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BACKGROUND: Most people with dementia live in the community, not in residential care. Therefore, quality informal care for them is critical for managing behavioural and psychological symptoms of dementia (BPSD). Music therapy has been shown to reduce BPSD. However, no randomised controlled trial has examined the effects of music interventions delivered by caregivers in home settings. The HOME-based caregiver-delivered music intervention for people living with dementia (HOMESIDE) trial aims to evaluate the effectiveness of a 12-week music intervention in addition to standard care for BPSD. This article describes the statistical analysis plan. METHODS AND ANALYSIS: HOMESIDE is a large, pragmatic international three-arm parallel-group randomised controlled trial. Dyads (persons with dementia and caregiver) in Australia, Germany, the UK, Poland and Norway were randomised to receive music and standard care, reading and standard care or standard care alone. The primary outcome is BPSD (proxy) of the person living with dementia, measured using the Neuropsychiatric Inventory-Questionnaire (NPI-Q) at 90 and 180 days post-randomisation. Longitudinal analysis will compare NPI-Q severity between music and standard care versus standard care alone. Secondary outcomes include quality of life and depression (both person with dementia and caregiver), cognition (person with dementia only), distress, resilience, competence and caregiver-patient relationship (caregiver only). Treatment effects will be obtained at 90 and 180 days post-randomisation, where applicable. Safety outcomes (adverse events, hospitalisations, deaths) will be summarised. DISCUSSION: This statistical analysis plan provides a detailed methodology for the analysis of HOMESIDE and will improve the validity of the study and reduce the potential for bias. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12618001799246. Registered on November 05, 2018. CLINICALTRIALS: gov NCT03907748. Registered

INTRODUCTION: Exercise and physical activity have been shown to improve cognition for people living with mild cognitive impairment (MCI). There is strong evidence for the benefits of aerobic exercise and medium evidence for participating in regular strength training for people with MCI. However, people living with MCI fall two times as often as those without cognitive impairment and the evidence is currently unknown as to whether balance training for people with MCI is beneficial, as has been demonstrated for older people without cognitive impairment. The aim of this study is to determine whether a balance-focused multimodal exercise intervention improves balance and reduces falls for people with MCI, compared with a control group receiving usual care. METHODS AND ANALYSIS: This single blind randomised controlled trial (Balance on the Brain) will be offered to 396 people with MCI living in the community. The multimodal exercise intervention consists of two balance programmes and a walking programme to be delivered by physiotherapists over a 6-month intervention period. All participants will be followed up over 12 months (for the intervention group, this involves 6-month intervention and 6-month maintenance). The primary outcomes are (1) balance performance and (2) rate of falls. Physical performance, levels of physical activity and sedentary behaviour, quality of life and cognition are secondary outcomes. A health economic analysis will be undertaken to evaluate the cost-effectiveness of the intervention compared with usual care. ETHICS AND DISSEMINATION: Ethics approval has been received from the South Metropolitan Health Service Human Research Ethics Committee (HREC), Curtin University HREC and the Western Australia Department of Health HREC; and approval has been received to obtain data for health costings from Services Australia. The results will be disseminated through peer-review publications, conference presentations and online platforms. TRIAL REGISTRATION N

In this article the affiliation details for Ulman Lindenberger were incorrectly given as ‘Department of Psychiatry and Psychotherapy, University Medical Center Hamburg-Eppendorf, Hamburg, Germany’ but should have been ‘Center for Lifespan Psychology, Max Planck Institute for Human Development, Berlin, Germany’, ‘Max Planck UCL Centre for Computational Psychiatry and Ageing Research, Berlin, Germany’. The original article has been corrected.

Introduction: Exercise and physical activity have been shown to improve cognition for people living with mild cognitive impairment (MCI). There is strong evidence for the benefits of aerobic exercise and medium evidence for participating in regular strength training for people with MCI. However, people living with MCI fall two times as often as those without cognitive impairment and the evidence is currently unknown as to whether balance training for people with MCI is beneficial, as has been demonstrated for older people without cognitive impairment. The aim of this study is to determine whether a balance-focused multimodal exercise intervention improves balance and reduces falls for people with MCI, compared with a control group receiving usual care. Methods and analysis: This single blind randomised controlled trial (Balance on the Brain) will be offered to 396 people with MCI living in the community. The multimodal exercise intervention consists of two balance programmes and a walking programme to be delivered by physiotherapists over a 6-month intervention period. All participants will be followed up over 12 months (for the intervention group, this involves 6-month intervention and 6-month maintenance). The primary outcomes are (1) balance performance and (2) rate of falls. Physical performance, levels of physical activity and sedentary behaviour, quality of life and cognition are secondary outcomes. A health economic analysis will be undertaken to evaluate the cost-effectiveness of the intervention compared with usual care. Ethics and dissemination: Ethics approval has been received from the South Metropolitan Health Service Human Research Ethics Committee (HREC), Curtin University HREC and the Western Australia Department of Health HREC; and approval has been received to obtain data for health costings from Services Australia. The results will be disseminated through peer-review publications, conference presentations and online platforms.

