significant increase in synaptophysin immunolabeled puncta in the hippocampal subregion, CA1, in APPSWE/PS1dE9 mice was detected, with no significant synaptic density changes observed in CA3, or the Fr2 region of the prefrontal cortex. Moreover, a significant increase in hippocampal BDNF was detected in APPSWE/PS1dE9 mice exposed to EE, however, no changes were detected in neocortex or between Wt animals. These results demonstrate that mid to later-life cognitive enrichment has the potential to promote synaptic and cognitive health in ageing, and to enhance compensatory capacity for synaptic connectivity in pathological ageing associated with Aβ deposition. [ABSTRACT FROM AUTHOR]

Aim At a time of increasing dementia prevalence, this research explores the cost of treatment and length of stay associated with the syndrome in a large regional hospital. Methods Database analysis of 4332 recorded admissions to a large regional Australian hospital among adults aged 55 years and older during winter 2013 and 2014. Results Costs of hospital treatment and length of stay for people with a diagnosis of dementia who presented to a regional hospital were significantly greater than people with no diagnosis over two years. Costs were unrelated to age or likelihood of death in hospital. Prevalence of dementia admissions was low, but treated conditions indicate that the syndrome may be an underlying, and potentially unrecognised, factor in many admissions. Conclusion Dementia imposes a large cost and resource burden on a regional hospital. Improved identification of the syndrome on admission and implementation of best-evidence management of dementia in regional hospitals may improve care efficiency. [ABSTRACT FROM AUTHOR]

The association between level of educational attainment and cognitive performance is well studied. People with higher education perform better across a broad range of cognitive tasks. However, there is uncertainty as to whether education moderates the trajectory of age-related cognitive decline. This review paper addresses the potential link between education and age-related cognitive decline by evaluating relevant research published since 2000. Studies reporting data on education and its association with the rate of cognitive decline across various cognitive domains were reviewed. A total of 10 studies were identified with a mean follow-up period of 7.6 years; each contained a population-based, non-demented sample. In the majority of studies, results showed that education did not moderate age-associated cognitive decline. The few studies that did find an association between education and decline in specific cognitive functions should be interpreted with caution because of methodological issues. The literature reveals little consistent evidence that normal age-related cognitive decline is moderated by education attainment. This supports a passive theory of cognitive reserve: people with a higher level of education will continue to perform at a higher level of cognitive functioning than their lower educated peers, which may delay the onset of impairment in the future. [ABSTRACT FROM AUTHOR]

