Development of a smartphone screening test for preclinical Alzheimer's disease and validation across the dementia continuum.

BACKGROUND: Dementia prevalence is predicted to triple to 152 million globally by 2050. Alzheimer's disease (AD) constitutes 70% of cases. There is an urgent need to identify individuals with preclinical AD, a 10-20-year period of progressive brain pathology without noticeable cognitive symptoms, for targeted risk reduction. Current tests of AD pathology are either too invasive, specialised or expensive for population-level assessments. Cognitive tests are normal in preclinical AD. Emerging evidence demonstrates that movement analysis is sensitive to AD across the disease continuum, including preclinical AD. Our new smartphone test, TapTalk, combines analysis of hand and speech-like movements to detect AD risk. This study aims to [1] determine which combinations of hand-speech movement data most accurately predict preclinical AD [2], determine usability, reliability, and validity of TapTalk in cognitively asymptomatic older adults and [3], prospectively validate TapTalk in older adults who have cognitive symptoms against cognitive tests and clinical diagnoses of Mild Cognitive Impairment and AD dementia. METHODS: Aim 1 will be addressed in a cross-sectional study of at least 500 cognitively asymptomatic older adults who will complete computerised tests comprising measures of hand motor control (finger tapping) and oro-motor control (syllabic diadochokinesis). So far, 1382 adults, mean (SD) age 66.20 (7.65) years, range 50-92 (72.07% female) have been recruited. Motor measures will be compared to a blood-based AD biomarker, phosphorylated tau 181 to develop an algorithm that classifies preclinical AD risk. Aim 2 comprises three sub-studies in cognitively asymptomatic adults: (i) a cross-sectional study of 30-40 adults to determine the validity of data collection from different types of smartphones, (ii) a prospective cohort study of 50-100 adults ≥ 50 years old to determine usability and test-retest reliability, and (iii) a prospective cohort study of ~1,000 adults ≥ 50 years old to validate against cognitive measures. Aim 3 will be addressed in a cross-sectional study of ~200 participants with cognitive symptoms to validate TapTalk against Montreal Cognitive Assessment and interdisciplinary consensus diagnosis. DISCUSSION: This study will establish the precision of TapTalk to identify preclinical AD and estimate risk of cognitive decline. If accurate, this innovative smartphone app will enable low-cost, accessible screening of individuals for AD risk. This will have wide applications in public health initiatives and clinical trials. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT06114914, 29 October 2023. Retrospectively registered.

Estimating presymptomatic episodic memory impairment using simple hand movement tests: A cross-sectional study of a large sample of older adults.

INTRODUCTION: Finding low-cost methods to detect early-stage Alzheimer's disease (AD) is a research priority for neuroprotective drug development. Presymptomatic Alzheimer's is associated with gait impairment but hand motor tests, which are more accessible, have hardly been investigated. This study evaluated how home-based Tasmanian (TAS) Test keyboard tapping tests predict episodic memory performance. METHODS: 1169 community participants (65.8 ± 7.4 years old; 73% female) without cognitive symptoms completed online single-key and alternate-key tapping tests and episodic memory, working memory, and executive function cognitive tests. RESULTS: All single-key (R2 adj  = 8.8%, ΔAIC = 5.2) and alternate-key (R2 adj  = 9.1%, ΔAIC = 8.8) motor features predicted episodic memory performance relative to demographic and mood confounders only (R2 adj  = 8.1%). No tapping features improved estimation of working memory. DISCUSSION: Brief self-administered online hand movement tests predict asymptomatic episodic memory impairment. This provides a potential low-cost home-based method for stratification of enriched cohorts. HIGHLIGHTS: We devised two brief online keyboard tapping tests to assess hand motor function. 1169 cognitively asymptomatic adults completed motor- and cognitive tests online. Impaired hand motor function predicted reduced episodic memory performance. This brief self-administered test may aid stratification of community cohorts.

Temporal changes in the microglial proteome of male and female mice after a diffuse brain injury using label-free quantitative proteomics.