BACKGROUND: Primary care practitioners are being called upon to work with their patients to reduce dementia risk. However, it is unclear who should do what with whom, when, and under what circumstances. OBJECTIVE: This scoping review aimed to identify clinical guidelines for dementia risk reduction (DRR) in primary care settings, synthesize the guidelines into actionable behaviors, and appraise the guidelines for specificity. METHODS: Terms related to "dementia", "guidelines", and "risk reduction" were entered into two academic databases and two web search engines. Guidelines were included if they referred specifically to clinical practices for healthcare professionals for primary prevention of dementia. Included guidelines were analyzed using a directed content analysis method, underpinned by the Action-Actor-Context-Target-Time framework for specifying behavior. RESULTS: Eighteen guidelines were included in the analysis. Together, the guidelines recommended six distinct clusters of actions for DRR. These were to 1) invite patients to discuss DRR, 2) identify patients with risk factors for dementia, 3) discuss DRR, 4) manage dementia risk factors, 5) signpost to additional support, and 6) follow up. Guidelines recommended various actors, contexts, targets, and times for performing these actions. Together, guidelines lacked specificity and were at times contradictory. CONCLUSION: Currently available guidelines allow various approaches to promoting DRR in primary care. Primary care teams are advised to draw on the results of the review to decide which actions to undertake and the locally appropriate actors, contexts, targets, and times for these actions. Documenting these decisions in more specific, local guidelines for promoting DRR should facilitate implementation.

AIM: Nutrition-based applications ("apps") offer enormous research potential, however evidence of their use and acceptability among older adults is limited. We compared self-reported and dietitian-adjusted dietary intake records among adults aged 55 to 75 years using the Research Food Diary (RFD) app. METHODS: Participants were recruited from the 45 and Up Study and completed a 3-day food record using the RFD. A follow-up dietetic telephone interview was performed to confirm the electronic dietary data. Independent of these interviews, a set of adjustments based on dietetic skills, nutritional database knowledge, food composition and dietary assessment was established to resolve probable reporting errors. The "adjusted" and "dietitian-assisted" records were compared to self-reported records for nutrient intakes and serves of The Five Food Groups using one-way repeated measures analysis of variance. RESULTS: Sixty-two participants were recruited, with 48 using the RFD app which included eight records without any identified errors. Reporting errors contained in the raw self-reported records included: food items with missing/implausible quantities or insufficient descriptions to allow automatic coding. After removal of unusable records, 44 records were analysed. Differences were found between the self-reported and adjusted records for protein, calcium, vitamin B12 , zinc and dairy food serves (all P < .001; differences up to 8%). No significant differences were found between the adjusted and dietitian-assisted measures. CONCLUSIONS: Similarities between adjusted and dietitian-assisted records suggest carefully applied dietetic assumptions are likely to improve accuracy of self-reported intake data where dietitian interviews are not possible. We provide four key recommendations to guide this process.

Background:Behavioral and psychological symptoms of dementia (BPSD) are very prevalent among individuals with dementia living in residential aged care. The development and implementation of new non-pharmacological interventions to reduce BPSD requires knowledge on the current perception and clinical practice of the care staff. We analyzed clinical care notes to examine the way residential aged care staff reported and managed BPSD in their daily clinical practice.Methods:We examined semi-structured care notes relating to the presentation and management of behaviors of 76 older residents (67% female; aged 67-101; 75% with formal dementia diagnosis) prior to participating in the Australian BPSDPLUS Program. As part of standard clinical practice in three residential aged care facilities, staff document the presentation and management of behaviors amongst residents. Using an inductive thematic analytical approach, we analyzed the reported data in the one and a half months prior to commencing participation in the BPSDPLUS Program. Care notes were coded and analyzed by two independent assessors and they discussed themes until consensus was reached.Results:A total of 465 behavior charts were completed in the one and a half months prior to the commencement of the BPSDPLUS Program. The number of behavioral charts varied widely across residents (Mean=7.3, range 0–93). Behaviors such as refusal of care, repetitive verbal behaviors, and wandering were most often mentioned, while apathy and affective and psychotic symptoms were seldomly reported. When confronted with BPSD, the clinical care notes indicated that care staff tend to respond in a reactive manner by reassuring, redirecting

