Herpes zoster vaccination and new diagnoses of dementia: A quasi-randomized study in Australia.

Increasing evidence suggests that neurotropic herpesviruses could play a role in the development of dementia, possibly through a neuroinflammatory process. Herpes zoster (HZ) vaccination has been reported to lead to a reduced probability of being diagnosed with dementia in several correlational studies and in a prior analysis by our team in Wales. This present study constitutes the first investigation to use a quasi-randomized study design in an electronic health record dataset from a large and diverse nation (Australia) to aim to determine the effect of HZ vaccination on dementia. In Australia, starting on November 1 2016, live-attenuated HZ vaccination was provided for free to individuals aged 70 to 79 years of age through primary care providers. Thus, those whose 80th birthday was just a few days prior to November 1 2016 never became eligible, whereas those whose 80th birthday was just a few days later were eligible. The key advantage of our approach is that one would not expect that these population groups who differ in their age by only a minute degree would, on average, differ in any of their health characteristics and behaviors. We used detailed primary healthcare records with week-of-birth information from 65 general practices across Australia. We analyzed our data using a regression discontinuity approach. Our sample consisted of 101,219 patients. As expected, patients born just before versus shortly after the date-of-birth eligibility threshold (November 2 1936) for HZ vaccination were well-balanced in their past preventive health services uptake and chronic disease diagnoses. There was an abrupt increase of 15.7 (95% CI: [12.2 - 19.3], p < 0.001) percentage points in the probability of ever receiving HZ vaccination between patients born shortly before versus shortly after the eligibility threshold. The eligibility rules of the HZ vaccination program, thus, created comparison groups just on either side of the date-of-birth eligibility threshold who were similar to each other, except for a large difference in their probability of receiving the intervention (HZ vaccination) of interest. Eligibility for HZ vaccination (i.e., being born shortly before versus shortly after November 2 1936) decreased the probability of receiving a new dementia diagnosis over 7.4 years by 2.0 percentage points (95% CI: [0.3 - 3.7], p = 0.021). Being eligible for HZ vaccination did not affect the probability of taking up other preventive health services (including other vaccinations), nor the probability of being diagnosed with other common chronic conditions than dementia. This study provides important evidence on the potential benefits of HZ vaccination for dementia because its quasi-randomized design allows for conclusions that are more likely to be causal than those of the existing associational evidence.

Contrast Sensitivity, Visual Field, Color Vision, Motion Perception, and Cognitive Impairment: A Systematic Review.

OBJECTIVES: To examine relationships between visual function (ie, contrast sensitivity, visual field, color vision, and motion perception) and cognitive impairment, including any definition of "cognitive impairment," mild cognitive impairment, or dementia. DESIGN: Systematic review and meta-analyses. SETTING AND PARTICIPANTS: Any settings; participants with (cases) or without (controls) cognitive impairment. METHODS: We searched 4 databases (to January 2024) and included published studies that compared visual function between cases and controls. Standardized mean differences (SMD) with 95% CIs were calculated where data were available. Data were sufficient for meta-analyses when cases were people with dementia. The Joanna Briggs Institute checklists were used for quality assessment. RESULTS: Fifty-one studies/69 reports were included. Cross-sectional evidence shows that people with dementia had worse contrast sensitivity function and color vision than controls: measured by contrast sensitivity (log units) on letter charts, SMD -1.22 (95% CI -1.98, -0.47), or at varied spatial frequencies, -0.92 (-1.28, -0.57); and by pseudoisochromatic plates, -1.04 (-1.59, -0.49); color arrangement, -1.30 (-2.31, -0.29); or matching tests, -0.51 (-0.78, -0.24). They also performed more poorly on tests of motion perception, -1.20 (-1.73, -0.67), and visual field: mean deviation, -0.87 (-1.29, -0.46), and pattern standard deviation, -0.69 (-1.24, -0.15). Results were similar when cases were limited to participants with clinically diagnosed Alzheimer disease. Sources of bias included lack of clarity on study populations or settings and definitions of cognitive impairment. The 2 included longitudinal studies with follow-ups of approximately 10 years were of good quality but reported inconsistent results. CONCLUSIONS AND IMPLICATIONS: In the lack of longitudinal data, cross-sectional studies indicate that individuals with cognitive impairment have poorer visual function than those with normal cognition. Additional longitudinal data are needed to understand whether poor visual function precedes cognitive impairment and the most relevant aspects of visual function, dementia pathologies, and domains of cognition.

