Interventions For Prevention Of Dementia Research Articles

Social activities in multidomain dementia prevention interventions: insights from practice and a blueprint for the future

IntroductionSocial activities are important for health and act as a driver of cognitive reserve during aging. In this perspective paper, we describe challenges and outline future (research) endeavors to establish better operationalization of social activities in multidomain interventions to prevent dementia.BodyWe first address the lack of conceptual clarity, which makes it difficult to measure engagement in social activities. Second, drawing from our experience with the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER), we discuss social activities in multidomain dementia prevention interventions. Using qualitative data from the Multimodal Preventive Trial for Alzheimer’s Disease (MIND-ADmini), we reflect on participant experiences with social activities. Third, we address the potential and challenges of digital solutions in promoting social activities in interventions for dementia prevention. Finally, we share insights from a workshop on digital technology, where we consulted with individuals with and without cognitive impairment who have been involved in three European projects (i.e., EU-FINGERS, Multi-MeMo, and LETHE).DiscussionBased on these insights, we advocate for research that strengthens and accelerates the integration of social activities into multidomain interventions for dementia prevention. We propose several ways to achieve this: (a) by conducting mixed methods research to formulate a broadly accepted definition and instructions to measure social activities; (b) by focusing on promoting engagement in social activities beyond the intervention setting; and (c) by exploring the needs and preferences of older adults towards digitally-supported interventions and co-design of new technologies that enrich in-person social activities.

Nutrition for dementia prevention: a state of the art update for clinicians.

Dementia prevalence continues to rise. It is therefore essential to provide feasible and effective recommendations to encourage healthy brain ageing and reduce dementia risk across the population. Appropriate nutrition represents a potential strategy to mitigate dementia risk and could be recommended by clinicians as part of mid-life health checks and other health initiatives to reduce dementia prevalence. The purpose of this review is to provide a clinician-focused update on the current state of the knowledge on nutrition and dementia prevention. Narrative review. Strong evidence exists to support the consumption of healthy, plant-based dietary patterns (e.g. Mediterranean, MIND or Nordic diet) for maintaining cognitive function and reducing dementia risk in later life and is supported by dementia prevention guideline from leading public health bodies (e.g. World Health Organization). Emerging evidence suggests potential cognitive benefits of consuming specific nutrients/foods (e.g. n-3 fatty acids or fish, flavonols and B-vitamins) and multi-nutrient compounds (e.g. Fortasyn Connect). Challenges and opportunities for integrating nutritional/dietary interventions for dementia prevention into clinical practice are explored in this review. Appropriate nutrition represents an important factor to help facilitate healthy cognitive ageing and allay dementia risk. The information provided in this article can help clinicians provide informed opinions on appropriate nutritional strategies as part of mid-life Health Checks and other risk reduction initiatives.

Abstract 46: Midlife and Late-Life Population Attributable Fractions of Dementia Risk Factors in the United States: A Cohort Study From the Dementia Risk Pooling Project

Introduction: Dementia cases in the US are projected to nearly double from 5.3 million in 2019 to 10.5 million by 2050. Research has suggested that 41% of US dementia cases may be prevented by eliminating several specific modifiable risk factors. Still, few studies examine risk factor variation between midlife and late-life. Previous studies have also been limited by sample diversity and size. The Dementia Risk Pooling Project (DRPP) is a consortium of longitudinal cohorts including several underrepresented racial/ethnic groups pooled at the individual level. Methods: We estimated individual and combined population attributable fractions (PAF) for seven modifiable risk factors in midlife (aged 45-64) and late-life (aged 65+), using data from six US cohorts in DRPP. We also used potential impact fractions (PIF) to estimate dementia cases that could be prevented due to risk factor reduction in midlife and late-life based upon the National Alzheimer’s Advisory Council goal of a 15% reduction in dementia risk factors by 2030. Results: In a sample of 41,432 unique participants (ppts), risk factor exposure was measured in midlife for 29,983 ppts (60% female, 77% white) and in late-life for 30,633 ppts (56% female, 70% white). During follow-up, 4,186 midlife ppts and 4,893 late-life ppts developed dementia. We found that eliminating midlife risk factors could prevent a greater proportion of dementia cases [PAF 41.3%, 27.9%-54.6%] compared to late-life risk factors [23.1%, 12.4%-33.7%]. Midlife physical inactivity [18.8%, 15.1%-22.4%] appeared to be the greatest contributor. Late-life hypertension and depression appeared to contribute to 9.8% [5.5%-13.9%] and 4.2% [3.5%-5.0%] of cases, respectively. Given the US prevalence of dementia in 2020, we estimate that a 15% reduction in physical inactivity alone could prevent 148,339 dementia cases. Conclusion: The importance of modifiable risk factors for dementia may vary with age. These estimates could inform the timing of public health interventions for dementia prevention.