Genetic association studies have identified 44 common genome-wide significant risk loci for late-onset Alzheimer’s disease (LOAD). However, LOAD genetic architecture and prediction are unclear. Here we estimate the optimal P-threshold (Poptimal) of a genetic risk score (GRS) for prediction of LOAD in three independent datasets comprising 676 cases and 35,675 family history proxy cases. We show that the discriminative ability of GRS in LOAD prediction is maximised when selecting a small number of SNPs. Both simulation results and direct estimation indicate that the number of causal common SNPs for LOAD may be less than 100, suggesting LOAD is more oligogenic than polygenic. The best GRS explains approximately 75% of SNP-heritability, and individuals in the top decile of GRS have ten-fold increased odds when compared to those in the bottom decile. In addition, 14 variants are identified that contribute to both LOAD risk and age at onset of LOAD.

Background: There is a need to develop interventions to reduce the risk of dementia in the community by addressing lifestyle factors and chronic diseases over the adult life course. Objective: This study aims to evaluate a multidomain dementia risk reduction intervention, Body Brain Life in General Practice (BBL-GP), targeting at-risk adults in primary care. Methods: A pragmatic, parallel, three-arm randomized trial involving 125 adults aged 18 years or older (86/125, 68.8% female) with a BMI of ≥25 kg/m2 or a chronic health condition recruited from general practices was conducted. The arms included (1) BBL-GP, a web-based intervention augmented with an in-person diet and physical activity consultation; (2) a single clinician–led group, Lifestyle Modification Program (LMP); and (3) a web-based control. The primary outcome was the Australian National University Alzheimer Disease Risk Index Short Form (ANU-ADRI-SF). Results: Baseline assessments were conducted on 128 participants. A total of 125 participants were randomized to 3 groups (BBL-GP=42, LMP=41, and control=42). At immediate, week 18, week 36, and week 62 follow-ups, the completion rates were 43% (18/42), 57% (24/42), 48% (20/42), and 48% (20/42), respectively, for the BBL-GP group; 71% (29/41), 68% (28/41), 68% (28/41), and 51% (21/41), respectively, for the LMP group; and 62% (26/42), 69% (29/42), 60% (25/42), and 60% (25/42), respectively, for the control group. The primary outcome of the ANU-ADRI-SF score was lower for the BBL-GP group than the control group at all follow-ups. These comparisons were all significant at the 5% level for estimates adjusted for baseline differences (immediate: difference in means −3.86, 95% CI −6.81 to −0.90, P=.01; week 18: difference in means −4.05, 95% CI −6.81 to −1.28, P<.001; week 36: difference in means −4.99, 95% CI −8.04 to −1.94, P<.001; and week 62: difference in means −4.62, 95% CI −7.62 to −1.62, P<.001). Conclusions: A web-based multidomain dementia risk reduct

Introduction Superior cognitive performance in older adults may reflect underlying resistance to age‐associated neurodegeneration. While elevated amyloid β (Aβ) deposition (Aβ+) has been associated with increased cortical atrophy, it remains unknown whether “SuperAgers” may be protected from Aβ‐associated neurodegeneration. Methods Neuropsychologically defined SuperAgers (n = 172) and cognitively normal for age (n = 172) older adults from the Australian Imaging, Biomarkers and Lifestyle study were case matched. Rates of cortical atrophy over 8 years were examined by SuperAger classification and Aβ status. Results Of the case‐matched SuperAgers and cognitively normal for age older adults, 40.7% and 40.1%, respectively, were Aβ+. Rates of age‐ and Aβ‐associated atrophy did not differ between the groups on any measure. Aβ− individuals displayed the slowest rates of atrophy. Discussion Maintenance of superior memory in late life does not reflect resistance to age‐ or Aβ‐associated atrophy. However, those individuals who reached old age without cognitive impairment nor elevated Aβ deposition (i.e. Aβ−) displayed reduced rates of cortical atrophy.

