Journal of Alzheimer's Disease - Volume 70, issue s1

Authors: McFall, G. Peggy | McDermott, Kirstie L. | Dixon, Roger A.

Article Type: Research Article

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 M age=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. Show more

Keywords: Biomarkers, dementia prevention, memory trajectories, protective factors, risk factors, Victoria Longitudinal Study

DOI: 10.3233/JAD-180571

Citation: Journal of Alzheimer's Disease, vol. 70, no. s1, pp. S101-S118, 2019

Authors: Evans, Isobel E.M. | Martyr, Anthony | Collins, Rachel | Brayne, Carol | Clare, Linda

Article Type: Research Article

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. Show more

Keywords: Aging, cognition, cognitive reserve, social isolation

DOI: 10.3233/JAD-180501

Citation: Journal of Alzheimer's Disease, vol. 70, no. s1, pp. S119-S144, 2019

Authors: Peters, Ruth | Ee, Nicole | Peters, Jean | Booth, Andrew | Mudway, Ian | Anstey, Kaarin J.

Article Type: Research Article

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 (PM2.5 ), 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. Show more

Keywords: Air pollutants, cognitive decline, dementia, particulate matter

DOI: 10.3233/JAD-180631

Citation: Journal of Alzheimer's Disease, vol. 70, no. s1, pp. S145-S163, 2019

Authors: Anstey, Kaarin J. | Ee, Nicole | Eramudugolla, Ranmalee | Jagger, Carol | Peters, Ruth

Article Type: Research Article

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, quality, and representativeness of evidence, we conducted a review of reviews of risk factors for Alzheimer’s disease (AD), Vascular dementia (VaD), and Any Dementia. 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 midlife 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, meta-analysis data were unavailable from Latin America/Caribbean. Midlife specific data were only available for cholesterol and arthritis. Conclusion: There is a lack of midlife 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. Show more

Keywords: Alzheimer’s disease, cohort studies, meta-analysis, prevention, risk factor, vascular dementia

DOI: 10.3233/JAD-190181

Citation: Journal of Alzheimer's Disease, vol. 70, no. s1, pp. S165-S186, 2019

Authors: Cox, Kay L. | Cyarto, Elizabeth V. | Ellis, Kathryn A. | Ames, David | Desmond, Patricia | Phal, Pramit | Sharman, Matthew J. | Szoeke, Cassandra | Rowe, Christopher C. | Masters, Colin L. | You, Emily | Burrows, Sally | Lai, Michelle M.Y. | Lautenschlager, Nicola T.

Article Type: Research Article

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. Show more

Keywords: Adherence, cerebrovascular disease, mild cognitive impairment, physical activity, subjective memory complaints

DOI: 10.3233/JAD-180521

Citation: Journal of Alzheimer's Disease, vol. 70, no. s1, pp. S187-S205, 2019

Authors: Yaffe, Kristine | Barnes, Deborah E. | Rosenberg, Dori | Dublin, Sascha | Kaup, Allison R. | Ludman, Evette J. | Vittinghoff, Eric | Peltz, Carrie B. | Renz, Anne D. | Adams, Kristin J. | Larson, Eric B.

Article Type: Research Article

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. Show more

Keywords: Alzheimer’s disease, dementia, health promotion, integrated delivery of health care, risk reduction behavior

DOI: 10.3233/JAD-180634

Citation: Journal of Alzheimer's Disease, vol. 70, no. s1, pp. S207-S220, 2019

Authors: Heffernan, Megan | Andrews, Gavin | Fiatarone Singh, Maria A. | Valenzuela, Michael | Anstey, Kaarin J. | Maeder, Anthony J. | McNeil, John | Jorm, Louisa | Lautenschlager, Nicola T. | Sachdev, Perminder S. | Ginige, Jeewani A. | Hobbs, Megan J. | Boulamatsis, Christos | Chau, Tiffany | Cobiac, Lynne | Cox, Kay L. | Daniel, Kenneth | Flood, Victoria M. | Guerrero, Yareni | Gunn, Jane | Jain, Nidhi | Kochan, Nicole A. | Lampit, Amit | Mavros, Yorgi | Meiklejohn, Jacinda | Noble, Yian | O’Leary, Fiona | Radd-Vagenas, Sue | Walton, Courtney C. | Maintain Your Brain Collaborative Team | Brodaty, Henry

Article Type: Research Article

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 internet-based 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. Show more

Keywords: Alzheimer’s disease, clinical trial, cognitive decline, cognitive training, dementia, depression, non-pharmacological, physical activity, nutrition, randomized controlled trial

DOI: 10.3233/JAD-180572

Citation: Journal of Alzheimer's Disease, vol. 70, no. s1, pp. S221-S237, 2019

Authors: Wan Nasri, Wan Nurzulaikha | Makpol, Suzana | Mazlan, Musalmah | Tooyama, Ikuo | Wan Ngah, Wan Zurinah | Damanhuri, Hanafi Ahmad

Article Type: Research Article

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. Show more

Keywords: Alzheimer’s disease, hippocampus, microarray analysis, tocotrienol-rich fraction, transgenic mouse

DOI: 10.3233/JAD-180496

Citation: Journal of Alzheimer's Disease, vol. 70, no. s1, pp. S239-S254, 2019

Authors: Vanoh, Divya | Shahar, Suzana | Razali, Rosdinom | Ali, Nazlena Mohamad | Manaf, Zahara Abdul | Mohd Noah, Shahrul Azman | Nur, Amrizal Muhammad

Article Type: Research Article

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. Show more

Keywords: Cognitive, cost, disability, informational support, older adults, randomized controlled trial, web-based health education, WESIHAT 2.0©

DOI: 10.3233/JAD-180464

Citation: Journal of Alzheimer's Disease, vol. 70, no. s1, pp. S255-S270, 2019

Authors: Derby, Carol A. | Katz, Mindy J. | Rozner, Sara | Lipton, Richard B. | Hall, Charles B.

Article Type: Research Article

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. Show more

Keywords: Cohort analysis, epidemiologic methods, incidence study, mild cognitive impairment

DOI: 10.3233/JAD-181141

Citation: Journal of Alzheimer's Disease, vol. 70, no. s1, pp. S271-S281, 2019

Authors: Oliveira, Deborah | Jun Otuyama, Leonardo | Mabunda, Dirceu | Mandlate, Flavio | Gonçalves-Pereira, Manuel | Xavier, Miguel | Laks, Jerson | Ferri, Cleusa P.

Article Type: Research Article

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. Show more

Keywords: Alzheimer’s disease, dementia, low- and middle-income countries, prevention, risk reduction

DOI: 10.3233/JAD-180636

Citation: Journal of Alzheimer's Disease, vol. 70, no. s1, pp. S283-S291, 2019

Authors: Meguro, Kenichi | Dodge, Hiroko H.

Article Type: Review Article

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. Show more

Keywords: Community, kurihara project, mild cognitive impairment, tajiri project, vascular dementia, vascular MCI

DOI: 10.3233/JAD-180899

Citation: Journal of Alzheimer's Disease, vol. 70, no. s1, pp. S293-S302, 2019

Authors: Collins, Rachel | Silarova, Barbora | Clare, Linda

Article Type: Research Article

Abstract: Background: Understanding the 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. Show more

Keywords: Commissioner, government, modifiable risk, primary healthcare, policymaker

DOI: 10.3233/JAD-180608

Citation: Journal of Alzheimer's Disease, vol. 70, no. s1, pp. S303-S318, 2019