Abstract 67: Risk and Time-Course of Post-Stroke Dementia: A Population-Wide Cohort Study, 2002-2022

Background: People with acute stroke are at high risk of dementia. Population-wide data on the risk and time-course of dementia after stroke are lacking. Methods: We conducted a population-wide analysis of over 15 million people in Ontario, Canada between 2002-2022. Using linked administrative databases, we compared all 90-day survivors of first acute ischemic stroke or intracerebral hemorrhage (ICH) to controls in the general population and with acute myocardial infarction (AMI) by matching 1:1 on age, sex, rural residence, neighborhood marginalization, and vascular comorbidities, and excluded people with prior dementia. We evaluated the rate of dementia per 100 person-years using a validated definition which included hospitalization, physician claims, and medications, and calculated cause-specific hazard ratios overall and across follow-up time. Results: We identified 180,940 people with acute stroke, of which 33,765 (18.7%) developed dementia over mean follow-up of 5.5 years (max 20y). The rate of dementia per 100 person-years was highest after acute stroke compared to the general population (3.40 vs. 1.88) and compared to AMI (3.23 vs. 1.81). The overall risk of dementia was higher in those with acute stroke compared to the general population (HR 1.79, 95% CI 1.76-1.82; Figure 1A), and particularly after ICH (HR 2.43, 2.31-2.57). The results were similar when compared to AMI (HR 1.77, 1.74-1.80; Figure 1C). There was an almost 3-fold elevation of dementia risk in the first year after stroke, decreasing to 1.5-fold by 5 years and remaining elevated even 20 years after (Figure 1B/1D). Conclusion: In this large, population-wide study almost one fifth of people developed dementia after stroke, with an 80% higher risk of developing dementia compared to matched controls. The risk was highest early after stroke but remained elevated 20 years after, raising the urgency of developing interventions for dementia prevention in acute and chronic survivors of stroke.

Strategic Multimodal Intervention in at‐risk Elderly Indians for Prevention of Dementia (SMRUTHI INDIA): A cohort multiple randomised controlled trial (cmRCT)

AbstractBackgroundThe major burden of dementia will be falling on Low and middle‐income countries in the next few decades. One of the major strategies to counter the rise in dementia burden is primary prevention, especially in at‐risk elderly individuals.MethodStrategic Multimodal Intervention in at‐risk Elderly Indians for Prevention of Dementia (SMRUTHI INDIA) is designed as a Cohort Multiple Randomised Controlled Trial (cmRCT) under a prospective community‐based cohort in rural India with long‐term follow‐up over many years. The rural cohort will be established in four zones of India, under the Indian Council of Medical Research (ICMR), Model Rural Health Research Units (MRHRUs) at Himachal Pradesh (North), Tripura (East), Rajasthan (West) and Karnataka (South). We plan to recruit 10000 participants with age > = 55 years and CAIDE score > = 6. SMRUTHI INDIA will be established in 2 phases. Phase 1 involves establishing a cohort (phase 1a) and development, followed by validation of the multimodal care bundle (phase 1 b). The care bundle preparation will have a development phase, acceptability and adaptability phase followed by feasibility testing involving a pilot RCT in a single centre. Phase 2 involves testing multiple interventions in cmRCT, and the first intervention to be tested will be the multimodal care bundle. The primary outcome will be the incidence of all‐cause dementia.ResultSMRUTHI INDIA will establish in parallel a large prospective rural cohort of at‐risk elderly in India and develop a culturally adapted and context‐specific multimodal care bundle. At the end of Phase 1, we will have the results of the pilot RCT on the feasibility of multimodal care bundle.ConclusionSMRUTHI INDIA is a landmark cohort multiple randomised controlled trial (cmRCT) which will assess multiple interventions for the primary prevention of dementia for the first time in India.Funding: Department of Health Research, Indian Council of Medical Research (ICMR)