The aim of this Australian study was to investigate effects on depression of a 6-month individually tailored home-based exercise program for caregivers, designed to be done with the person they care for. Ninety-one caregiver-care recipient dyads and 30 caregiver-only participants (caregivers scoring ≥4 on the 15 item Geriatric Depression Scale (GDS-15)) were randomized into one of three groups: exercise intervention (n=50, 34 dyads and 16 caregiver only), social support control (n= 50, 42 dyads and 8 caregiver only) or usual care control (n= 21, 15 dyads and 6 caregiver only). The exercise group completed an individualised program based on the Otago-plus. The primary outcome was the proportion of participants with GDS-15 ≤4. Outcome assessors were blinded to group assignment. There were no significant difference in depression between the physical activity intervention group and the social control (OR 1.06, 95% Confidence Interval (CI) 0.44, 2.56) and the physical activity intervention group and the usual care control (OR 1.51 95% CI 0.46, 4.94) at six months or at 12-months. However, more than 50% of caregivers in all three groups no longer had a GDS-15 score >4 at 6 months. Sub-group analysis revealed that after 6 months caregivers in the exercise group caring for someone with an MMSE ≥24 were significantly less depressed than those caring for someone with an MMSE score of <24 compared with social (p value <0.02) and usual care groups (p value < 0.02). A dyad exercise intervention may be beneficial for those caring for someone without cognitive decline.

INTRODUCTION: Pharmacological interventions to address behavioural and psychological symptoms of dementia (BPSD) can have undesirable side effects, therefore non-pharmacological approaches to managing symptoms may be preferable. Past studies show that music therapy can reduce BPSD, and other studies have explored how formal caregivers use music in their caring roles. However, no randomised study has examined the effects on BPSD of music interventions delivered by informal caregivers (CGs) in the home setting. Our project aims to address the need for improved informal care by training cohabiting family CGs to implement music interventions that target BPSD, and the quality of life (QoL) and well-being of people with dementia (PwD) and CGs. METHODS AND ANALYSIS: A large international three-arm parallel-group randomised controlled trial will recruit a sample of 495 dyads from Australia, Germany, UK, Poland and Norway. Dyads will be randomised equally to standard care (SC), a home-based music programme plus SC, or a home-based reading programme plus SC for 12 weeks. The primary outcome is BPSD of PwD (measured using the Neuropsychiatric Inventory-Questionnaire). Secondary outcomes will examine relationship quality between CG and PwD, depression, resilience, competence, QoL for CG and QoL for PwD. Outcomes will be collected at baseline, at the end of the 12-week intervention and at 6 months post randomisation. Resource Utilisation in Dementia will be used to collect economic data across the life of the intervention and at 6-month follow-up. We hypothesise that the music programme plus SC will generate better results than SC alone (primary comparison) and the reading programme plus SC (secondary comparison). ETHICS AND DISSEMINATION: Ethical approval has been obtained for all countries. Results will be presented at national and international conferences and published in scientific journals and disseminated to consumer and caregiver representatives and the community. TRIAL

INTRODUCTION: Depression is a common disorder among older people living in residential aged care facilities. Several trials have demonstrated the effectiveness of behavioural therapies in treating depressive symptoms in older adults living in the community and in residential aged care. Behavioural Activation is demonstrably effective even when delivered by non-specialists (staff without formal psychological training), although strategies for adapting its use in residential aged care facilities are yet to be explored. This study will determine whether training residential care staff in the use of a structured Behavioural Activation programme is more effective at decreasing depressive symptoms among older residents than internet-based training about depression recognition and management alone. METHOD AND ANALYSIS: The behavioural activation in nursing homes to treat depression (BAN-Dep) trial is a pragmatic two-arm parallel clustered randomised controlled trial. It will recruit 666 residents aged 60 or older from 100 residential aged care facilities, which will be randomly assigned to the Behavioural Activation or control intervention. Staff in both treatment groups will be encouraged to complete the Beyondblue Professional Education to Aged Care e-learning programme to improve their recognition of and ability to respond to depression in older adults. Selected staff from intervention facilities will undergo additional training to deliver an 8-module Behavioural Activation programme to residents with subthreshold symptoms of depression-they will receive ongoing Mental support from trained Behavioural Activation therapists. Outcome measures will be collected by blind research officer at baseline and after 3, 6 and 12 months. The Patient Health Questionnaire-9 is the primary outcome measure of the study. ETHICS AND DISSEMINATION: The trial will comply with the principles of the Declaration of Helsinki for Human Rights and is overseen by the University of Western Australi

