A cardiovascular risk prediction model for older people

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

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 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

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 20–65 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): 0.71–0.95] and sports (HR: 0.74, 95% CI: 0.64–0.87) 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: 0.52–0.77). 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

Sleep Duration and Sleep Quality in Relation to 12-Year Cardiovascular Disease Incidence: The MORGEN Study

Study Objectives: We studied sleep duration and sleep quality in relation to cardiovascular disease (CVD) incidence. Design/Setting: Dutch population-based cohort study. Participants: 20,432 men and women aged 20-65 y with no history of CVD. Interventions: N/A Measurements: Sleep duration and sleep quality were assessed by a self-administered questionnaire. Morbidity data, vital status, and causes of death were obtained through linkage with several national registries. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were calculated using Cox proportional hazards models. Results: During 10-15 years of follow-up, 1,486 CVD and 1,148 coronary heart disease (CHD) events occurred. Short sleepers (= 6 h) had a 15% higher risk of total CVD (HR: 1.15; 95%CI: 1.00-1.32) and a 23% higher risk of CHD (HR: 1.23 [1.04-1.45]) compared to normal sleepers (7 h) after adjustment for all confounders. Additional adjustment for intermediate biological risk factors attenuated these relative risks to 1.11 (0.97-1.27) for total CVD and to 1.19 (1.00-1.40) for CHD. Short sleepers with poor sleep quality had a 63% higher risk of CVD (HR: 1.63 [1.21-2.19]) and a 79% higher risk of CHD incidence (HR: 1.79 [1.24-2.58]) compared to normal sleepers with good sleep quality, after adjustments for all confounders. We observed no associations between long sleep duration (= 9 h) and CVD or CHD incidence. Conclusions: Short sleepers, especially those with poor sleep quality, have an increased risk of total CVD and CHD incidence. Future investigations should not only focus on sleep duration, but should also take sleep quality into account

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

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

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

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

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