Plant but not animal sourced nitrate intake is associated with lower dementia-related mortality in the Australian Diabetes, Obesity, and Lifestyle Study.

Introduction: Dietary nitrate is potentially beneficial for cardiovascular, cerebrovascular, and nervous systems due to its role as a nitric oxide (NO) precursor. Increased nitrate intake improves cardiovascular health and therefore could protect against dementia, given the cardiovascular-dementia link. Objective: To investigate the association between source-dependent nitrate intake and dementia-related mortality. As individuals with diabetes are at higher risk of dementia, a secondary aim was to investigate if the associations between nitrate and dementia varied by diabetes mellitus (DM) and pre-diabetes status. Methods: This study involved 9,149 participants aged ≥25 years from the well-characterised Australian Diabetes, Obesity, and Lifestyle (AusDiab) Study followed over a period of 17 years. Intakes of plant-sourced, vegetable-sourced, naturally occurring animal-sourced nitrate, and processed meat (where nitrate is an allowed additive)-sourced nitrate were assessed from a 74-item food frequency questionnaire completed by participants at baseline and nitrate databases were used to estimate nitrate from these different dietary sources. Associations between source-dependent nitrate intake and dementia-related mortality were assessed using multivariable-adjusted Cox proportional hazards models adjusted for demographics, lifestyle, and dietary factors. Results: Over 17 years of follow-up, 93 (1.0%) dementia-related deaths occurred of 1,237 (13.5%) total deaths. In multivariable-adjusted models, participants with the highest intakes of plant-sourced nitrate (median intake 98 mg/day) had a 57% lower risk of dementia-related mortality [HR (95% CI): 0.43 (0.22, 0.87)] compared to participants with lowest intakes of plant-sourced nitrate (median intake 35 mg/day). A 66% lower risk was also seen for higher intakes of vegetable-sourced nitrate [HR (95% CI): 0.34 (0.17, 0.66)]. No association was observed for animal-sourced nitrate, but the risk was two times higher amongst those who consumed the most processed meat-sourced nitrate intake [HR (95%): 2.10 (1.07, 4.12)]. The highest intake of vegetable-sourced nitrate was associated with a lower risk of dementia-related mortality for those with and without DM and pre-diabetes. Conclusion: Encouraging the intake of nitrate-rich vegetables, such as green leafy vegetables and beetroot, may lower the risk of dementia-related mortality, particularly in individuals with (pre-) diabetes who are at a higher dementia risk.

Blood Pressure, Antihypertensive Use, and Late-Life Alzheimer and Non-Alzheimer Dementia Risk: An Individual Participant Data Meta-Analysis.

BACKGROUND AND OBJECTIVES: Previous randomized controlled trials and longitudinal studies have indicated that ongoing antihypertensive use in late life reduces all-cause dementia risk, but the specific impact on Alzheimer dementia (AD) and non-AD risk remains unclear. This study investigates whether previous hypertension or antihypertensive use modifies AD or non-AD risk in late life and the ideal blood pressure (BP) for risk reduction in a diverse consortium of cohort studies. METHODS: This individual participant data meta-analysis included community-based longitudinal studies of aging from a preexisting consortium. The main outcomes were risk of developing AD and non-AD. The main exposures were hypertension history/antihypertensive use and baseline systolic BP/diastolic BP. Mixed-effects Cox proportional hazards models were used to assess risk and natural splines were applied to model the relationship between BP and the dementia outcomes. The main model controlled for age, age2, sex, education, ethnoracial group, and study cohort. Supplementary analyses included a fully adjusted model, an analysis restricting to those with >5 years of follow-up and models that examined the moderating effect of age, sex, and ethnoracial group. RESULTS: There were 31,250 participants from 14 nations in the analysis (41% male) with a mean baseline age of 72 (SD 7.5, range 60-110) years. Participants with untreated hypertension had a 36% (hazard ratio [HR] 1.36, 95% CI 1.01-1.83, p = 0.0406) and 42% (HR 1.42, 95% CI 1.08-1.87, p = 0.0135) increased risk of AD compared with "healthy controls" and those with treated hypertension, respectively. Compared with "healthy controls" both those with treated (HR 1.29, 95% CI 1.03-1.60, p = 0.0267) and untreated hypertension (HR 1.69, 95% CI 1.19-2.40, p = 0.0032) had greater non-AD risk, but there was no difference between the treated and untreated groups. Baseline diastolic BP had a significant U-shaped relationship (p = 0.0227) with non-AD risk in an analysis restricted to those with 5-year follow-up, but otherwise there was no significant relationship between baseline BP and either AD or non-AD risk. DISCUSSION: Antihypertensive use was associated with decreased AD but not non-AD risk throughout late life. This suggests that treating hypertension throughout late life continues to be crucial in AD risk mitigation. A single measure of BP was not associated with AD risk, but DBP may have a U-shaped relationship with non-AD risk over longer periods in late life.

