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.

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.

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.

Gender differences in modifiable dementia risk factors in monolingual and bilingual Australian adults.

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.

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.

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.

Modifiable Risk Factors for Dementia Among Migrants, Refugees and Asylum Seekers in Australia: A Systematic Review.

While the prevalence of non-communicable disease risk factors is understood to be higher among migrants than for people born in host nations, little is known about the dementia risk profile of migrants, refugees and asylum seekers. This systematic review examines published literature to understand what is currently reported about 12 identified modifiable risk factors for dementia among migrants, refugees, and asylum seekers residing in Australia. Three literature databases (PubMed/CINAHL/MEDLINE) were systematically searched to find articles reporting excessive alcohol consumption, traumatic brain injury, air pollution, lack of education, hypertension, hearing impairment, smoking, obesity, depression, physical inactivity, diabetes, and limited social contact in Australia's migrant, refugee and asylum seeker population samples. Papers were systematically reviewed following PRISMA guidelines. A total of 763 studies were found, of which 676 articles were excluded, and 79 articles remained. Despite wide variability in study design, size and purpose, the prevalence and correlates of modifiable risk factors of dementia appears markedly different among the studied samples. Compared with Australian-born participants, migrant samples had a higher prevalence of depression, social isolation, physical inactivity and diabetes mellitus. Insufficient information or conflicting evidence prevented inference about prevalence and correlates for the remaining dementia risk factors. A better understanding of the prevalence and correlates of modifiable dementia risk factors is needed in Australia's migrant, refugee and asylum seeker populations. This information, together with a deeper understanding of the contextual and cultural contributing factors affecting people who arrive in Australia through differing pathways is needed before preventive interventions can be realistically targeted and sensitively implemented.

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.

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.

Effects of a Mindfulness App on Employee Stress in an Australian Public Sector Workforce: Randomized Controlled Trial.

BACKGROUND: Workplace-based mindfulness programs have good evidence for improving employee stress and mental health outcomes, but less is known about their effects on productivity and citizenship behaviors. Most of the available evidence is derived from studies of mindfulness programs that use class-based approaches. Mindfulness apps can increase access to training, but whether self-directed app use is sufficient to realize benefits equivalent to class-based mindfulness programs is unknown. OBJECTIVE: We assessed the effectiveness of a mindfulness app, both with and without supporting classes, for reducing employees' perceived stress. Changes in mindfulness, mental health, quality of life, perceptions of job demand, control and support, productivity indicators, organizational citizenship, and mindful behaviors at work were also investigated. METHODS: Tasmanian State Service employees were invited by the Tasmanian Training Consortium to a 3-arm randomized controlled trial investigating the effects of a mindfulness app on stress. The app used in the Smiling Mind Workplace Program formed the basis of the intervention. The app includes lessons, activities, and guided meditations, and is supported by 4 instructional emails delivered over 8 weeks. Engagement with the app for 10-20 minutes, 5 days a week, was recommended. Reported data were collected at baseline (time point 0), 3 months from baseline (time point 1 [T1]), and at 6-month follow-up (time point 2). At time point 0, participants could nominate a work-based observer to answer surveys about participants' behaviors. Eligible participants (n=211) were randomly assigned to self-guided app use plus four 1-hour classes (app+classes: 70/211, 33.2%), self-guided app use (app-only: 71/211, 33.6%), or waitlist control (WLC; 70/211, 33.2%). Linear mixed effects models were used to assess changes in the active groups compared with the WLC at T1 and for a head-to-head comparison of the app+classes and app-only groups at follow-up. RESULTS: App use time was considerably lower than recommended (app+classes: 120/343 minutes; app-only: 45/343 minutes). Compared with the WLC at T1, no significant change in perceived stress was observed in either active group. However, the app+classes group reported lower psychological distress (ß=-1.77, SE 0.75; P=.02; Cohen d=-0.21) and higher mindfulness (ß=.31, SE 0.12; P=.01; Cohen d=0.19). These effects were retained in the app+classes group at 6 months. No significant changes were observed for the app-only group or for other outcomes. There were no significant changes in observer measures at T1, but by time point 2, the app+classes participants were more noticeably mindful and altruistic at work than app-only participants. CONCLUSIONS: Including classes in the training protocol appears to have motivated engagement and led to benefits, whereas self-guided app use did not realize any significant results. Effect sizes were smaller and less consistent than meta-estimates for class-based mindfulness training. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Register ACTRN12617001386325; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=372942&isReview.

Automated analysis of propositional idea density in older adults.