Decentralized clinical trials for medications to reduce the risk of dementia: Consensus report and guidance.

INTRODUCTION: Recent growth in the functionality and use of technology has prompted an increased interest in the potential for remote or decentralized clinical trials in dementia. There are many potential benefits associated with decentralized medication trials, but we currently lack specific recommendations for their delivery in the dementia field. METHODS: A modified Delphi method engaged an expert panel to develop recommendations for the conduct of decentralized medication trials in dementia prevention. A working group of researchers and clinicians with expertise in dementia trials further refined the recommendations. RESULTS: Overall, the recommendations support the delivery of decentralized trials in dementia prevention provided adequate safety checks and balances are included. A total of 40 recommendations are presented, spanning aspects of decentralized clinical trials, including safety, dispensing, outcome assessment, and data collection. DISCUSSION: These recommendations provide an accessible, pragmatic guide for the design and conduct of remote medication trials for dementia prevention. HIGHLIGHTS: Clinical trials of medication have begun adopting decentralized approaches. Researchers in the field lack guidance on what would be appropriate circumstances and frameworks for what would be appropriate circumstances and frameworks for the use of decentralized trial methods in dementia prevention. The present report provides consensus-based expert recommendations for decentralized clinical trials for dementia prevention.

Estimating Gender Differences in the Association between Cognitive Resilience and Mild Cognitive Impairment Incidence.

INTRODUCTION: Recent evidence suggests that the influence of verbal intelligence and education on the onset of subjective cognitive decline may be modulated by gender, where education contributes less to cognitive resilience (CR) in women than in men. This study aimed to examine gender differences in the association between CR and mild cognitive impairment (MCI) incidence in an Australian population-based cohort. METHODS: We included 1,806 participants who had completed at least the first two waves and up to four waves of assessments in the Personality and Total Health (PATH) Through Life study (baseline: 49% female, male = 62.5, SD = 1.5, age range = 60-66 years). CR proxies included measures of educational attainment, occupation skill, verbal intelligence, and leisure activity. Discrete-time survival analyses were conducted to examine gender differences in the association between CR proxies and MCI risk, adjusting for age and apolipoprotein E4 status. RESULTS: Gender differences were only found in the association between occupation and MCI risk, where lower occupation skill was more strongly associated with higher risk in men than in women (odds ratio [OR] = 1.30, 95% confidence interval [CI] [1.07, 1.57]). In both genders, after adjusting for education and occupation, one SD increase in leisure activity was associated with lower MCI risk by 32% (OR = 0.76, 95% CI [0.65, 0.89]). Higher scores in verbal intelligence assessment were associated with reduced risk of MCI by 28% (OR = 0.78, 95% CI [0.69, 0.89]). CONCLUSION: Occupational experience may contribute to CR differently between genders. Life course cognitive engagement and verbal intelligence may be more protective against MCI than education and occupation for both men and women.

Social contact as a strategy to reduce stigma in low- and middle-income countries: A systematic review and expert perspectives.

Social contact (SC) has been identified as a promising strategy for stigma reduction. Different types of SC exist. Various scholars defined positive factors to strengthen SC. This study aims to investigate the application and effectiveness of SC as a strategy to reduce stigmatisation across stigmas, settings and populations in low- and middle-income countries (LMICs). We specifically examine the use of positive factors. A systematic review was conducted in twelve electronic databases using key terms related to stigma AND social contact AND intervention AND LMICs. Data were synthesised narratively. Study quality was assessed with the Joanna Briggs Institute critical appraisal checklists. Additionally, semi-structured interviews were used with first/corresponding authors of included publications to investigate their practical experiences with SC. Forty-four studies (55 publications) were identified. Various stigmas (n = 16) were targeted, including mental health (43%). Indirect (n = 18) and direct contact (n = 16) were used most frequently, followed by collaboration, imagined and vicarious contact, or a combination. The most applied additional strategy was education. Almost half of the studies, explicitly or implicitly, described positive factors for SC, such as PWLE training or disconfirming stereotypes. The majority suggested that SC is effective in reducing stigma, although inconsistent reporting overshadows conclusions. Perspectives of people with lived experience (PWLE) were infrequently included. Expert perspectives stressed the importance of contextualisation, PWLE participation, and evaluation of SC. This study provides an overview of SC as a stigma reduction strategy within LMICs. Conclusions about which type of SC is more effective or whether SC is more effective for a specific stigma category cannot be drawn. We recommend future research to strengthen reporting on effectiveness as well as PWLE perspective and SC processes, and to further critically examine the potential of SC. An overview of positive factors applied to strengthen SC is provided, which can stimulate reflection and guide future SC.