Evaluation of the effectiveness of three different interventions on older driver safety over a 12-month period: study protocol for a randomised controlled trial.

INTRODUCTION: The growing population of older drivers presents challenges for road safety attributed to age-related declines and increased crash fatality rates. However, enabling older people to maintain their health and independence through continued safe driving is important. This study focuses on the urgent need for cost-effective interventions that reduce crash risk while supporting older drivers to remain driving safely for longer. Our study aims to evaluate the effectiveness of three behavioural interventions for older driver safety. These include an online road-rules refresher workshop, tailored feedback on driving performance and two tailored driving lessons. METHODS AND ANALYSIS: A single-blind three-parallel group superiority randomised controlled trial will be conducted with 198 urban licensed drivers aged 65 years and older, allowing for 4% attrition. This sample size provides 80% power to detect a difference with an alpha of 0.05. Participants will be selected based on a standardised on-road test that identifies them as moderately unsafe drivers. Interventions, spanning a 3-month period, aim to improve driving safety. Their effectiveness will be assessed through a standardised on-road assessment of driving safety at 3 months (T1) and 12 months postintervention (T2). Additionally, monthly self-reported driving diaries will provide data on crashes and incidents.This trial has the potential to identify cost-effective approaches for improving safety for older drivers and contribute to evidence-based health policy, clinical practice and guidelines. ETHICS AND DISSEMINATION: Ethical approval was obtained by the University of New South Wales Human Research Ethics Committee (HC190439, 22 August 2019). The results of the study will be disseminated in peer-reviewed journals and research conferences. TRIAL REGISTRATION NUMBER: ACTRN12622001515785.

Neighbourhood environments and cognitive health in the longitudinal Personality and Total Health (PATH) through life study: A 12-year follow-up of older Australians.

BACKGROUND: Urban neighbourhood environments may impact older adults' cognitive health. However, longitudinal studies examining key environmental correlates of cognitive health are lacking. We estimated cross-sectional and longitudinal associations of neighbourhood built and natural environments and ambient air pollution with multiple cognitive health outcomes in Australian urban dwellers aged 60+ years. METHODS: The study included 1160 participants of the PATH Through Life study (60+ cohort) who were followed up for 12 years (four assessments; 2001/02 to 2013/15) and with data on socio-demographics, health, cognitive functions and diagnoses, and full residential address. Neighbourhood environmental features encompassed population and street-intersection densities, non-commercial land use mix, transit points, presence of blue space, percentages of commercial land, parkland and tree cover, and annual average PM2.5 and NO2 concentrations. All exposures except for tree cover were assessed at two time points. Generalised additive mixed models estimated associations of person-level average, and within-person changes in, exposures with cognitive functions. Multi-state hidden Markov models estimated the associations of neighbourhood attributes with transitions to/from mild cognitive impairment (MCI). RESULTS: Dense, destination-rich neighbourhoods were associated with a lower likelihood of transition to MCI and reversal to no MCI. Positive cross-sectional and longitudinal associations of non-commercial land use mix, street intersection density and percentage of commercial land were observed especially with global cognition and processing speed. While access to parkland and blue spaces were associated with a lower risk of transition to MCI, the findings related to cognitive functions were mixed and supportive of an effect of parkland on verbal memory only. Higher levels of PM2.5 and NO2 were consistently associated with steeper declines and/or decreases in cognitive functions and worse cognitive states across time. CONCLUSION: To support cognitive health in ageing populations, neighbourhoods need to provide an optimal mix of environmental complexity, destinations and access to the natural environment and, at the same time, minimise ambient air pollution.