Introduction It has been estimated that a 10%-25% reduction in seven key risk factors could potentially prevent 1.1-3.0 million Alzheimer's disease cases globally. In addition, as dementia is preceded by more subtle cognitive deficits which have substantial social and economic impact, effective preventative interventions would likely have more extensive benefits. The current study evaluates in primary care a multidomain risk-reduction intervention targeting adults with high risk of developing dementia. Methods and analysis A randomised controlled trial (RCT) is being conducted to evaluate three intervention programmes using a pragmatic approach suitable to the clinic: (1) a 12-week online and face-To-face dementia risk-reduction intervention (Body Brain Life-General Practice (BBL-GP)); (2) a 6-week face-To-face group lifestyle modification programme (LMP); and (3) a 12-week email-only programme providing general health information. We aim to recruit 240 participants, aged 18 and over, to undergo a comprehensive cognitive and physical assessment at baseline and follow-ups (postintervention, 18, 36 and 62 weeks). The primary outcome is dementia risk measured with the modified version of the Australian National University-Alzheimer's Disease Risk Index Short Form. Secondary outcomes are cognitive function measured with Trails A and B, and the Digit Symbol Modalities Test; physical activity with moderate-vigorous physical activity and the International Physical Activity Questionnaire; depression with the Centre for Epidemiological Studies Depression; cost evaluation with the 12-item Short Form Health Survey, Framingham Coronary Heart Disease Risk Score and Australian Type 2 Diabetes Risk Assessment Tool; diet quality with the Australian Recommended Food Score; and sleep quality with the Pittsburgh Sleep Quality Index. Ethics and dissemination This RCT is a novel pragmatic intervention applied in a primary care setting to reduce the dementia risk exposure in adults at hi

© 2018 The Author(s). Background: Two-thirds of older Australians are sedentary. Fitness trackers have been popular with younger people and may encourage older adults to become more active. Older adults may have different gait patterns and as such it is important to establish whether fitness trackers are valid and reliable for this population. The aim of the study was to test the reliability and validity of two fitness trackers (Fitbit Flex and ChargeHR) by step count when worn by older adults. Reliability and validity were tested in two conditions: 1) in the laboratory using a two-minute-walk-test (2MWT) and 2) in a free-living environment. Methods: Two 2MWTs were completed while wearing the fitness trackers. Participants were videoed during each test. Participants were then given one fitness tracker and a GENEactiv accelerometer to wear at home for 14-days. Results: Thirty-one participants completed two 2MWTs and 30 completed the free-living procedure. Intra Class Correlation's of the fitness trackers with direct observation of steps (criterion validity) was high (ICC:0.86,95%CI:0.76,0.93). However, both fitness trackers underestimated steps. Excellent test-retest reliability (ICC = 0.75) was found between the two 2MWTs for each device, particularly the ChargeHR devices. Good strength of agreement was found for total distance and steps (fitness tracker) and moderate-to-vigorous physical activity (GENEactiv) for the free-living environment (Spearman Rho's 0.78 and 0.74 respectively). Conclusion: Reliability and validity of the Flex and ChargeHR when worn by older adults is good, however both devices underestimated step count within the laboratory environment. These fitness trackers appear suitable for consumer use and promoting physical activity for older adults.

Alzheimer's Disease (AD) is the most common form of dementia, characterised by extracellular amyloid deposition as plaques and intracellular neurofibrillary tangles of tau protein. As no current clinical test can diagnose individuals at risk of developing AD, the aim of this project is to evaluate a blood-based biomarker panel to identify individuals who carry this risk. We analysed the levels of 22 biomarkers in clinically classified healthy controls (HC), mild cognitive impairment (MCI) and Alzheimer's participants from the well characterised Australian Imaging, Biomarker and Lifestyle (AIBL) study of aging. High levels of IL-10 and IL-12/23p40 were significantly associated with amyloid deposition in HC, suggesting that these two biomarkers might be used to detect at risk individuals. Additionally, other biomarkers (Eotaxin-3, Leptin, PYY) exhibited altered levels in AD participants possessing the APOE ϵ4 allele. This suggests that the physiology of some potential biomarkers may be altered in AD due to the APOE ϵ4 allele, a major risk factor for AD. Taken together, these data highlight several potential biomarkers that can be used in a blood-based panel to allow earlier identification of individuals at risk of developing AD and/or early stage AD for which current therapies may be more beneficial.

