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Introduction Promising evidence is emerging for the procognitive, anti-inflammatory and neuroprotective properties of dietary flavonoids, particularly anthocyanins that provide red, purple and blue plant pigments.Methods and analysis The ‘Food for Thought’ study is a multicentre, 6-month randomised, parallel 3-arm clinical trial. Its primary aim is to investigate whether anthocyanin consumption, either through diet or supplementation, can prevent memory loss progression and improve inflammatory and cardiovascular health in older adults at risk for dementia. Eligible participants will include those aged 60–85 years with a diagnosis of amnestic mild cognitive impairment or with a self-referral of memory concerns and scoring ≤13 on the Memory Index Score within the Telephone Montreal Cognitive Assessment screening test. Participants will be randomised to one of three arms: High anthocyanin (‘purple foods’) diet (aiming for a target of 250 mg anthocyanins/day); freeze-dried product derived from blackcurrants (250 mg anthocyanins/day); or control (coloured maltose powder). The primary outcome is auditory anterograde memory functioning assessed by the Buschke and Grober Free and Cued Selective Reminding Test-Immediate Recall. Secondary outcomes are additional cognitive functions including processing speed, working memory, aspects of executive functioning (attentional shifting and word generativity) and premorbid estimate as well as subjective memory problems and self-reported depression symptoms. Additional secondary outcomes are blood pressure, inflammatory biomarkers, brain-derived neurotrophic factor, fatty acid profile, apolipoprotein E and polyphenol metabolites, gut microbiota composition and function and vascular and microvascular endothelial function tests. Repeated measures analysis of variance and/or mixed linear modelling will evaluate changes over time, with the inclusion of covariates.Ethics and dissemination Ethics approval has been obtained from the Greater Western Human Research Ethics Committee (2021/ETH12083). A Consumer Advisory Group was established to guide and review the protocol and dissemination strategy. The results of this trial are intended to be published in a peer-reviewed journal.Trial sponsor National Health and Medical Research Centre Dementia Collaborative Research Centre.Start date of clinical trial: 02 September 2022.Expected end date: 11 October 2024.Trial registration number ACTRN12622000065796.

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.

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.

Introduction Middle-aged multidomain risk reduction interventions targeting modifiable risk factors for dementia may delay or prevent a third of dementia cases in later life. We describe the protocol of a cluster randomised controlled trial (cRCT), HAPPI MIND (Holistic Approach in Primary care for PreventIng Memory Impairment aNd Dementia). HAPPI MIND will evaluate the efficacy of a multidomain, nurse-led, mHealth supported intervention for assessing dementia risk and reducing associated risk factors in middle-aged adults in the Australian primary care setting.Methods and analysis General practice clinics (n≥26) across Victoria and New South Wales, Australia, will be recruited and randomised. Practice nurses will be trained to implement the HAPPI MIND intervention or a brief intervention. Patients of participating practices aged 45–65 years with ≥2 potential dementia risk factors will be identified and recruited (approximately 15 patients/clinic). Brief intervention participants receive a personalised report outlining their risk factors for dementia based on Australian National University Alzheimer’s Disease Risk Index (ANU-ADRI) scores, education booklet and referral to their general practitioner as appropriate. HAPPI MIND participants receive the brief intervention as well as six individualised dementia risk reduction sessions with a nurse trained in motivational interviewing and principles of behaviour change, a personalised risk reduction action plan and access to the purpose-built HAPPI MIND smartphone app for risk factor self-management. Follow-up data collection will occur at 12, 24 and 36 months. Primary outcome is ANU-ADRI score change at 12 months from baseline. Secondary outcomes include change in cognition, quality of life and individual risk factors of dementia.Ethics and dissemination Project approved by Monash University Human Research Ethics Committee (ID: 28273). Results will be disseminated in peer-reviewed journals and at healthcare conferences. If effective in reducing dementia risk, the HAPPI MIND intervention could be integrated into primary care, scaled up nationally and sustained over time.Trial registration number ACTRN12621001168842.

Introduction Digital health interventions are cost-effective and easily accessible, but there is currently a lack of effective online options for dementia prevention especially for people at risk due to mild cognitive impairment (MCI) or subjective cognitive decline (SCD).Methods and analysis MyCOACH (COnnected Advice for Cognitive Health) is a tailored online dementia risk reduction programme for adults aged ≥65 living with MCI or SCD. The MyCOACH trial aims to evaluate the programme’s effectiveness in reducing dementia risk compared with an active control over a 64-week period (N=326). Eligible participants are randomly allocated to one of two intervention arms for 12 weeks: (1) the MyCOACH intervention programme or (2) email bulletins with general healthy ageing information (active control). The MyCOACH intervention programme provides participants with information about memory impairments and dementia, memory strategies and different lifestyle factors associated with brain ageing as well as practical support including goal setting, motivational interviewing, brain training, dietary and exercise consultations, and a 26-week post-intervention booster session. Follow-up assessments are conducted for all participants at 13, 39 and 65 weeks from baseline, with the primary outcome being exposure to dementia risk factors measured using the Australian National University-Alzheimer’s Disease Risk Index. Secondary measures include cognitive function, quality of life, functional impairment, motivation to change behaviour, self-efficacy, morale and dementia literacy.Ethics and dissemination Ethical approval was obtained from the University of New South Wales Human Research Ethics Committee (HC210012, 19 February 2021). The results of the study will be disseminated in peer-reviewed journals and research conferences.Trial registration number ACTRN12621000977875.

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.

Abstract 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.