Impact of type 2 diabetes and its duration on incidence rates of dementia death and medication prescription in the Australian population during 2003-2016.

AIMS: To quantify rates of dementia treatment and death among Australians with type 2 diabetes relative to those without diabetes using linked national registries of Australia. METHODS: The study included 891,418 people with type 2 diabetes registered on the National Diabetes Services Scheme and a randomly sampled, population-based comparison group (n = 1,131,369). Outcomes included dementia death (all-cause dementia, Alzheimer's disease (AD) or vascular dementia), and first prescription of cholinesterase inhibitors or memantine. RESULTS: Excess dementia risk was observed in the diabetes group for the composite outcome of all-cause dementia death or dementia medication prescription but varied with age at diabetes diagnosis and its duration. At age 70, the rate of dementia death/medication prescription was ∼1.3 (95% CI 1.2, 1.3) and 1.1 (95% CI 1.1, 1.2) times higher in people with ten and five years of diabetes duration, respectively. Individual outcomes showed that diabetes was associated with a higher incidence of vascular dementia death, whereas an increased risk of AD death was only observed beyond âˆ¼10 years of diabetes duration. Further, the incidence of dementia medication prescription was lower among people with diabetes. CONCLUSIONS: A higher incidence of AD death in the setting of 10+ years of diabetes duration coupled with a lower incidence of AD treatment suggests an under-recognition of this dementia phenotype among people with type 2 diabetes.

Sex and gender differences in cognitive resilience to aging and Alzheimer's disease.

Sex and gender-biological and social constructs-significantly impact the prevalence of protective and risk factors, influencing the burden of Alzheimer's disease (AD; amyloid beta and tau) and other pathologies (e.g., cerebrovascular disease) which ultimately shape cognitive trajectories. Understanding the interplay of these factors is central to understanding resilience and resistance mechanisms explaining maintained cognitive function and reduced pathology accumulation in aging and AD. In this narrative review, the ADDRESS! Special Interest Group (Alzheimer's Association) adopted a multidisciplinary approach to provide the foundations and recommendations for future research into sex- and gender-specific drivers of resilience, including a sex/gender-oriented review of risk factors, genetics, AD and non-AD pathologies, brain structure and function, and animal research. We urge the field to adopt a sex/gender-aware approach to resilience to advance our understanding of the intricate interplay of biological and social determinants and consider sex/gender-specific resilience throughout disease stages. HIGHLIGHTS: Sex differences in resilience to cognitive decline vary by age and cognitive status. Initial evidence supports sex-specific distinctions in brain pathology. Findings suggest sex differences in the impact of pathology on cognition. There is a sex-specific change in resilience in the transition to clinical stages. Gender and sex factors warrant study: modifiable, immune, inflammatory, and vascular.

Population attributable fractions of modifiable risk factors for dementia: a systematic review and meta-analysis.

