Factors Predicting Engagement of Older Adults With a Coach-Supported eHealth Intervention Promoting Lifestyle Change and Associations Between Engagement and Changes in Cardiovascular and Dementia Risk: Secondary Analysis of an 18-Month Multinational Randomized Controlled Trial.

BACKGROUND: Digital health interventions could help to prevent age-related diseases, but little is known about how older adults engage with such interventions, especially in the long term, or whether engagement is associated with changes in clinical, behavioral, or biological outcomes in this population. Disparities in engagement levels with digital health interventions may exist among older people and be associated with health inequalities. OBJECTIVE: This study aimed to describe older adults' engagement with an eHealth intervention, identify factors associated with engagement, and examine associations between engagement and changes in cardiovascular and dementia risk factors (blood pressure, cholesterol, BMI, physical activity, diet, and cardiovascular and dementia risk scores). METHODS: This was a secondary analysis of the 18-month randomized controlled Healthy Ageing Through Internet Counselling in the Elderly trial of a tailored internet-based intervention encouraging behavior changes, with remote support from a lifestyle coach, to reduce cardiovascular and cognitive decline risk in 2724 individuals aged ≥65 years, recruited offline in the Netherlands, Finland, and France. Engagement was assessed via log-in frequency, number of lifestyle goals set, measurements entered and messages sent to coaches, and percentage of education materials read. Clinical and biological data were collected during in-person visits at baseline and 18 months. Lifestyle data were self-reported on a web-based platform. RESULTS: Of the 1389 intervention group participants, 1194 (85.96%) sent at least one message. They logged in a median of 29 times, and set a median of 1 goal. Higher engagement was associated with significantly greater improvement in biological and behavioral risk factors, with evidence of a dose-response effect. Compared with the control group, the adjusted mean difference (95% CI) in 18-month change in the primary outcome, a composite z-score comprising blood pressure, BMI, and cholesterol, was -0.08 (-0.12 to -0.03), -0.04 (-0.08 to 0.00), and 0.00 (-0.08 to 0.08) in the high, moderate, and low engagement groups, respectively. Low engagers showed no improvement in any outcome measures compared with the control group. Participants not using a computer regularly before the study engaged much less with the intervention than those using a computer up to 7 (adjusted odds ratio 5.39, 95% CI 2.66-10.95) or ≥7 hours per week (adjusted odds ratio 6.58, 95% CI 3.21-13.49). Those already working on or with short-term plans for lifestyle improvement at baseline, and with better cognition, engaged more. CONCLUSIONS: Greater engagement with an eHealth lifestyle intervention was associated with greater improvement in risk factors in older adults. However, those with limited computer experience, who tended to have a lower level of education, or who had poorer cognition engaged less. Additional support or forms of intervention delivery for such individuals could help minimize potential health inequalities associated with the use of digital health interventions in older people.

Multi-domain interventions for the prevention of dementia and cognitive decline.