Summary: Background: There is a need to know how changes in health expectancy differ for population subgroups globally. The aim of this study was to estimate 10-year trends in health expectancies by individual markers of socioeconomic position from three points over the lifecourse, evaluating how compression and expansion of morbidity have varied within a national population. Methods: We analysed data from two cohorts of the Household Income and Labour Dynamics in Australia survey. The cohorts were followed annually from 2001 to 2007 (n=4720; baseline age range 50–100 years) and 2011 to 2017 (n=6632; baseline age range 50–99 years). Health expectancies were estimated at age 65 years for four outcomes reflecting activity limitations, disability, perceived health, and mental health. Cohort differences were compared by gender, age left school, occupational prestige, and housing tenure. Findings: Women with low socioeconomic position were the only group with no improvements in life expectancy across the two cohorts. Among men with low education and all women gains in life expectancy comprised entirely of years lived with global activity limitations. Compression of years lived with severe-disability, poor self-rated health, and poor mental health was most consistently observed for men and women with high education and home ownership. Occupational prestige did not greatly differentiate cohort differences in health expectancies. Interpretation: Over the past two decades in Australia, social disparities in health expectancies have at least been maintained, and have increased for some outcomes. Equitable gains in health expectancies should be a major public health goal, and will help support sustainable health and social care systems. Funding: Australian Research Council.

Hearing loss is one of the most common long-term health conditions associated with ageing, and a considerable contributor to Australia’s late-life disability burden. Acquired hearing loss in adulthood presents significant challenges for the social, physical, mental and cognitive health of many Australians. These wide-ranging individual and societal impacts have been highlighted by a number of high-profile national inquiries into Australia’s hearing health during the past decade. Yet hearing loss remains poorly recognised and is undertreated in many communities. In this perspective article we argue that effective public health measures such as limiting occupational and recreational exposure to hazardous noise and ototoxic chemicals, promoting hearing health behaviours, early detection, improved access to hearing health services, and urban design, are all critical to mitigating these adverse outcomes. We also make the case for updated epidemiological data about hearing loss among older Australians.

BackgroundFactors contributing to the accurate measurement of self-reported physical activity are not well understood in middle-aged adults. We investigated the associations between two self-reported surveys and objectively measured physical activity in middle-aged adults, and the influence of individual and sociodemographic factors on these associations, at different intensities utilizing an observational study design.MethodsParticipants (n = 156) wore a SenseWear Armband™ (SWA) for a continuous seven-day period over the triceps of the left arm, to measure energy expenditure in metabolic equivalents. Participants also completed the Physical Activity Recall questionnaire (PAR) and Active Australia Survey (AAS). Associations were analyzed separately in general linear models for each intensity. The influence of individual and sociodemographic factors was assessed through moderator analyses.ResultsThe PAR and SWA were significantly positively associated at moderate (β = 0.68, 95% CI 0.16-1.20), vigorous (β = 0.36, 95% CI 0.20-0.53), moderate-to-vigorous physical activity (MVPA) (β = 0.52, 95% CI 0.20-0.83), and total METmins (β = 0.63, 95% CI 0.35-0.90), the AAS and SWA were associated at all intensities (moderate (β = 0.41, 95% CI 0.15-0.67), vigorous (β = 0.32, 95% CI 0.19-0.46), MVPA (β = 0.42, 95% CI 0.18-0.65) and total METmins (β = 0.62, 95% CI 0.29-0.96). A significant interaction between the PAR and sex for vigorous-intensity unveiled a weaker association in women. Both surveys tended to under-report physical activity. The largest margins of error were present at light and moderate intensities. For the PAR, participants reported over 20 hours, or 69% less light physical activity than recorded by the SWA per week. For the AAS, participants reported over 7 hours, or 38% less moderate physical activity. Compared to lighter intensities, time spent at a vigorous intensity was overreported by participants with the PAR and AAS by 91 and 43 minutes per week, respectively. The addition of Body Mass Index (BMI) resulted in non-significant interactions between the PAR and SWA for moderate-intensity, and the AAS and SWA for vigorous-intensity; a significant interaction between AAS and BMI indicated that the strength of the association differed by BMI for vigorous-intensity.ConclusionsThe PAR and AAS are not equivalent to the SWA, and sex and BMI may alter the associations between the measures.

Introduction Falls significantly reduce independence and quality of life in older age. Balance-specific exercise prevents falls in people aged 60+ years. Yoga is growing in popularity and can provide a high challenge to balance; however, the effect of yoga on falls has not been evaluated. This trial aims to establish the effect on falls of a yoga exercise programme compared with a yoga relaxation programme in community-dwellers aged 60+ years.Method and Analysis This randomised controlled trial will involve 560 community-dwelling people aged 60+ years. Participants will be randomised to either: (1) the Successful AGEing (SAGE) yoga exercise programme or (2) a yoga relaxation programme. Primary outcome is rate of falls in the 12 months post randomisation. Secondary outcomes include mental well-being, physical activity, health-related quality of life, balance self-confidence, physical function, pain, goal attainment and sleep quality at 12 months after randomisation. The number of falls per person-year will be analysed using negative binomial regression models to estimate between-group difference in fall rates. Generalised linear models will assess the effect of group allocation on the continuously scored secondary outcomes, adjusting for baseline scores. An economic analysis will compare the cost-effectiveness and cost-utility of the two yoga programmes.Ethics and dissemination Protocol was approved by the Human Research Ethics Committee at The University of Sydney, Australia (approval 2019/604). Trial results will be disseminated via peer-reviewed articles, conference presentations, lay summaries.Trial registration number The protocol for this trial is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12619001183178).