Impact of genetic risk in multidomain lifestyle preventive interventions

AbstractBackgroundInteractions between genetic and lifestyle‐related risk factors for dementia have been investigated mainly in observational studies, with conflicting results. Less is known about whether genetic risk factors for dementia (not just APOE4 allele but also polygenic risk beyond APOE4) have an impact on the effects of multidomain lifestyle preventive interventions on cognition. Although there is overlap between risk factors for dementia and e.g. cardiovascular diseases (CVD), it is unclear if CVD genetic risk may also have an impact on potential intervention benefits.MethodThe FINGER randomized controlled trial included 1260 participants aged 60‐77 years and at risk for dementia from the general Finnish population. Cognition improved more during 2 years in the multidomain lifestyle intervention (diet, exercise, cognitive training, social activities and cardiovascular risk monitoring) compared with control (regular health advice) group. Genetic risk scores for Alzheimer’s disease (AD‐GRS, excluding APOE) and CVD‐GRS were selected based on existing literature, and calculated using GWAS data from FINGER participants.ResultPrevious findings indicated that the FINGER intervention had clear cognitive benefits among APOE4 carriers. Preliminary results suggested a less straightforward impact of AD‐GRS, especially after adjustment for APOE4. There seemed to be a pattern of more intervention‐related cognitive benefit among participants with lower compared with higher CVD‐GRS.ConclusionAPOE4, AD‐GRS and CVD‐GRS may have different impact on the cognitive benefits of multidomain lifestyle interventions for dementia prevention. Ongoing World‐Wide FINGERS trials in populations with a variety of genetic profiles will create opportunities for more detailed investigation of genetic‐lifestyle interactions in the context of preventive interventions.

Population-level interventions for the primary prevention of dementia: a complex evidence review

BackgroundDementia is a leading, global public health challenge. Recent evidence supporting a decrease in age-specific incidence of dementia in high-income countries (HICs) suggests that risk reduction is possible through improved life-course public health. Despite this, efforts to date have been heavily focused on individual-level approaches, which are unlikely to significantly reduce dementia prevalence or inequalities in dementia. In order to inform policy, we identified the population-level interventions for dementia risk reduction with the strongest evidence base. MethodsWe did this complex, multistage, evidence review to summarise the empirical, interventional evidence for population-level interventions to reduce or control each of the 12 modifiable life-course risk factors for dementia identified by the Lancet commission. We conducted a series of structured searches of peer-reviewed and grey literature databases (eg, Medline, Trip database, Cochrane library, Campbell Collaboration, the WHO, and Google Scholar), in January, March, and June, 2023. Search terms related to risk factors, prevention, and population-level interventions, without language restrictions. We extracted evidence of effectiveness and key contextual information to aid consideration and implementation of interventions by policymakers. We performed a narrative synthesis and evidence grading, and we derived a population-level dementia risk reduction intervention framework, structured by intervention type. This study is registered with PROSPERO, ID:CRD42023396193. FindingsWe identified clear and consistent evidence for the effectiveness of 26 population-level interventions to reduce the prevalence of nine of the risk factors, of which 23 have been empirically evaluated in HICs, and 16 in low-income and middle-income countries. We identified interventions that acted through fiscal levers (n=5; eg, removing primary school fees), marketing or advertising levers (n=5; eg, plain packaging of tobacco products), availability levers (n=8; eg, cleaner fuel replacement programmes for cooking stoves), and legislative levers (n=8; eg, mandated provision of hearing protective equipment at noisy workplaces). We were not able to recommend any interventions for diabetes (other than indirectly through action on obesity and physical inactivity), depression, or social isolation. InterpretationThis complex evidence review provides policymakers and public health professionals with an evidence-based framework to help develop and implement population-level approaches for dementia risk reduction that could significantly reduce the population's risk of dementia and reduce health inequalities. FundingNone.

Association between the estimated 10‐year cardiovascular mortality risk and cognitive function in older adults: results from the FINGER trial