BACKGROUND: Dementia is a worldwide concern. Its global prevalence is increasing. Currently, no effective medical treatment exists to cure or to delay the onset of cognitive decline or dementia. Up to 40% of dementia is attributable to potentially modifiable risk factors, which has led to the notion that targeting these risk factors might reduce the incidence of cognitive decline and dementia. Since sporadic dementia is a multifactorial condition, thought to derive from multiple causes and risk factors, multi-domain interventions may be more effective for the prevention of dementia than those targeting single risk factors. OBJECTIVES: To assess the effects of multi-domain interventions for the prevention of cognitive decline and dementia in older adults, including both unselected populations and populations at increased risk of cognitive decline and dementia. SEARCH METHODS: We searched ALOIS, the Cochrane Dementia and Cognitive Improvement Group's register, MEDLINE (Ovid SP), Embase (Ovid SP), PsycINFO (Ovid SP), CINAHL (EBSCOhost), Web of Science Core Collection (ISI Web of Science), LILACS (BIREME), and ClinicalTrials.gov on 28 April 2021. We also reviewed citations of reference lists of included studies, landmark papers, and review papers to identify additional studies and assessed their suitability for inclusion in the review. SELECTION CRITERIA: We defined a multi-domain intervention as an intervention with more than one component, pharmacological or non-pharmacological, but not consisting only of two or more drugs with the same therapeutic target. We included randomised controlled trials (RCTs) evaluating the effect of such an intervention on cognitive functioning and/or incident dementia. We accepted as control conditions any sham intervention or usual care, but not single-domain interventions intended to reduce dementia risk. We required studies to have a minimum of 400 participants and an intervention and follow-up duration of at least 12 months. DATA COLLECTION AND ANALYSIS: We initially screened search results using a 'crowdsourcing' method in which members of Cochrane's citizen science platform identify RCTs. We screened the identified citations against inclusion criteria by two review authors working independently. At least two review authors also independently extracted data, assessed the risk of bias and applied the GRADE approach to assess the certainty of evidence. We defined high-certainty reviews as trials with a low risk of bias across all domains other than blinding of participants and personnel involved in administering the intervention (because lifestyle interventions are difficult to blind). Critical outcomes were incident dementia, incident mild cognitive impairment (MCI), cognitive decline measured with any validated measure, and mortality. Important outcomes included adverse events (e.g. cardiovascular events), quality of life, and activities of daily living (ADL).  Where appropriate, we synthesised data in random-effects meta-analyses. We expressed treatment effects as risk ratios (RRs) and mean differences (MDs) with 95% confidence intervals (CIs). MAIN RESULTS: We included nine RCTs (18.452 participants) in this review. Two studies reported incident dementia as an outcome; all nine studies reported a measure for cognitive functioning. Assessment of cognitive functioning was very heterogeneous across studies, ranging from complete neuropsychological assessments to short screening tests such as the mini-mental state examination (MMSE). The duration of the interventions varied from 12 months to 10 years. We compared multi-domain interventions against usual care or a sham intervention. Positive MDs and RRs <1 favour multi-domain interventions over control interventions. For incident dementia, there was no evidence of a difference between the multi-domain intervention group and the control group (RR 0.94, 95% CI 0.76 to 1.18; 2 studies; 7256 participants; high-certainty evidence). There was a small difference in composite Z-score for cognitive function measured with a neuropsychological test battery (NTB) (MD 0.03, 95% CI 0.01 to 0.06; 3 studies; 4617 participants; high-certainty evidence) and with the Montreal Cognitive Assessment (MoCA) scale (MD 0.76 point, 95% CI 0.05 to 1.46; 2 studies; 1554 participants), but the certainty of evidence for the MoCA was very low (due to serious risk of bias, inconsistency and indirectness) and there was no evidence of an effect on the MMSE (MD 0.02 point, 95% CI -0.06 to 0.09; 6 studies; 8697participants; moderate-certainty evidence). There was no evidence of an effect on mortality (RR 0.93, 95% CI 0.84 to 1.04; 4 studies; 11,487 participants; high-certainty evidence). There was high-certainty evidence for an interaction of the multi-domain intervention with ApoE4 status on the outcome of cognitive function measured with an NTB (carriers MD 0.14, 95% CI 0.04 to 0.25, noncarriers MD 0.04, 95% CI -0.02 to 0.10, P for interaction 0.09). There was no clear evidence for an interaction with baseline cognitive status (defined by MMSE-score) on cognitive function measured with an NTB (low baseline MMSE group MD 0.06, 95% CI 0.01 to 0.11, high baseline MMSE group MD 0.01, 95% CI -0.01 to 0.04, P for interaction 0.12), nor was there clear evidence for an effect in participants with a Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) score > 6 points (MD 0.07, 95%CI -0.00 to 0.15). AUTHORS' CONCLUSIONS: We found no evidence that multi-domain interventions can prevent incident dementia based on two trials. There was a small improvement in cognitive function assessed by a NTB in the group of participants receiving a multi-domain intervention, although this effect was strongest in trials offering cognitive training within the multi-domain intervention, making it difficult to rule out a potential learning effect. Interventions were diverse in terms of their components and intensity.

Dementia risk scores as surrogate outcomes for lifestyle-based multidomain prevention trials-rationale, preliminary evidence and challenges.

INTRODUCTION: Although not designed as such, dementia risk scores might be useful surrogate outcomes for dementia prevention trials. Their suitability may be improved by using continuous scoring systems, taking into account all changes in risk factors, not only those crossing cut-off values. METHODS: In three large multidomain dementia prevention trials with 1.5 to 2 years of follow-up (Multidomain Alzheimer Preventive Trial, Prevention of Dementia by Intensive Vascular Care and Healthy Ageing Through Internet Counselling in the Elderly) we assessed (1) responsiveness (sensitivity to change) and (2) actual and simulated intervention effects of the original and crude/weighted z-score versions of the cardiovascular risk factors, aging and incidence of dementia, and Lifestyle for Brain Health scores. RESULTS: All versions of the risk scores were generally responsive, and able to detect small though statistically significant between-group differences after multidomain interventions. Simulated intervention effects were well detected in z-score versions as well as in the original scores. DISCUSSION: Dementia risk scores and their z-score versions show potential as surrogate outcomes. How changes in risk scores affect dementia remains to be determined.

Effectiveness of a 6-year multidomain vascular care intervention to prevent dementia (preDIVA): a cluster-randomised controlled trial.

BACKGROUND: Cardiovascular risk factors are associated with an increased risk of dementia. We assessed whether a multidomain intervention targeting these factors can prevent dementia in a population of community-dwelling older people. METHODS: In this open-label, cluster-randomised controlled trial, we recruited individuals aged 70-78 years through participating general practices in the Netherlands. General practices within each health-care centre were randomly assigned (1:1), via a computer-generated randomisation sequence, to either a 6-year nurse-led, multidomain cardiovascular intervention or control (usual care). The primary outcomes were cumulative incidence of dementia and disability score (Academic Medical Center Linear Disability Score [ALDS]) at 6 years of follow-up. The main secondary outcomes were incident cardiovascular disease and mortality. Outcome assessors were masked to group assignment. Analyses included all participants with available outcome data. This trial is registered with ISRCTN, number ISRCTN29711771. FINDINGS: Between June 7, 2006, and March 12, 2009, 116 general practices (3526 participants) within 26 health-care centres were recruited and randomly assigned: 63 (1890 participants) were assigned to the intervention group and 53 (1636 participants) to the control group. Primary outcome data were obtained for 3454 (98%) participants; median follow-up was 6·7 years (21 341 person-years). Dementia developed in 121 (7%) of 1853 participants in the intervention group and in 112 (7%) of 1601 participants in the control group (hazard ratio [HR] 0·92, 95% CI 0·71-1·19; p=0·54). Mean ALDS scores measured during follow-up did not differ between groups (85·7 [SD 6·8] in the intervention group and 85·7 [7·1] in the control group; adjusted mean difference -0·02, 95% CI -0·38 to 0·42; p=0·93). 309 (16%) of 1885 participants died in the intervention group, compared with 269 (16%) of 1634 participants in the control group (HR 0·98, 95% CI 0·80-1·18; p=0·81). Incident cardiovascular disease did not differ between groups (273 [19%] of 1469 participants in the intervention group and 228 [17%] of 1307 participants in the control group; HR 1·06, 95% CI 0·86-1·31; p=0·57). INTERPRETATION: A nurse-led, multidomain intervention did not result in a reduced incidence of all-cause dementia in an unselected population of older people. This absence of effect might have been caused by modest baseline cardiovascular risks and high standards of usual care. Future studies should assess the efficacy of such interventions in selected populations. FUNDING: Dutch Ministry of Health, Welfare and Sport; Dutch Innovation Fund of Collaborative Health Insurances; and Netherlands Organisation for Health Research and Development.