BACKGROUND: More than 57 million people have dementia worldwide. Evidence indicates a change in dementia prevalence and incidence in high-income countries, which is likely to be due to improved life-course population health. Identifying key modifiable risk factors for dementia is essential for informing risk reduction and prevention strategies. We therefore aimed to estimate the population attributable fraction (PAF) for dementia associated with modifiable risk factors. METHODS: In this systematic review and meta-analysis, we searched Embase, MEDLINE, and PsycINFO, via Ovid, from database inception up to June 29, 2023, for population-derived or community-based studies and reviews reporting a PAF value for one or more modifiable risk factor for later-life dementia (prevalent or incident dementia in people aged ≥60 years), with no restrictions on dementia subtype, the sex or baseline age of participants, or the period of study. Articles were independently screened for inclusion by four authors, with disagreements resolved through consensus. Data including unweighted and weighted PAF values (weighted to account for communality or overlap in risk) were independently extracted into a predefined template by two authors and checked by two other authors. When five or more unique studies investigated a given risk factor or combination of the same factors, random-effects meta-analyses were used to calculate a pooled PAF percentage estimate for the factor or combination of factors. The review protocol was registered on PROSPERO, CRD42022323429. FINDINGS: 4024 articles were identified, and 74 were included in our narrative synthesis. Overall, PAFs were reported for 61 modifiable risk factors, with sufficient data available for meta-analysis of 12 factors (n=48 studies). In meta-analyses, the highest pooled unweighted PAF values were estimated for low education (17·2% [95% CI 14·4-20·0], p<0·0001), hypertension (15·8% [14·7-17·1], p<0·0001), hearing loss (15·6% [10·3-20·9], p<0·0001), physical inactivity (15·2% [12·8-17·7], p<0·0001), and obesity (9·4% [7·3-11·7], p<0·0001). According to weighted PAF values, low education (9·3% [6·9-11·7], p<0·0001), physical inactivity (7·3% [3·9-11·2], p=0·0021), hearing loss (7·2% [5·2-9·7], p<0·0001), hypertension (7·1% [5·4-8·8], p<0·0001), and obesity (5·3% [3·2-7·4], p=0·0001) had the highest pooled estimates. When low education, midlife hypertension, midlife obesity, smoking, physical inactivity, depression, and diabetes were combined (Barnes and Yaffe seven-factor model; n=9 studies), the pooled unweighted and weighted PAF values were 55·0% (46·5-63·5; p<0·0001) and 32·0% (26·6-37·5; p<0·0001), respectively. The pooled PAF values for most individual risk factors were higher in low-income and middle-income countries (LMICs) versus high-income countries. INTERPRETATION: Governments need to invest in a life-course approach to dementia prevention, including policies that enable quality education, health-promoting environments, and improved health. This investment is particularly important in LMICs, where the potential for prevention is high, but resources, infrastructure, budgets, and research focused on ageing and dementia are limited. FUNDING: UK Research and Innovation (Medical Research Council).

Barriers Experienced by Community-Dwelling Older Adults Navigating Formal Care: Evidence From an Australian Population-Based National Survey.

OBJECTIVES: This study aims to identify the relationship between psychosocial factors and unmet needs among community-dwelling older adults who have received or who expect to receive formal home-based aged care services. METHODS: A subsample of the national Survey of Disability, Ageing and Carers was used to examine the prevalence of having any unmet needs among older adults navigating care. We also examined associations between older adults' psychosocial factors and their unmet needs using logistic regression. RESULTS: Regression analyses highlighted that perceived social isolation (OR = 1.62, 95% CI: 1.30-2.01), high/very high psychological distress (OR = 2.11, 95% CI: 1.52-2.93), and occasional assistance from informal support (OR = 1.92, 95% CI: 1.22-3.05) were associated with increased odds of having unmet needs, after adjusting for other covariates. DISCUSSION: Our study suggests that older adults facing psychosocial difficulties or lacking informal support are more likely to encounter barriers in accessing formal care. Future policy should address the psychosocial needs and support networks of older adults.

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.

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.

A Scoping Survey to Inform Design of Digital Dementia Risk Reduction Interventions for Adults Concerned about their Cognitive Health.