Traumatic brain injury (TBI) triggers neuroinflammatory cascades mediated by microglia, which promotes tissue repair in the short-term. These cascades may exacerbate TBI-induced tissue damage and symptoms in the months to years post-injury. However, the progression of the microglial function across time post-injury and whether this differs between biological sexes is not well understood. In this study, we examined the microglial proteome at 3-, 7-, or 28-days after a midline fluid percussion injury (mFPI) in male and female mice using label-free quantitative proteomics. Data are available via ProteomeXchange with identifier PXD033628. We identified a reduction in microglial proteins involved with clearance of neuronal debris via phagocytosis at 3- and 7-days post-injury. At 28 days post-injury, pro-inflammatory proteins were decreased and anti-inflammatory proteins were increased in microglia. These results indicate a reduction in microglial clearance of neuronal debris in the days post-injury with a shift to anti-inflammatory function by 28 days following TBI. The changes in the microglial proteome that occurred across time post-injury did not differ between biological sexes. However, we did identify an increase in microglial proteins related to pro-inflammation and phagocytosis as well as insulin and estrogen signaling in males compared with female mice that occurred with or without a brain injury. Although the microglial response was similar between males and females up to 28 days following TBI, biological sex differences in the microglial proteome, regardless of TBI, has implications for the efficacy of treatment strategies targeting the microglial response post-injury.

Isolated rapid eye movement sleep behaviour disorder (iRBD) in the Island Study Linking Ageing and Neurodegenerative Disease (ISLAND) Sleep Study: protocol and baseline characteristics.

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.

An online, public health framework supporting behaviour change to reduce dementia risk: interim results from the ISLAND study linking ageing and neurodegenerative disease.

BACKGROUND: Unmanaged cardiometabolic health, low physical and cognitive activity, poor diet, obesity, smoking and excessive alcohol consumption are modifiable health risk factors for dementia and public health approaches to dementia prevention have been called for. The Island Study Linking Ageing and Neurodegenerative Disease (ISLAND) is a dementia prevention public health study examining whether improving knowledge about modifiable dementia risk factors supports behaviour changes that reduce future dementia risk. METHODS: Residents of Tasmania, Australia, aged 50 + years who joined the 10-year ISLAND study were asked to complete annual online surveys about their knowledge, motivations and behaviours related to modifiable dementia risk. ISLAND included two knowledge-based interventions: a personalised Dementia Risk Profile (DRP) report based on survey responses, and the option to do a 4-week Preventing Dementia Massive Open Online Course (PDMOOC). Longitudinal regression models assessed changes in the number and type of risk factors, with effects moderated by exposures to the DRP report and engagement with the PDMOOC. Knowledge and motivational factors related to dementia risk were examined as mediators of risk behaviour change. RESULTS: Data collected between October 2019 and October 2022 (n = 3038, av. 63.7 years, 71.6% female) showed the mean number of modifiable dementia risk factors per participant (range 0 to 9) reduced from 2.17 (SD 1.24) to 1.66 (SD 1.11). This change was associated with the number of exposures to the DRP report (p = .042) and was stronger for PDMOOC participants (p = .001). The interaction between DRP and PDMOOC exposures yielded a significant improvement in risk scores (p = .004). The effect of PDMOOC engagement on behaviour change was partly mediated by increased knowledge (12%, p = .013). Self-efficacy enhanced the effect of knowledge on behaviour change, while perceived susceptibility to dementia mitigated this relationship. CONCLUSIONS: The ISLAND framework and interventions, a personalised DRP report and the four-week PDMOOC, work independently and synergistically to increase dementia risk knowledge and stimulate health behaviour change for dementia risk reduction. ISLAND offers a feasible and scalable public health approach for redressing the rising prevalence of dementia.

Family carers of people living with dementia and discussion board engagement in the Understanding Dementia Massive Open Online Course.

