Volume 70, Supplement 1, IN PROGRESS

Supplement: International Research Network on Dementia Prevention (Guest Editors: Ruth Peters, Kaarin Anstey)

Editorial
Kaarin J. Anstey, Ruth Peters
Dementia, Risk, Risk Reduction, and Translation into Practice: An International Research Network for Dementia Prevention (IRNDP) Special Issue

Editorial
M. Maria Glymour, Rachel A. Whitmer
Using Cross-Cultural Studies to Improve Evidence on Dementia Prevention: Lessons from the Special Issue Sponsored by the International Research Network on Dementia Prevention (IRNDP)

Editorial
Carol Brayne, Edo Richard
Prevention of Cognitive Decline: A Goal in Sight?

Editorial
Claire E. Sexton, Kristine Yaffe
Population-Based Approaches to Dementia Prevention

Julian W. Sacre, Dianna J. Magliano, Paul Z. Zimmet, Kevan R. Polkinghorne, Steven J. Chadban, Kaarin J. Anstey, Jonathan E. Shaw
Associations of Chronic Kidney Disease Markers with Cognitive Function: A 12-Year Follow-Up Study
Abstract:
Background: The role of chronic kidney disease (CKD) as a risk factor for cognitive impairment independent of their shared antecedents remains controversial. Objective: To determine whether kidney damage (indicated by albuminuria) or kidney dysfunction (estimated glomerular filtration rate [eGFR] <60 ml/min/1.73 m2) predict future (12-year) cognitive function independently of their shared risk factors. Methods: We studied 4,128 individuals from the 1999/00 population-based Australian Diabetes, Obesity, and Lifestyle (AusDiab) Study who returned in 2011/12 for follow-up cognitive function testing. Albuminuria was defined by urinary albumin:creatinine ≥3.5 (women) or ≥2.5 mg/mmol (men). Kidney dysfunction was indicated by eGFR <60 ml/min/1.73 m2. Cognitive function domains assessed included memory (California Verbal Learning Test [CVLT]) and processing speed (Symbol Digit Modalities Test [SDMT]). Results: Baseline albuminuria and kidney dysfunction were identified in 142 (3.4%) and 39 (0.9%) individuals, respectively, with minimal overlap (n=7). Those with albuminuria demonstrated concurrently reduced 12-year SDMT (p=0.084) and CVLT scores (p=0.005) following adjustment for age, sex, and education. However, only CVLT performance remained worse (p=0.027) following additional adjustment for myocardial infarction, stroke, and related risk factors (hypertension, diabetes, dyslipidemia, smoking, BMI, physical activity, and alcohol intake). Indeed, these collective covariates were responsible for 47% of the effect of albuminuria on SDMT, but only 21% of its effect on CVLT. Kidney dysfunction was not associated with either SDMT or CVLT performance (p>0.10). Conclusions: Albuminuria predicted worse memory function at 12 years follow-up, whereas its effect on processing speed was driven largely by differences in cardiovascular risk. Kidney dysfunction based on eGFR predicted neither cognitive domain.

Kay Deckers, Astrid Nooyens, Martin van Boxtel, Frans Verhey, Monique Verschuren, Sebastian Köhler
Gender and Educational Differences in the Association between Lifestyle and Cognitive Decline over 10 Years: The Doetinchem Cohort Study
Abstract: Background: Several modifiable risk factors for cognitive decline have been identified, but whether differences by gender and educational level exist is unclear. Objective: The present study aims to clarify this by prospectively investigating the relationship between health- and lifestyle factors and cognitive functioning in different subgroups defined by gender and educational level. Methods: 2,347 cognitive healthy individuals (mean age=54.8, SD=6.8, range: 41-71; 51.8% female; 26.2% low education) from the Doetinchem Cohort Study were examined for cognitive function at baseline, and at 5- and 10-year follow-up. Health- and lifestyle factors were captured by a poly-environmental risk score labelled ‘LIfestyle for BRAin Health’ (LIBRA). This score consists of 12 modifiable risk and protective factors for cognitive decline and dementia, with higher scores indicating greater risk (range: -2.7 to +12.7). Heterogeneity in associations between LIBRA and decline in verbal memory, cognitive flexibility, and mental speed between males and females and individuals with different levels of education were assessed in linear mixed models. Results: Overall, higher LIBRA scores predicted faster decline in verbal memory, cognitive flexibility, and mental speed over 10 years. Higher LIBRA scores were further associated with increased risk for incident cognitive impairment (one-point increase in LIBRA: HR = 1.09, 1.04-1.14, p = 0.001). In general, these effects were similar across gender and educational level. Conclusion: A composite risk score comprising unhealthy lifestyle and relatively poor health in midlife is significantly associated with a worse course of cognition 10 years later. These associations were for the most part unrelated to gender or educational differences.