BackgroundWith no effective treatments for cognitive decline or dementia, improving the evidence base for modifiable risk factors is a research priority. This study investigated associations between risk factors and late-life cognitive decline on a global scale, including comparisons between ethno-regional groups.Methods and findingsWe harmonized longitudinal data from 20 population-based cohorts from 15 countries over 5 continents, including 48,522 individuals (58.4% women) aged 54-105 (mean = 72.7) years and without dementia at baseline. Studies had 2-15 years of follow-up. The risk factors investigated were age, sex, education, alcohol consumption, anxiety, apolipoprotein E ε4 allele (APOE*4) status, atrial fibrillation, blood pressure and pulse pressure, body mass index, cardiovascular disease, depression, diabetes, self-rated health, high cholesterol, hypertension, peripheral vascular disease, physical activity, smoking, and history of stroke. Associations with risk factors were determined for a global cognitive composite outcome (memory, language, processing speed, and executive functioning tests) and Mini-Mental State Examination score. Individual participant data meta-analyses of multivariable linear mixed model results pooled across cohorts revealed that for at least 1 cognitive outcome, age (B = -0.1, SE = 0.01), APOE*4 carriage (B = -0.31, SE = 0.11), depression (B = -0.11, SE = 0.06), diabetes (B = -0.23, SE = 0.10), current smoking (B = -0.20, SE = 0.08), and history of stroke (B = -0.22, SE = 0.09) were independently associated with poorer cognitive performance (p < 0.05 for all), and higher levels of education (B = 0.12, SE = 0.02) and vigorous physical activity (B = 0.17, SE = 0.06) were associated with better performance (p < 0.01 for both). Age (B = -0.07, SE = 0.01), APOE*4 carriage (B = -0.41, SE = 0.18), and diabetes (B = -0.18, SE = 0.10) were independently associated with faster cognitive decline (p < 0.05 for all). Different effects between Asian people and white people included stronger associations for Asian people between ever smoking and poorer cognition (group by risk factor interaction: B = -0.24, SE = 0.12), and between diabetes and cognitive decline (B = -0.66, SE = 0.27; p < 0.05 for both). Limitations of our study include a loss or distortion of risk factor data with harmonization, and not investigating factors at midlife.ConclusionsThese results suggest that education, smoking, physical activity, diabetes, and stroke are all modifiable factors associated with cognitive decline. If these factors are determined to be causal, controlling them could minimize worldwide levels of cognitive decline. However, any global prevention strategy may need to consider ethno-regional differences.

BackgroundThe prevalence of dementia varies around the world, potentially contributed to by international differences in rates of age-related cognitive decline. Our primary goal was to investigate how rates of age-related decline in cognitive test performance varied among international cohort studies of cognitive aging. We also determined the extent to which sex, educational attainment, and apolipoprotein E ε4 allele (APOE*4) carrier status were associated with decline.Methods and findingsWe harmonized longitudinal data for 14 cohorts from 12 countries (Australia, Brazil, France, Greece, Hong Kong, Italy, Japan, Singapore, Spain, South Korea, United Kingdom, United States), for a total of 42,170 individuals aged 54-105 y (42% male), including 3.3% with dementia at baseline. The studies began between 1989 and 2011, with all but three ongoing, and each had 2-16 assessment waves (median = 3) and a follow-up duration of 2-15 y. We analyzed standardized Mini-Mental State Examination (MMSE) and memory, processing speed, language, and executive functioning test scores using linear mixed models, adjusted for sex and education, and meta-analytic techniques. Performance on all cognitive measures declined with age, with the most rapid rate of change pooled across cohorts a moderate -0.26 standard deviations per decade (SD/decade) (95% confidence interval [CI] [-0.35, -0.16], p < 0.001) for processing speed. Rates of decline accelerated slightly with age, with executive functioning showing the largest additional rate of decline with every further decade of age (-0.07 SD/decade, 95% CI [-0.10, -0.03], p = 0.002). There was a considerable degree of heterogeneity in the associations across cohorts, including a slightly faster decline (p = 0.021) on the MMSE for Asians (-0.20 SD/decade, 95% CI [-0.28, -0.12], p < 0.001) than for whites (-0.09 SD/decade, 95% CI [-0.16, -0.02], p = 0.009). Males declined on the MMSE at a slightly slower rate than females (difference = 0.023 SD/decade, 95% CI [0.011, 0.035], p < 0.001), and every additional year of education was associated with a rate of decline slightly slower for the MMSE (0.004 SD/decade less, 95% CI [0.002, 0.006], p = 0.001), but slightly faster for language (-0.007 SD/decade more, 95% CI [-0.011, -0.003], p = 0.001). APOE*4 carriers declined slightly more rapidly than non-carriers on most cognitive measures, with processing speed showing the greatest difference (-0.08 SD/decade, 95% CI [-0.15, -0.01], p = 0.019). The same overall pattern of results was found when analyses were repeated with baseline dementia cases excluded. We used only one test to represent cognitive domains, and though a prototypical one, we nevertheless urge caution in generalizing the results to domains rather than viewing them as test-specific associations. This study lacked cohorts from Africa, India, and mainland China.ConclusionsCognitive performance declined with age, and more rapidly with increasing age, across samples from diverse ethnocultural groups and geographical regions. Associations varied across cohorts, suggesting that different rates of cognitive decline might contribute to the global variation in dementia prevalence. However, the many similarities and consistent associations with education and APOE genotype indicate a need to explore how international differences in associations with other risk factors such as genetics, cardiovascular health, and lifestyle are involved. Future studies should attempt to use multiple tests for each cognitive domain and feature populations from ethnocultural groups and geographical regions for which we lacked data.