OBJECTIVES: This study compared discussion board involvement between family carers and non-carers in the Understanding Dementia Massive Open Online Course (UD-MOOC). METHODS: A mixed methods observational cohort study of family carers and non-carers was undertaken over the February-April 2020 UD-MOOC. Discussion board engagement was measured as number of posts and replies and examined longitudinally using mixed models. Discussion topics were explored through structural topic models (STM). Subsequently, thematic analysis of STM derived-topic exemplars was conducted to contextualise these discussions. RESULTS: Family carers were (n = 2320) found to post (p < 0.001) and reply (p = 0.029) significantly more often than non-carers (n = 2392). Of the 32-STM derived-topics, meaningful activities (mean Δ = 0.007, 95% CrI [0.005-0.100]), personal stories of diagnosis (mean Δ = 0.007, 95% CrI [0.005-0.009]), and family history of dementia (mean Δ = 0.006, 95% CrI [0.004-0.008]) were discussed significantly more frequently by family carers compared to non-carers. CONCLUSION: These results may reflect underlying motivational differences and circumstantial relevance. Perhaps the greater engagement by family carers is related to a sense of having inadequate relevant offline social resources, where engagement in the UD-MOOC discussion boards may serve as means to share experiences with others.

The TAS Test project: a prospective longitudinal validation of new online motor-cognitive tests to detect preclinical Alzheimer's disease and estimate 5-year risks of cognitive decline and dementia.

BACKGROUND: The worldwide prevalence of dementia is rapidly rising. Alzheimer's disease (AD), accounts for 70% of cases and has a 10-20-year preclinical period, when brain pathology covertly progresses before cognitive symptoms appear. The 2020 Lancet Commission estimates that 40% of dementia cases could be prevented by modifying lifestyle/medical risk factors. To optimise dementia prevention effectiveness, there is urgent need to identify individuals with preclinical AD for targeted risk reduction. Current preclinical AD tests are too invasive, specialist or costly for population-level assessments. We have developed a new online test, TAS Test, that assesses a range of motor-cognitive functions and has capacity to be delivered at significant scale. TAS Test combines two innovations: using hand movement analysis to detect preclinical AD, and computer-human interface technologies to enable robust 'self-testing' data collection. The aims are to validate TAS Test to [1] identify preclinical AD, and [2] predict risk of cognitive decline and AD dementia. METHODS: Aim 1 will be addressed through a cross-sectional study of 500 cognitively healthy older adults, who will complete TAS Test items comprising measures of motor control, processing speed, attention, visuospatial ability, memory and language. TAS Test measures will be compared to a blood-based AD biomarker, phosphorylated tau 181 (p-tau181). Aim 2 will be addressed through a 5-year prospective cohort study of 10,000 older adults. Participants will complete TAS Test annually and subtests of the Cambridge Neuropsychological Test Battery (CANTAB) biennially. 300 participants will undergo in-person clinical assessments. We will use machine learning of motor-cognitive performance on TAS Test to develop an algorithm that classifies preclinical AD risk (p-tau181-defined) and determine the precision to prospectively estimate 5-year risks of cognitive decline and AD. DISCUSSION: This study will establish the precision of TAS Test to identify preclinical AD and estimate risk of cognitive decline and AD. If accurate, TAS Test will provide a low-cost, accessible enrichment strategy to pre-screen individuals for their likelihood of AD pathology prior to more expensive tests such as blood or imaging biomarkers. This would have wide applications in public health initiatives and clinical trials. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05194787 , 18 January 2022. Retrospectively registered.

Exploring perceptions of eating with dementia: Findings from a massive open online course.