Levels of frailty and frailty progression in older urban- and regional-living First Nations Australians.

OBJECTIVES: To explore the prevalence of frailty, association between frailty and mortality, and transitions between frailty states in urban- and regional-living First Nations Australians. STUDY DESIGN: Secondary analysis of longitudinal data from the Koori Growing Old Well Study. First Nations Australians aged 60 years or more from five non-remote communities were recruited in 2010-2012 and followed up six years later (2016-2018). Data collected at both visits were used to derive a 38-item Frailty Index (FI). The FI (range 0-1.0) was classified as robust (<0.1), pre-frail (0.1- < 0.2), mildly (0.2- < 0.3), moderately (0.3- < 0.4) or severely frail (≥0.4). MAIN OUTCOME MEASURES: Association between frailty and mortality, examined using logistic regression and transitions in frailty (the percentage of participants who changed frailty category) during follow-up. RESULTS: At baseline, 313 of 336 participants (93 %) had sufficient data to calculate a FI. Median FI score was 0.26 (interquartile range 0.21-0.39); 4.79 % were robust, 20.1 % pre-frail, 31.6 % mildly frail, 23.0 % moderately frail and 20.5 % severely frail. Higher baseline frailty was associated with mortality among severely frail participants (adjusted odds ratio 7.11, 95 % confidence interval 2.51-20.09) but not moderately or mildly frail participants. Of the 153 participants with a FI at both baseline and follow-up, their median FI score increased from 0.26 to 0.28. CONCLUSIONS: Levels of frailty in this First Nations cohort are substantially higher than in similar-aged non-Indigenous populations. Screening for frailty before the age of 70 years may be warranted in First Nations Australians. Further research is urgently needed to determine the factors that are driving such high levels of frailty and propose solutions to prevent or manage frailty in this population.

A 10-week intergenerational program bringing together community-living older adults and preschool children (INTERACTION): a pilot feasibility non-randomised clinical trial.

BACKGROUND: Social isolation and low levels of physical activity are strong drivers for frailty, which is linked to poor health outcomes and transition to long-term care. Frailty is multifactorial, and thus an integrated approach is needed to maintain older adults' health and well-being. Intergenerational programs represent a novel multifactorial approach to target frailty, social isolation and physical decline but these have not yet been rigorously tested in Australia. Here, we present the results of our pilot study which aimed to test the feasibility of a 10-week intergenerational program between older adults and preschool children. METHODS: A non-randomised wait-listed controlled trial was conducted. Participants were allocated to either the intervention or wait-list control group. The intervention group received 10 weekly 2-h intergenerational sessions led by trained child educators; the control group continued with their usual routine and received their intergenerational program after the 10-week control period. All participants were assessed at baseline and 10 weeks. The primary outcome was the feasibility and acceptability of the program including measures of recruitment eligibility, adherence and effective data collection across the multiple domains important for frailty, including functional mobility and balance, grip strength, cognitive function, mood, social engagement, quality of life and concerns about falling. RESULTS: Nineteen adults were included, with nine in the intervention and ten in the control group. A total of 42% of older adults screened were eligible, 75% of participants were present at each intervention session and the overall attrition rate was 21% (n = 4). The reasons for participant absence were primarily health-related. Missing data was minimal for the majority of assessments but more apparent for the cognitive testing where completion rates ranged from 53 to 79% for baseline tests and 73 to 100% for those who received follow-up testing. CONCLUSIONS: The high program compliance and low attrition show that a 10-week intergenerational program embedded in the local community, designed for community-living older adults and preschool children, is feasible and acceptable to older adults. Our next trial will test the efficacy of intergenerational programs in this setting.

Hypertension and Mild Cognitive Impairment: State-of-the-Art Review.