Zulzikry Hafiz Abu Bakar, Hanafi Ahmad Damanhuri, Suzana Makpol, Wan Mohd Aizat Wan Kamaruddin, Nur Fathiah Abdul Sani, Ahmad Imran Zaydi Amir Hamzah, Khairun Nain Nor Aripin, Mohd Dzulkhairi Mohd Rani, Nor Azila Noh, Rosdinom Razali, Musalmah Mazlan, Hamzaini Abdul Hamid, Mazlyfarina Mohamad, Wan Zurinah Wan Ngah
Effect of Age on the Protein Profile of Healthy Malay Adults and its Association with Cognitive Function Competency
Abstract: Background: Many studies on biochemical and psychological variables have aimed to elucidate the association between aging and cognitive function. Demographic differences and protein expression have been reported to play a role in determining the cognitive capability of a population. Objective: This study aimed to determine the effect of age on the protein profile of Malay individuals and its association with cognitive competency. Methods: A total of 160 individuals were recruited and grouped accordingly. Cognitive competency of each subject was assessed with several neuropsychological tests. Plasma samples were collected and analyzed with Q Exactive HF Orbitrap. Proteins were identified and quantitated with MaxQuant and further analyzed with Perseus to determine differentially expressed proteins. PANTHER, Reactome, and STRING were applied for bioinformatics output. Results: Our data showed that the Malay individuals are vulnerable to the deterioration of cognitive function with aging, and most of the proteins were differentially expressed in concordance. Several physiological components and pathways were shown to be involved, giving a hint of a promising interpretation on the induction of aging toward the state of the Malays’ cognitive function. Nevertheless, some proteins have shown a considerable interaction with the generated protein network, which provides a direction of focus for further investigation. Conclusion: This study demonstrated notable changes in the expression of several proteins as age increased. These changes provide a promising platform for understanding the biochemical factors affecting cognitive function in the Malay population. The exhibited network of protein-protein interaction suggests the possibility of implementing regulatory intervention in ameliorating Malay cognitive function.

Nicolas Cherbuin, Erin I. Walsh, A. Matthew Prina
Chronic Obstructive Pulmonary Disease and Risk of Dementia and Mortality in Lower to Middle Income Countries
Abstract: Background: Chronic obstructive pulmonary disease (COPD) is a major disease burden which accounts for 5% of all deaths globally, with most of those (>90%) occurring in lower to middle income countries (LMIC). It is also emerging as an important modifiable dementia risk factor. Objective: To address the knowledge gap surrounding the nature of the associations between COPD, dementia, and mortality, and the geographical variation of those associations in LMIC. Methods: Data from the 10/66 study surveying 15,394 participants (mean age 74 years, 62% female) across 8 countries was used to estimate the prevalence of self-reported COPD and its association with incident dementia and premature death. Proportional sub-hazards models using a cumulative incidence function were applied to identify the probability of incident dementia onset given the risk of premature death, with estimates pooled across countries via random effect meta-analysis. Results: Over the 3-year follow-up, almost 10% of participants developed dementia and 14% were deceased. COPD was not significantly associated with dementia incidence except in Cuba. However, fully adjusted models indicated that individuals with COPD were at a 28% increased risk of premature death, a trend present across most countries when analyzed individually. Conclusion: The link between COPD and dementia is currently somewhat different and weaker in LMIC than in developed countries. This may be because premature death in the populations studied mask the development of clinical dementia. Given the global trend toward increased life expectancy, it is critical that the disease burden associated with COPD be addressed without delay if a further rise in dementia prevalence associated with COPD is to be avoided in LMIC.