This paper discusses the use of secondments as a tool to increase knowledge translation between academics and policy makers by developing individual capacity. A case study is presented of a reciprocal secondment between a government department and a university. Enablers of knowledge translation included flexibility and support, a prior relationship between the two organisations, and a government culture that values use of research in policy making. Barriers included the lack of a planned approach with agreed outcomes, and a lack of evaluation at the end of the secondment. Recommendations for future secondments include establishing ongoing secondments between organisations; trialling different types of secondments; and having a detailed plan at the beginning of a secondment, including how the success of the secondment will be measured, and a formal evaluation at the end.

Background: Currently, little is known about the types of evidence used by policy makers. This study aimed to investigate how policy makers in the health domain use and evaluate evidence and how this differs from academic epidemiologists. By having a better understanding of how policy makers select, evaluate and use evidence, academics can tailor the way in which that evidence is produced, potentially leading to more effective knowledge translation.Methods: An exploratory mixed-methods study design was used. Quantitative measures were collected via an anonymous online survey (n= 28), with sampling from three health-related government and non-government organisations. Semi-structured interviews with policy makers (n=20) and epidemiologists (n=6) were conducted to gather qualitative data. Results: Policy makers indicated systematic reviews were the preferred research resource (19%), followed closely by qualitative research (16%). Neither policy makers nor epidemiologists used grading instruments to evaluate evidence. In the web survey policy makers reported that consistency and strength of evidence (93%), the quality of data (93%), bias in the evidence (79%) and recency of evidence (79%) were the most important factors taken into consideration when evaluating the available evidence. The same results were found in the qualitative interviews. Epidemiologists focused on the methodology used in the study. The most cited barriers to using robust evidence, according to policy makers, were political considerations (60%), time limitations (55%), funding (50%) and research not being applicable to current policies (50%). Conclusion: The policy makers investigated did not report a systematic approach to evaluating evidence. Although there was some overlap between what policy makers and epidemiologists identified as high quality evidence, there was also some important differences. This suggests that the best scientific evidence may not routinely be used in the development of policy. In essence the policy making process relied on other jurisdictions’ policies and the opinions of internal staff members as primary evidence sources to inform policy decisions. Findings of this study suggest that efforts should be directed towards making scientific information more systematically available to policy makers.

BackgroundThe prevention of falls among older people is a major public health challenge. Exercises that challenge balance are recognized as an efficacious fall prevention strategy. Given that small-scale trials have indicated that diverse dance styles can improve balance and gait of older adults, two of the strongest risk factors for falls in older people, this study aimed to determine whether social dance is effective in i) reducing the number of falls and ii) improving physical and cognitive fall-related risk factors.Methods and findingsA parallel two-arm cluster randomized controlled trial was undertaken in 23 self-care retirement villages (clusters) around Sydney, Australia. Eligible villages had to have an appropriate hall for dancing, house at least 60 residents, and not be currently offering dance as a village activity. Retirement villages were randomised using a computer generated randomisation method, constrained using minimisation. Eligible participants had to be a resident of the village, be able to walk at least 50 m, and agree to undergo physical and cognitive testing without cognitive impairment. Residents of intervention villages (12 clusters) were offered twice weekly one-hour social dancing classes (folk or ballroom dancing) over 12 mo (80 h in total). Programs were standardized across villages and were delivered by eight dance teachers. Participants in the control villages (11 clusters) were advised to continue with their regular activities.Main outcomesfalls during the 12 mo trial and Trail Making Tests.Secondary outcomesThe Physiological Performance Assessment (i.e., postural sway, proprioception, reaction time, leg strength) and the Short Physical Performance Battery; health-related physical and mental quality of life from the Short-Form 12 (SF-12) Survey. Data on falls were obtained from 522 of 530 (98%) randomised participants (mean age 78 y, 85% women) and 424 (80%) attended the 12-mo reassessment, which was lower among folk dance participants (71%) than ballroom dancing (82%) or control participants (82%, p = 0.04). Mean attendance at dance classes was 51%. During the period, 444 falls were recorded; there was no significant difference in fall rates between the control group (0.80 per person-year) and the dance group (1.03 per person-year). Using negative binomial regression with robust standard errors the adjusted Incidence Rate Ratio (IRR) was 1.19 (95% CI: 95% CI = 0.83, 1.71). In exploratory post hoc subgroup analysis, the rate of falls was higher among dance participants with a history of multiple falls (IRR = 2.02, 95% CI: 1.15, 3.54, p = 0.23 for interaction) and with the folk dance intervention (IRR = 1.68, 95% CI: 1.03, 2.73). There were no significant between-group differences in executive function test (TMT-B = 2.8 s, 95% CI: -6.2, 11.8). Intention to treat (ITT) analysis revealed no between-group differences at 12-mo follow-up in the secondary outcome measures, with the exception of postural sway, favouring the control group. Exploratory post hoc analysis by study completers and style indicated that ballroom dancing participants apparently improved their gait speed by 0.07 m/s relative to control participants (95% CI: 0.00, 0.14, p = 0.05). Study limitations included allocation to style based on logistical considerations rather than at random; insufficient power to detect differential impacts of different dance styles and smaller overall effects; variation of measurement conditions across villages; and no assessment of more complex balance tasks, which may be more sensitive to changes brought about by dancing.ConclusionsSocial dancing did not prevent falls or their associated risk factors among these retirement villages' residents. Modified dance programmes that contain "training elements" to better approximate structured exercise programs, targeted at low and high-risk participants, warrant investigation.Trial registrationThe Australian New Zealand Clinical Trials Registry ACTRN12612000889853.