Previous research suggests oral and written language can act as barometers of an individual's cognitive function, potentially providing a screening tool for the earliest stages of Alzheimer's disease (AD) and other forms of dementia. Idea density is a measure of the rate at which ideas, or elementary predications, are expressed and may provide an ideal measure for early detection of deficits in language. Previous research has shown that when no restrictions are set on the topic of the idea, a decrease in propositional idea density (PID) is associated with an increased risk of developing AD. However, this has been limited by moderate sample sizes and manual transcribing. Technological advancement has enabled the automated calculation of PID from tools such as the Computerized Propositional Idea Density Rater (CPIDR). We delivered an online autobiographical writing task to older adult Australians from ISLAND (Island Study Linking Ageing and Neurodegenerative Disease). Linear regression models were fitted in R. We analysed text files (range 10-1180 words) using CPIDRv5 provided by 3316 (n = 853 males [25.7%], n = 2463 females [74.3%]) ISLAND participants. Over 358,957 words written in 3316 written autobiographical responses were analysed. Mean PID was higher in females (53.5 [±3.69]) than males (52.6 [±4.50]). Both advancing age and being male were significantly associated with a decrease in PID (p < .001). Automated methods of language analysis hold great promise for the early detection of subtle deficits in language capacity. Although our effect sizes were small, PID may be a sensitive measure of deficits in language in ageing individuals and is able to be collected at scale using online methods of data capture.

Mindfulness Is Associated With Lower Stress and Higher Work Engagement in a Large Sample of MOOC Participants.

Objective: This study aimed to understand the associations between mindfulness, perceived stress, and work engagement in a very large sample of English-speaking adults, from 130 different countries. It also aimed to assess participants' self-reported changes following a 6-week mindfulness massive open online course (MOOC). Methods: Participants in the 6-week MOOC were invited to complete pre-post online surveys. Cross-sectional associations were assessed using univariate linear models, followed by structural equation models to test mediation pathways in baseline data (N = 16,697). Self-reported changes in mindfulness, stress and engagement following training were assessed using paired t-tests (n = 2,105). Results: Each standard deviation unit increase in mindfulness was associated with a 0.52 standard deviation unit decrease in perceived stress, and with 0.06 standard deviation unit increment in work engagement. 73% of the influence of mindfulness on engagement was direct. Following the mindfulness MOOC, participants reported higher mindfulness (d = 1.16), reduced perceived stress (d = 1.00) and a small improvement in work engagement (d = 0.29). Conclusions: Mindfulness was associated with lower perceived stress and higher work engagement in both cross-sectional and longitudinal analyses. These findings support mindfulness as a potentially protective and modifiable personal resource. The MOOC format offers a low cost, highly accessible means for extending the reach and potential benefits of mindfulness training to large numbers of people.

Change in modifiable dementia risk factors during COVID-19 lockdown: The experience of over 50s in Tasmania, Australia.

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.

A systematic review and meta-analysis of workplace mindfulness training randomized controlled trials.

This meta-analytic review responds to promises in the research literature and public domain about the benefits of workplace mindfulness training. It synthesizes randomized controlled trial evidence from workplace-delivered training for changes in mindfulness, stress, mental health, well-being, and work performance outcomes. Going beyond extant reviews, this article explores the influence of variability in workforce and intervention characteristics for reducing perceived stress. Meta-effect estimates (Hedge's g) were computed using data from 23 studies. Results indicate beneficial effects following training for mindfulness (g = 0.45, p < .001) and stress (g = 0.56, p < .001), anxiety (g = 0.62, p < .001) and psychological distress (g = 0.69, p < .001), and for well-being (g = 0.46, p = .002) and sleep (g = 0.26, p = .003). No conclusions could be drawn from pooled data for burnout due to ambivalence in results, for depression due to publication bias, or for work performance due to insufficient data. The potential for integrating the construct of mindfulness within job demands-resources, coping, and prevention theories of work stress is considered in relation to the results. Limitations to study designs and reporting are addressed, and recommendations to advance research in this field are made. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Workplace mental health: An international review of guidelines.

The aim of this systematic review was to determine the quality and comprehensiveness of guidelines developed for employers to detect, prevent, and manage mental health problems in the workplace. An integrated approach that combined expertise from medicine, psychology, public health, management, and occupational health and safety was identified as a best practice framework to assess guideline comprehensiveness. An iterative search strategy of the grey literature was used plus consultation with experts in psychology, public health, and mental health promotion. Inclusion criteria were documents published in English and developed specifically for employers to detect, prevent, and manage mental health problems in the workplace. A total of 20 guidelines met these criteria and were reviewed. Development documents were included to inform quality assessment. This was performed using the AGREE II rating system. Our results indicated that low scores were often due to a lack of focus on prevention and rather a focus on the detection and treatment of mental health problems in the workplace. When prevention recommendations were included they were often individually focused and did not include practical tools or advice to implement. An inconsistency in language, lack of consultation with relevant population groups in the development process and a failure to outline and differentiate between the legal/minimum requirements of a region were also observed. The findings from this systematic review will inform translation of scientific evidence into practical recommendations to prevent mental health problems within the workplace. It will also direct employers, clinicians, and policy-makers towards examples of best-practice guidelines.