Effect of using repeated measurements of a Mediterranean style diet on the strength of the association with cardiovascular disease during 12 years: the Doetinchem Cohort Study.

BACKGROUND: In cohort studies, often only one baseline measurement of dietary intake is available. This may underestimate the strength of the association with cardiovascular diseases (CVD). OBJECTIVE: The main objective is to compare the strength of the association of a Mediterranean style diet with CVD using one baseline measurement of diet versus three repeated measurements over a 10-year period. DESIGN: We used dietary and lifestyle data of three rounds of the Doetinchem Cohort Study. At baseline, 7,769 persons aged 20-65 years were examined. Diet was assessed with a 178 item validated food-frequency questionnaire and operationalized with the Mediterranean Diet Score (MDS) ranging from 0 to 9. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CI). Analyses were adjusted for age, sex, and repeated measurements of smoking, sports, total energy intake, and educational level. RESULTS: Comparing an MDS of ≥5.5-9 to an MDS of 0-<3.5, baseline MDS was associated with a 23% lower risk [HR 0.77 (95% CI 0.53-1.11)] and the updated mean with a 35% lower risk [HR 0.65 (0.43-0.97)] of a composite of fatal CVD, nonfatal myocardial infarction, and stroke (composite CVD). For fatal CVD, baseline MDS was associated with a 13% lower risk [HR 0.87 (0.36-2.07)] and the updated mean with a 56% lower risk [HR 0.44 (0.19-1.05)]. CONCLUSION: The strength of the association between a Mediterranean style diet and CVD is likely underestimated because most studies so far used only one baseline measurement.

Antihypertensive medication classes and risk of incident dementia in primary care patients: a longitudinal cohort study in the Netherlands.

Background: Hypertension is a modifiable risk factor for dementia affecting over 70% of individuals older than 60. Lowering dementia risk through preferential treatment with antihypertensive medication (AHM) classes that are otherwise equivalent in indication could offer a cost-effective, safe, and accessible approach to reducing dementia incidence globally. Certain AHM-classes have been associated with lower dementia risk, potentially attributable to angiotensin-II-receptor (Ang-II) stimulating properties. Previous study results have been inconclusive, possibly due to heterogeneous methodology and limited power. We aimed to comprehensively investigate associations between AHM (sub-)classes and dementia risk using large-scale continuous, real-world prescription and outcome data from primary care. Methods: We used data from three Dutch General Practice Registration Networks. Primary endpoints were clinical diagnosis of incident all-cause dementia and mortality. Using Cox regression analysis with time-dependent covariates, we compared the use of angiotensin-converting enzyme inhibitors (ACEi) to angiotensin receptor blockers (ARBs), beta blockers, calcium channel blockers (CCBs), and diuretics; and Ang-II-stimulating- to Ang-II-inhibiting AHM. Findings: Of 133,355 AHM-using participants, 5877 (4.4%) developed dementia, and 14,079 (10.6%) died during a median follow-up of 7.6 [interquartile range = 4.1-11.0] years. Compared to ACEi, ARBs [HR = 0.86 (95% CI = 0.80-0.92)], beta blockers [HR = 0.81 (95% CI = 0.75-0.87)], CCBs [HR = 0.77 (95% CI = 0.71-0.84)], and diuretics [HR = 0.65 (95% CI = 0.61-0.70)] were associated with significantly lower dementia risks. Regarding competing risk of death, beta blockers [HR = 1.21 (95% CI = 1.15-1.27)] and diuretics [HR = 1.69 (95% CI = 1.60-1.78)] were associated with higher, CCBs with similar, and ARBs with lower [HR = 0.83 (95% CI = 0.80-0.87)] mortality risk. Dementia [HR = 0.88 (95% CI = 0.82-0.95)] and mortality risk [HR = 0.86 (95% CI = 0.82-0.91)] were lower for Ang-II-stimulating versus Ang-II-inhibiting AHM. There were no interactions with sex, diabetes, cardiovascular disease, and number of AHM used. Interpretation: Among patients receiving AHM, ARBs, CCBs, and Ang-II-stimulating AHM were associated with lower dementia risk, without excess mortality explaining these results. Extensive subgroup and sensitivity analyses suggested that confounding by indication did not importantly influence our findings. Dementia risk may be influenced by AHM-classes' angiotensin-II-receptor stimulating properties. An RCT comparing BP treatment with different AHM classes with dementia as outcome is warranted. Funding: Netherlands Organisation for Health, Research and Development (ZonMw); Stoffels-Hornstra Foundation.