Background: Digital dementia risk reduction interventions are cost-effective and scalable. However, it is unknown how they are perceived by people already experiencing cognitive concerns or decline. Objective: To understand the current use, interest, and preferences for online learning courses and interest in learning about factors influencing brain health and dementia risk among adults ≥45. To explore potential differences between individuals experiencing cognitive concerns and those without. Methods: Adults aged 45 and older completed a survey on technology use and healthy ageing (n = 249, Mean age = 65.6, 76.3% female). The Memory Assessment Clinic-Questionnaire was used to assess subjective memory decline, and 153 participants met the study criteria for cognitive concerns (≥25). Results: Almost all participants (98.4%) reported using two or more digital devices, and 51.8% reported increasing device usage following COVID-19. Most (92.1%) were interested in learning about healthy living and memory within an online course, and over 80% indicated a high interest in learning about dementia risk factors. People with cognitive concerns were more likely to report using a 'routine or system' to aid memory than people without (82.4% versus 62.9%, p = 0.001). However, no significant difference was found in technology use, course preferences, or interest in learning about different risk factors. Conclusions: We conclude that adults 45 years and over are interested in online methods for learning about brain health and offer unique insights into adapting dementia prevention programs for cognitive concerns.

Associations between fruit and vegetable intakes and incident depression in middle-aged and older adults from 10 diverse international longitudinal cohorts.

BACKGROUND: Emerging observational evidence supports a role for higher fruit and vegetable intake in protecting against the development of depression. However, there is a scarcity of research in older adults or in low- to middle-income countries (LMICs). METHODS: Participants were 7801 community-based adults (mean age 68.6 ± 8.0 years, 55.8 % female) without depression, from 10 diverse cohorts, including four cohorts from LMICs. Fruit and vegetable intake was self-reported via comprehensive food frequency questionnaire, short food questionnaire or diet history. Depressive symptoms were assessed using validated measures, and depression defined applying validated cut-offs. The associations between baseline fruit and vegetable intakes and incident depression over a follow-up period of three to nine years were examined using Cox regression. Analyses were performed by cohort with results meta-analysed. RESULTS: There were 1630 cases of incident depression (21 % of participants) over 40,258 person-years of follow-up. Higher intake of fruit was associated with a lower risk of incident depression (HR 0.87, 95%CI [0.77, 0.99], I2 = 4 %). No association was found between vegetable intake and incident depression (HR 0.93, 95%CI [0.84, 1.04], I2 = 0 %). LIMITATIONS: Diverse measures used across the different cohorts and the modest sample size of our study compared with prior studies may have prevented an association being detected for vegetable intake. CONCLUSIONS: Our study supports a role for fruit, but not vegetable intake in protecting against depression. Research investigating different types of fruits and vegetables using standardised measures in larger cohorts of older adults from low- and middle-income countries is warranted.

The AUstralian multidomain Approach to Reduce dementia Risk by prOtecting brain health With lifestyle intervention study (AU-ARROW): A study protocol for a single-blind, multi-site, randomized controlled trial.

INTRODUCTION: The Finnish Geriatric Intervention Study (FINGER) led to the global dementia risk reduction initiative: World-Wide FINGERS (WW-FINGERS). As part of WW-FINGERS, the Australian AU-ARROW study mirrors aspects of FINGER, as well as US-POINTER. METHOD: AU-ARROW is a randomized, single-blind, multisite, 2-year clinical trial (n = 600; aged 55-79). The multimodal lifestyle intervention group will engage in aerobic exercise, resistance training and stretching, dietary advice to encourage MIND diet adherence, BrainHQ cognitive training, and medical monitoring and health education. The Health Education and Coaching group will receive occasional health education sessions. The primary outcome measure is the change in a global composite cognitive score. Extra value will emanate from blood biomarker analysis, positron emission tomography (PET) imaging, brain magnetic resonance imaging (MRI), and retinal biomarker tests. DISCUSSION: The finalized AU-ARROW protocol is expected to allow development of an evidence-based innovative treatment plan to reduce cognitive decline and dementia risk, and effective transfer of research outcomes into Australian health policy. Highlights: Study protocol for a single-blind, randomized controlled trial, the AU-ARROW Study.The AU-ARROW Study is a member of the World-Wide FINGERS (WW-FINGERS) initiative.AU-ARROW's primary outcome measure is change in a global composite cognitive score.Extra significance from amyloid PET imaging, brain MRI, and retinal biomarker tests.Leading to development of an innovative treatment plan to reduce cognitive decline.