Kylie Radford, Louise M. Lavrencic, Kim Delbaere, Brian Draper, Robert Cumming, Gail Daylight, Holly A. Mack, Simon Chalkley, Hayley Bennett, Gail Garvey, Thi Yen Hill, Danielle Lasschuit, Gerald A. Broe
Factors Associated with the High Prevalence of Dementia in Older Aboriginal Australians
Abstract: Dementia prevalence in Aboriginal and Torres Strait Islander Australians is three to five times higher than the general Australian population. A better understanding of the underlying biomedical and social risk factors is needed to guide dementia prevention in Aboriginal Australians. The current study is the first to examine potential risk factors for dementia in the majority urban and regional population, with a representative sample of 336 Aboriginal Australians aged 60 years and older. Participants included 45 people with a dementia diagnosis (n=27 probable/possible Alzheimer’s disease); and 286 people without dementia. Univariate logistic regression analyses (controlling for age) identified childhood trauma, mid-life factors (history of unskilled work, past high-risk alcohol use), and medical factors (history of stroke, head injury with loss of consciousness, epilepsy) as risk factors for dementia. Multivariable analysis revealed age, childhood trauma, unskilled work, stroke, and head injury as independent predictors of all-cause dementia. A range of comorbid factors related to dementia was also identified (i.e., functional impairment, incontinence, recent hospital admission, low body mass index, living in residential care, depression, current high-risk alcohol use, social isolation, low physical activity levels). These findings extend previous outcomes in a remote Aboriginal population by highlighting that life-course social determinants of health, in addition to neurological disorders, likely play an important role in elevating dementia risk. Certain psychosocial and medical exposures are highly prevalent in Aboriginal Australians, similar to other indigenous populations, and should be considered when designing targeted and culturally appropriate prevention initiatives to reduce the burden of dementia.

Isaac M. Danat, Angela Clifford, Martin Partridge, Weiju Zhou, Aishat T. Bakre, Anthony Chen, Danielle McFeeters, Tina Smith, Yuhui Wan, John Copeland, Kaarin J. Anstey, Ruoling Chen
Impacts of Overweight and Obesity in Older Age on the Risk of Dementia: A Systematic Literature Review and a Meta-Analysis
Abstract: Background: It is unclear whether overweight and obesity in older age reduces or increases the risk of incident dementia. Objective: To assess the impacts of overweight and obesity in older age on incident dementia. Methods: We searched cohort studies reporting body weight measured in older age and dementia through PubMed, Embase, Medline, PyschInfo, and Cochrane library until July 2016. Sixteen articles were identified for the review. We pooled data from them and a new unpublished study from China, to calculate relative risk (RR) of incident dementia in relation to body mass index (BMI) and waist circumference (WC). Results: All 16 cohort studies were undertaken in high income countries, with follow-up periods ranging between 3 to 18 years. Thirteen studies showed an inverse association between BMI and dementia, and three studies demonstrated a positive association. Pooled RR of dementia in relation to continuous BMI from 14 studied populations, including the new Chinese data was 0.97 (95%CI 0.95-1.00); in those with followed up < 9 years was 0.95 (0.93-0.96) while in ≥9 years follow-up was 1.03 (0.96-1.11). In five studied populations examining categorical BMI, RR of dementia in older people classified as overweight and obese was 0.98 (0.54-1.77) and 1.17 (0.65-2.10) respectively, in comparison with other weights. The pooled WC data showed no association between increased WC and reduced risk of dementia. Conclusion: The current evidence did not support a paradox on beneficial impacts of overweight and obesity in older age on incident dementia. More studies with long term follow up are needed to clarify the association of body weight in older age with dementia risk.