Prevention of dementia using mobile phone applications (PRODEMOS): a multinational, randomised, controlled effectiveness-implementation trial.

BACKGROUND: The expected increase of dementia prevalence in the coming decades will mainly be in low-income and middle-income countries and in people with low socioeconomic status in high-income countries. This study aims to reduce dementia risk factors in underserved populations at high-risk using a coach-supported mobile health (mHealth) intervention. METHODS: This open-label, blinded endpoint, hybrid effectiveness-implementation randomised controlled trial (RCT) investigated whether a coach-supported mHealth intervention can reduce dementia risk in people aged 55-75 years of low socioeconomic status in the UK or from the general population in China with at least two dementia risk factors. The primary effectiveness outcome was change in cardiovascular risk factors, ageing, and incidence of dementia (CAIDE) risk score from baseline to after 12-18 months of intervention. Implementation outcomes were coverage, adoption, sustainability, appropriateness, acceptability, fidelity, feasibility, and costs assessed using a mixed-methods approach. All participants with complete data on the primary outcome, without imputation of missing outcomes were included in the analysis (intention-to-treat principle). This trial is registered with ISRCTN, ISRCTN15986016, and is completed. FINDINGS: Between Jan 15, 2021, and April 18, 2023, 1488 people (601 male and 887 female) were randomly assigned (734 to intervention and 754 to control), with 1229 (83%) of 1488 available for analysis of the primary effectiveness outcome. After a mean follow-up of 16 months (SD 2·5), the mean CAIDE score improved 0·16 points in the intervention group versus 0·01 in the control group (mean difference -0·16, 95% CI -0·29 to -0·03). 1533 (10%) invited individuals responded; of the intervention participants, 593 (81%) of 734 adopted the intervention and 367 (50%) of 734 continued active participation throughout the study. Perceived appropriateness (85%), acceptability (81%), and fidelity (79%) were good, with fair overall feasibility (53% of intervention participants and 58% of coaches), at low cost. No differences in adverse events between study arms were found. INTERPRETATION: A coach-supported mHealth intervention is modestly effective in reducing dementia risk factors in those with low socioeconomic status in the UK and any socioeconomic status in China. Implementation is challenging in these populations, but those reached actively participated. Whether this intervention will result in less cognitive decline and dementia requires a larger RCT with long follow-up. FUNDING: EU Horizon 2020 Research and Innovation Programme and the National Key R&D Programmes of China. TRANSLATION: For the Mandarin translation of the abstract see Supplementary Materials section.

Antihypertensive medication classes and the risk of dementia over a decade of follow-up.

INTRODUCTION: Use of angiotensin II (ATII)-stimulating antihypertensive medication (AHM), including angiotensin receptor blockers (ARBs) and dihydropyridine calcium channel blockers (CCBs), has been associated with lower dementia risk. Previous studies had relatively short follow-up periods. The aim of this study is to investigate if these effects are sustained over longer periods. METHODS: This post hoc observational analysis was based on data from a dementia prevention trial (preDIVA and its observational extension), among Dutch community-dwelling older adults without prior diagnosis of dementia. Differential associations between AHM classes and incident dementia were studied after 7.0 and 10.4 years, based on the median follow-up durations of dementia cases and all participants. RESULTS: After 7 years, use of ATII-stimulating antihypertensives [hazard ratio = 0.68, 95% confidence interval (CI) = 0.47-1.00], ARBs (hazard ratio = 0.54, 95% CI = 0.31-0.94) and dihydropyridine CCBs (hazard ratio = 0.52, 95% CI = 0.30-0.91) was associated with lower dementia risk. After 10.4 years, associations for ATII-stimulating antihypertensives, ARBs and dihydropyridine CCBs attenuated (hazard ratio = 0.80, 95% CI = 0.61-1.04; hazard ratio = 0.75, 95% CI = 0.53-1.07; hazard ratio = 0.73, 95% CI = 0.51-1.04 respectively), but still suggested lower dementia risk when compared with use of other AHM classes. Results could not be explained by competing risk of mortality. CONCLUSION: Our results suggest that use of ARBs, dihydropyridine CCBs and ATII-stimulating antihypertensives is associated with lower dementia risk over a decade, although associations attenuate over time. Apart from methodological aspects, differential effects of antihypertensive medication classes on incident dementia may in part be temporary, or decrease with ageing.

Attitudes and views on healthy lifestyle interventions for the prevention of dementia and cardiovascular disease among older people with low socioeconomic status: a qualitative study in the Netherlands.