BACKGROUND: Mid-life hypertension is associated with cognitive decline and dementia in later life. Reducing high blood pressure (BP) with antihypertensive agents is a well-researched strategy to prevent dementia and mild cognitive impairment (MCI). However, there is still limited direct evidence to support the approach, and particularly for the treatment of the very old and those with existing MCI. METHODS: This review presents an overview of the current evidence for the relationship between MCI and hypertension, and of the potential pathophysiological mechanisms related to cognitive decline and incidence dementia in relation to aging. RESULTS: Although observational data are near consistent in showing an association between mid-life hypertension and MCI and/or dementia, the evidence in relation to hypertension in younger adults and the very old (age >80 years) is much more limited. Most of the commonly available antihypertensive agents appear to provide beneficial effects in reducing the risk dementia, but there is limited evidence to support such treatment in those with existing MCI. CONCLUSIONS: Further studies are needed to determine the optimal levels of BP control across different age groups, especially in adults with MCI, and which class(es) of antihypertensive agents and duration of treatment best preserve cognitive function in those at risk of, or with established, MCI.

Work engagement, psychological empowerment and relational coordination in long-term care: A mixed-method examination of nurses' perceptions and experiences.

Nurse engagement, empowerment and strong relationships among staff, residents and families, are essential to attract and retain a suitably qualified and skilled nursing workforce for safe, quality care. There is, however, limited research that explores engagement, empowerment and relational coordination in long-term care (LTC). Nurses from an older persons' mental health and dementia LTC unit in Australia participated in this study. Forty-one nurses completed a survey measuring psychological empowerment, work engagement and relational coordination. Twenty-nine nurses participated in individual interviews to further explore these concepts. Although nurses reported high psychological empowerment and work engagement, their relationships with key stakeholders varied. Our findings suggest that nurses in LTC require both supports and opportunities to contribute as active members of the multiprofessional care team that includes tailored education, professional development and positive interactions within the care team. Regular support is needed to enable nurses to feel empowered, foster relationships and communication, and facilitate work engagement. Based on these findings, we suggest that it is important to find ways to ensure that all who provide care perceive that they are part of the whole care team and able to contribute to the care and well-being of people in LTC.

Umbrella review and Delphi study on modifiable factors for dementia risk reduction.

A 2013 systematic review and Delphi consensus study identified 12 modifiable risk and protective factors for dementia, which were subsequently merged into the "LIfestyle for BRAin health" (LIBRA) score. We systematically evaluated whether LIBRA requires revision based on new evidence. To identify modifiable risk and protective factors suitable for dementia risk reduction, we combined an umbrella review of systematic reviews and meta-analyses with a two-round Delphi consensus study. The review of 608 unique primary studies and opinions of 18 experts prioritized six modifiable factors: hearing impairment, social contact, sleep, life course inequalities, atrial fibrillation, and psychological stress. Based on expert ranking, hearing impairment, social contact, and sleep were considered the most suitable candidates for inclusion in updated dementia risk scores. As such, the current study shows that dementia risk scores need systematic updates based on emerging evidence. Future studies will validate the updated LIBRA score in different cohorts. HIGHLIGHTS: An umbrella review was combined with opinions of 18 dementia experts. Various candidate targets for dementia risk reduction were identified. Experts prioritized hearing impairment, social contact, and sleep. Re-assessment of dementia risk scores is encouraged. Future work should evaluate the predictive validity of updated risk scores.

Reducing stigma impacting children and adolescents in low- and middle-income countries: The development of a common multi-component stigma reduction intervention.

INTRODUCTION: Stigmatisation impedes health and quality of life. Evidence regarding stigma reduction interventions is, albeit growing, limited. There is a gap in the availability and evidence of interventions for reducing stigma among children and adolescents, especially in low- and middle-income countries. This paper describes the process that led to a stigma reduction intervention impacting children and adolescents in low- and middle-income countries, following previously conducted formative research. METHODS: In this study, we conducted (i) online stakeholder consultations (FGD) (n = 43), including a survey assessing intervention acceptability, appropriateness, feasibility and scalability (n = 16); and (ii) preliminary field-testing of intervention content online and in a refugee settlement in Uganda. FINDINGS: Stakeholder consultation showed the initial version of STRETCH (Stigma Reduction to Trigger Change for Children), albeit positively received, required adaptations. We made adjustments to i) take into account implementation duration, intervention flexibility and intersectionality; (ii) strengthen the involvement of individuals, including adolescents/youth, with lived stigma experience; (iii) target people close to individuals with lived stigma experience; and (iv) address feasibility and sustainability concerns. Preliminary field-testing simplified STRETCH while adding a community outreach component and revisiting the intervention setup, to ensure STRETCH can also be applied from a modular perspective. CONCLUSION: We conducted a process to develop a child-focused multi-component stigma reduction intervention, with intended applicability across stigmas and settings. This paper provides an overview of the intervention development process, generating intervention-specific learnings with generic value. STRETCH aims to reduce stigmatisation at the implementing organisation, create community-wide reflection and stigma reduction demand, and reduce stigmatisation among various target groups.

