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.

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.

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.

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.

The impact of mild cognitive impairment on decision-making under explicit risk conditions: Evidence from the Personality and Total Health (PATH) Through Life longitudinal study.

OBJECTIVE: Previous research has indicated that cognition and executive function are associated with decision-making, however the impact of mild cognitive impairment (MCI) on decision-making under explicit risk conditions is unclear. This cross-sectional study examined the impact of MCI, and MCI subtypes, on decision-making on the Game of Dice Task (GDT), among a cohort of older adults. METHOD: Data from 245 older adult participants (aged 72-78 years) from the fourth assessment of the Personality and Total Health Through Life study were analyzed. A diagnostic algorithm identified 103 participants with MCI, with subtypes of single-domain amnestic MCI (aMCI-single; n = 38), multi-domain amnestic MCI (aMCI-multi; n = 31), and non-amnestic MCI (n = 33), who were compared with an age-, sex-, education-, and income-matched sample of 142 cognitively unimpaired older adults. Decision-making scores on the GDT (net score, single number choices, and strategy changes) were compared between groups using nonparametric tests. RESULTS: Participants with MCI showed impaired performance on the GDT, with higher frequencies of single number choices and strategy changes. Analyses comparing MCI subtypes indicated that the aMCI-multi subtype showed increased frequency of single number choices compared to cognitively unimpaired participants. Across the sample of participants, decision-making scores were associated with measures of executive function (cognitive flexibility and set shifting). CONCLUSION: MCI is associated with impaired decision-making performance under explicit risk conditions. Participants with impairments in multiple domains of cognition showed the clearest impairments. The GDT may have utility in discriminating between MCI subtypes.

Large Discrepancies in Dementia Mortality Reported in Vital Statistics: The Need for Improved Data to Inform Policy.

PURPOSE: There is limited understanding of the intercountry comparability of dementia mortality data. This study compares reported dementia mortality in national vital statistics between countries and over time. In countries with low dementia reporting, this study identifies other causes to which dementia may be misclassified. METHODS: Using the World Health Organization (WHO) Mortality Database, we calculated the ratio of reported to expected (Global Burden of Disease estimated) age-standardized dementia death rates in 90 countries from 2000 to 2019. Other causes to which dementia may be misclassified were identified as having relatively high cause fractions compared with other countries. PATIENTS: No patients were involved. RESULTS: There is a large intercountry variation in reported dementia mortality rates. The ratio of reported to expected dementia mortality exceeded 100% in high-income countries but was below 50% in other super regions. In countries with low reported dementia mortality, cardiovascular diseases, ill-defined causes, and pneumonia have relatively high cause fractions and may be misclassified from dementia. DISCUSSION: Large discrepancies in dementia mortality reporting between countries, including often implausibly low reported mortality, makes comparison extremely difficult. Improved guidance for and training of certifiers and the use of multiple cause-of-death data can help strengthen the policy utility of dementia mortality data.

Longitudinal Effects of Physical Activity Change on Hippocampal Volumes over up to 12 Years in Middle and Older Age Community-Dwelling Individuals.

The objectives of this study were to investigate the long-term associations between changes in physical activity levels and hippocampal volumes over time, while considering the influence of age, sex, and APOE-ε4 genotype. We investigated the effects of change in physical activity on hippocampal volumes in 411 middle age (mean age = 47.2 years) and 375 older age (mean age = 63.1 years) adults followed up to 12 years. An annual volume decrease was observed in the left (middle age: 0.46%; older age: 0.51%) but not in the right hippocampus. Each additional 10 metabolic equivalents (METs, ~2 h of moderate exercise) increase in weekly physical activity was associated with 0.33% larger hippocampal volume in middle age (equivalent to ~1 year of typical aging). In older age, each additional MET was associated with 0.05% larger hippocampal volume; however, the effects declined with time by 0.005% per year. For older age APOE-ε4 carriers, each additional MET was associated with a 0.10% increase in hippocampal volume. No sex effects of physical activity change were found. Increasing physical activity has long-term positive effects on hippocampal volumes and appears especially beneficial for older APOE-ε4 carriers. To optimize healthy brain aging, physical activity programs should focus on creating long-term exercise habits.

Multi-domain prognostic models used in middle-aged adults without known cognitive impairment for predicting subsequent dementia.