OBJECTIVES: Individuals with a low socioeconomic status (SES) have an increased risk of cardiovascular disease (CVD) and dementia, partly due to the high prevalence of unhealthy behaviours in this population. Interventions targeting lifestyle-related risk factors can potentially delay or prevent CVD and dementia onset. In this study, we explore the attitudes, experiences and views of low SES older adults on healthy lifestyles for the prevention of CVD and dementia. We also aim to study the potential role for coach-supported mobile health (mHealth) use, facilitating the development of the Prevention of Dementia using Mobile Phone Applications intervention. DESIGN: We performed semi-structured interviews and used thematic analysis to analyse the data. SETTING: Recruitment through multiple general practices in the Netherlands. PARTICIPANTS: Dutch non-demented adults aged ≥55, at increased risk of dementia, who possess a smartphone. Participants were purposively sampled on age, sex and history of CVD and diabetes. RESULTS: Between May 2018 and June 2019, we performed 19 interviews. Five main themes were: (1) participants perceived little influence on their future health, (2) the sacrifices of healthy lifestyles outweighed the potential benefits, (3) physical complaints or disease could prompt behaviour change, (4) participants perceived they had limited self-efficacy to change their behaviour and (5) the social network had an important role in behaviour change. Needs regarding mHealth support were an easy-to-use smartphone application with trustworthy health information, which is provided in a non-obligatory way. CONCLUSIONS: Low SES older adults may benefit from lifestyle interventions that aim to improve self-efficacy levels by (remote) human support. Appropriateness and attractiveness of such interventions may increase when taking into account the participant's own autonomy, and when emphasising the direct gains of lifestyle changes for daily life. Moreover, involving the social network may be a valuable approach when developing lifestyle interventions for low SES older adults. TRIAL REGISTRATION NUMBER: PRODEMOS trial, ISRCTN15986016; Pre-results.

Low Values for Blood Pressure, BMI, and Non-HDL Cholesterol and the Risk of Late-Life Dementia.

BACKGROUND AND OBJECTIVES: Low values of blood pressure, body mass index (BMI), and non-high-density lipoprotein (HDL) cholesterol have all been associated with increased dementia risk in late life, but whether these risk factors have an additive effect is unknown. This study assessed whether a combination of late-life low values for systolic blood pressure (SBP), BMI, and non-HDL cholesterol is associated with a higher dementia risk than individual low values of these risk factors. METHODS: This is a post hoc analysis based on an observational extended follow-up of the Prevention of Dementia by Intensive Vascular Care (preDIVA) trial, including community-dwelling individuals, aged 70-78 years and free from dementia at baseline. We assessed the association of baseline low values of SBP, BMI, and non-HDL cholesterol with incident dementia using Cox regression analyses. First, we assessed the respective associations between quintiles of each risk factor and dementia. Second, we explored whether combinations of low values for cardiovascular risk factors increased dementia risk, adjusted for interaction and potential confounders. RESULTS: During a median follow-up of 10.3 years (interquartile range 7.0-10.9 years), 308 of 2,789 participants (11.0%) developed dementia, and 793 (28.4%) died. For all risk factors, the lowest quintile was associated with the highest adjusted risk for dementia. Individuals with 1, 2, and 3 low values had adjusted HRs of 1.18 (95% CI 0.93-1.51), 1.28 (95% CI 0.85-1.93), and 4.02 (95% CI 2.04-7.93), respectively, compared with those without any low values. This effect was not driven by any specific combination of 2 risk factors and could not be explained by competing risk of death. DISCUSSION: Older individuals with low values for SBP, BMI, or non-HDL cholesterol have a higher dementia risk compared with individuals without any low values. Dementia risk was substantially higher in individuals with low values for all 3 risk factors than expected based on a dose-response relationship. This suggests the presence of an overarching phenomenon that involves multiple risk factors simultaneously, rather than resulting from independent effects of each individual risk factor. TRIAL REGISTRATION INFORMATION: ISRCTN registry preDIVA: ISRCTN29711771. Date of study submission to ISRCTN registry: February 14, 2006. Recruitment start date: January 1, 2006. doi.org/10.1186/ISRCTN29711771.

Cycling and sports, but not walking, are associated with 10-year cardiovascular disease incidence: the MORGEN Study.

BACKGROUND: Physical activity is inversely related to cardiovascular diseases. However, the type of activities that contribute most to these beneficial effects remain unclear. For this reason, we investigated self-reported leisure time physical activities in relation to fatal/nonfatal cardiovascular disease incidence. DESIGN: The Dutch Monitoring Project on Risk Factors for Chronic Diseases Study, carried out between 1993 and 1997, is a prospective cohort study of over 23000 men and women aged 20­65 years from the general Dutch population. METHODS: From 1994 till 1997 physical activity was assessed with a questionnaire in 7451 men and 8991 women who were followed for an average of 9.8 years. Cox proportional hazards models were used adjusting for age, sex, other physical activities, smoking, alcohol consumption, and educational level. RESULTS: Almost the entire study population (97%) was engaged in walking, about 75% in regular cycling, and about half the population in sports or gardening. Cycling [hazard ratio (HR): 0.82, 95% confidence interval (CI): 0.71­0.95] and sports (HR: 0.74, 95% CI: 0.64­0.87) were both inversely related to cardiovascular disease incidence, whereas walking and gardening were not. For sports (P < 0.001), but not for cycling (P = 0.06), we found a dose - response relationship with respect to cardiovascular disease incidence. Engaging in both cycling and sports resulted in an even greater risk reduction (HR: 0.64, 95% CI: 0.52­0.77). CONCLUSION: In this relatively active population, types of activities of at least moderate intensity, such as cycling and sports were associated with lower CVD incidence, whereas activities of lower intensity, such as walking and gardening, were not.

Design and Development of a Mobile Health (mHealth) Platform for Dementia Prevention in the Prevention of Dementia by Mobile Phone Applications (PRODEMOS) Project.