Measuring health-related stigma: Exploring challenges and research priorities to improve assessment.

Despite the advances in stigma research, measuring health-related stigma continues to be challenging and knowledge gaps remain. This study gained insight into challenges and research priorities related to the assessment of health-related stigma. Interviews were conducted with 14 stigma researchers, followed by a survey that was completed by 36 respondents. The findings showed a diverse range of research priorities. Among the top ranked priorities were the need for robust measurement properties of existing scales (content validity, responsiveness, validation across settings), exploration and assessment of subtle changes in stigma, and investigation on ways to assess actual behaviour and discrimination. Various challenges with the cross-cultural use of measures were identified, along with a research opportunity to shorten the cross-cultural validation process. Other identified research priorities related to: studying multi-level intersectional stigma; focusing on positive features that counter stigma; rephrasing negative and offending scale items; developing generic measures; and, the further development of practical tools to support researchers with scale implementation. The defined research priorities can guide future studies to advance stigma measurements and, as our ability to measure is critical for our understanding, enhance our knowledge about the complex stigma processes.

Orthostatic Hypotension, Hypertension Treatment, and Cardiovascular Disease: An Individual Participant Meta-Analysis.

Importance: There are ongoing concerns about the benefits of intensive vs standard blood pressure (BP) treatment among adults with orthostatic hypotension or standing hypotension. Objective: To determine the effect of a lower BP treatment goal or active therapy vs a standard BP treatment goal or placebo on cardiovascular disease (CVD) or all-cause mortality in strata of baseline orthostatic hypotension or baseline standing hypotension. Data Sources: Individual participant data meta-analysis based on a systematic review of MEDLINE, EMBASE, and CENTRAL databases through May 13, 2022. Study Selection: Randomized trials of BP pharmacologic treatment (more intensive BP goal or active agent) with orthostatic hypotension assessments. Data Extraction and Synthesis: Individual participant data meta-analysis extracted following PRISMA guidelines. Effects were determined using Cox proportional hazard models using a single-stage approach. Main Outcomes and Measures: Main outcomes were CVD or all-cause mortality. Orthostatic hypotension was defined as a decrease in systolic BP of at least 20 mm Hg and/or diastolic BP of at least 10 mm Hg after changing position from sitting to standing. Standing hypotension was defined as a standing systolic BP of 110 mm Hg or less or standing diastolic BP of 60 mm Hg or less. Results: The 9 trials included 29 235 participants followed up for a median of 4 years (mean age, 69.0 [SD, 10.9] years; 48% women). There were 9% with orthostatic hypotension and 5% with standing hypotension at baseline. More intensive BP treatment or active therapy lowered risk of CVD or all-cause mortality among those without baseline orthostatic hypotension (hazard ratio [HR], 0.81; 95% CI, 0.76-0.86) similarly to those with baseline orthostatic hypotension (HR, 0.83; 95% CI, 0.70-1.00; P = .68 for interaction of treatment with baseline orthostatic hypotension). More intensive BP treatment or active therapy lowered risk of CVD or all-cause mortality among those without baseline standing hypotension (HR, 0.80; 95% CI, 0.75-0.85), and nonsignificantly among those with baseline standing hypotension (HR, 0.94; 95% CI, 0.75-1.18). Effects did not differ by baseline standing hypotension (P = .16 for interaction of treatment with baseline standing hypotension). Conclusions and Relevance: In this population of hypertension trial participants, intensive therapy reduced risk of CVD or all-cause mortality regardless of orthostatic hypotension without evidence for different effects among those with standing hypotension.

Use of Antihypertensives, Blood Pressure, and Estimated Risk of Dementia in Late Life: An Individual Participant Data Meta-Analysis.