G. Peggy McFall, Kirstie L. McDermott, Roger A. Dixon
Modifiable Risk Factors Discriminate Memory Trajectories in Non-Demented Aging: Precision Factors and Targets for Promoting Healthier Brain Aging and Preventing Dementia?
Abstract: Background: Non-demented cognitive aging trajectories are characterized by vast level and slope differences and a spectrum of outcomes, including dementia. Objective: The goal of AD risk management (and its corollary, promoting healthy brain aging) is aided by two converging objectives: 1) classifying dynamic distributions of non-demented cognitive trajectories, and 2) identifying modifiable risk-elevating and risk-reducing factors that discriminate stable or normal trajectory patterns from declining or pre-impairment patterns. Method: Using latent class growth analysis we classified three episodic memory aging trajectories for n=882 older adults (baseline Mage=71.6, SD=8.9, range= 53-95, female=66%): Stable (SMA; above average level, sustained slope), Normal (NMA; average level, moderately declining slope), and Declining (DMA; below average level, substantially declining slope). Using random forest analyses, we simultaneously assessed 17 risk/protective factors from non-modifiable demographic, functional, psychological, and lifestyle domains. Within two age strata (Young-Old, Old-Old), three pairwise prediction analyses identified important discriminating factors. Results: Prediction analyses revealed that different modifiable risk predictors, both shared and unique across age strata, discriminated SMA (i.e., education, depressive symptoms, living status, body mass index, heart rate, social activity) and DMA (i.e., lifestyle activities [cognitive, self-maintenance, social], grip strength, heart rate, gait) groups. Conclusion: Memory trajectory analyses produced empirical classes varying in level and slope. Prediction analyses revealed different predictors of SMA and DMA that also varied by age strata. Precision approaches for promoting healthier memory aging—and delaying memory impairment—may identify modifiable factors that constitute specific targets for intervention in the differential context of age and non-demented trajectory patterns.

Isobel E.M. Evans, Anthony Martyr, Rachel Collins, Carol Brayne, Linda Clare
Social Isolation and Cognitive Function in Later Life: A Systematic Review and Meta-Analysis
Abstract: Background: There is some evidence to suggest that social isolation may be associated with poor cognitive function in later life. However, findings are inconsistent and there is wide variation in the measures used to assess social isolation. Objective: We conducted a systematic review and meta-analysis to investigate the association between social isolation and cognitive function in later life. Methods: A search for longitudinal studies assessing the relationship between aspects of social isolation (including social activity and social networks) and cognitive function (including global measures of cognition, memory, and executive function) was conducted in PsycInfo, CINAHL, PubMed, and AgeLine. A random effects meta-analysis was conducted to assess the overall association between measures of social isolation and cognitive function. Sub-analyses investigated the association between different aspects of social isolation and each of the measures of cognitive function. Results: Sixty-five articles were identified by the systematic review and 51 articles were included in the meta-analysis. Low levels of social isolation characterized by high engagement in social activity and large social networks were associated with better late-life cognitive function (r = 0.054, 95% CI: 0.043, 0.065). Sub-analyses suggested that the association between social isolation and measures of global cognitive function, memory, and executive function were similar and there was no difference according to gender or number of years follow-up. Conclusions: Aspects of social isolation are associated with cognitive function in later life. There is wide variation in approaches to measuring social activity and social networks across studies which may contribute to inconsistencies in reported findings.

Ruth Peters, Nicole Ee, Jean Peters, Andrew Booth, Ian Mudway, Kaarin J. Anstey
Air Pollution and Dementia: A Systematic Review
Abstract: Background: Both air pollution and dementia are current and growing global issues. There are plausible links between exposure to specific air pollutants and dementia. Objective: To systematically review the evidence base with respect to the relationship between air pollution and later cognitive decline and dementia. Methods: Medline, Embase, and PsychINFO® were searched from their inception to September 2018, for publications reporting on longitudinal studies of exposure to air pollution and incident dementia or cognitive decline in adults. Studies reporting on exposure to tobacco smoke including passive smoking or on occupational exposure to pollutants were excluded. Using standard Cochrane methodology, two readers identified relevant abstracts, read full text publications, and extracted data into structured tables from relevant papers, as defined by inclusion and exclusion criteria. Papers were also assessed for validity. CRD42018094299. Results: From 3,720 records, 13 papers were found to be relevant, with studies from the USA, Canada, Taiwan, Sweden, and the UK. Study follow-up ranged from one to 15 years. Pollutants examined included particulate matter ≤ 2.5 μ (PM 2.5), nitrogen dioxide (NO2), nitrous oxides (NOx), carbon monoxide (CO), and ozone. Studies varied in their methodology, population selection, assessment of exposure to pollution, and method of cognitive testing. Greater exposure to PM2.5, NO2/NOx, and CO were all associated with increased risk of dementia. The evidence for air pollutant exposure and cognitive decline was more equivocal. Conclusion: Evidence is emerging that greater exposure to airborne pollutants is associated with increased risk of dementia.