Background: Mobile health (mHealth) has the potential to bring preventive healthcare within reach of populations with limited access to preventive services, by delivering personalized support at low cost. Although numerous mHealth interventions are available, very few have been developed following an evidence-based rationale or have been tested for efficacy. This article describes the systematic development of a coach-supported mHealth application to improve healthy lifestyles for the prevention of dementia and cardiovascular disease in the United Kingdom (UK) and China. Methods: Development of the Prevention of Dementia by Mobile Phone applications (PRODEMOS) platform built upon the experiences with the Healthy Aging Through Internet Counseling in the Elderly (HATICE) eHealth platform. In the conceptualization phase, experiences from the HATICE trial and needs and wishes of the PRODEMOS target population were assessed through semi-structured interviews and focus group sessions. Initial technical development of the platform was based on these findings and took place in consecutive sprint sessions. Finally, during the evaluation and adaptation phase, functionality and usability of the platform were evaluated during pilot studies in UK and China. Results: The PRODEMOS mHealth platform facilitates self-management of a healthy lifestyle by goal setting, progress monitoring, and educational materials on healthy lifestyles. Participants receive remote coaching through a chat functionality. Based on lessons learned from the HATICE study and end-users, we made the intervention easy-to-use and included features to personalize the intervention. Following the pilot studies, in which in total 77 people used the mobile application for 6 weeks, the application was made more intuitive, and we improved its functionalities. Conclusion: Early involvement of end-users in the development process and during evaluation phases improved acceptability of the mHealth intervention. The actual use and usability of the PRODEMOS intervention will be assessed during the ongoing PRODEMOS randomized controlled trial, taking a dual focus on effectiveness and implementation outcomes.

Prevention of dementia using mobile phone applications (PRODEMOS): protocol for an international randomised controlled trial.

INTRODUCTION: Profiles of high risk for future dementia are well understood and are likely to concern mostly those in low-income and middle-income countries and people at greater disadvantage in high-income countries. Approximately 30%-40% of dementia cases have been estimated to be attributed to modifiable risk factors, including hypertension, smoking and sedentary lifestyle. Tailored interventions targeting these risk factors can potentially prevent or delay the onset of dementia. Mobile health (mHealth) improves accessibility of such prevention strategies in hard-to-reach populations while at the same time tailoring such approaches. In the current study, we will investigate the effectiveness and implementation of a coach-supported mHealth intervention, targeting dementia risk factors, to reduce dementia risk. METHODS AND ANALYSIS: The prevention of dementia using mobile phone applications (PRODEMOS) randomised controlled trial will follow an effectiveness-implementation hybrid design, taking place in the UK and China. People are eligible if they are 55-75 years old, of low socioeconomic status (UK) or from the general population (China); have ≥2 dementia risk factors; and own a smartphone. 2400 participants will be randomised to either a coach-supported, interactive mHealth platform, facilitating self-management of dementia risk factors, or a static control platform. The intervention and follow-up period will be 18 months. The primary effectiveness outcome is change in the previously validated Cardiovascular Risk Factors, Ageing and Incidence of Dementia dementia risk score. The main secondary outcomes include improvement of individual risk factors and cost-effectiveness. Implementation outcomes include acceptability, adoption, feasibility and sustainability of the intervention. ETHICS AND DISSEMINATION: The PRODEMOS trial is sponsored in the UK by the University of Cambridge and is granted ethical approval by the London-Brighton and Sussex Research Ethics Committee (reference: 20/LO/01440). In China, the trial is approved by the medical ethics committees of Capital Medical University, Beijing Tiantan Hospital, Beijing Geriatric Hospital, Chinese People's Liberation Army General Hospital, Taishan Medical University and Xuanwu Hospital. Results will be published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: ISRCTN15986016.

Association of Benzodiazepine and Anticholinergic Drug Usage With Incident Dementia: A Prospective Cohort Study of Community-Dwelling Older Adults.

OBJECTIVES: To examine the association of benzodiazepines and anticholinergic drug usage with the risk of dementia. DESIGN: Prospective cohort study. SETTING: Community-dwelling participants, recruited in family practices in the Netherlands. PARTICIPANTS: In total, 3526 individuals aged 70 to 78 years without dementia within 116 participating family practices. METHODS: Information about drug use was reported at baseline and at 2-year follow-up and was cross-checked with the participants' electronic health records. Anticholinergic drug exposure was defined by the anticholinergic cognitive burden score. Participants were evaluated for dementia during follow-up assessments every 2 years, supplemented by information from electronic health records and the National Death Registry. RESULTS: During a median follow-up of 6.7 years, dementia developed in 233 participants (7%). In participants using benzodiazepines, 6% developed dementia vs 7% in nonusers [hazard ratio (HR) 0.71, 95% confidence interval (CI) 0.58-1.07]. Persistent usage of benzodiazepines at baseline and after 2-year follow-up did not substantially alter the point-estimate (HR 0.60, 95% CI 0.34-1.10). Use of any anticholinergic drugs was not associated with incident dementia (HR 1.01, 95% CI 0.50-1.10). Dementia risk was significantly increased for participants with persistent drug use with a high anticholinergic cognitive burden score (HR 1.95, 95% CI 1.13-3.38) though this effect was absent when excluding participants taking antidepressants or antipsychotics (HR 0.42, 95% CI 0.06-3.01). CONCLUSIONS AND IMPLICATIONS: In our study population, benzodiazepine usage was not associated with an increased risk of dementia. Persistent high anticholinergic exposure was associated with an increased risk of dementia over 6 years of follow-up, and this association was driven by antidepressant or antipsychotic drug use, suggesting confounding by indication bias contributing to this. Although this observation could ameliorate prescription hesitance, healthcare providers are still advised to carefully weigh the potential benefits of benzodiazepines and anticholinergic drugs against the associated adverse health outcomes.