People with dementia are at high risk of malnutrition as a result of progressive symptoms that affect eating. Maximising opportunities to enhance nutrition and strategies to encourage eating are a crucial part of providing care. Caregiver knowledge and a person-centred approach to eating is essential to reduce symptom burden and maintain quality of life. There is currently limited research investigating first person perceptions of eating with dementia, particularly beyond small sample sizes. Therefore, this paper aims to explore community perceptions of how best to encourage eating for people with dementia using findings from an online course. Within the Understanding Dementia Massive Open Online Course, responses to the following statement were collected: 'If I had dementia, the things that might help me to eat include…'. A total of 3,651 participant responses were collected from the 2018 and 2019 course enrolments and analysed using structural topic modelling and secondary thematic analysis. The majority of participants were female, tertiary educated Australians over 50 years old. A third were paid caregivers. Thirteen topics were isolated from topic modelling that can be reduced into six broad categories: food type personalisation, meal choice, meal presentation, eating environment, eating assistance and end of life nutrition. Participant responses demonstrated diverse awareness of important aspects to encourage eating in dementia. Findings support the need for improved uptake of nutritional strategies in practice and education on eating with dementia to support caregivers.

Consumer Access, Appraisal, and Application of Services and Information for Dementia (CAAASI-Dem): a validation study.

Objectives: The Consumer Access, Appraisal, and Application of Services and Information for Dementia (CAAASI-Dem) was developed to examine individuals' self-assessed confidence in their ability to access, appraise and use dementia services and information. The CAAASI-Dem is the only tool to date to measure this crucial component of dementia literacy. This study was designed to validate its structural validity.Method: Data was collected from 3277 participants enrolled in an on-line dementia course. The five-factor structure of the CAAASI-Dem, which was derived from a previous exploratory factor analysis, was evaluated using confirmatory factor analysis. Internal reliability, convergent and divergent validity, and known-groups validity were assessed. Results: The five-factor model demonstrated good fit with the observed data with the removal of 2 items and movement of 1 item across the factors. The resultant 24-item five-factor CAAASI-Dem showed very good sub-scale internal reliability and satisfactory convergent and divergent validity. There was good discrimination between groups of participants with different levels of care experience.Conclusion: The results provided evidence for the 24-item CAAASI-Dem as a valid and reliable five-dimensional scale. Limitations of the study are discussed, and recommendations are made for future research and practice.

Clinical impact of antipsychotic and benzodiazepine reduction: findings from a multicomponent psychotropic reduction program within long-term aged care.

OBJECTIVES: To explore the relationships between dose changes to antipsychotic and/or benzodiazepine medications and resident outcomes, including variations in neuropsychiatric symptoms, quality of life (QoL), and social withdrawal, within a multicomponent, interdisciplinary antipsychotic and benzodiazepine dose reduction program. DESIGN: Prospective, observational, longitudinal study. INTERVENTION: The Reducing Use of Sedatives (RedUSe) project involved 150 Australian Long-Term Care Facilities (LTCFs) incorporating auditing and benchmarking of prescribing, education, and multidisciplinary sedative reviews. SETTING: A convenience sample of LTCFs (n = 28) involved in RedUSe between January 2015 and March 2016. PARTICIPANTS: Permanent residents (n = 206) of LTCFs involved in RedUSe taking an antipsychotic and/or benzodiazepine daily. Residents were excluded if they had a severe psychiatric condition where antipsychotic therapy should generally be maintained long-term (e.g., bipolar disorder, schizophrenia) or were considered end-stage palliative. MEASUREMENTS: Neuropsychiatric symptoms (Neuropsychiatric Inventory, Cohen-Mansfield Agitation Inventory (CMAI)), QoL (Assessment of Quality of Life-4D), and social withdrawal (Multidimensional Observation Scale for Elderly Subjects-withdrawal subscale) were measured at baseline and 4 months where nursing staff completed psychometric tests as proxy raters. RESULTS: There was no evidence that psychometric measures were worsened following dose reductions. In fact, dose reduction was associated with small, albeit non-statistically significant, improvements in behavior, particularly less physically non-aggressive behavior with both drug groups (-0.36 points per 10% reduction in antipsychotic dose, -0.17 per 10% reduction in benzodiazepine dose) and verbally agitated behavior with benzodiazepine reduction (-0.16 per 10% dose reduction), as measured with the CMAI. Furthermore, antipsychotic reduction was associated with non-statistically significant improvements in QoL and social withdrawal. CONCLUSIONS: Antipsychotic and benzodiazepine dose reduction in LTCFs was not associated with deterioration in neuropsychiatric symptoms, QoL, or social withdrawal. Trends toward improved agitation with antipsychotic and benzodiazepine dose reduction require further evaluation in larger, prospective, controlled studies.