AbstractBackgroundDementia risk scores could be instrumental in the implementation of multidomain lifestyle interventions for dementia prevention. However, as relatively new tools, their performance requires further validation. Given the extensive overlap between risk factors for dementia and cardiovascular disease (CVD), multidomain interventions usually have an important vascular component and better‐established cardiovascular risk scores could become useful in this context. More evidence is needed on their ability to predict the risk of cognitive decline and dementia. SCORE/SCORE‐Older People (OP) are the official tools of the European Society of Cardiology to estimate the 10‐year CVD‐mortality risk. In this study, we investigated the association between SCORE/SCORE‐OP and cognitive function within FINGER, the first large trial showing the efficacy of a multidomain lifestyle‐ and vascular‐based intervention in preventing cognitive decline.MethodSCORE (age<65) and SCORE‐OP (age≥65) were calculated in the population of the 2‐year FINGER trial (N = 1236, baseline and 24 months). The cognitive outcomes (baseline, 12 and 24 months) were the overall z‐score from a Neuropsychological Test Battery (NTB, 14 tests, primary outcome) and the z‐scores of the NTB cognitive domains (Memory, Executive Function, and Processing Speed, secondary outcomes). The associations between (i) SCORE/SCORE‐OP and cognition, (ii) SCORE/SCORE‐OP and changes in cognition, and (iii) changes SCORE‐OP and changes in cognition were assessed using linear mixed‐models repeated‐measures with maximum likelihood estimation.ResultHigher baseline risk of CVD‐mortality, estimated with SCORE/SCORE‐OP, was significantly and consistently associated with worse cognition, (NTB total composite: Estimate = ‐0.036; CI: ‐0.042 to ‐0.030; P‐value>0.0001; individual NTB cognitive domains: P‐values<0.0001) and yearly lower improvement in cognitive performance (NTB total composite: Estimate = ‐0.009, CI: ‐0.011 to ‐0.007, P‐value>0.0001; individual NTB cognitive domains: P‐values<0.0001). 2‐year change in SCORE‐OP was not significantly associated with changes in cognition during the FINGER study period.ConclusionSCORE/SCORE‐OP could be useful in predicting the risk of cognitive decline in a trial aimed at improving lifestyle and vascular‐related risk factors of dementia. However, more evidence is needed on their efficacy in predicting dementia risk and the response to multidomain lifestyle‐ and vascular‐ based interventions. Future studies on other well‐established and easy‐access cardiovascular risk scores could also provide relevant findings.

Circulating cardiac biomarkers, structural brain changes, and dementia: Emerging insights and perspectives.

Diseases of the heart and brain are strongly linked to each other, and cardiac dysfunction is associated with cognitive decline and dementia. This link between cardiovascular disease and dementia offers opportunities for dementia prevention through prevention and treatment of cardiovascular risk factors and heart disease. Increasing evidence suggests the clinical utility of cardiac biomarkers as risk markers for structural brain changes and cognitive impairment. We propose the hypothesis that structural brain changes are the link between impaired cardiac function, as captured by blood-based cardiac biomarkers, and cognitive impairment. This review provides an overview of the literature and illustrates emerging insights into the association of markers of hemodynamic stress (natriuretic peptides) and markers of myocardial injury (cardiac troponins) with imaging findings of brain damage and cognitive impairment or dementia. Based on these findings, we discuss potential pathophysiological mechanisms underlying the association of cardiac biomarkers with structural brain changes and dementia. We suggest testable hypotheses and a research plan to close the gaps in understanding the mechanisms linking vascular damage and neurodegeneration, and to pave the way for targeted effective interventions for dementia prevention. From a clinical perspective, cardiac biomarkers open the window for early identification of patients at risk of dementia, who represent a target population for preventive interventions targeting modifiable cardiovascular risk factors to avert cognitive decline and dementia.

Objectively measured physical activity and cognition in cognitively normal older adults: A longitudinal analysis of the Australian Imaging Biomarkers and Lifestyle (AIBL) study

AbstractBackgroundPhysical inactivity is one of the greatest modifiable risk factors for dementia and research shows physical activity can delay cognitive decline in older adults. However, much of this research has used subjective physical activity data and a single follow‐up cognitive assessment. Further studies using objectively measured physical activity and comprehensive cognitive data measured at multiple timepoints are required.MethodsParticipants were 199 community‐dwelling cognitively normal older adults (68.7 5.9 years) from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study. Actigraphy was used to measure physical activity at baseline, yielding measures of intensity (peak counts), total activity (total counts) and energy expenditure (kilocalories; k/cal). Cognitive function was assessed using a cognitive battery administered every 18‐months from baseline (3‐11 years follow‐up), yielding composite scores for episodic memory, executive function, attention and processing speed, and global cognition.ResultsHigher baseline energy expenditure predicted improvements in episodic memory and maintained global cognition over time (β = 0.011, SE = 0.005, p = 0.031; β = 0.009, SE = 0.004, p = 0.047, respectively). Both physical activity intensity and total activity predicted global cognition, such that those with higher peak and total counts had better cognition over time (β = 0.012, SE = 0.004, p = 0.005; β = 0.012, SE = 0.004, p = 0.005, respectively). Finally, higher total activity predicted improved episodic memory over time (β = 0.011, SE = 0.005, p = .022).ConclusionThese results suggest that physical activity is associated with preserved cognitive function over time, and that activity intensity may play an important role. This research further highlights the importance of early intervention to prevent cognitive decline and may aid in informing lifestyle interventions for dementia prevention.

Avoiding Over-Reliance on Multi-Domain Interventions for Dementia Prevention.