Pooling individual participant data from randomized controlled trials: Exploring potential loss of information.

BACKGROUND: Pooling individual participant data to enable pooled analyses is often complicated by diversity in variables across available datasets. Therefore, recoding original variables is often necessary to build a pooled dataset. We aimed to quantify how much information is lost in this process and to what extent this jeopardizes validity of analyses results. METHODS: Data were derived from a platform that was developed to pool data from three randomized controlled trials on the effect of treatment of cardiovascular risk factors on cognitive decline or dementia. We quantified loss of information using the R-squared of linear regression models with pooled variables as a function of their original variable(s). In case the R-squared was below 0.8, we additionally explored the potential impact of loss of information for future analyses. We did this second step by comparing whether the Beta coefficient of the predictor differed more than 10% when adding original or recoded variables as a confounder in a linear regression model. In a simulation we randomly sampled numbers, recoded those < = 1000 to 0 and those >1000 to 1 and varied the range of the continuous variable, the ratio of recoded zeroes to recoded ones, or both, and again extracted the R-squared from linear models to quantify information loss. RESULTS: The R-squared was below 0.8 for 8 out of 91 recoded variables. In 4 cases this had a substantial impact on the regression models, particularly when a continuous variable was recoded into a discrete variable. Our simulation showed that the least information is lost when the ratio of recoded zeroes to ones is 1:1. CONCLUSIONS: Large, pooled datasets provide great opportunities, justifying the efforts for data harmonization. Still, caution is warranted when using recoded variables which variance is explained limitedly by their original variables as this may jeopardize the validity of study results.

Association of anthropometry and weight change with risk of dementia and its major subtypes: A meta-analysis consisting 2.8 million adults with 57 294 cases of dementia.

Uncertainty exists regarding the relation of body size and weight change with dementia risk. As populations continue to age and the global obesity epidemic shows no sign of waning, reliable quantification of such associations is important. We examined the relationship of body mass index, waist circumference, and annual percent weight change with risk of dementia and its subtypes by pooling data from 19 prospective cohort studies and four clinical trials using meta-analysis. Compared with body mass index-defined lower-normal weight (18.5-22.4 kg/m2 ), the risk of all-cause dementia was higher among underweight individuals but lower among those with upper-normal (22.5-24.9 kg/m2 ) levels. Obesity was associated with higher risk in vascular dementia. Similarly, relative to the lowest fifth of waist circumference, those in the highest fifth had nonsignificant higher vascular dementia risk. Weight loss was associated with higher all-cause dementia risk relative to weight maintenance. Weight gain was weakly associated with higher vascular dementia risk. The relationship between body size, weight change, and dementia is complex and exhibits non-linear associations depending on dementia subtype under scrutiny. Weight loss was associated with an elevated risk most likely due to reverse causality and/or pathophysiological changes in the brain, although the latter remains speculative.

A cardiovascular risk prediction model for older people: Development and validation in a primary care population.

Cardiovascular risk prediction is mainly based on traditional risk factors that have been validated in middle-aged populations. However, associations between these risk factors and cardiovascular disease (CVD) attenuate with increasing age. Therefore, for older people the authors developed and internally validated risk prediction models for fatal and non-fatal CVD, (re)evaluated the predictive value of traditional and new factors, and assessed the impact of competing risks of non-cardiovascular death. Post hoc analyses of 1811 persons aged 70-78 year and free from CVD at baseline from the preDIVA study (Prevention of Dementia by Intensive Vascular care, 2006-2015), a primary care-based trial that included persons free from dementia and conditions likely to hinder successful long-term follow-up, were performed. In 2017-2018, Cox-regression analyses were performed for a model including seven traditional risk factors only, and a model to assess incremental predictive ability of the traditional and eleven new factors. Analyses were repeated accounting for competing risk of death, using Fine-Gray models. During an average of 6.2 years of follow-up, 277 CVD events occurred. Age, sex, smoking, and type 2 diabetes mellitus were traditional predictors for CVD, whereas total cholesterol, HDL-cholesterol, and systolic blood pressure (SBP) were not. Of the eleven new factors, polypharmacy and apathy symptoms were predictors. Discrimination was moderate (concordance statistic 0.65). Accounting for competing risks resulted in slightly smaller predicted absolute risks. In conclusion, we found, SBP, HDL, and total cholesterol no longer predict CVD in older adults, whereas polypharmacy and apathy symptoms are two new relevant predictors. Building on the selected risk factors in this study may improve CVD prediction in older adults and facilitate targeting preventive interventions to those at high risk.

Healthy ageing through internet counselling in the elderly (HATICE): a multinational, randomised controlled trial.