Measuring consumer access, appraisal and application of services and information for dementia (CAAASI-Dem): a key component of dementia literacy.

BACKGROUND: The ability to locate, navigate and use dementia services and information, either for oneself or in providing care for others, is an essential component of dementia literacy. Despite dementia literacy being understood to be inadequate in many settings, no validated instrument exists to measure these elements. Here we describe the development and preliminary validation of the Consumer Access, Appraisal and Application of Services and Information for Dementia (CAAASI-Dem) tool. METHODS: Items were adapted from existing health literacy tools and guided by discussion posts in the Understanding Dementia Massive Open Online Course (UDMOOC). Following expert review and respondent debriefing, a modified CAAASI-Dem was administered to UDMOOC participants online. On the basis of descriptive statistics, inter-item and item total correlations and qualitative feedback, this was further refined and administered online to a second cohort of UDMOOC participants. Exploratory factor analysis identified underlying factor structure. Items were retained if they had significant factor loadings on one factor only. Each factor required at least three items with significant factor loadings. Internal consistency of factors in the final model was evaluated using Cronbach's alpha coefficients. RESULTS: From a pool of 70 initial items with either a 5-point Likert scale (Not at all confident - Extremely confident; or Strongly agree - Strongly disagree) or a binary scale (Yes - No), 65 items were retained in CAAASI-Dem-V1. Statistical and qualitative analysis of 1412 responses led to a further 34 items being removed and 11 revised to improve clarity. The 31 item CAAASI-Dem-V2 tool was subsequently administered to 3146 participants, one item was removed due to redundancy and EFA resulted in the removal of an additional 4 items and determination of a five factor structure: Evaluation and engagement; Readiness; Social supports; Specific dementia services; and Practical aspects. CONCLUSIONS: The five factors and 26 constituent items in CAAASI-Dem align with functional, critical, and communicative aspects of dementia health literacy from the perspective of the carer. As a screening tool for people living with dementia and their carers, CAAASI-Dem potentially provides a means to determine support needs and may be a key component of the dementia literacy assessment toolbox.

RedUSe: reducing antipsychotic and benzodiazepine prescribing in residential aged care facilities.

OBJECTIVE: To assess the impact of a multi-strategic, interdisciplinary intervention on antipsychotic and benzodiazepine prescribing in residential aged care facilities (RACFs). Design, setting: Prospective, longitudinal intervention in Australian RACFs, April 2014 - March 2016. PARTICIPANTS: 150 RACFs (with 12 157 residents) comprised the main participant group; two further groups were consultant pharmacists (staff education) and community pharmacies (prescribing data). Data for all RACF residents, excluding residents receiving respite or end-stage palliative care, were included. INTERVENTION: A multi-strategic program comprising psychotropic medication audit and feedback, staff education, and interdisciplinary case review at baseline and 3 months; final audit at 6 months. MAIN OUTCOME MEASURE: Mean prevalence of regular antipsychotic and benzodiazepine prescribing at baseline, and at 3 and 6 months. Secondary measures: chlorpromazine and diazepam equivalent doses/day/resident; proportions of residents for whom drug was ceased or the dose reduced; prevalence of antidepressant and prn (as required) psychotropic prescribing (to detect any substitution practice). RESULTS: During the 6-month intervention, the proportion of residents prescribed antipsychotics declined by 13% (from 21.6% [95% CI, 20.4-22.9%] to 18.9% [95% CI, 17.7-20.1%]), and that of residents regularly prescribed benzodiazepines by 21% (from 22.2% [95% CI, 21.0-23.5%] to 17.6% [95% CI, 16.5-18.7]; each, P < 0.001). Mean chlorpromazine equivalent dose declined from 22.9 mg/resident/day (95% CI, 19.8-26.0) to 20.2 mg/resident/day (95% CI, 17.5-22.9; P < 0.001); mean diazepam equivalent dose declined from 1.4 mg/resident/day (95% CI, 1.3-1.5) to 1.1 mg/resident/day (95% CI, 0.9-1.2; P < 0.001). For 39% of residents prescribed antipsychotics and benzodiazepines at baseline, these agents had been ceased or their doses reduced by 6 months. There was no substitution by sedating antidepressants or prn prescribing of other psychotropic agents. CONCLUSIONS: The RedUSe program achieved significant reductions in the proportions of RACF residents prescribed antipsychotics and benzodiazepines. TRIAL REGISTRATION: Australian New Zealand Clinical Trials, ACTRN12617001257358.