Importance: The utility of antihypertensives and ideal blood pressure (BP) for dementia prevention in late life remains unclear and highly contested. Objectives: To assess the associations of hypertension history, antihypertensive use, and baseline measured BP in late life (age >60 years) with dementia and the moderating factors of age, sex, and racial group. Data Source and Study Selection: Longitudinal, population-based studies of aging participating in the Cohort Studies of Memory in an International Consortium (COSMIC) group were included. Participants were individuals without dementia at baseline aged 60 to 110 years and were based in 15 different countries (US, Brazil, Australia, China, Korea, Singapore, Central African Republic, Republic of Congo, Nigeria, Germany, Spain, Italy, France, Sweden, and Greece). Data Extraction and Synthesis: Participants were grouped in 3 categories based on previous diagnosis of hypertension and baseline antihypertensive use: healthy controls, treated hypertension, and untreated hypertension. Baseline systolic BP (SBP) and diastolic BP (DBP) were treated as continuous variables. Reporting followed the Preferred Reporting Items for Systematic Review and Meta-Analyses of Individual Participant Data reporting guidelines. Main Outcomes and Measures: The key outcome was all-cause dementia. Mixed-effects Cox proportional hazards models were used to assess the associations between the exposures and the key outcome variable. The association between dementia and baseline BP was modeled using nonlinear natural splines. The main analysis was a partially adjusted Cox proportional hazards model controlling for age, age squared, sex, education, racial group, and a random effect for study. Sensitivity analyses included a fully adjusted analysis, a restricted analysis of those individuals with more than 5 years of follow-up data, and models examining the moderating factors of age, sex, and racial group. Results: The analysis included 17 studies with 34 519 community dwelling older adults (20 160 [58.4%] female) with a mean (SD) age of 72.5 (7.5) years and a mean (SD) follow-up of 4.3 (4.3) years. In the main, partially adjusted analysis including 14 studies, individuals with untreated hypertension had a 42% increased risk of dementia compared with healthy controls (hazard ratio [HR], 1.42; 95% CI 1.15-1.76; P = .001) and 26% increased risk compared with individuals with treated hypertension (HR, 1.26; 95% CI, 1.03-1.53; P = .02). Individuals with treated hypertension had no significant increased dementia risk compared with healthy controls (HR, 1.13; 95% CI, 0.99-1.28; P = .07). The association of antihypertensive use or hypertension status with dementia did not vary with baseline BP. There was no significant association of baseline SBP or DBP with dementia risk in any of the analyses. There were no significant interactions with age, sex, or racial group for any of the analyses. Conclusions and Relevance: This individual patient data meta-analysis of longitudinal cohort studies found that antihypertensive use was associated with decreased dementia risk compared with individuals with untreated hypertension through all ages in late life. Individuals with treated hypertension had no increased risk of dementia compared with healthy controls.

Study protocol for development and validation of a single tool to assess risks of stroke, diabetes mellitus, myocardial infarction and dementia: DemNCD-Risk.

INTRODUCTION: Current efforts to reduce dementia focus on prevention and risk reduction by targeting modifiable risk factors. As dementia and cardiometabolic non-communicable diseases (NCDs) share risk factors, a single risk-estimating tool for dementia and multiple NCDs could be cost-effective and facilitate concurrent assessments as compared with a conventional single approach. The aim of this study is to develop and validate a new risk tool that estimates an individual's risk of developing dementia and other NCDs including diabetes mellitus, stroke and myocardial infarction. Once validated, it could be used by the public and general practitioners. METHODS AND ANALYSIS: Ten high-quality cohort studies from multiple countries were identified, which met eligibility criteria, including large representative samples, long-term follow-up, data on clinical diagnoses of dementia and NCDs, recognised modifiable risk factors for the four NCDs and mortality data. Pooled harmonised data from the cohorts will be used, with 65% randomly allocated for development of the predictive model and 35% for testing. Predictors include sociodemographic characteristics, general health risk factors and lifestyle/behavioural risk factors. A subdistribution hazard model will assess the risk factors' contribution to the outcome, adjusting for competing mortality risks. Point-based scoring algorithms will be built using predictor weights, internally validated and the discriminative ability and calibration of the model will be assessed for the outcomes. Sensitivity analyses will include recalculating risk scores using logistic regression. ETHICS AND DISSEMINATION: Ethics approval is provided by the University of New South Wales Human Research Ethics Committee (UNSW HREC; protocol numbers HC200515, HC3413). All data are deidentified and securely stored on servers at Neuroscience Research Australia. Study findings will be presented at conferences and published in peer-reviewed journals. The tool will be accessible as a public health resource. Knowledge translation and implementation work will explore strategies to apply the tool in clinical practice.