BACKGROUND: Dementia, a global health priority, has no current cure. Around 50 million people worldwide currently live with dementia, and this number is expected to treble by 2050. Some health conditions and lifestyle behaviours can increase or decrease the risk of dementia and are known as 'predictors'. Prognostic models combine such predictors to measure the risk of future dementia. Models that can accurately predict future dementia would help clinicians select high-risk adults in middle age and implement targeted risk reduction. OBJECTIVES: Our primary objective was to identify multi-domain prognostic models used in middle-aged adults (aged 45 to 65 years) for predicting dementia or cognitive impairment. Eligible multi-domain prognostic models involved two or more of the modifiable dementia predictors identified in a 2020 Lancet Commission report and a 2019 World Health Organization (WHO) report (less education, hearing loss, traumatic brain injury, hypertension, excessive alcohol intake, obesity, smoking, depression, social isolation, physical inactivity, diabetes mellitus, air pollution, poor diet, and cognitive inactivity). Our secondary objectives were to summarise the prognostic models, to appraise their predictive accuracy (discrimination and calibration) as reported in the development and validation studies, and to identify the implications of using dementia prognostic models for the management of people at a higher risk for future dementia. SEARCH METHODS: We searched MEDLINE, Embase, PsycINFO, CINAHL, and ISI Web of Science Core Collection from inception until 6 June 2022. We performed forwards and backwards citation tracking of included studies using the Web of Science platform.  SELECTION CRITERIA: We included development and validation studies of multi-domain prognostic models. The minimum eligible follow-up was five years. Our primary outcome was an incident clinical diagnosis of dementia based on validated diagnostic criteria, and our secondary outcome was dementia or cognitive impairment determined by any other method. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the references, extracted data using a template based on the CHecklist for critical Appraisal and data extraction for systematic Reviews of prediction Modelling Studies (CHARMS), and assessed risk of bias and applicability of included studies using the Prediction model Risk Of Bias ASsessment Tool (PROBAST). We synthesised the C-statistics of models that had been externally validated in at least three comparable studies.  MAIN RESULTS: We identified 20 eligible studies; eight were development studies and 12 were validation studies. There were 14 unique prognostic models: seven models with validation studies and seven models with development-only studies. The models included a median of nine predictors (range 6 to 34); the median number of modifiable predictors was five (range 2 to 11). The most common modifiable predictors in externally validated models were diabetes, hypertension, smoking, physical activity, and obesity. In development-only models, the most common modifiable predictors were obesity, diabetes, hypertension, and smoking. No models included hearing loss or air pollution as predictors. Nineteen studies had a high risk of bias according to the PROBAST assessment, mainly because of inappropriate analysis methods, particularly lack of reported calibration measures. Applicability concerns were low for 12 studies, as their population, predictors, and outcomes were consistent with those of interest for this review. Applicability concerns were high for nine studies, as they lacked baseline cognitive screening or excluded an age group within the range of 45 to 65 years. Only one model, Cardiovascular Risk Factors, Ageing, and Dementia (CAIDE), had been externally validated in multiple studies, allowing for meta-analysis. The CAIDE model included eight predictors (four modifiable predictors): age, education, sex, systolic blood pressure, body mass index (BMI), total cholesterol, physical activity and APOEƐ4 status. Overall, our confidence in the prediction accuracy of CAIDE was very low; our main reasons for downgrading the certainty of the evidence were high risk of bias across all the studies, high concern of applicability, non-overlapping confidence intervals (CIs), and a high degree of heterogeneity. The summary C-statistic was 0.71 (95% CI 0.66 to 0.76; 3 studies; very low-certainty evidence) for the incident clinical diagnosis of dementia, and 0.67 (95% CI 0.61 to 0.73; 3 studies; very low-certainty evidence) for dementia or cognitive impairment based on cognitive scores. Meta-analysis of calibration measures was not possible, as few studies provided these data. AUTHORS' CONCLUSIONS: We identified 14 unique multi-domain prognostic models used in middle-aged adults for predicting subsequent dementia. Diabetes, hypertension, obesity, and smoking were the most common modifiable risk factors used as predictors in the models. We performed meta-analyses of C-statistics for one model (CAIDE), but the summary values were unreliable. Owing to lack of data, we were unable to meta-analyse the calibration measures of CAIDE. This review highlights the need for further robust external validations of multi-domain prognostic models for predicting future risk of dementia in middle-aged adults.

Mixed Evidence of an Association between Self-Rated Hearing Difficulties and Falls: Prospective Analysis of Two Longitudinal Studies.