Given the unknown therapeutic value of targeting Alzheimer's disease pathology and the discovery of robust risk factors for dementia, non-pharmacological risk reduction (RR) is increasingly offered as an alternative to targeting Alzheimer's disease pathology. While RR will surely be a useful tool to make public health gains, we propose solutions to three possible issues with over-reliance on multi-domain interventions to achieve RR: limited individual impact, an exclusive focus on later life, and overlooking social determinants of dementia. We argue in favor of a broader debate within the research community and greater society about how different therapeutic avenues should be explored.

Multimorbidity and dementia risk in hospitalised patients: an administrative data linkage study of hospital patients in Northern Ireland.

IntroductionWhile chronic disease is a risk factor for dementia (Shang et al., 2020) studies addressing multimorbidity and dementia risk are limited. Multimorbidity leads to steeper dementia progression (Bauer, 2014; Haaksma, 2019) impacting cognitive dysfunction, cognitive decline and impairment (Wei, 2020; Vassilaki, 2015). Multimorbidity has generally been examined using a dose- response disease count, something cited as impractical for clinicians due to information deficits on identifying disease specific pathways (Whitty, 2020). Thus, differentiating disease clusters and dementia risk will provide insight into the pathophysiology of dementia, while informing priority targets for early intervention, potentially reducing burden and secondary care costs.
 AimTo investigate dementia risk and mortality in older adults with different disease patterns, characteristics of hospital admissions, medication use and the role of locale of residence.
 Data linkage and analysisWe used national data defined by the NHAIS, including basic demographics for all patients aged fifty-five plus and registered with a GP in Northern Ireland. The linked data comprised: Patient Admissions and Discharges (from 2013-2021); Electronically captured prescribing data, area-type of usual residence; Multiple Deprivation Indicators; and GRO mortality data (including cause of death). We identified multimorbidity through validated algorithms for ICD-10 coding of thirty morbidities in administrative hospital diagnostics data (Tonelli et al., 2019). The same data identified dementia-free patients at baseline. Latent Class Analysis assigned patient groups by the patterning of multimorbidity states, following them through the study period, with analysis in relation to subsequent diagnoses of both clinical dementia and mortality. As age has a potential modifier effect we tested through age group stratified analyses. A series of multinomial logistic regression models further examine (for the multimorbidity sub-groups of interest) risks associated socio-demographic, socio-economic, medication use and household indicators at the individual, family and area level.
 ResultsMultimorbidity occurs in two thirds, approximately, of this hospital population of older adults. By age sixty-five years, most people are multimorbid. We identify subgroups of multimorbidity associated with dementia onset and mortality, combinations of diabetes, hypertension, chronic kidney disease and cancer multimorbidity are highlighted as higher-risk conditions for increased dementia incidence and mortality. Greater disease burden is associated with frequent healthcare service use, medication use and is more common in the most socioeconomically deprived, compared with the least deprived.
 DiscussionEvidence on multimorbidity patterns and dementia is limited (Grande, 2021). Our study suggests that people with combinations of diabetes, hypertension, chronic kidney disease and cancer multimorbidity are associated with increased risks for dementia and socio demographic and economic circumstances further increase this risk. Overlapping combinations comprising chronic kidney disease + hypertension, or diabetes + hypertension, were a significant proportion of total secondary care costs for patients with multimorbidity; combinations comprising chronic heart failure + chronic kidney disease + hypertension had the highest proportion of total cost from potentially preventable emergency admissions (Stokes et al., 2021). Our finding support the body and mind connection in dementia development. Thus, we note that cardiovascular health is associated with dementia (Grande, 2021). Often described as a heart-brain connection, cardiovascular disease leads to higher dementia risk due to a number of mechanisms including but not limited to chronic inflammation (Grande, 2021). Identifying such high-risk groups will facilitate tailored interventions for dementia prevention and the reduction of healthcare use and costs.

Dysfunction of the blood–brain barrier in Alzheimer's disease: Evidence from human studies