How is palliative care understood in the context of dementia? Results from a massive open online course.

BACKGROUND: A palliative approach to the care of people with dementia has been advocated, albeit from an emergent evidence base. The person-centred philosophy of palliative care resonates with the often lengthy trajectory and heavy symptom burden of this terminal condition. AIM: To explore participants' understanding of the concept of palliative care in the context of dementia. The participant population took an online course in dementia. DESIGN: The participant population took a massive open online course on 'Understanding Dementia' and posted answers to the question: 'palliative care means …' We extracted these postings and analysed them via the dual methods of topic modelling analysis and thematic analysis. SETTING/PARTICIPANTS: A total of 1330 participants from three recent iterations of the Understanding Dementia Massive Open Online Course consented to their posts being used. Participants included those caring formally or informally for someone living with dementia as well as those with a general interest in dementia Results: Participants were found to have a general awareness of palliative care, but saw it primarily as terminal care, focused around the event of death and specialist in nature. Comfort was equated with pain management only. Respondents rarely overtly linked palliative care to dementia. CONCLUSIONS: A general lack of palliative care literacy, particularly with respect to dementia, was demonstrated by participants. Implications for dementia care consumers seeking palliative care and support include recognition of the likely lack of awareness of the relevance of palliative care to dementia. Future research could access online participants more directly about their understandings/experiences of the relationship between palliative care and dementia.

Modifiable dementia risk factors and AT(N) biomarkers: findings from the EPAD cohort.

Introduction: Modifiable risk factors account for a substantial proportion of Alzheimer's disease (AD) cases and we currently have a discrete AT(N) biomarker profile for AD biomarkers: amyloid (A), p-tau (T), and neurodegeneration (N). Here, we investigated how modifiable risk factors relate to the three hallmark AT(N) biomarkers of AD. Methods: Participants from the European Prevention of Alzheimer's Dementia (EPAD) study underwent clinical assessments, brain magnetic resonance imaging, and cerebrospinal fluid collection and analysis. Generalized additive models (GAMs) with penalized regression splines were modeled in the AD Workbench on the NTKApp. Results: A total of 1,434 participants were included (56% women, 39% APOE ε4+) with an average age of 65.5 (± 7.2) years. We found that modifiable risk factors of less education (t = 3.9, p < 0.001), less exercise (t = 2.1, p = 0.034), traumatic brain injury (t = -2.1, p = 0.036), and higher body mass index (t = -4.5, p < 0.001) were all significantly associated with higher AD biomarker burden. Discussion: This cross-sectional study provides further support for modifiable risk factors displaying neuroprotective associations with the characteristic AT(N) biomarkers of AD.

Brief webcam test of hand movements predicts episodic memory, executive function, and working memory in a community sample of cognitively asymptomatic older adults.

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.

A profile of students in a university-based distance dementia education program: Implications for policy and practice.