INTRODUCTION: This study aimed to assess the extent to which a single item of self-reported hearing difficulties is associated with future risk of falling among community-dwelling older adults. METHODS: We used data from two Australian population-based cohorts: three waves from the PATH Through Life study (PATH; n = 2,048, 51% men, age 66.5 ± 1.5 SD years) and three waves from the Concord Health and Ageing in Men Project (CHAMP; n = 1,448, 100% men with mean age 77.3 ± 5.3 SD years). Hearing difficulties were recorded on a four-point ordinal scale in PATH and on a dichotomous scale in CHAMP. The number of falls in the past 12 months was reported at each wave in both studies. In CHAMP, incident falls were also ascertained by triannual telephone call cycles for up to four years. Multivariable-adjusted random intercept negative binomial regression models were used to estimate the association between self-reported hearing difficulties and number of falls reported at the following wave or 4-monthly follow-ups. RESULTS: In PATH, self-reported hearing difficulties were associated with a higher rate of falls at follow-up (incidence rate ratio = 1.15, 95% CI = 1.03-1.27 per a one-level increase in self-reported hearing difficulties), after adjusting for sociodemographic characteristics, health behaviours, physical functioning, balance, mental health, medical conditions, and medications. There were no significant associations between hearing difficulties and the rate of falls based on either repeated survey or 4-monthly follow-ups in CHAMP. CONCLUSION: Though we find mixed results, findings from PATH data indicate an ordinal measure of self-reported hearing loss may be predictive of falls incidence in young-old adults. However, the null findings in the male-only CHAMP preclude firm conclusions of a link between hearing loss and falls risk.

Parental history of dementia and the risk of dementia: A cross-sectional analysis of a global collaborative study.

BACKGROUND: Parental history of dementia appears to increase the risk of dementia, but there have been inconsistent results. We aimed to investigate whether the association between parental history of dementia and the risk of dementia are different by dementia subtypes and sex of parent and offspring. METHODS: For this cross-sectional study, we harmonized and pooled data for 17,194 older adults from nine population-based cohorts of eight countries. These studies conducted face-to-face diagnostic interviews, physical and neurological examinations, and neuropsychological assessments to diagnose dementia. We investigated the associations of maternal and paternal history of dementia with the risk of dementia and its subtypes in offspring. RESULTS: The mean age of the participants was 72.8 ± 7.9 years and 59.2% were female. Parental history of dementia was associated with higher risk of dementia (odds ratio [OR] = 1.47, 95% confidence interval [CI] = 1.15-1.86) and Alzheimer's disease (AD) (OR = 1.72, 95% CI = 1.31-2.26), but not with the risk of non-AD. This was largely driven by maternal history of dementia, which was associated with the risk of dementia (OR = 1.51, 95% CI = 1.15-1.97) and AD (OR = 1.80, 95% CI = 1.33-2.43) whereas paternal history of dementia was not. These results remained significant when males and females were analyzed separately (OR = 2.14, 95% CI = 1.28-3.55 in males; OR = 1.68, 95% CI = 1.16-2.44 for females). CONCLUSIONS: Maternal history of dementia was associated with the risk of dementia and AD in both males and females. Maternal history of dementia may be a useful marker for identifying individuals at higher risk of AD and stratifying the risk for AD in clinical trials.

Who displays dementia-related stigma and what does the general public know about dementia? Findings from a nationally representative survey.

OBJECTIVES: To identify the characteristics of those who tend to hold stigmatising beliefs and behaviours towards people living with dementia to inform dementia education and the targeting of interventions to reduce dementia-related stigma.A nationally representative telephone survey of 1000 Australians aged 18-93 years was conducted to assess general knowledge of dementia and dementia-related stigma. A single open-ended question was used to assess participants' general knowledge of dementia. Modified items from the Lay Public Dimension of the Family Stigma in Alzheimer's Disease Scale were used to assess dementia-related stigma.Only 26% of participants demonstrated good dementia knowledge while almost half of the participants had a mixed understanding of dementia. Dementia-related negative cognitive attributions were found to be higher in (1) the older age cohorts, (2) amongst individuals who know someone with dementia, (3) speak a language other than English at home, and (4) have a better understanding of dementia. Older age cohorts, men, those who do not know someone with dementia, and those who speak a non-English language at home also reported significantly higher discriminatory behavioural reactions compared to the younger age cohorts, females, those who know someone with dementia, and those who speak English only at home.This study identifies a need for improved public education about dementia. A structured approach to the development of strategies that is specifically tailored to different age, gender and cultural groups may provide a beneficial approach to help improve dementia knowledge and reduce dementia-related stigma in the population.