Background: A physically active lifestyle has the potential to prevent cognitive decline and dementia, yet the optimal type of physical activity/exercise remains unclear. Dance is of special interest as it complex sensorimotor rhythmic activity with additional cognitive, social and affective dimensions. Objectives: to determine whether dance benefits executive function more than walking, an activity that is simple and functional. Methods: Two-arm randomised controlled trial among community-dwelling older adults. The intervention group received 1 hour of ballroom dancing twice weekly over 8 months (~69sessions) in local community dance studios. The control group received a combination of a home walking program with a pedometer and optional biweekly group-based walking in local community park to facilitate socialisation. Main outcomes: Main outcomes: executive function tests: processing speed and task shift by the Trail Making Tests (TMT), response inhibition by the Stroop Colour-Word Test (SCWT), working memory by the Digit Span Backwards (DSB) test, immediate and delayed verbal recall by the Rey Auditory Verbal Learning Test (RAVLT) and visuospatial recall by the Brief Visuospatial Memory Test (BVST). Results: One hundred and fifteen adults (69.5 years, SD6.4) completed baseline and delayed baseline (3 weeks apart) before being randomised to either dance (n=60) or walking (n=55). Of those randomized, 79 (68%) completed the follow-up measurements (32 weeks from baseline). In the dance group only, ‘non-completers’ had significant lower baseline scores on all executive function tests than those completed the full program. Intention-to-treat analyses showed no group effect. In a random effects model including participants who completed all measurements, adjusted for baseline score and covariates (age, education, estimated verbal intelligence, community), a between group effect in favour of dance was noted only for BVST total learning (Cohen’s D Effect size 0.29, p=.07) and delayed recall (Cohen’s D Effect size=0.34, p=.06) Conclusion: The superior potential of dance over walking on executive functions of cognitively healthy and active older adults was not supported. Dance improved one of the cognitive domains (spatial memory) important for learning dance. Controlled trials targeting inactive older adults and of a higher dose may produce stronger effects, particularly for novice dancers.

The rising prevalence of cognitive impairment is an increasing challenge with the ageing of our populations but little is known about the burden in low- and middle- income Latin American and Caribbean countries (LAC) that are aging more rapidly than their developed counterparts. We examined life expectancies with cognitive impairment (CILE) and free of cognitive impairment (CIFLE) in seven developing LAC countries.Data from The Survey on Health, Well-being and Ageing in LAC (N = 10,597) was utilised and cognitive status was assessed by the Mini-Mental State Examination (MMSE). The Sullivan Method was applied to estimate CILE and CIFLE. Logistic regression was used to determine the effect of age, gender and education on cognitive outcome. Meta-regression models were fitted for all 7 countries together to investigate the relationship between CIFLE and education in men and women at age 60.The prevalence of CI increased with age in all countries except Uruguay and with a significant gender effect observed only in Mexico where men had lower odds of CI compared to women [OR = 0.464 95% CInt (0.268 - 0.806)]. Low education was associated with increased prevalence of CI in Brazil [OR = 4.848 (1.173-20.044)], Chile [OR = 3.107 (1.098-8.793), Cuba [OR = 2.295 (1.247-4.225)] and Mexico [OR = 3.838 (1.368-10.765). For males, total life expectancy (TLE) at age 60 was highest in Cuba (19.7 years) and lowest in Brazil and Uruguay (17.6 years). TLE for females at age 60 was highest for Chileans (22.8 years) and lowest for Brazilians (20.2 years). CIFLE for men was greatest in Cuba (19.0 years) and least in Brazil (16.7 years). These differences did not appear to be explained by educational level (Men: p = 0.408, women: p = 0.695).Increasing age, female sex and low education were associated with higher CI in LAC reflecting patterns found in other countries.

BACKGROUND:Changes in criteria and differences in populations studied and methodology have produced a wide range of prevalence estimates for mild cognitive impairment (MCI). METHODS:Uniform criteria were applied to harmonized data from 11 studies from USA, Europe, Asia and Australia, and MCI prevalence estimates determined using three separate definitions of cognitive impairment. RESULTS:The published range of MCI prevalence estimates was 5.0%-36.7%. This was reduced with all cognitive impairment definitions: performance in the bottom 6.681% (3.2%-10.8%); Clinical Dementia Rating of 0.5 (1.8%-14.9%); Mini-Mental State Examination score of 24-27 (2.1%-20.7%). Prevalences using the first definition were 5.9% overall, and increased with age (P < .001) but were unaffected by sex or the main races/ethnicities investigated (Whites and Chinese). Not completing high school increased the likelihood of MCI (P ≤ .01). CONCLUSION:Applying uniform criteria to harmonized data greatly reduced the variation in MCI prevalence internationally.

Background: Higher dietary intake of potassium, calcium, and magnesium is protective against ischemic strokes while being also associated with a decreased risk of all-cause dementia. The effect of dietary iron intake on cerebral function is less clear but iron is also implicated in Alzheimer neuropathology. The aim of this study was to investigate whether dietary intake of these minerals was also associated with increased risk of Mild Cognitive Impairment (amnestic) and other Mild Cognitive Disorders. Methods: Associations between dietary mineral intake and risk of MCI/MCD was assessed in cognitively healthy individuals (n=1406, 52% female, mean age 62.5 years) living in the community who were followed up over 8 years. Relative risk was assessed with Cox hazard ratios after controlling for health and socio-demographic covariates. Results: Higher magnesium intake was associated with a reduced risk of developing MCI/MCD (MCI:Hazard Ratio (HR) 0.07,95% Confidence Interval (CI) 0.01-0.56, p=0.013; MCD: HR 0.47,95%CI 0.22-.99,p=0.046) in multivariate analyses. Higher intake of potassium (MCI: HR 1.09,95%CI 1.01-1.17,p=0.028; MCD: HR 1.05,95%CI 0.99-1.10,p=.107) and iron (MCI: HR 1.54,95%CI 1.03-2.29,p=0.034) was associated with an increased risk of developing MCI/MCD. Conclusions: These findings suggest that dietary intake of minerals known to be implicated in biological processes associated with vascular and Alzheimer’s pathology may contribute to disease progression earlier in the disease process and require further attention.