OBJECTIVE: The online program began in 2012 to support aged care workers without a tertiary education or vocational qualification. This paper documents changes in the student profile since initiation of the program, and how the program may support recommendations of the Royal Commission into Aged Care Quality and Safety and engage other educators, providers and policymakers. METHODS: Four hundred and seventy-one commencing undergraduate students completed a 16-item online survey in 2017 to document demographics and reasons for study. Categorical associations were assessed with univariate logistic regression in R v3.6. RESULTS: Most students (71%; 336) were aged between 41 and 60 years but the program now included younger (<41 years) and older (>80 years) people. Unlike the 2012 students, about 41% had tertiary-level qualifications, and 56% were employed in professional positions, including registered nurse, general practitioner and allied health professional. Professional and practice development was the primary reason for study; significantly so for younger (<41 years) participants in aged and dementia care (χ2 (5) = 18.15, p = 0.003) and for those with previous university experience (χ2 (4) = 22.17, p = 0.001). Older (≥61 years) participants enrolled to gain greater knowledge about dementia (χ2 (4) = 17.60, p = 0.002). CONCLUSIONS: Understanding the changed student profile guided program refinement to ensure the provision of effective, evidence-based education in dementia understanding and care. Work now focusses on increasing partnerships with aged care organisations, community and postsecondary training institutions to support a continuum of workforce development options, guided by the recommendations of the Royal Commission.

Does serum neurofilament light help predict accelerated cognitive ageing in unimpaired older adults?

Introduction: Neurofilament light (NfL) is a blood biomarker of neurodegeneration. While serum NfL levels have been demonstrated to increase with normal ageing, the relationship between serum NfL levels and normal age-related changes in cognitive functions is less well understood. Methods: The current study investigated whether cross-sectional serum NfL levels measured by single molecule array technology (Simoa®) mediated the effect of age on cognition, measured by a battery of neuropsychological tests administered biannually for 8 years, in a cohort of 174 unimpaired older adults (≥50 years) from the Tasmanian Healthy Brain Project. Mediation analysis was conducted using latent variables representing cognitive test performance on three cognitive domains - episodic memory, executive function, and language (vocabulary, comprehension, naming). Cognitive test scores for the three domains were estimated for each participant, coincident with blood collection in 2018 using linear Bayesian hierarchical models. Results: Higher serum NfL levels were significantly positively associated with age (p < 0.001 for all domains). Cognitive test scores were significantly negatively associated with age across the domains of executive function (p < 0.001), episodic memory (p < 0.001) and language (p < 0.05). However, serum NfL levels did not significantly mediate the relationship between age and cognitive test scores across any of the domains. Discussion: This study adds to the literature on the relationship between serum NfL levels and cognition in unimpaired older adults and suggests that serum NfL is not a pre-clinical biomarker of ensuing cognitive decline in unimpaired older adults.

Modifiable risk factors for dementia, cognition, and plasma phosphorylated tau 181 in a large-scale cohort of Australian older adults.

Alzheimer's disease (AD), the most common form of dementia, is preceded by years of silent pathological change. Our objective was to examine the associations between modifiable dementia risk factors, cognition, and plasma phosphorylated p-tau 181, a hallmark biomarker of AD in a large-scale community cohort. Participants (n = 738, mean age 65.41 years) from the Island Study Linking Ageing and Neurodegenerative Disease responded to online assessments collecting demographics, adherence to dementia risk factors and cognitive function, and provided a blood sample for analysis. We found less education was significantly associated with lower cognitive scores. Modifiable dementia risk factors were not associated with plasma p-tau 181. Further, we did not observe any significant relationships between plasma p-tau 181 and cognition. Nonmodifiable factors such as age, education, sex, and apolipoprotein E epsilon 4 displayed significant associations with cognition and plasma p-tau 181. In a cognitively healthy community cohort of Tasmanian Australians, we did not observe any associations between modifiable risk factors for dementia and plasma p-tau 181. Nonmodifiable risk factors were associated with both cognition and plasma p-tau. This contributes to a growing body of evidence investigating confounding factors in the interpretation of blood-based biomarkers for dementia.