The neurofilament light (NFL) subunit is considered as an obligate subunit polymer for neuronal intermediate filaments comprising the neurofilament (NF) triplet proteins. We examined cytoskeletal protein levels in the cerebral cortex of NFL knockout (KO) mice at postnatal day 4 (P4), 5 months, and 12 months of age compared with age-matched wild-type (WT) mice of a similar genetic background (C57BL/6). The absence of NFL protein resulted in a significant reduction of phosphorylated and dephosphorylated NFs (NF-P, NF-DP), the medium NF subunit (NFM), and the intermediate filament α-internexin (INT) at P4. At 5 months, NF-DP, NFM, and INT remained significantly lower in knockouts. At 12 months, NF-P was again significantly decreased, and INT significantly increased, in KOs compared with wild type. In addition, protein levels of class III neuron-specific β-tubulin and microtubule-associated protein 2 were significantly increased in NFL KO mice at P4, 5 months, and 12 months, whereas β-actin levels were significantly decreased at P4. Immunocytochemical studies demonstrated that NF-DP accumulated abnormally in the perikarya of cortical neurons by 5 months of age in NFL KO mice. Neurons that lacked NF triplet proteins, such as calretinin-immunolabeled nonpyramidal cells, showed no alterations in density or cytoarchitectural distribution in NFL KO mice at 5 months relative to WT mice, although calretinin protein levels were decreased significantly after 12 months in NFL KO mice. These findings suggest that a lack of NFL protein alters the expression of cytoskeletal proteins and disrupts other NF subunits, causing intracellular aggregation but not gross structural changes in cortical neurons or cytoarchitecture. The data also indicate that changes in expression of other cytoskeletal proteins may compensate for decreased NFs. J. Comp. Neurol. 521:1817-1827, 2013. © 2012 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Axotomized neurons have the innate ability to undergo regenerative sprouting but this is often impeded by the inhibitory central nervous system environment. To gain mechanistic insights into the key molecular determinates that specifically underlie neuronal regeneration at a transcriptomic level, we have undertaken a DNA microarray study on mature cortical neuronal clusters maintained in vitro at 8, 15, 24 and 48 hrs following complete axonal severance. A total of 305 genes, each with a minimum fold change of ±1.5 for at least one out of the four time points and which achieved statistical significance (one-way ANOVA, P < 0.05), were identified by DAVID and classified into 14 different functional clusters according to Gene Ontology. From our data, we conclude that post-injury regenerative sprouting is an intricate process that requires two distinct pathways. Firstly, it involves restructuring of the neurite cytoskeleton, determined by compound actin and microtubule dynamics, protein trafficking and concomitant modulation of both guidance cues and neurotrophic factors. Secondly, it elicits a cell survival response whereby genes are regulated to protect against oxidative stress, inflammation and cellular ion imbalance. Our data reveal that neurons have the capability to fight insults by elevating biological antioxidants, regulating secondary messengers, suppressing apoptotic genes, controlling ion-associated processes and by expressing cell cycle proteins that, in the context of neuronal injury, could potentially have functions outside their normal role in cell division. Overall, vigilant control of cell survival responses against pernicious secondary processes is vital to avoid cell death and ensure successful neurite regeneration. [ABSTRACT FROM AUTHOR]

J. Neurochem. (2010) 112, 1147–1155. Acute axonal shear and stretch in the brain induces an evolving form of axonopathy and is a major cause of ongoing motor, cognitive and emotional dysfunction. We have utilized an in vitro model of mild axon bundle stretch injury, in cultured primary cortical neurons, to determine potential early critical cellular alterations leading to secondary axonal degeneration. We determined that transient axonal stretch injury induced an initial acute increase in intracellular calcium, principally derived from intracellular stores, which was followed by a delayed increase in calcium over 48 h post-injury (PI). This progressive and persistent increase in intracellular calcium was also associated with increased frequency of spontaneous calcium fluxes as well as cytoskeletal abnormalities. Additionally, at 48 h post-injury, stretch-injured axon bundles demonstrated filopodia-like sprout formation that preceded secondary axotomy and degeneration. Pharmacological inhibition of the calcium-activated phosphatase, calcineurin, resulted in reduced secondary axotomy ( p < 0.05) and increased filopodial sprout length. In summary, these results demonstrate that stretch injury of axons induced an initial substantial release of calcium from intracellular stores with elevated intracellular calcium persisting over 2 days. These long-lasting calcium alterations may provide new insight into the earliest neuronal abnormalities that follow traumatic brain injury as well as the key cellular changes that lead to the development of diffuse axonal injury and secondary degeneration. [ABSTRACT FROM AUTHOR]

Objective: To reveal views about dementia diagnosis derived from a larger study of information needs of carers of people with dementia in Tasmania, Australia. Methods: Over 100 participants, including family carers, health professionals and dementia service personnel, met as discrete focus groups. Data pertinent to dementia diagnosis were segregated and subjected to across-group comparative analysis. Results: The term dementia held connotations of stigma and futility, despite stated benefits of having a diagnosis. General practitioners were regarded as pivotal but having inadequate diagnostic and treatment options. While most health professionals advocated a longitudinal diagnostic process, this created considerable stress for family carers who sought a speedy process. Without a diagnosis, some dementia-specific services were undeliverable. Conclusion: Dementia diagnosis is steeped in deep-rooted difficulties and stressful implications, compounded by carers’ differing needs and interests. Better understanding between care providers of their conflicting and consistent views could contribute to better dementia care. [ABSTRACT FROM AUTHOR]