Attention Deficit/Hyperactivity Disorder (ADHD) is a common neuropsychiatric disorder that has not been well studied in older adults. In this study we examined relationships between ADHD symptoms and cognitive ability and compared them between middle-age (MA; 48-52 years) and older-age (OA; 68-74 years) adults sampled from the same population. ADHD, mood disorder symptoms and cognitive abilities were assessed in a large population-based sample (n = 3443; 50% male). We measured current ADHD symptoms using the adult ADHD Self-Report Scale (ASRS), which we found to have the same underlying structure in both cohorts. Older adults reported significantly lower levels of ADHD symptoms and 2.2% of the OA cohort scored equal or above the ASRS cut-off score of 14 (which has been previously associated with ADHD diagnosis) compared with 6.2% of MA adults. Symptom levels were not significantly different between males and females. Using multi-group structural equation modelling we compared ADHD symptom-cognitive performance relationships between the two age groups. Generally higher ADHD symptoms were associated with poorer cognitive performance in the MA cohort. However, higher levels of inattention symptoms were associated with better verbal ability in both cohorts. Surprisingly, greater hyperactivity was associated with better task-switching abilities in older adults. In the OA cohort ADHD symptom-cognition relationships are indirect, mediated largely through the strong association between depression symptoms and cognition. Our results suggest that ADHD symptoms decrease with age and that their relationships with co-occurring mood disorders and cognitive performance also change. Although symptoms of depression are lower in older adults, they are much stronger predictors of cognitive performance and likely mediate the effect of ADHD symptoms on cognition in this age group. These results highlight the need for age-appropriate diagnosis and treatment of comorbid ADHD and mood disorders.

BackgroundMidlife body weight status has been found to affect late life dementia outcomes. A cohort projections model was developed to assess the impact of midlife body mass index (BMI) profile on dementia in older Australians.MethodsA baseline projection using age-sex specific dementia prevalence rates was constructed and the results of scenarios that took account of midlife BMI were compared with those from population ageing only.ResultsThis modelling predicts that if the rising trend in midlife obesity and declining trend in midlife normal weight in Australia are to be taken into account in projecting future numbers of Australians with dementia then the number of people aged 65 or more years with dementia, by 2050, would be 14% higher than that expected from demographic ageing only. If midlife obesity prevalence was decreased to 20% and normal weight increased to 40% over the period of 2015-2025, then dementia cases among persons aged 65-69 years would be lower by about 10% in 2050 compared with the "doing nothing to stop current trends in obesity" projection.ConclusionThe rising tide of obesity in Australian adults will increase the dementia epidemic expected in future years.

The Australian National University AD Risk Index (ANU-ADRI, http://anuadri.anu.edu.au) is a self-report risk index developed using an evidence-based medicine approach to measure risk of Alzheimer's disease (AD). We aimed to evaluate the extent to which the ANU-ADRI can predict the risk of AD in older adults and to compare the ANU-ADRI to the dementia risk index developed from the Cardiovascular Risk Factors, Aging and Dementia (CAIDE) study for middle-aged cohorts.This study included three validation cohorts, i.e., the Rush Memory and Aging Study (MAP) (n = 903, age ≥53 years), the Kungsholmen Project (KP) (n = 905, age ≥75 years), and the Cardiovascular Health Cognition Study (CVHS) (n = 2496, age ≥65 years) that were each followed for dementia. Baseline data were collected on exposure to the 15 risk factors included in the ANU-ADRI of which MAP had 10, KP had 8 and CVHS had 9. Risk scores and C-statistics were computed for individual participants for the ANU-ADRI and the CAIDE index.For the ANU-ADRI using available data, the MAP study c-statistic was 0·637 (95% CI 0·596-0·678), for the KP study it was 0·740 (0·712-0·768) and for the CVHS it was 0·733 (0·691-0·776) for predicting AD. When a common set of risk and protective factors were used c-statistics were 0.689 (95% CI 0.650-0.727), 0.666 (0.628-0.704) and 0.734 (0.707-0.761) for MAP, KP and CVHS respectively. Results for CAIDE ranged from c-statistics of 0.488 (0.427-0.554) to 0.595 (0.565-0.625).A composite risk score derived from the ANU-ADRI weights including 8-10 risk or protective factors is a valid, self-report tool to identify those at risk of AD and dementia. The accuracy can be further improved in studies including more risk factors and younger cohorts with long-term follow-up.