The pathological processes leading to synapse loss, neuronal loss, brain atrophy and gliosis in Alzheimer's disease (AD) and their relation to vascular disease and immunological changes are yet to be fully explored. Amyloid-β (Aβ) aggregation, vascular damage and altered immune response interact at the blood-brain barrier (BBB), affecting the brain endothelium and fuelling neurodegeneration. The aim of the present systematic literature review was to critically appraise and to summarise the published evidence on the clinical correlations and pathophysiological concepts of BBB damage in AD, focusing on human data. The PubMed, Cochrane, Medline and Embase databases were searched for original research articles, systematic reviews and meta-analyses, published in English language from 01/2000 to 07/2021, using the keywords Alzheimer*, amyloid-β or β-amyloid or abeta and BBB. This review shows that specific changes of intercellular structures, reduced expression of transendothelial carriers, induction of vasoactive mediators and activation of both astroglia and monocytes/macrophages characterise BBB damage in human AD and AD models. BBB dysfunction on magnetic resonance imaging takes place early in the disease course in AD-specific brain regions. The toxic effects of Aβ and apolipoprotein E (ApoE) are likely to induce a non-cerebral-amyloid-angiopathy-related degeneration of endothelial cells, independently of cerebrovascular disease; however, some of the observed structural changes may just arise with age. Small vessel disease, ApoE, loss of pericytes, proinflammatory signalling and cerebral amyloid angiopathy enhance BBB damage. Novel therapeutic approaches for AD, including magnetic resonance-guided focused ultrasound, aim to open the BBB, potentially leading to an improved drainage of Aβ along perivascular channels and increased elimination from the brain. In vitro treatments with ApoE-modifying agents yielded promising effects on modulating BBB function. Reducing cardiovascular risk factors represents one of the most promising interventions for dementia prevention at present. However, further research is needed to elucidate the connection of BBB damage and tau pathology, the role of proinflammatory mediators in draining macromolecules and cells from the cerebral parenchyma, including their contribution to cerebral amyloid angiopathy. Improved insight into these pathomechanisms may allow to shed light on the role of Aβ deposition as a primary versus a secondary event in the complex pathogenesis of AD.

How lifestyle shapes the brain: Associations between physical activity, sleep, beta‐amyloid and cognitive function in older adults

AbstractBackgroundLifestyle factors such as sleep and physical activity influence risk of cognitive decline and dementia. Higher habitual physical activity and optimal sleep are associated with better cognitive function and lower levels of Alzheimer’s disease biomarkers, including beta‐amyloid (Aß). There is currently a poor understanding of how physical activity may influence the relationship between sleep and cognition, and whether exercise and sleep interact to influence cognition and Aß. Developing this understanding is crucial for creating effective lifestyle interventions for dementia prevention.MethodData from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study were utilised to determine whether self‐reported physical activity moderates the cross‐sectional relationship between self‐reported sleep parameters (duration, efficiency, latency, disturbance, quality), cognitive function (episodic memory, attention and processing speed, executive function), and brain Aß (quantified by amyloid positron emission tomography, using the Centiloid scale). Analyses were adjusted for age, sex, APOE ε4 carriage, mood, premorbid intelligence, and collection point. Participants were 404 community‐dwelling cognitively normal older adults aged 60 and above (75.3 5.7 years). Data from a subset of participants (n = 220, aged 75.2 5.6 years) were used for analyses with AB as the outcome.ResultPhysical activity moderated the relationship between sleep duration and episodic memory (ß = ‐.09, SE = .03, p = .005), and sleep efficiency and episodic memory (ß = ‐.08, SE = .03, p = .016). Physical activity moderated the relationship between sleep duration and A® (ß = ‐.12, SE = .06, p = .036), and sleep quality and Aß (ß = .12, SE = .06, p = .029).ConclusionPhysical activity may play an important role in the relationship between sleep and cognitive function, and sleep and brain Aß. Future longitudinal and intervention studies in this area are crucial for informing interventions for dementia prevention.

What are the effects of multi-domain interventions for prevention of dementia and cognitive decline?

What are the effects of multi-domain interventions for prevention of dementia and cognitive decline?

Multimorbidity burden and dementia risk in older adults: The role of inflammation and genetics.

IntroductionWe investigate dementia risk in older adults with different disease patterns and explore the role of inflammation and apolipoprotein E (APOE) genotype.MethodsA total of 2,478 dementia‐free participants with two or more chronic diseases (ie, multimorbidity) part of the Swedish National study on Aging and Care in Kungsholmen (SNAC‐K) were grouped according to their multimorbidity patterns and followed to detect clinical dementia. The potential modifier effect of C‐reactive protein (CRP) and apolipoprotein E (APOE) genotype was tested through stratified analyses.ResultsPeople with neuropsychiatric, cardiovascular, and sensory impairment/cancer multimorbidity had increased hazards for dementia compared to the unspecific (Hazard ration (HR) 1.66, 95% confidence interval [CI] 1.13‐2.42; 1.61, 95% CI 1.17‐2.29; 1.32, 95% CI 1.10‐1.71, respectively). Despite the lack of statistically significant interaction, high CRP increased dementia risk within these patterns, and being APOE ε4 carriers heightened dementia risk for neuropsychiatric and cardiovascular multimorbidity.DiscussionIndividuals with neuropsychiatric, cardiovascular, and sensory impairment/cancer patterns are at increased risk for dementia and APOE ε4, and inflammation may further increase the risk. Identifying such high‐risk groups might allow tailored interventions for dementia prevention.