CogDrisk, ANU-ADRI, CAIDE, and LIBRA Risk Scores for Estimating Dementia Risk.

Importance: While the Australian National University-Alzheimer Disease Risk Index (ANU-ADRI), Cardiovascular Risk Factors, Aging, and Dementia (CAIDE), and Lifestyle for Brain Health (LIBRA) dementia risk tools have been widely used, a large body of new evidence has emerged since their publication. Recently, Cognitive Health and Dementia Risk Index (CogDrisk) and CogDrisk for Alzheimer disease (CogDrisk-AD) risk tools have been developed for the assessment of dementia and AD risk, respectively, using contemporary evidence; comparison of the relative performance of these risk tools is limited. Objective: To evaluate the performance of CogDrisk, ANU-ADRI, CAIDE, LIBRA, and modified LIBRA (LIBRA with age and sex estimates from ANU-ADRI) in estimating dementia and AD risks (with CogDrisk-AD and ANU-ADRI). Design, Setting, and Participants: This population-based cohort study obtained data from the Rush Memory and Aging Project (MAP), the Cardiovascular Health Study Cognition Study (CHS-CS), and the Health and Retirement Study-Aging, Demographics and Memory Study (HRS-ADAMS). Participants who were free of dementia at baseline were included. The factors were component variables in the risk tools that included self-reported baseline demographics, medical risk factors, and lifestyle habits. The study was conducted between November 2021 and March 2023, and statistical analysis was performed from January to June 2023. Main outcomes and measures: Risk scores were calculated based on available factors in each of these cohorts. Area under the receiver operating characteristic curve (AUC) was calculated to measure the performance of each risk score. Multiple imputation was used to assess whether missing data may have affected estimates for dementia risk. Results: Among the 6107 participants in 3 validation cohorts included for this study, 2184 participants without dementia at baseline were available from MAP (mean [SD] age, 80.0 [7.6] years; 1606 [73.5%] female), 548 participants without dementia at baseline were available from HRS-ADAMS (mean [SD] age, 79.5 [6.3] years; 288 [52.5%] female), and 3375 participants without dementia at baseline were available from CHS-CS (mean [SD] age, 74.8 [4.9] years; 1994 [59.1%] female). In all 3 cohorts, a similar AUC for dementia was obtained using CogDrisk, ANU-ADRI, and modified LIBRA (MAP cohort: CogDrisk AUC, 0.65 [95% CI, 0.61-0.69]; ANU-ADRI AUC, 0.65 [95% CI, 0.61-0.69]; modified LIBRA AUC, 0.65 [95% CI, 0.61-0.69]; HRS-ADAMS cohort: CogDrisk AUC, 0.75 [95% CI, 0.71-0.79]; ANU-ADRI AUC, 0.74 [95% CI, 0.70-0.78]; modified LIBRA AUC, 0.75 [95% CI, 0.71-0.79]; CHS-CS cohort: CogDrisk AUC, 0.70 [95% CI, 0.67-0.72]; ANU-ADRI AUC, 0.69 [95% CI, 0.66-0.72]; modified LIBRA AUC, 0.70 [95% CI, 0.68-0.73]). The CAIDE and LIBRA also provided similar but lower AUCs than the 3 aforementioned tools (eg, MAP cohort: CAIDE AUC, 0.50 [95% CI, 0.46-0.54]; LIBRA AUC, 0.53 [95% CI, 0.48-0.57]). The performance of CogDrisk-AD and ANU-ADRI in estimating AD risks was also similar. Conclusions and relevance: CogDrisk and CogDrisk-AD performed similarly to ANU-ADRI in estimating dementia and AD risks. These results suggest that CogDrisk and CogDrisk-AD, with a greater range of modifiable risk factors compared with other risk tools in this study, may be more informative for risk reduction.

Preferences and Perspectives of Australian General Practitioners Towards a New "Four-in-One" Risk Assessment Tool for Preventative Health: The LEAD! GP Project.