Kaarin J. Anstey, Nicole Ee, Ranmalee Eramudugolla, Carol Jagger, Ruth Peters
A Systematic Review of Meta-Analyses that Evaluate Risk Factors for Dementia to Evaluate the Quantity, Quality, and Global Representativeness of Evidence
Abstract: Background: The translation of evidence on dementia risk factors into clinical advice requires careful evaluation of the methodology and scope of data from which risk estimates are obtained. Objective: To evaluate the quantity and quality and of evidence, we conducted a review of reviews of risk factors for Alzheimer’s disease (AD), Vascular dementia (VaD), and Any Dementia with the aim of evaluating the quantity, quality, and representativeness of evidence. Methods: PubMed, Cochrane library, and the Global Index Medicus were searched to identify meta-analyses of observational studies of risk factors for AD, VaD, and Any Dementia. PROSPERO CRD42017053920. Results: Meta-analysis data were available for 34 risk factors for AD, 26 risk factors for Any Dementia, and eight for VaD. Quality of evidence varied greatly in terms of the number of contributing studies, whether data on mid-life exposure was available, and consistency of measures. The most evidence was available for cardiovascular risk factors. The most geographically representative evidence (five of six global regions) was available for alcohol, physical activity, diabetes, high midlife BMI, antihypertensives, and motor function. Evidence from Australia/Oceana or Africa was limited. With the exception of diabetes, evidence from Latin America/Caribbean was unavailable. Midlife specific data were only available for cholesterol and arthritis. Conclusion: There is a lack of mid-life specific data, limited data on VaD, and a lack of geographical representation for many risk factors for dementia. The quality, quantity, and representativeness of evidence needs to be considered before recommendations are made about the relevance of risk factors in mid or late life or for dementia subtypes.

Kay L. Cox, Elizabeth V. Cyarto, Kathryn A. Ellis,, David Ames, Patricia Desmond, Pramit Phal, Matthew J. Sharman, Cassandra Szoeke, Christopher C. Rowe, Colin L. Masters, Emily You , Sally Burrows, Michelle M.Y. Lai, Nicola T. Lautenschlager
A Randomized Controlled Trial of Adherence to a 24-Month Home-Based Physical Activity Program and the Health Benefits for Older Adults at Risk of Alzheimer’s Disease: The AIBL Active-Study
Abstract: Background: Previous studies have demonstrated that physical activity (PA) interventions can improve physical and cognitive outcomes in older adults, but most have been relatively short in duration (<1 year) with a few having specifically targeting individuals at risk of developing Alzheimer's disease. Objective: To examine adherence and physical health outcomes in a 24-month home-based PA intervention in older adults at risk of Alzheimer's disease. Methods: Participants 60 years and older with mild cognitive impairment (MCI) or subjective memory complaints (SMC) with at least 1 cerebrovascular risk factor recruited from The Australian Imaging Biomarkers and Lifestyle Flagship Study of Aging (AIBL) were randomized to a PA or control group (n = 106). The control group continued with their usual lifestyle. The PA group received a 24-month home-based program with a target of 150 minutes/week of moderate PA and a behavioral intervention. Retention (participants remaining) and PA adherence (PA group only, percent PA completed to the PA prescribed) were determined at 6, 12, 18, and 24 months. Assessments at baseline, 6, 12, and 24 months included, PA; fitness; body composition and fat distribution. Key outcome measures were PA adherence and PA. Results: The 24-month retention rate (97.2%) and the median PA adherence 91.67% (Q1-Q3, 81.96, 100.00) were excellent. In the long-term the intervention group achieved significantly better improvements in PA levels, leg strength, fat mass and fat distribution compared to the control. Conclusion: This study demonstrates that in this target group, long-term PA adherence is achievable and has physical health benefits.