The Japan-Multimodal Intervention Trial for Prevention of Dementia (J-MINT): The Study Protocol for an 18-Month, Multicenter, Randomized, Controlled Trial.

Background/ObjectivesThe Japan-multimodal intervention trial for prevention of dementia (J-MINT) is intended to verify the effectiveness of multi-domain interventions and to clarify the mechanism of cognitive improvement and deterioration by carrying out assessment of dementia-related biomarkers, omics analysis and brain imaging analysis among older adults at high risk of dementia. Moreover, the J-MINT trial collaborates with partnering private enterprises in the implementation of relevant interventional measures. This manuscript describes the study protocol.Design/SettingEighteen-month, multi-centered, randomized controlled trial.ParticipantsWe plan to recruit 500 older adults aged 65–85 years with mild cognitive impairment. Subjects will be centrally randomized into intervention and control groups at a 1:1 allocation ratio using the dynamic allocation method with all subjects stratified by age, sex, and cognition.InterventionThe multi-domain intervention program includes: (1) management of vascular risk factors; (2) group-based physical exercise and self-monitoring of physical activity; (3) nutritional counseling; and (4) cognitive training. Health-related information will be provided to the control group every two months.MeasurementsThe primary and secondary outcomes will be assessed at baseline, 6-, 12-, and 18-month follow-up. The primary outcome is the change from baseline to 18 months in a global composite score combining several neuropsychological domains. Secondary outcomes include: cognitive change in each neuropsychological test, incident dementia, changes in blood and dementia-related biomarkers, changes in geriatric assessment including activities of daily living, frailty status and neuroimaging, and number of medications taken.ConclusionsThis trial that enlist the support of private enterprises will lead to the creation of new services for dementia prevention as well as to verify the effectiveness of multi-domain interventions for dementia prevention.Electronic Supplementary MaterialSupplementary material is available for this article at 10.14283/jpad.2021.29 and is accessible for authorized users.

Development, Validation and Field Evaluation of the Singapore Longitudinal Ageing Study (SLAS) Risk Index for Prediction of Mild Cognitive Impairment and Dementia.

Mild cognitive impairment (MCI) is a critical pre-dementia target for preventive interventions. There are few brief screening tools based on self-reported personal lifestyle and health-related information for predicting MCI that have been validated for their generalizability and utility in primary care and community settings. To develop and validate a MCI risk prediction index, and evaluate its field application in a pilot community intervention trial project. Two independent population-based cohorts in the Singapore Longitudinal Ageing Study (SLAS). We used SLAS1 as a development cohort to construct the risk assessment instrument, and SLA2 as a validation cohort to verify its generalizability. community-based screening and lifestyle intervention Participants: (1) SLAS1 cognitively normal (CN) aged ≥55 years with average 3 years (N=1601); (2) SLAS2 cohort (N=3051) with average 4 years of follow up. (3) 437 participants in a pilot community intervention project. The risk index indicators included age, female sex, years of schooling, hearing loss, depression, life satisfaction, number of cardio-metabolic risk factors (wide waist circumference, pre-diabetes or diabetes, hypertension, dyslipidemia). Weighted summed scores predicted probabilities of MCI or dementia. A self-administered questionnaire field version of the risk index was deployed in the pilot community project and evaluated using pre-intervention baseline cognitive function of participants. Risk scores were associated with increasing probabilities of progression to MCI-or-dementia in the development cohort (AUC=0.73) and with increased prevalence and incidence of MCI-or-dementia in the validation cohort (AUC=0.74). The field questionnaire risk index identified high risk individuals with strong correlation with RBANS cognitive scores in the community program (p<0.001). The SLAS risk index is accurate and replicable in predicting MCI, and is applicable in community interventions for dementia prevention.

Age and the association between apolipoprotein E genotype and Alzheimer disease: A cerebrospinal fluid biomarker-based case-control study.