BACKGROUND: Although web-based interventions have been promoted for cardiovascular risk management over the past decade, there is limited evidence for effectiveness of these interventions in people older than 65 years. The healthy ageing through internet counselling in the elderly (HATICE) trial aimed to determine whether a coach-supported internet intervention for self-management can reduce cardiovascular risk in community-dwelling older people. METHODS: This prospective open-label, blinded endpoint clinical trial among people age 65 years or over at increased risk of cardiovascular disease randomly assigned participants in the Netherlands, Finland, and France to an interactive internet intervention stimulating coach-supported self-management or a control platform. Primary outcome was the difference from baseline to 18 months on a standardised composite score (Z score) of systolic blood pressure, LDL cholesterol, and body-mass index (BMI). Secondary outcomes included individual risk factors and cardiovascular endpoints. This trial is registered with the ISRCTN registry, 48151589, and is closed to accrual. FINDINGS: Among 2724 participants, complete primary outcome data were available for 2398 (88%). After 18 months, the primary outcome improved in the intervention group versus the control group (0·09 vs 0·04, respectively; mean difference -0·05, 95% CI -0·08 to -0·01; p=0·008). For individual components of the primary outcome, mean differences (intervention vs control) were systolic blood pressure -1·79 mm Hg versus -0·67 mm Hg (-1·12, -2·51 to 0·27); BMI -0·23 kg/m2 versus -0·08 kg/m2 (-0·15, -0·28 to -0·01); and LDL -0·12 mmol/L versus -0·07 mmol/L (-0·05, -0·11 to 0·01). Cardiovascular disease occurred in 30 (2·2%) of 1382 patients in the intervention versus 32 (2·4%) of 1333 patients in the control group (hazard ratio 0·86, 95% CI 0·52 to 1·43). INTERPRETATION: Coach-supported self-management of cardiovascular risk factors using an interactive internet intervention is feasible in an older population, and leads to a modest improvement of cardiovascular risk profile. When implemented on a large scale this could potentially reduce the burden of cardiovascular disease. FUNDING: European Commission Seventh Framework Programme.

Modifiable dementia risk score to study heterogeneity in treatment effect of a dementia prevention trial: a post hoc analysis in the preDIVA trial using the LIBRA index.

BACKGROUND: Selecting high-risk participants for dementia prevention trials based on a modifiable dementia risk score may be advantageous, as it increases the opportunity for intervention. We studied whether a multi-domain intervention can prevent all-cause dementia and cognitive decline in older people across three different levels of a modifiable dementia risk score. METHODS: Prevention of Dementia by Intensive Vascular Care (preDIVA) is a randomised controlled trial studying the effect of multi-domain vascular care during 6-8 years on incident all-cause dementia in community-dwelling people aged 70-78 years. For this post hoc analysis, we stratified preDIVA participants in tertiles based on their baseline LIfestyle for BRAin Health (LIBRA) index, a modifiable dementia risk score. With Cox proportional hazards regression, the intervention effect on dementia was assessed. The effect on cognition was measured every 2 years with the Mini-Mental State Examination and Visual Association Test. RESULTS: Dementia developed in 220 of 3274 (6.7%) participants. In participants with a low, intermediate and high LIBRA index, the hazard ratio (HR) of the intervention on incident dementia was respectively 0.71 (95% CI 0.45-1.12), 1.06 (95% CI 0.66-1.69) and 1.02 (95% CI 0.64-1.62). Also, when adding the non-modifiable risk factors age, education and sex to the index, results were comparable (respectively HR 0.88, 95% CI 0.54-1.43; HR 0.91, 95% CI 0.57-1.47; HR 0.92, 95% CI 0.59-1.41). There was no statistically significant intervention effect on cognition during follow-up across the LIBRA groups. CONCLUSIONS: In the preDIVA study population aged 70-78 years, the LIBRA modifiable dementia risk score did not identify a (high-)risk group in whom the multi-domain intervention was effective in preventing dementia or cognitive decline. TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number registry, ISRCTN29711771 . Registered on 14 February 2006.

Effects of Primary Cardiovascular Prevention on Vascular Risk in Older Adults.

INTRODUCTION: Primary cardiovascular prevention through simultaneously targeting multiple risk factors may be even more effective than single risk factor modification in older adults. The effects of multicomponent cardiovascular prevention on cardiovascular risk are explored. STUDY DESIGN: Post hoc analysis of the cluster randomized Prevention of Dementia by Intensive Vascular care trial. SETTING/PARTICIPANTS: Community-dwelling older adults aged 70-78 years, free from cardiovascular disease at baseline (n=2,254, 63.9% of the Prevention of Dementia by Intensive Vascular care trial population). INTERVENTION: Between 2006 and 2015, the intervention group received nurse-led vascular care every 4 months at the general practitioner practice, the control group received care as usual. MAIN OUTCOME MEASURES: Cardiovascular disease events and Systematic COronary Risk Evaluation in Older People (SCORE-OP), an index based on six risk factors for cardiovascular mortality. Effects were adjusted for clustering and assessed using mixed effects Cox proportional-hazard models and linear mixed models respectively. RESULTS: There was no effect of the intervention on cardiovascular disease events (hazard ratio=0.99, 95% CI=0.71, 1.38). During a median follow-up of 6.1 years, SCORE-OP increased from 14.0% and 13.9% to 23.9% and 25.0% in the intervention and control group, respectively (adjusted mean difference in increment in SCORE-OP between the study groups 0.60%, 95% CI= -0.01, 1.20). Exploratory analyses showed a larger reduction of 2.4 mmHg (95% CI=0.9, 3.9) in systolic blood pressure and 1.9% (95% CI=0.4, 3.4) in current cigarette smoking in the intervention group compared with the control group. CONCLUSIONS: Multicomponent cardiovascular prevention did not improve the overall risk profile in older adults in a primary prevention setting, relative to usual care. However, exploratory analyses showed an effect on blood pressure and smoking cessation. Possibly, contrast between study groups was too small because of the Hawthorne (being part of a study) effect and increasing quality of (preventive) health care for older adults, to yield an effect on the risk profile.