Kristine Yaffe, Deborah E. Barnes, Dori Rosenberg, Sascha Dublin, Allison R. Kaup, Evette J. Ludman, Eric Vittinghoff, Carrie B. Peltz, Anne D. Renz, Kristin J. Adams, Eric B. Larson
Systematic Multi-Domain Alzheimer’s Risk Reduction Trial (SMARRT): Study Protocol
Abstract: This article describes the protocol for the Systematic Multi-domain Alzheimer’s Risk Reduction Trial (SMARRT), a single-blind randomized pilot trial to test a personalized, pragmatic, multi-domain Alzheimer’s disease (AD) risk reduction intervention in a US integrated healthcare delivery system. Study participants will be 200 higher-risk older adults (age 70-89 years with subjective cognitive complaints, low normal performance on cognitive screen, and ≥ two modifiable risk factors targeted by our intervention) who will be recruited from selected primary care clinics of Kaiser Permanente Washington, oversampling people with non-white race or Hispanic ethnicity. Study participants will be randomly assigned to a two-year Alzheimer’s risk reduction intervention (SMARRT) or a Health Education (HE) control. Randomization will be stratified by clinic, race/ethnicity (non-Hispanic white versus non-white or Hispanic), and age (70-79, 80-89). Participants randomized to the SMARRT group will work with a behavioral coach and nurse to develop a personalized plan related to their risk factors (poorly controlled hypertension, diabetes with evidence of hyper or hypoglycemia, depressive symptoms, poor sleep quality, contraindicated medications, physical inactivity, low cognitive stimulation, social isolation, poor diet, smoking). Participants in the HE control group will be mailed general health education information about these risk factors for AD. The primary outcome is two-year cognitive change on a cognitive test composite score. Secondary outcomes include: 1) improvement in targeted risk factors, 2) individual cognitive domain composite scores, 3) physical performance, 4) functional ability, 5) quality of life, and 6) incidence of mild cognitive impairment, AD, and dementia. Primary and secondary outcomes will be assessed in both groups at baseline and 6, 12, 18, and 24 months.

Megan Heffernan, Gavin Andrews, Maria A. Fiatarone Singh, Michael Valenzuela, Kaarin J. Anstey, Anthony Maeder, John McNeil, Louisa Jorm, Nicola Lautenschlager, Perminder Sachdev, Anupama Ginige, Megan Hobbs, Christos Boulamatsis, Tiffany Chau, Lynne Cobiac, Kay Cox, Kenneth Daniel, Victoria M. Flood, Yareni Guerrero, Jane Gunn, Nidhi Jain, Nicole A. Kochan, Amit Lampit, Yorgi Mavros, Jacinda Meiklejohn, Yian Noble, Fiona O’Leary, Sue Radd-Vagenas, Courtney Walton, Maintain Your Brain Collaborative Team, Henry Brodaty
Maintain Your Brain: Protocol of a 3-Year Randomized Controlled Trial of a Personalized Multi-Modal Digital Health Intervention to Prevent Cognitive Decline Among Community Dwelling 55 to 77 Year Olds
Abstract: Background: Maintain Your Brain (MYB) is a randomized controlled trial of an online multi-modal lifestyle intervention targeting modifiable dementia risk factors with its primary aim being to reduce cognitive decline in an older age cohort. Methods: MYB aims to recruit 8,500 non-demented community dwelling 55 to 77 year olds from the Sax Institute’s 45 and Up Study in New South Wales, Australia. Participants will be screened for risk factors related to four modules that comprise the MYB intervention: physical activity, nutrition, mental health, and cognitive training. Targeting risk factors will enable interventions to be personalized so that participants receive the most appropriate modules. MYB will run for three years and up to four modules will be delivered sequentially each quarter during year one. Upon completing a module, participants will continue to receive less frequent booster activities for their eligible modules (except for the mental health module) until the end of the trial. Discussion: MYB will be the largest trial to attempt to prevent cognitive decline and potentially dementia. If successful, MYB will provide a model for not just effective intervention among older adults, but an intervention that is scalable for broad use.

Wan Nurzulaikha Wan Nasri, Suzana Makpol, Musalmah Mazlan, Ikuo Tooyama, Wan Zurinah Wan Ngah, Hanafi Ahmad Damanhuri
Tocotrienol Rich Fraction Supplementation Modulate Brain Hippocampal Gene Expression in APPswe/PS1dE9 Alzheimer’s Disease Mouse Model
Abstract: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by loss of memory and other cognitive abilities. AD is associated with aggregation of amyloid-β (Aβ) deposited in the hippocampal brain region. Our previous work has shown that tocotrienol rich fraction (TRF) supplementation was able to attenuate the blood oxidative status, improve behavior, and reduce fibrillary-type Aβ deposition in the hippocampus of an AD mouse model. In the present study, we investigate the effect of 6 months of TRF supplementation on transcriptome profile in the hippocampus of APPswe/PS1dE9 double transgenic mice. TRF supplementation can alleviate AD conditions by modulating several important genes in AD. Moreover, TRF supplementation attenuated the affected biological process and pathways that were upregulated in the AD mouse model. Our findings indicate that TRF supplementation can modulate hippocampal gene expression as well as biological processes that can potentially delay the progression of AD.