Recent research suggests that diet quality influences depression risk; however, a lack of experimental evidence leaves open the possibility that residual confounding explains the observed relationships. The aim of this study was to document the cross-sectional and longitudinal associations between dietary patterns and symptoms of depression and to undertake a detailed examination of potential explanatory factors, particularly socioeconomic circumstances, in the diet-depression relationship.Data were drawn from the Personality and Total Health (PATH) Through Life Study, a longitudinal community study following three age cohorts (20+; 40+; 60+yrs) from south-eastern Australia over three assessment periods (n=3663). Regression analyses evaluated the cross-sectional and longitudinal relationships between dietary patterns, depressive symptoms, age, detailed measures of socioeconomic circumstances, other health behaviours, and cardiovascular risk factors.The lowest tertile of prudent (healthy) dietary pattern and the highest tertile of western (unhealthy) dietary pattern were associated with an increased likelihood of depressive symptoms. However, these contemporaneous associations were explained by adjustment for detailed measures of socioeconomic circumstances and physical activity. In prospective analyses, lower scores on the healthy dietary pattern and higher scores on the unhealthy dietary pattern independently predicted increased depressive symptoms across time, before and after adjustment for potential confounders and baseline depressive symptoms, but only for those in the oldest cohort. Dietary patterns did not explain the relationship between socioeconomic position and depressive symptoms.The results of this study confirm that the relationship between habitual dietary intake and depressive symptoms is somewhat explained by socioeconomic circumstances and other health behaviours, but suggest that long term exposure to unhealthy dietary habits independently predisposes to depression over the lifecourse.

Background: The association between dual sensory loss (DSL) and mental health has been well established. However, most studies have relied on self-report data and lacked measures that would enable researchers to examine causal pathways between DSL and depression. This study seeks to extend this research by examining the effects of DSL on mental health, and identify factors that explain the longitudinal associations between sensory loss and depressive symptoms. Methods: Piecewise linear-mixed models were used to analyse 16-years of longitudinal data collected on up to five occasions from 1611 adults (51% men) aged between 65 and 103 years. Depressive symptoms were assessed by the Centre for Epidemiological Studies Depression (CES-D). Vision loss (VL) was defined by corrected visual acuity greater than 0.3 logMAR in the better eye, blindness or glaucoma. Hearing loss (HL) was defined by pure tone average (PTA) greater than 25 dB in the better hearing ear. Analyses were adjusted for socio-demographics, medical conditions, lifestyle behaviours, Activities of Daily Living (ADLs), cognitive function, and social engagement. Results: Unadjusted models indicated that higher levels of depressive symptoms were associated with HL (B=1.16, SE=0.33) and DSL (B=2.15, SE=0.39) but not VL. Greater rates of change in depressive symptoms were also evident after the onset of HL (B=0.16, SE=0.06, p

This study examined the prevalence of co-morbid age-related eye disease and symptoms of depression and anxiety in late life, and the relative roles of visual function and disease in explaining symptoms of depression and anxiety. A community-based sample of 662 individuals aged over 70 years was recruited through the electoral roll. Vision was measured using a battery of tests including high and low contrast visual acuity, contrast sensitivity, motion sensitivity, stereoacuity, Useful Field of View and visual fields. Depression and anxiety symptoms were measured using the Goldberg scales. The prevalence of self-reported eye disease (cataract, glaucoma or age-related macular degeneration) in the sample was 43.4%, with 7.7% reporting more than one form of ocular pathology. Of those with no eye disease, 3.7% had clinically significant depressive symptoms. This rate was 6.7% among cataract patients, 4.3% among those with glaucoma, and 10.5% for age-related macular degeneration. Generalized linear models adjusting for demographics, general health, treatment and disability examined self-reported eye disease and visual function as correlates of depression and anxiety. Depressive symptoms were associated with cataract only, age-related macular degeneration, comorbid eye diseases and reduced low contrast visual acuity. Anxiety was significantly associated with self-reported cataract, and reduced low contrast visual acuity, motion sensitivity and contrast sensitivity. We found no evidence for elevated rates of depressive or anxiety symptoms associated with self-reported glaucoma. The results support previous findings of high rates of depression and anxiety in cataract and age-related macular degeneration, and in addition show that mood and anxiety are associated with objective measures of visual function independently of self-reported eye disease. The findings have implications for the assessment and treatment of mental health in the context of late-life visual impairment.

ContextType 2 diabetes is associated with cerebral atrophy, cognitive impairment and dementia. We recently showed higher glucose levels in the normal range not to be free of adverse effects and to be associated with greater hippocampal and amygdalar atrophy in older community-dwelling individuals free of diabetes.ObjectiveThis study aimed to determine whether blood glucose levels in the normal range (Design setting and participants210 cognitively healthy individuals (68-73 years) without diabetes, glucose intolerance or metabolic syndrome were assessed in the large, community-based Personality and Total Health Through Life (PATH) study.Main outcome measureBaseline blood glucose levels in the normal range (3.2-6.1 mmol/l) were used to determine regional brain volumes and associated cognitive function at wave 3.ResultsHigher blood glucose levels in the normal range were associated with lower grey/white matter regional volumes in the frontal cortices (middle frontal gyrus, inferior frontal gyrus precentral gyrus). Moreover, identified cerebral regions were associated with poorer cognitive performance and the structure-function associations were gender specific to men.ConclusionThese findings stress the need to re-evaluate what is considered as healthy blood glucose levels, and consider the role of higher normal blood glucose as a risk factor for cerebral health, cognitive function and dementia. A better lifetime management of blood glucose levels may contribute to improved cerebral and cognitive health in later life and possibly protect against dementia.