OBJECTIVE: Delay in seeking diagnosis of dementia is common in China. Misinformation and poor knowledge about dementia may contribute to it. The study was designed to explore the nationwide dementia literacy among older adults in urban China and to investigate the factors associated with overall dementia literacy. METHODS: In a cross-sectional study, a convenience sample of 3,439 community-dwelling old adults aged 60 and over was recruited from 34 cities in 20 provinces between June 20 and August 20, 2014. All participants were administered the face-to-face mental health literacy questionnaire, which included the prevalence, symptoms, intention, and options for treatment of dementia. Stepwise multivariate regression analysis was used to explore factors associated with overall dementia literacy. RESULTS: The response rate was 87.4%. The overall dementia literacy was 55.5% (SD = 20.9%) among all respondents. The correct response rate was higher for questions on symptoms (58.7-89.6%), but lower for questions on the prevalence (22.2%) and choosing appropriate professional care personnel (22.2%). Being male [OR = 1.256, 95% CI (1.022-1.543)], having lower per capita annual income [OR = 1.314, 95% CI (1.064-1.623)], lower education [OR = 1.462, 95% CI (1.162-1.839)], and suspected depression [OR = 1.248, 95% CI (1.009-1.543)] were negatively associated with overall dementia literacy. CONCLUSION: Dementia literacy among community-dwelling older adults in urban China remains very low, in particular about the impact of dementia and appropriate treatment personnel. Community educational programs aiming to close this knowledge gap are encouraged to focus on those in the population at highest risk of low dementia literacy.

Dementia was made a National Health Priority in Australia in 2012 in recognition of the growing population diagnosed and living with the condition. In 2013, an estimated 322,000 people with dementia were living in Australia. This figure is projected to increase substantially to 400,000 by 2020 and 900,000 by 2050. Between 2009 and 2011, dementia was the third leading underlying cause of death in the country. Compared to those without dementia, those with dementia are more likely to be admitted to hospital, their length of stay is more likely to be longer, the costs associated with hospitalisation tend to be higher and they are more likely to experience negative health outcomes. A study conducted in NSW on dementia care in hospitals found that 35% of the health budget was spent on providing care to those with dementia. Improving the care experience of those with dementia is of growing concern. Admission to hospital can be confusing and frightening for a person with dementia as they struggle to understand what is happening and where they are. Reminiscence provides a practical and easy to use approach that enables family, carers and staff to engage more meaningfully with the person with dementia. This manual provides practical information that staff and volunteers can use to adopt and implement reminiscence within everyday care of people with dementia who are hospitalised.

© 2016 Informa UK Limited, trading as Taylor & Francis Group. Purpose/Aim of the study: Poor cardiovascular health, including obesity and altered lipid profiles at mid-life, are linked to increased risk of Alzheimer's disease (AD). The biological mechanisms linking cardiovascular health and cognitive function are unclear though are likely to be multifactorial. This study examined the association between various lipoproteins and cognitive functioning in ageing women. Materials and Methods: We investigated the relationship between readily available biomarkers (i.e. serum lipoprotein) and cognitive decline in domains associated with increased risk of AD (e.g. episodic verbal memory performance and subjective memory complaint). We report cross-sectional data investigating the relationship between serum total cholesterol, triglycerides, high-density lipoprotein (HDL-C) and low-density lipoprotein with verbal memory and learning ability in 130 women with and without memory complaints (n = 71 and 59, respectively) drawn from a study investigating cognitively healthy Western Australians (average age 62.5 years old). Results: After statistical modelling that controlled for the effects of age, depression and apolipoprotein E genotype, HDL-C was significantly associated with better verbal learning and memory performance, specifically short and long delay-free recalls (F = 3.062; p < .05 and F = 3.2670; p < .05, respectively). Conclusion: Our cross-sectional findings suggest that the positive effect of HDL-C on verbal memory may be present much earlier than previously reported and provide further support for the role of HDL-C in healthy brain ageing. Further exploration of the protective effect of HDL-C on cognitive function in ageing is warranted through follow-up, longitudinal studies.