Divya Vanoh, Suzana Shahar, Rosdinom Razali, Nazlena Mohamad Ali, Zahara Abdul Manaf, Shahrul Azman Mohd Noah, Amrizal Muhammad Nur
The Effectiveness of a Web-Based Health Education Tool, WESIHAT 2.0, among Older Adults: A Randomized Controlled Trial
Abstract: Background: Intervention strategies, especially online based approaches, are considered to be beneficial in improving the health of the senior. The effectiveness of such approaches is yet to be determined. Objective: This study aims to determine the effectiveness of the web-based application, WESIHAT 2.0©, for improving cognitive function, physical fitness, biochemical indices, and psychosocial variables among older adults in Klang Valley, Malaysia. The cost analysis of WESIHAT 2.0© was also determined. Method: The study utilized a two-arm randomized controlled trial with 25 subjects in each of the intervention and control groups. The participants chosen for the study included those who were 60 years and above with at least secondary education and had internet access using a computer at home. The intervention group was exposed to the website (30 minutes per day, 4 days per week) for six months, while the control group was given health education pamphlets. Activity-Based Costing method was used to determine the cost saved using WESIHAT 2.0© as compared to using the pamphlet. Results: Significant intervention effects were observed for self-perception of disability and informational support scores. WESIHAT 2.0© was able to save costs in improving the self-perception of disability score and the informational support score at MYR 6.92 and MYR 13.52, respectively, compared to the conventional method. Conclusion: WESIHAT 2.0© was able to save costs in improving the self-perceived disability and informational support scores for the intervention group.

Carol A. Derby, Mindy J. Katz, Sara Rozner, Richard B. Lipton, Charles B. Hall
A Birth Cohort Analysis of Amnestic Mild Cognitive Impairment Incidence in the Einstein Aging Study (EAS) Cohort
Abstract: Background: The transition from normal cognition to Alzheimer’s disease is considered a continuum, with amnestic mild cognitive impairment (aMCI) an intermediate clinical cognitive state. Although prior work suggests that dementia incidence rates may be declining, there is little information regarding temporal trends in aMCI incidence. Objective: To determine whether age specific rates of aMCI have changed over sequential birth cohorts among individuals included in the population-based Einstein Aging Study (EAS) cohort. A secondary objective was to examine trends in aMCI rates among Blacks and Whites and by sex. Methods: Age specific incidence of aMCI was examined by birth year among 1,233 individuals age 70 years and above enrolled in the population-based EAS cohort between November 1, 1993 and February 22, 2016 and who had at least one annual follow-up assessment (5,321 person years of follow-up). Poisson regression was used to determine whether there has been a change in age specific aMCI rates over sequential years of birth. Results: No significant change in aMCI rates was identified in the overall cohort, among Blacks or Whites, or among males or females born between 1899 and 1946. Conclusions: Despite a trend for decreased dementia incidence in the EAS cohort, rates of incident aMCI have not changed. These apparently conflicting results may indicate a delay or decrease in the rates of transition from aMCI to dementia within the cohort. However, further studies are needed to confirm whether rates of aMCI have changed in other populations, and how aMCI rates are related to secular trends in dementia risk factors.