BACKGROUND: Dementia risk reduction is a public health priority and general practitioners (GPs) play a pivotal role in preventative healthcare. Therefore, risk assessment tools should be designed with GPs' preferences and perspectives in mind. OBJECTIVE: The LEAD! GP project aimed to investigate Australian GPs' preferences and perspectives relating to design, use and implementation of a new risk assessment tool that simultaneously calculates risk for four outcomes- dementia, diabetes mellitus, myocardial infarct, and stroke. METHODS: A mixed methods study using semi-structured interviews of a diverse group of 30 Australian GPs was conducted. Interview transcripts were analyzed thematically. Demographics and questions that elicited categorical answers were analyzed descriptively. RESULTS: Overall, GPs felt that preventative healthcare was important with some finding it rewarding, and others finding it difficult. GPs currently use many risk assessment tools. GPs' perception of the usefulness and negatives/barriers of tools related to clinical practice applicability, patient engagement, and practical aspects. The largest barrier was lack of time. GPs responded positively to the concept of a four-in-one tool and preferred it to be relatively short, supported by practice nurses and some patient involvement, linked to education resources, available in different formats, and integrated into practice software. CONCLUSION: GPs recognize the importance of preventative healthcare and the potential benefit of a new tool that simultaneously predicts risk for those four outcomes. Findings provide important guidance to inform the final development and piloting of this tool with potential to improve efficiency and practical integration of preventative healthcare for dementia risk reduction.

Testing times for dementia: a community survey identifying contemporary barriers to risk reduction and screening.

BACKGROUND: Advances in pharmacological and non-pharmacological dementia interventions may mean future dementia prevention incorporates a combination of targeted screening and lifestyle modifications. Elucidating potential barriers which may prevent community engagement with dementia prevention initiatives is important to maximise the accessibility and feasibility of these initiatives across the lifespan. METHODS: Six hundred seven adults aged over 18 years completed a 54-item, multiple-choice survey exploring contemporary attitudes towards, and barriers to, dementia risk reduction and screening relative to other common health conditions. Participants were sourced from Australia's largest, paid, data analytics service (ORIMA). RESULTS: Finances (p = .009), poor motivation (p = .043), and time (p ≤ .0001) emerged as significant perceived barriers to dementia risk reduction behaviours. Lack of time was more likely to be reported by younger, relative to older, participants (p ≤ .0001), while females were more likely than males to report financial (p = .019) and motivational (p = .043) factors. Binary logistic regression revealed willingness to undertake dementia testing modalities was significantly influenced by gender (genetic testing, p = .012; saliva, p = .038, modifiable risk factors p = .003), age (cognitive testing, p ≤ .0001; blood, p = .010), and socio-economic group (retinal imaging, p = .042; modifiable risk-factor screening, p = .019). Over 65% of respondents felt adequately informed about risk reduction for at least one non-dementia health condition, compared to 30.5% for dementia. CONCLUSIONS: This study found perceived barriers to dementia risk reduction behaviours, and the willingness to engage in various dementia testing modalities, was significantly associated with socio-demographic factors across the lifespan. These findings provide valuable insight regarding the accessibility and feasibility of potential methods for identifying those most at risk of developing dementia, as well as the need to better promote and support wide-scale engagement in dementia risk reduction behaviours across the lifespan.

Higher systolic blood pressure in early-mid adulthood is associated with poorer cognitive performance in those with a dominantly inherited Alzheimer's disease mutation but not in non-carriers. Results from the DIAN study.

BACKGROUND: The Dominantly Inherited Alzheimer Network (DIAN) is a longitudinal observational study that collects data on cognition, blood pressure (BP), and other variables from autosomal-dominant Alzheimer's disease mutation carriers (MCs) and non-carrier (NC) family members in early to mid-adulthood, providing a unique opportunity to evaluate BP and cognition relationships in these populations. METHOD: We examined cross-sectional and longitudinal relationships between systolic and diastolic BP and cognition in DIAN MC and NC. RESULTS: Data were available from 528 participants, who had a mean age of 38 (SD = 11) and were 42% male and 61% MCs, at a median follow-up of 2 years. Linear-multilevel models found only cross-sectional associations in the MC group between higher systolic BP and poorer performance on language (ß = -0.181 [-0.318, -0.044]), episodic memory (-0.212 [-0.375, -0.049]), and a composite cognitive measure (-0.146 [-0.276, -0.015]). In NCs, the relationship was cross-sectional only and present for language alone. DISCUSSION: Higher systolic BP was cross-sectionally but not longitudinally associated with poorer cognition, particularly in MCs. BP may influence cognition gradually, but further longitudinal research is needed.