Regeneration of the adult central nervous system may require recapitulation of developmental events and therefore involve the re-expression of developmentally significant proteins. We have investigated whether the L1 cell adhesion molecule, and its binding partner, the ezrin-radixin-moesin (ERM) proteins are involved in the neuronal regenerative response to injury. Hippocampal and cortical neurons were culturedin vitroon either an L1 substrate or poly-L-lysine, and ERM and other neuronal proteins were localized immunocytochemically both developmentally and following neurite transection of neurons maintained in long-term culture. Activated ERM was localized to growth cones up to 7 daysin vitrobut relatively mature cultures (21 daysin vitro) were devoid of active ERM proteins. However, ERM proteins were localized to the growth cones of sprouting neuronal processes that formed several hours after neurite transection. In addition, the L1 substrate, relative to poly-L-lysine, resulted in significantly longer regenerative neurites, as well as larger growth cones with more filopodia. Furthermore, neurons derived from the cortex formed significantly longer post-injury neurite sprouts at 6 h post-injury than hippocampal derived neurons grown on both substrates. We have demonstrated that L1 and the ERM proteins are involved in the neuronal response to injury, and that neurons derived from the hippocampus and cortex may have different post-injury regenerative neurite sprouting abilities. [ABSTRACT FROM AUTHOR]

Oligodendroglial cytoplasmic inclusions composed of α-synuclein filamentous aggregates are the pathological hallmark of multiple system atrophy (MSA). We found that cortical tissue from MSA cases contains increased detergent-resistant high-molecular-weight α-synuclein species. To analyse these species, we immunopurified α-synuclein aggregates from pathological samples and examined their ultrastructures using scanning electron and atomic force microscopies. Purified aggregates consisted of bundles of filaments. After treatment with 1% sarcosine or 2% 3-[(3-cholamidopropyl) dimethyl-ammonio]-1-propanesulfonate (CHAPS) detergents, we observed frequent 30–50 nm annular particles, probably released from pathological aggregates due to the dissociation of filaments by the detergents. Antibody recognition imaging using a specific anti-α-synuclein antibody confirmed that the annular structures were positive for α-synuclein. In contrast to pathological α-synuclein, detergent treatment of recombinant α-synuclein yielded only smaller, 10–18 nm spherical particles. Our results demonstrate that detergent treatment of pathological MSA α-synuclein aggregates, but not recombinant α-synuclein, yields discrete α-synuclein-positive species with annular morphologies. The ability of the pathological α-synuclein to form annular aggregates may be an important factor contributing to the toxicity of the protein in disease that may have implications in designing therapeutic strategies aimed at detoxifying α-synuclein aggregates. [ABSTRACT FROM AUTHOR]

Recent data suggests that metallothioneins (MTs) are major neuroprotective proteins within the CNS. In this regard, we have recently demonstrated that MT-IIA (the major human MT-I/-II isoform) promotes neural recovery following focal cortical brain injury. To further investigate the role of MTs in cortical brain injury, MT-I/-II expression was examined in several different experimental models of cortical neuron injury. While MT-I/-II immunoreactivity was not detectable in the uninjured rat neocortex, by 4 days, following a focal cortical brain injury, MT-I/-II was found in astrocytes aligned along the injury site. At latter time points, astrocytes, at a distance up to several hundred microns from the original injury tract, were MT-I/-II immunoreactive. Induced MT-I/-II was found both within the cell body and processes. Using a cortical neuron/astrocyte co-culture model, we observed a similar MT-I/-II response following in vitro injury. Intriguingly, scratch wound injury in pure astrocyte cultures resulted in no change in MT-I/-II expression. This suggests that MT induction was specifically elicited by neuronal injury. Based upon recent reports indicating that MT-I/-II are major neuroprotective proteins within the brain, our results provide further evidence that MT-I/-II plays an important role in the cellular response to neuronal injury. [ABSTRACT FROM AUTHOR]

No abstract. [ABSTRACT FROM AUTHOR]