Deborah Oliveira, Leonardo Jun Otuyama, Dirceu Mabunda, Flavio Mandlate, Manuel Gonçalves-Pereira, Miguel Xavier, Jerson Laks, Cleusa P. Ferri
Reducing the Number of People with Dementia Through Primary Prevention in Mozambique, Brazil, and Portugal: An Analysis of Population-Based Data
Abstract: Background: Most people with dementia live in low- and middle-income countries and little is known about the potential for reducing these numbers by reducing key risk factors. Objective: To investigate the potential for dementia incidence reduction in Brazil, Mozambique, and Portugal (a culturally related, high-income country). Methods: We replicated previously published methods and based on the relative risks from previous studies, we estimated the population-attributable risk (PAR) of dementia in Mozambique, Brazil, and Portugal for seven modifiable risk factors associated with dementia (low educational attainment, physical inactivity, midlife hypertension, midlife obesity, depression, smoking, and diabetes mellitus). The combined PAR was calculated and adjusted for associations between risk factors. The potential for risk factor reduction was assessed by examining the effect of relative reductions of 10% and 20% per decade for each of the risk factors on projections for dementia cases for each decade until 2050. Results: After adjusting for non-independence of risk factors, 24.4%, 32.3%, and 40.1% of dementia cases could be related to seven potentially modifiable risk factors in Mozambique, Brazil, and Portugal, respectively. Reducing the prevalence of each risk factor by 20% per decade could, by 2050, potentially reduce the prevalence of dementia in Mozambique, Brazil, and Portugal by 12.9%, 16.2%, and 19.5%, respectively. Conclusion: There is a substantial difference between the countries in the percentage of dementia cases that could be attributable to the seven potentially modifiable risk factors. The proportion of cases that could be prevented by 2050 if measures were taken to address these main risk factors was higher in Portugal than in Brazil and Mozambique. Each country or region should consider their unique risk factor profile when developing dementia risk reduction programs.

Review
Kenichi Meguro, Hiroko H. Dodge
Vascular Mild Cognitive Impairment: Identifying Disease in Community-Dwelling Older Adults, Reducing Risk Factors, and Providing Support. The Osaki-Tajiri and Kurihara Projects
Abstract: Vascular mild cognitive impairment (MCI) is a critical disease. Its prognosis includes not only onset of vascular dementia, but also death by cardiovascular disease. The vascular risk factors for vascular MCI are treatable, and appropriate treatment can prevent or delay the progression to dementia. Therefore, this group is an excellent candidate for secondary prevention. However, community-dwelling older adults with vascular MCI are often undetected and are not clinically identified until they develop frank dementia. Furthermore, older adults with undetected vascular MCI often have decreased ability to follow their medication regimens and this poor medication adherence worsens their vascular comorbidities. This vicious cycle needs to be prevented through community-based interventions. There is evidence that treatment of hypertension or diabetes mellitus could lead to a reduced incidence of vascular MCI and dementia. In this review article, we first explain the background and etiology of vascular MCI. We then summarize phenotype of subcortical vascular dementia which is often unrecognized or ‘‘hidden” in the community. Then we introduce the Osaki-Tajiri and Kurihara Projects which have been conducted in Northern Japan, as an example of prevention projects aimed to identify early-stage vascular MCI in the community, reduce the risk factors and facilitate their treatment. Early identification of vascular MCI in the community could lead to a large reduction in the dementia burden worldwide. The outreach efforts presented here could be useful in developing secondary prevention strategies targeted to vascular MCI.

Rachel Collins, Barbora Silarova, Linda Clare
Dementia Primary Prevention Policies and Strategies and Their Local Implementation: A Scoping Review Using England as a Case Study
Abstract: Background: Understanding policy context and how policy is implemented at the local and clinical level is an important precursor to developing preventive strategies focusing on dementia risk reduction in primary healthcare settings. Objective: Using England as a case study, we review policies and strategies relevant to dementia prevention from the national to local level and how these are translated into primary healthcare services. Methods: We conducted a scoping review covering: 1) identification of national, regional, and local policies and strategies that include dementia prevention; 2) identification of national guidelines for implementing dementia prevention at the clinical level; and 3) evaluation of the implementation of these at the clinical level. Results: Dementia prevention is addressed in national policy, and this filters through to regional and local levels. Focus on dementia prevention is limited and variable. Reference to modifiable risk factors is associated with other non-communicable diseases, placing less emphasis on factors more dementia specific. Evidence of implementation of dementia prevention policies at the clinical level is limited and inconsistent. Available evidence suggests messages about dementia prevention may best be delivered through primary healthcare services such as the National Health Service (NHS) Health Check. Conclusion: The limitations identified in this review could be addressed through development of a national policy focused specifically on dementia prevention. This could provide a platform for increasing knowledge and understanding among the general population and healthcare professionals. It would be important for such a policy to cover the full range of modifiable risk factors relevant to dementia.