Sex-Specific Protective Effects of Cognitive Reserve on Age-Related Cognitive Decline: A 5-Year Prospective Cohort Study.

BACKGROUND AND OBJECTIVES: Females have a higher age-adjusted incidence of Alzheimer disease than males but the reasons for this remain unclear. One proposed contributing factor is that, historically, females had less access to education and, therefore, may accumulate less cognitive reserve. However, educational attainment is confounded by IQ, which in itself is a component of cognitive reserve and does not differ between sexes. Steeper age-related cognitive declines are associated with increased risk of dementia. We, therefore, evaluated the moderating effects of 2 proxies for cognitive reserve, education and IQ, on the steepness of age-related declining cognitive trajectories in unimpaired older males and females. METHODS: The Tasmanian Healthy Brain Project, a long-term cohort study, recruited healthy Australians aged 50-80 years without cognitive impairment. Baseline cognitive reserve was measured using educational history and IQ, measured by the Wechsler Test of Adult Reading, Full Scale Predicted IQ (WTAR-FSIQ). Cognitive trajectories for language, executive function, and episodic and working memory over 5 years were extracted from neuropsychological assessments. The adjusted effects of education, estimated IQ, and APOE allelic variant on cognitive trajectories were compared between males and females. RESULTS: Five hundred sixty-two individuals (mean [SD] age 60 [6.7] years; 68% male; 33% APOE ε4+) were followed up over 5 years with 1,924 assessments and 24,946 cognitive test scores (annualized attrition rate 6.6% per year). Estimated IQ correlated with years of education (p < 0.001). Estimated IQ interacted with sex to moderate age-related cognitive trajectories (p = 0.03; adjusted for education); lower IQ males experienced steeper declining trajectories than higher IQ males, but lower IQ females had similar steepness of declining trajectories to higher IQ females. Education was not associated with rate of cognitive decline (p = 0.67; adjusted for WTAR-FSIQ). There were no significant differences in age-related cognitive trajectories between APOE genotypes in either sex. DISCUSSION: IQ, a measure of cognitive reserve, predicted the steepness of declining cognitive trajectories in males only. Education did not explain as much variation in cognitive trajectories as IQ. Our findings do not support the hypothesis that historical sex disparities in access to education contribute to the higher female incidence of Alzheimer disease.

Island Study Linking Aging and Neurodegenerative Disease (ISLAND) Targeting Dementia Risk Reduction: Protocol for a Prospective Web-Based Cohort Study.

BACKGROUND: Up to 40% of incident dementia is considered attributable to behavioral and lifestyle factors. Given the current lack of medical treatments and the projected increase in dementia prevalence, a focus on prevention through risk reduction is needed. OBJECTIVE: We aim to increase dementia risk knowledge and promote changes in dementia risk behaviors at individual and population levels. METHODS: The Island Study Linking Aging and Neurodegenerative Disease (ISLAND) is a long-term prospective, web-based cohort study with nested interventions that will be conducted over a 10-year period. Target participants (n=10,000) reside in Tasmania and are aged 50 years or over. Survey data on knowledge, attitudes, and behaviors related to modifiable dementia risk factors will be collected annually. After each survey wave, participants will be provided with a personalized dementia risk profile containing guidelines for reducing risk across 9 behavioral and lifestyle domains and with opportunities to engage in educational and behavioral interventions targeting risk reduction. Survey data will be modeled longitudinally with intervention engagement indices, cognitive function indices, and blood-based biomarkers, to measure change in risk over time. RESULTS: In the initial 12 months (October 2019 to October 2020), 6410 participants have provided baseline data. The study is ongoing. CONCLUSIONS: Recruitment targets are feasible and efforts are ongoing to achieve a representative sample. Findings will inform future public health dementia risk reduction initiatives by showing whether, when, and how dementia risk can be lowered through educational and behavioral interventions, delivered in an uncontrolled real-world context. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/34688.