Residential aged care staff perceptions and responses towards neuropsychiatric symptoms: a mixed methods analysis of electronic healthcare records.

OBJECTIVES: To investigate electronic care notes to better understand reporting and management of neuropsychiatric symptoms (NPS) by residential aged care (RAC) staff. METHODS: We examined semi-structured care notes from electronic healthcare notes of 77 residents (67% female; aged 67-101; 79% with formal dementia diagnosis) across three RAC facilities. As part of standard clinical practice, staff documented the NPS presentation and subsequent management amongst residents. Using a mixed-method approach, we analyzed the type of NPS reported and explored care staff responses to NPS using inductive thematic analysis. RESULTS: 465 electronic care notes were recorded during the 18-month period. Agitation-related behaviors were most frequently reported across residents (48.1%), while psychosis (15.6%), affective symptoms (14.3%), and apathy (1.3%) were less often reported. Only 27.5% of the notes contained information on potential causes underlying NPS. When faced with NPS, care staff responded by either providing emotional support, meeting resident's needs, removing identified triggers, or distracting. CONCLUSION: Results suggest that RAC staff primarily detected and responded to those NPS they perceived as distressing. Findings highlight a potential under-recognition of specific NPS types, and lack of routine examination of NPS causes or systematic assessment and management of NPS. These observations are needed to inform the development and implementation of non-pharmacological interventions and care programs targeting NPS in RAC.Supplemental data for this article is available online at https://doi.org/10.1080/13607863.2022.2032597 .

What would a population-level approach to dementia risk reduction look like, and how would it work?

Dementia is a leading global public health challenge. Prevention approaches have traditionally focused on individual-level strategies. However, such approaches have limited potential, particularly for resource-constrained populations in which exposure to risk factors is greatest, and exposure to protective factors is lowest. A population-level approach to dementia risk reduction is therefore essential to meet the scale of the challenge and to tackle global inequalities in risk and incidence of disease. Such approaches can be highly cost effective. In this viewpoint article, we describe what such an approach should look like, barriers and facilitators to success, and how we should go about achieving it. We include 10 strategic goals to achieve population-level dementia risk reduction and protection enhancement, targeted at researchers, professionals, funders, science communicators, governments, businesses, and policy makers. If we are to significantly reduce the prevalence of dementia there must be increased emphasis on population-level approaches. HIGHLIGHTS: Dementia risk reduction is a global public health priority Population-level approaches change societal conditions to make them less conducive to dementia's modifiable risk factors, and increase exposure to protective factors. Urgent development of population-level approaches is required to reduce the prevalence of, and inequalities in, dementia Action is required from researchers, governments and business, funders, public health professionals, and science communicators.

Is the Rise in Reported Dementia Mortality Real? Analysis of Multiple-Cause-of-Death Data for Australia and the United States.

Official statistics in Australia and the United States show large recent increases in dementia mortality rates. In this study, we assessed whether these trends are biased by an increasing tendency of medical certifiers (predominantly physicians) to report on the death certificate that dementia was a direct cause of death. Regression models of multiple-cause-of-death data in Australia (2006-2016) and the United States (2006-2017) were constructed to adjust dementia mortality rates for changes in death certification practices. Compared with official statistics, the recent increase in adjusted age-standardized dementia death rates was less than half as large in Australia and about two-thirds as large in the United States. Further adjustment for changes in reporting of dementia anywhere on the death certificate implied even lower increases in dementia mortality. Declines in reporting of cardiovascular diseases as comorbid conditions also contributed to rises in dementia mortality rates. The increasing likelihood of dementia's being reported as directly leading to death largely explains recent increases in dementia mortality rates in both countries. However, studies have found that reported dementia on death certificates remains low compared with clinical evaluations of its prevalence. Improved guidance and training for certifiers in reporting of dementia on death certificates will help standardize mortality statistics within and between countries.

Social Cognition and Social Functioning in MCI and Dementia in an Epidemiological Sample.