© 2017 The Author(s). Background: Increasing physical activity (PA) effectively in those who are inactive is challenging. For those who have subjective memory complaints (SMC) or mild cognitive impairment (MCI) this is a greater challenge necessitating the need for more engaging and innovative approaches. The primary aim of this trial is to determine whether a home-based 6-month PA intervention with individual goal-setting and peer mentors (GM-PA) can significantly increase PA levels in insufficiently active older adults at increased risk of developing Alzheimer's disease (AD). Methods: Community living 60-80 year olds with SMC or MCI who do not engage in more than 60 min per week of moderate intensity PA will be recruited from memory clinics and the community via media advertisements to participate in this randomized, single-blind controlled trial. All participants will receive an individually tailored home-based PA program of 150 min of moderate intensity walking/week for 6 months. The intervention group will undertake individual goal-setting and behavioral education workshops with mentor support via telephone (GM-PA). Those randomized to the control group will have standard education workshops and Physical Activity Liaison (PAL) contact via telephone (CO-PA). Increase in PA is the primary outcome, fitness, cognitive, personality, demographic and clinical parameters will be measured and a health economic analysis performed. A saliva sample will be collected for APOE e4 genotyping. All participants will have a goal-setting interview to determine their PA goals. Active volunteers aged 50-85 years will be recruited from the community randomized and trained to provide peer support as mentors (intervention group) or PALS (control group) for the 6-month intervention. Mentors and PALS will have PA, exercise self-efficacy and mentoring self-efficacy measured. Participants in both groups are asked to attend 3 workshops in 6 months. At the first workshop, they will meet the

Alzheimer’s disease (AD) is a degenerative brain disorder and is the most common form of dementia. Minimally invasive approaches are required that combine biomarkers to identify individuals who are at risk of developing mild cognitive impairment (MCI) and AD, to appropriately target clinical trials for therapeutic discovery as well as lifestyle strategies aimed at prevention. Buccal mucosa cells from the Australian Imaging, Biomarkers and Lifestyle Flagship Study of Ageing cohort (n=60) were investigated for cytological markers that could be used to identify both MCI and AD individuals. Visual scoring of the buccal cytome demonstrated a significantly lower frequency of basal and karyorrhectic cells in the MCI group compared with controls. A high content, automated assay was developed using laser scanning cytometry to simultaneously measure cell types, nuclear DNA content and aneuploidy, neutral lipid content, putative Tau and amyloid-β (Aβ) in buccal cells. DNA content, aneuploidy, neutral lipids and Tau were similar in all groups. However, there was significantly lower Tau protein in both basal and karyolytic buccal cell types compared with differentiated buccal cells. Aβ, as measured by frequency of cells containing Aβ signal, as well as area and integral of Aβ signal, was significantly higher in the AD group compared with the control group. Buccal cell Aβ was correlated with mini-mental state examination (MMSE) scores (r = -0.436, P=0.001) and several blood-based biomarkers. Combining newly identified biomarkers from buccal cells with those already established may offer a potential route for more specific biomarker panels which may substantially increase the likelihood of better predictive markers for earlier diagnosis of AD.

Introduction: The objective of this study was to determine the utility of subjective memory decline (SMD) to predict episodic memory change and rates of clinical progression in cognitively normal older adults with evidence of high β-amyloid burden (CN Aβ+). Methods: Fifty-eight CN Aβ+ participants from the Australian Imaging, Biomarkers, and Lifestyle study responded to an SMD questionnaire and underwent comprehensive neuropsychological assessments. Participant data for three follow-up assessments were analyzed. Results: In CN Aβ+, subjects with high SMD did not exhibit significantly greater episodic memory decline than those with low SMD. High SMD was related to greater rates of progression to mild cognitive impairment or Alzheimer's disease (AD) dementia (hazard ratio = 5.1; 95% confidence interval, 1.4-20.0, P = .02) compared with low SMD. High SMD was associated with greater depressive symptomatology and smaller left hippocampal volume. Discussion: High SMD is a harbinger of greater rates of clinical progression in preclinical AD. Although SMD reflects broader diagnostic implications for CN Aβ+, more sensitive measures may be required to detect early subtle cognitive change.