The ε4 allele of apolipoprotein E (APOE) gene and increasing age are two of the most important known risk factors for developing Alzheimer disease (AD). The diagnosis of AD based on clinical symptoms alone is known to have poor specificity; recently developed diagnostic criteria based on biomarkers that reflect underlying AD neuropathology allow better assessment of the strength of the associations of risk factors with AD. Accordingly, we examined the global and age-specific association between APOE genotype and AD by using the A/T/N classification, relying on the cerebrospinal fluid (CSF) levels of β-amyloid peptide (A, β-amyloid deposition), phosphorylated tau (T, pathologic tau), and total tau (N, neurodegeneration) to identify patients with AD. This case-control study included 1,593 white AD cases (55.4% women; mean age 72.8 [range = 44-96] years) with abnormal values of CSF biomarkers from nine European memory clinics and the American Alzheimer's Disease Neuroimaging Initiative (ADNI) study. A total of 11,723 dementia-free controls (47.1% women; mean age 65.6 [range = 44-94] years) were drawn from two longitudinal cohort studies (Whitehall II and Three-City), in which incident cases of dementia over the follow-up were excluded from the control population. Odds ratio (OR) and population attributable fraction (PAF) for AD associated with APOE genotypes were determined, overall and by 5-year age categories. In total, 63.4% of patients with AD and 22.6% of population controls carried at least one APOE ε4 allele. Compared with non-ε4 carriers, heterozygous ε4 carriers had a 4.6 (95% confidence interval 4.1-5.2; p < 0.001) and ε4/ε4 homozygotes a 25.4 (20.4-31.2; p < 0.001) higher OR of AD in unadjusted analysis. This association was modified by age (p for interaction < 0.001). The PAF associated with carrying at least one ε4 allele was greatest in the 65-70 age group (69.7%) and weaker before 55 years (14.2%) and after 85 years (22.6%). The protective effect of APOE ε2 allele for AD was unaffected by age. Main study limitations are that analyses were based on white individuals and AD cases were drawn from memory centers, which may not be representative of the general population of patients with AD. In this study, we found that AD diagnosis based on biomarkers was associated with APOE ε4 carrier status, with a higher OR than previously reported from studies based on only clinical AD criteria. This association differs according to age, with the strongest effect at 65-70 years. These findings highlight the need for early interventions for dementia prevention to mitigate the effect of APOE ε4 at the population level.

Age Modifies the Association Between Apolipoprotein E Genotype and Alzheimer's Disease: A CSF Biomarker-Based Multicentric Case-Control Study

Background: We investigated the global and age-specific association between Apolipoprotein E (APOE) genotype and Alzheimer's disease (AD) in a large multicentric case-control study, using cerebrospinal fluid (CSF) biomarkers-based diagnostic criteria for AD. Methods: In this case-control design, data on 1,599 Caucasian AD cases with abnormal values of CSF biomarkers came from 9 European memory clinics and the Alzheimer's Disease Neuroimaging Initiative (ADNI) study. AD cases were compared to 11,724 dementia-free controls, drawn from two longitudinal cohort studies (Whitehall II and 3-City). Odds ratio (OR) and population attributable fraction (PAF) for AD associated with APOE genotypes were reported, overall and by 5-year age categories. Findings. 63*4% of CSF biomarker-defined AD patients and 22*6% of population controls carried at least one APOE e4 allele; respective percentages for APOE e4 homozygotes were 16*7% and 1*4%. Compared to none4 carriers, heterozygous e4 carriers had a 4*6 (95% confidence interval: 4*1 - 5*2) and e4/e4 homozygotes a 25*4 (20*5 - 31*3) higher OR of AD. This association was strongly modified by age (p for interaction < 0*001). The PAF associated with carrying at least one e4 allele was greatest in the 65-70 age group (69*7%), and weaker before 55 years (14*2%) and after 85 years (22*6%). There was some evidence of a stronger effect of APOE on AD risk in women. Interpretation: Incorporating biomarkers for diagnosis of AD led to a stronger association with APOE e4 than previously reported, perhaps due to better diagnostic accuracy. This association differs according to age, with the strongest effect at 65-70 years. These findings highlight the need for early interventions for dementia prevention to mitigate the effect of APOE e4 at the population level. Funding Statement: US National Institutes of Health, Fondation Plan Alzheimer. Declaration of Interests: ASM is supported by NIH/NIA R01AG056477. IZ is supported by the Robert-Koch-Institute through funds of Federal Ministry of Health (grant no. 1369-341) and DZNE (German Center for Neurodegenerative Diseases). KB reports consulting fees from Fujirebio Europe, IBL International, Roche Diagnostics. HZ is a co-founder of Brain Biomarker Solutions in Gothenburg AB, a GU Ventures-based platform company at the University of Gothenburg. MB has been a consultant for Araclon, Avid, Bayer, Elan, Grifols, Janssen/Pfizer, Lilly, Neuroptix, Nutricia, Roche, Sanofi, and Servier. All other authors declare no competing interests. Ethics Approval Statement: Ethical clearance was obtained by the institutional review boards of all participating sites (European memory centers and ADNI Study sites) and all participants provided written, informed consent.