OBJECTIVE: Social cognition is impaired in mild cognitive impairment (MCI) and dementia. However, its relationship to social functioning and perceived social support has yet to be explored. Here, we examine how theory of mind (ToM) relates to social functioning in MCI and dementia. METHODS: Older adults (cognitively normal = 1272; MCI = 132; dementia = 23) from the PATH Through Life project, a longitudinal, population-based study, were assessed on the Reading the Mind in the Eyes Test (RMET), measures of social functioning, and social well-being. The associations between RMET performance, social functioning, and cognitive status were analysed using generalised linear models, adjusting for demographic variables. RESULTS: Participants with MCI (b=-.52, 95% CI [-.70, -.33]) and dementia (b=-.78, 95% CI [-1.22, -.34]) showed poorer RMET performance than cognitively normal participants. Participants with MCI and dementia reported reduced social network size (b=-.21, 95% CI [-.40, -.02] and b=-.90, 95% CI [-1.38, -.42], respectively) and participants with dementia reported increased loneliness (b = .36, 95% CI [.06, .67]). In dementia, poorer RMET performance was associated with increased loneliness (b=-.07, 95% CI [-.14, -.00]) and a trend for negative interactions with partners (b=-.37, 95% CI [-.74, .00]), but no significant associations were found in MCI. CONCLUSIONS: MCI and dementia were associated with poor self-reported social function. ToM deficits were related to poor social function in dementia but not MCI. Findings highlight the importance of interventions to address social cognitive deficits in persons with dementia and education of support networks to facilitate positive interactions and social well-being.

Nutrition Module design in Maintain Your Brain: an internet-based randomised controlled trial to prevent cognitive decline and dementia.

The Maintain Your Brain (MYB) trial is one of the largest internet-delivered multidomain randomised controlled trial designed to target modifiable risk factors for dementia. It comprises four intervention modules: physical activity, nutrition, mental health and cognitive training. This paper explains the MYB Nutrition Module, which is a fully online intervention promoting the adoption of the 'traditional' Mediterranean Diet (MedDiet) pattern for those participants reporting dietary intake that does not indicate adherence to a Mediterranean-type cuisine or those who have chronic diseases/risk factors for dementia known to benefit from this type of diet. Participants who were eligible for the Nutrition Module were assigned to one of the three diet streams: Main, Malnutrition and Alcohol group, according to their medical history and adherence to the MedDiet at baseline. A short dietary questionnaire was administered weekly during the first 10 weeks and then monthly during the 3-year follow-up to monitor whether participants adopted or maintained the MedDiet pattern during the intervention. As the Nutrition Module is a fully online intervention, resources that promoted self-efficacy, self-management and process of change were important elements to be included in the module development. The Nutrition Module is unique in that it is able to individualise the dietary advice according to both the medical and dietary history of each participant; the results from this unique intervention will contribute substantively to the evidence that links the Mediterranean-type diet with cognitive function and the prevention of dementia and will increase our understanding of the benefits of a MedDiet in a Western country.

The influence of adiposity on the interactions between strength, physical function and cognition among older adults in the Australian Diabetes, Obesity and Lifestyle (AusDiab) study.

BACKGROUND: Being overweight or obese may be associated with lower physical and cognitive function, but in late-adulthood (≥ 65 years) evidence is mixed. This study aimed to investigate how being overweight or obese affected interactions between muscle strength, function and cognition in Australians aged ≥ 50 years, and whether interactions varied according to age (i.e. ≥ 50-65 vs > 65 years). METHODS: This study included 2368 adults [mean (standard deviation) age: 63 (7) years; 56% female] from the 2011/2012 Australian Diabetes, Obesity and Lifestyle (AusDiab) follow-up. Physical function was assessed via timed up-and-go (TUG) and muscle strength from knee extensor strength (KES). Cognition was assessed using Mini-Mental-State Exam (MMSE), Spot-the-Word (STW), California Verbal Learning Test (CVLT) and Symbol-Digit-Modalities Test (SDMT). Beta binomial regression was used to evaluate how being overweight or obese influenced strength, physical and cognitive function associations. RESULTS: Being overweight or obese did not affect strength-cognition associations regardless of sex or age. With slower physical function; obese females showed better STW (odds ratio [OR] 95% CI]: 1.070 [1.016, 1.127], P = 0.011); obese men better MMSE (OR [95% CI]: 1.157 [1.012, 1.322], P = 0.033); and obese men aged > 65 better CVLT (OR [95% CI]: 1.122 [1.035, 1.217], P = 0.019) and MMSE (OR [95% CI]: 1.233 [1.049, 1.449], P = 0.017) compared to normal weight participants. CONCLUSION: Slower physical function was associated with better performance in some cognitive domains in obese, but not in non-obese adults aged ≥ 50 years. These findings suggest some benefits of obesity to aspects of cognition when physical function is slower, but longitudinal follow-up studies are needed.