BACKGROUND: Family members, who provide the majority of care for persons with dementia, are especially vulnerable to developing depression. Interventions targeting their depressive symptoms have been proposed but their efficacies vary considerably. It has been suggested that interventions carried out in the home setting and involving both caregivers and care recipients are more efficacious. This study aims to compare the efficacy of a home-based structured exercise programme involving both persons with dementia and their caregivers with nonexercise social contact control in treating depression among caregivers. METHODS/DESIGN: This is a parallel-group, assessor-blind, randomised controlled trial. A total of 136 caregiver-care-recipient dyads (i.e. 272 participants in total) will be recruited and randomly allocated to either a home-based structured exercise (sitting Tai Chi) group or a social contact control group. The trial comprises a 3-month intervention phase followed by an extended observation phase of another 3 months. All participants will be assessed at baseline, 6th week, 12th week and 24th week. The primary outcome will be the reduction in depression among caregivers as measured by the Hamilton Rating Scale for Depression. The secondary outcomes will be burden, quality of life, cognitive performance and balance ability of the caregivers, as well as the neuropsychiatric symptoms, cognitive function, balance and functional abilities of the persons with dementia. We will also examine whether the brain-derived neurotrophic factor gene modulates mood changes in response to exercise. DISCUSSION: The findings offer a potential avenue of intervention by providing a low-cost, safe and effective treatment for depression among dementia caregivers, which may in turn also benefit the care recipients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02132039 , registered on 28 April 2014.

The ε4 polymorphism of the APOE gene confers a substantially increased risk of developing Alzheimer's disease. However, the influence of the ε4 allele on age-related cognitive functioning is more contentious. Previously, we demonstrated relatively little evidence for a role of the ε4 allele on baseline cognitive performance in older adults in the Australian Imaging, Biomarkers and Lifestyle (AIBL) Study of Ageing (Foster et al., 2013). We here investigated whether the APOE ε4 allele influenced cognitive status over time when the AIBL cohort was studied longitudinally over a 3-year period. The AIBL neuropsychological test battery was administered at baseline, after 18 months and again after 36 months. Participants comprised 764 Healthy Controls and 131 Mild Cognitively Impaired individuals enroled in the AIBL Study of Ageing. We compared individuals within each group with and without an ε4 allele. Healthy Controls with an ε4 allele manifested a modest acceleration in cognitive decline over 36 months on measures of verbal episodic memory. By contrast, Mild Cognitively Impaired individuals with an ε4 allele showed increased cognitive decline across a range of cognitive tasks, putatively reflecting early cognitive signs of Alzheimer's disease. Given the long prodromal period that has been noted in late onset Alzheimer's disease, we suggest that these findings are consistent with a prodromal account rather than a phenotypic account of ε4-related cognitive ageing.

Cognitive decline and dementia due to Alzheimer's disease (AD) have been associated with genetic, lifestyle, and environmental factors. A number of potentially modifiable risk factors should be taken into account when preventive or ameliorative interventions targeting dementia and its preclinical stages are investigated. Bone mineral density (BMD) and body composition are two such potentially modifiable risk factors, and their association with cognitive decline was investigated in this study. 164 participants, aged 34–87 years old (62.78 ± 9.27), were recruited for this longitudinal study and underwent cognitive and clinical examinations at baseline and after 3 years. Blood samples were collected for apolipoprotein E (APOE) genotyping and dual energy x-ray absorptiometry (DXA) was conducted at the same day as cognitive assessment. Using hierarchical regression analysis, we found that BMD and lean body mass, as measured using DXA were significant predictors of episodic memory. Age, gender, APOE status, and premorbid IQ were controlled for. Specifically, the List A learning from California Verbal Learning Test was significantly associated with BMD and lean mass both at baseline and at follow up assessment. Our findings indicate that there is a significant association between BMD and lean body mass and episodic verbal learning. While the involvement of modifiable lifestyle factors in human cognitive function has been examined in different studies, there is a need for further research to understand the potential underlying mechanisms.

Objectives: The adverse mental health effects of caring have been studied, frequently in carers of people with dementia. Less is known about the mental health of carers of people with other conditions. This study compared depression and burden in older carers looking after people with a variety of conditions. Design, methods and measures: Over 200 older carers interested in participating in the Improving Mood through Physical Activity in Carers and Care-recipient Trial were included in this cross-sectional study, using the Geriatric Depression Scale (GDS) and Zarit Burden Inventory (ZBI). Results: Overall there were 43% of carers who were depressed and a quarter of them reported moderate-to-severe burden. Carers of people with physical conditions had the highest levels of depression and burden. Patient diagnosis, hours spent caring, and burden were associated with depression, while hours spent caring and carer depression were associated with burden. These factors contributed approximately 25-30% of the variance of depression and burden, respectively. Conclusions: The diagnosis of the patient was a factor associated with depression, and older carers of people with physical conditions were at the highest risk. It is important for clinicians to assess the mental health of all carers, regardless of the patient diagnosis.