Attention deficit/hyperactivity disorder (ADHD) is the most prevalent childhood psychiatric condition. It frequently persists into adulthood and can have serious health and other adverse consequences. The majority of previous adult ADHD studies have focused on young adults so that relatively little is known about ADHD symptoms and their effects in mid and late life. In addition, effects of subclinical levels of attention deficit and hyperactivity have not been studied in detail. In this study we investigated ADHD symptoms and related impairment in a large population-based sample of middle-aged Australian adults (n = 2091; 47% male). Applying the WHO adult ADHD Self Report Screener (ASRS) we observed that 6.2% of participants had scores that were previously associated with ADHD diagnosis. No significant gender difference in the distribution of ASRS scores was observed. Multiple regression analyses indicated strong positive correlations between symptoms of ADHD and depression/anxiety and significant negative associations (p

Most individuals successfully maintain psychological well-being even when exposed to trauma or adversity. Emotional resilience or the ability to thrive in the face of adversity is determined by complex interactions between genetic makeup, previous exposure to stress, personality, coping style, availability of social support, etc. Recent studies have demonstrated that childhood trauma diminishes resilience in adults and affects mental health. The Dopamine receptor D4 (DRD4) exon III variable number tandem repeat (VNTR) polymorphism was reported to moderate the impact of adverse childhood environment on behaviour, mood and other health-related outcomes. In this study we investigated whether DRD4-exIII-VNTR genotype moderates the effect of childhood adversities (CA) on resilience. In a representative population sample (n = 1148) aged 30-34 years, we observed an interactive effect of DRD4 genotype and CA (β = 0.132; p = 0.003) on resilience despite no main effect of the genotype when effects of age, gender and education were controlled for. The 7-repeat allele appears to protect against the adverse effect of CA since the decline in resilience associated with increased adversity was evident only in individuals without the 7-repeat allele. Resilience was also significantly associated with approach-/avoidance-related personality measures (behavioural inhibition/activation system; BIS/BAS) measures and an interactive effect of DRD4-exIII-VNTR genotype and CA on BAS was observed. Hence it is possible that approach-related personality traits could be mediating the effect of the DRD4 gene and childhood environment interaction on resilience such that when stressors are present, the 7-repeat allele influences the development of personality in a way that provides protection against adverse outcomes.

BackgroundThe association between brain white matter lesions and cognitive impairment in old age is well established. However, little is known about this association in midlife. As this information will inform policy for early preventative healthcare initiatives, we investigated non-periventricular frontal, temporal, parietal and occipital lobe white matter hyperintensities (WMH) in relation to cognitive function in 428 (232 women) community-dwelling adults aged 44 to 48 years.ResultsFrontal white matter lesions were significantly associated with greater intraindividual RT variability in women, while temporal WMH were associated with face recognition deficits in men. Parietal and occipital lobe lesions were unrelated to cognitive performance. These findings did not differ when education and a range of health variables, including vascular risk factors, were taken into account.ConclusionGender differences in WMH-cognition associations are discussed, and we conclude that small vessel disease is present in midlife and has functional consequences which are generally not recognized. Preventative strategies should, therefore, begin early in life.

Background and Purpose: Defining how brain structures differ in pre-clinical dementia is important to better understand the pathological processes involved and to inform clinical practice. The aim of this study was to identify significant brain correlates (volume and asymmetry in volume) of mild cognitive disorders when compared to normal controls in a large community-based sample of young-old individuals who were assessed for cognitive impairment. Methods: Cortical and sub-cortical volumes were measured using a semi-automated method in 398 participants aged 65-70 years who were selected from a larger randomly sampled cohort and who agreed to undergo an MRI scan. Diagnoses were reached based on established protocols for MCI and a more inclusive category of any Mild Cognitive Disorder (any-MCD: which includes AAMI, AACD, OCD, MNC, CDR, MCI). Logistic regression analyses were used to assess the relationship between volume and asymmetry of theoretically relevant cerebral structures (predictors) and MCI or any-MCD while controlling for age, sex, and intra-cranial volume. Results: The main correlates of cognitive impairment assessed in multivariate analyses were hippocampal asymmetry (more to left, MCI: OR 0.83, 95%CI 0.71-0.96, p = .013; MCD: OR 0.86, 95%CI 0.77-0.97, p = .011), lateral ventricle asymmetry (more to left, MCI: OR 0.95, 95%CI 0.91-0.99, p = .009; MCD: OR 0.95, 95%CI 0.92-0.98, p = .004), and cerebellar cortex asymmetry (more to left, MCI: OR 1.51, 95%CI 1.13-2.01, p = .005). Conclusions: In this population-based cohort stronger associations were found between asymmetry measures, rather than raw volumes in cerebral structures, and mild cognitive disorders.

While manual tracing is the method of choice in measuring hippocampal volume, its time intensive nature and proneness to human error make automated methods attractive, especially when applied to large samples. Few studies have systematically compared the performance of the two techniques. In this study, we measured hippocampal volumes in a large (N = 403) population-based sample of individuals aged 44-48 years using manual tracing by a trained researcher and automated procedure using Freesurfer (http://surfer.nmr.mgh.harvard.edu) imaging suite. Results showed that absolute hippocampal volumes assessed with these methods were significantly different, with automated measures using the Freesurfer software suite being significantly larger, by 23% for the left and 29% for the right hippocampus. The correlation between the two methods varied from 0.61 to 0.80, with lower correlations for hippocampi with visible abnormalities. Inspection of 2D and 3D models suggested that this difference was largely due to greater inclusion of boundary voxels by the automated method and variations in subiculum/entorhinal segmentation. The correlation between left and right hippocampal volumes was very similar by the two methods. The relationship of hippocampal volumes to selected sociodemographic and cognitive variables was not affected by the measurement method, with each measure showing an association with memory performance and suggesting that both were equally valid for this purpose. This study supports the use of automated measures, based on Freesurfer in this instance, as being sufficiently reliable and valid particularly in the context of larger sample sizes when the research question does not rely on 'true' hippocampal volumes.