Attitudes toward own aging and cognition among individuals living with and without dementia: findings from the IDEAL programme and the PROTECT study.

BACKGROUND: It is unclear whether people with dementia (PwD) have more negative attitudes toward own aging (ATOA) than people without dementia and what factors influence ATOA among PwD. We investigated whether PwD have more negative ATOA than individuals without dementia and whether cognition and dementia subtype are associated with ATOA in PwD. METHODS: Data from the IDEAL and PROTECT studies were used to compare ATOA between 1502 PwD (mean (SD) age = 76.3 (8.5)) and 6377 individuals without dementia (mean (SD) age = 66.1 (7.1)). Linear regressions and ANOVA were used. RESULTS: PwD reported slightly more negative ATOA than people without dementia; this relationship disappeared after controlling for depression and self-rated health. In PwD more positive ATOA showed negligible associations with better general cognition, memory performance, verbal fluency, and visuospatial ability. However, after adjusting for covariates only better visuospatial ability predicted more positive ATOA. Additional analyses showed that before and after controlling for covariates, individuals with poorer self-reported visual acuity have more negative ATOA. Amongst dementia subtypes, people with Parkinson's disease dementia and dementia with Lewy bodies reported most negative ATOA. CONCLUSIONS: ATOA between PwD and people without dementia do not differ. ATOA in PwD appear to be affected not by cognitive impairment but by other characteristics that vary across dementia subtypes. Among PwD, those with Parkinson's disease dementia and dementia with Lewy bodies may have higher risk of experiencing negative ATOA due to the motor and visual impairments that they experience.

Associations between data-driven lifestyle profiles and cognitive function in the AusDiab study.

BACKGROUND: Mounting evidence highlights the importance of combined modifiable lifestyle factors in reducing risk of cognitive decline and dementia. Several a priori additive scoring approaches have been established; however, limited research has employed advanced data-driven approaches to explore this association. This study aimed to examine the association between data-driven lifestyle profiles and cognitive function in community-dwelling Australian adults. METHODS: A cross-sectional study of 4561 Australian adults (55.3% female, mean age 60.9 ± 11.3 years) was conducted. Questionnaires were used to collect self-reported data on diet, physical activity, sedentary time, smoking status, and alcohol consumption. Cognitive testing was undertaken to assess memory, processing speed, and vocabulary and verbal knowledge. Latent Profile Analysis (LPA) was conducted to identify subgroups characterised by similar patterns of lifestyle behaviours. The resultant subgroups, or profiles, were then used to further explore associations with cognitive function using linear regression models and an automatic Bolck, Croon & Hagenaars (BCH) approach. RESULTS: Three profiles were identified: (1) "Inactive, poor diet" (76.3%); (2) "Moderate activity, non-smokers" (18.7%); and (3) "Highly active, unhealthy drinkers" (5.0%). Profile 2 "Moderate activity, non-smokers" exhibited better processing speed than Profile 1 "Inactive, poor diet". There was also some evidence to suggest Profile 3 "Highly active, unhealthy drinkers" exhibited poorer vocabulary and verbal knowledge compared to Profile 1 and poorer processing speed and memory scores compared to Profile 2. CONCLUSION: In this population of community-dwelling Australian adults, a sub-group characterised by moderate activity levels and higher rates of non-smoking had better cognitive function compared to two other identified sub-groups. This study demonstrates how LPA can be used to highlight sub-groups of a population that may be at increased risk of dementia and benefit most from lifestyle-based multidomain intervention strategies.

The epidemiology is promising, but the trial evidence is weak. Why pharmacological dementia risk reduction trials haven't lived up to expectations, and where do we go from here?

There is an urgent need for interventions that can prevent or delay cognitive decline and dementia. Decades of epidemiological research have identified potential pharmacological strategies for risk factor modification to prevent these serious conditions, but clinical trials have failed to confirm the potential efficacy for such interventions. Our multidisciplinary international group reviewed seven high-potential intervention strategies in an attempt to identify potential reasons for the mismatch between the observational and trial results. In considering our findings, we offer constructive recommendations for the next steps. Overall, we observed some differences in the observational evidence base for the seven strategies, but several common methodological themes that emerged. These themes included the appropriateness of trial populations and intervention strategies, including the timing of interventions and other aspects of trials methodology. To inform the design of future clinical trials, we provide recommendations for the next steps in finding strategies for effective dementia risk reduction.