Risk factors and cognitive correlates of white matter hyperintensities in ethnically diverse populations without dementia: The COSMIC consortium.

INTRODUCTION: White matter hyperintensities (WMHs) are an important imaging marker for cerebral small vessel diseases, but their risk factors and cognitive associations have not been well documented in populations of different ethnicities and/or from different geographical regions. METHODS: We investigated how WMHs were associated with vascular risk factors and cognition in both Whites and Asians, using data from five population-based cohorts of non-demented older individuals from Australia, Singapore, South Korea, and Sweden (N = 1946). WMH volumes (whole brain, periventricular, and deep) were quantified with UBO Detector and harmonized using the ComBat model. We also harmonized various vascular risk factors and scores for global cognition and individual cognitive domains. RESULTS: Factors associated with larger whole brain WMH volumes included diabetes, hypertension, stroke, current smoking, body mass index, higher alcohol intake, and insufficient physical activity. Hypertension and stroke had stronger associations with WMH volumes in Whites than in Asians. No associations between WMH volumes and cognitive performance were found after correction for multiple testing. CONCLUSION: The current study highlights ethnic differences in the contributions of vascular risk factors to WMHs.

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.

Childhood adversity is associated with anxiety and depression in older adults: A cumulative risk and latent class analysis.

BACKGROUND: The long-lasting influence of childhood adversity on mental health is well documented; however empirical research examining how this association extends into older adults is limited. This study operationalises adversity using cumulative risk and latent class analysis (LCA) models to assess how adversity exposure and typologies may predict anxiety and depression in older adults. METHODS: Data came from the Personality and Total Health (PATH) Through Life Project (N = 2551, age 60-66). Participants retrospectively reported their childhood experiences of domestic adversity on a 17-item scale. Mental health was measured using four validated questionnaires of depression and anxiety. RESULTS: Linear and generalised additive models (GAM) indicated a dose-response relationship, where a greater number of cumulative adversities were associated with poorer scores on all four mental health measures. LCA identified a four-class solution; with high adversity and high parental dysfunction being associated with poorer mental health outcomes while moderate parental dysfunction and low adversity groups scored at healthy levels. Women reported higher overall anxiety than men, but no notable interactions between ACEs and gender were observed. Patterns revealed by LCA were similar to patterns shown by the cumulative risk model. LIMITATIONS: There is a large time gap from childhood to assessment, making our study susceptible to recall bias. Also, our findings were based on cross-sectional data, limiting causal inferences. CONCLUSION: Childhood adversity had independent and additive contributions to depression and anxiety in older adulthood, and both cumulative risk and person-centred approaches captured this relationship.

The Australian National University Alzheimer's Disease Risk Index (ANU-ADRI) score as a predictor for cognitive decline and potential surrogate outcome in the FINGER lifestyle randomized controlled trial.

BACKGROUND AND PURPOSE: The complex aetiology of Alzheimer's disease suggests prevention potential. Risk scores have potential as risk stratification tools and surrogate outcomes in multimodal interventions targeting specific at-risk populations. The Australian National University Alzheimer's Disease Risk Index (ANU-ADRI) was tested in relation to cognition and its suitability as a surrogate outcome in a multidomain lifestyle randomized controlled trial, in older adults at risk of dementia. METHODS: In this post hoc analysis of the Finnish Intervention Study to Prevent Cognitive Impairment and Disability (FINGER), ANU-ADRI was calculated at baseline, 12, and 24 months (n = 1174). The association between ANU-ADRI and cognition (at baseline and over time), the intervention effect on changes in ANU-ADRI, and the potential impact of baseline ANU-ADRI on the intervention effect on changes in cognition were assessed using linear mixed models with maximum likelihood estimation. RESULTS: A higher ANU-ADRI was significantly related to worse cognition, at baseline (e.g., estimate for global cognition [95% confidence interval] was -0.028 [-0.032 to -0.025]) and over the 2-year study (e.g., estimate for 2-year changes in ANU-ADRI and per-year changes in global cognition [95% confidence interval] was -0.068 [-0.026 to -0.108]). No significant beneficial intervention effect was reported for ANU-ADRI, and baseline ANU-ADRI did not significantly affect the response to the intervention on changes in cognition. CONCLUSIONS: The ANU-ADRI was effective for the risk prediction of cognitive decline. Risk scores may be crucial for the success of novel dementia prevention strategies, but their algorithm, the target population, and the intervention design should be carefully considered when choosing the appropriate tool for each context.

Protocol of a 12-week eHealth programme designed to reduce concerns about falling in community-living older people: Own Your Balance randomised controlled trial.

INTRODUCTION: Concerns about falling (CaF) are common in older people and have been associated with avoidance of activities of daily life. Exercise designed to prevent falls can reduce CaF, but the effects are usually short-lived. Cognitive behavioural therapy (CBT) can reduce CaF for longer but is not readily available in the community and unlikely to prevent falls. A multidomain intervention that combines CBT, motivational interviewing and exercise could be the long-term solution to treat CaF and reduce falls in older people with CaF. This paper describes the design of a randomised controlled trial to test the effectiveness of two different 12 week self-managed eHealth programmes to reduce CaF compared with an active control. METHODS: A total of 246 participants (82 per group) aged 65 and over, with substantial concerns about falls or balance will be recruited from the community. They will be randomised into: (1) myCompass-Own Your Balance (OYB) (online CBT programme) intervention or (2) myCompass-OYB plus StandingTall intervention (an eHealth balance exercise programme), both including motivational interviewing and online health education or (3) an active control group (online health education alone). The primary outcome is change in CaF over 12 months from baseline of both intervention groups compared with control. The secondary outcomes at 2, 6 and 12 months include balance confidence, physical activity, habitual daily activity, enjoyment of physical activity, social activity, exercise self-efficacy, rate of falls, falls health literacy, mood, psychological well-being, quality of life, exercise self-efficacy, programme adherence, healthcare use, user experience and attitudes towards the programme. An intention-to-treat analysis will be applied. The healthcare funder's perspective will be adopted for the economic evaluation if appropriate. ETHICS AND DISSEMINATION: Ethical approval was obtained from the South Eastern Sydney Local Health District Human Research Ethics Committee (2019/ETH12840). Results will be disseminated via peer-reviewed journals, local and international conferences, community events and media releases. TRIAL REGISTRATION NUMBER: ACTRN12621000440820.

Sex and gender differences in risk scores for dementia and Alzheimer's disease among cisgender, transgender, and non-binary adults.

INTRODUCTION: Few studies have explored dementia risk according to sex and gender including for transgender and non-binary adults. This study evaluated dementia risk factors and risk scores among cisgender, transgender, and non-binary adults. METHODS: Observational data were drawn from the 2019 Behavioral Risk Factor Surveillance System. A matched-cohort approach was used to develop sex (male, female) and gender identity cohorts (cisgender men, cisgender women, transgender men, transgender women, and non-binary adults) for comparison. Dementia risk scores were calculated using established mid-life and late-life risk score algorithms. RESULTS: Males had higher overall mid-life dementia risk, and lower late-life Alzheimer's disease risk compared to females. Transgender men, transgender women, and non-binary adults had higher overall late-life risk compared to both cisgender men and women. DISCUSSION: Future research is needed to build the evidence base for specific risk factors that may be contributing to higher overall risk among understudied and underserved gender groups. HIGHLIGHTS: Using data from the 2019 Behavioral Risk Factor Surveillance System, this matched-cohort study found that those assigned female at birth had lower overall mid-life dementia risk and higher overall late-life Alzheimer's disease (AD) risk compared to those assigned male at birth. Transgender men, transgender women, and non-binary adults all showed higher overall late-life AD risk compared to cisgender men and cisgender women. Between-group differences were found in the incidence of specific risk and protective factors for dementia and AD.