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Observational studies have shown consistently that modifiable risk factors during life are associated with increased dementia risk in old age but randomized controlled trials (RCTs) on dementia prevention evaluating the treatment of these risk factors did not find consistent effects on cognitive outcomes. The discrepancy in findings is potentially attributable to inherent differences between the two study designs. Although RCTs are the gold standard for establishing causality, designing and conducting an RCT for dementia prevention is complex. Quasi-experimental studies (QESs) may contribute to investigating causality without randomization. QESs use variation in exposure to a risk factor or intervention in an observational setting to deduct causal effects. Design-specific approaches are used to control for confounding, the main caveat of QESs. In this article we address the challenges, opportunities, and limitations of QESs for research into dementia prevention. Highlights: Despite consistent associations between modifiable risk factors and dementia, the mostly neutral effects of randomized controlled trials (RCTs) challenge the causality of these associations. RCTs in the field of dementia prevention are often problematic due to ethical, practical, or financial constraints, and their results may have limited generalizability. Four quasi-experimental study (QES) designs may be suitable to study causality between risk factors and dementia; we critically appraise these study designs for dementia-prevention studies. We describe how specific QES designs can be used to study the effects of risk-factor modification for 12 known risk factors for dementia.

Background: Older people with subjective memory complaints (SMC) and Instrumental Activities of Daily Living impairments (IADL-I) have an increased risk of developing dementia. Previous reports suggest that the predictive value of SMC and IADL-I may differ between sexes, leaving possible consequences for personalized risk prediction and prognosis. However, none of these studies addressed the competing risk of death, which may substantially differ between sexes. Objective: We investigated sex-differences in the association between IADL-I, SMC, and incident dementia and mortality as competing risk. Methods: 3,409 community-dwelling older people without dementia (mean age 74.3±2.5), were followed for 6.7 years (median). Baseline SMC were assessed using the 15-item Geriatric Depression Scale memory question, and IADL-I using the Academic Medical Center Linear Disability Score. Potential sex-differences in the predictive value of SMC and IADL-I were assessed using Cox regression models with an interaction term for sex. Results: HRs for isolated SMC and SMC + IADL-I and risk of dementia were higher in women (HR: 2.02, 95% CI = 0.91–4.46, p = 0.08; HR:2.85, 95% CI = 1.65–4.91, p

ObjectiveTo assess whether angiotensin II–stimulating antihypertensives (thiazides, dihydropyridine calcium channel blockers, and angiotensin I receptor blockers) convey a lower risk of incident dementia compared to angiotensin II–inhibiting antihypertensives (angiotensin-converting enzyme inhibitors, β-blockers, and nondihydropyridine calcium channel blockers), in accordance with the “angiotensin hypothesis.”MethodsWe performed Cox regression analyses of incident dementia (or mortality as competing risk) during 6–8 years of follow-up in a population sample of 1,909 community-dwelling individuals (54% women) without dementia, aged 70–78 (mean 74.5 ± 2.5) years.ResultsAfter a median of 6.7 years of follow-up, dementia status was available for 1,870 (98%) and mortality for 1,904 (>99%) participants. Dementia incidence was 5.6% (27/480) in angiotensin II–stimulating, 8.2% (59/721) in angiotensin II–inhibiting, and 6.9% (46/669) in both antihypertensive type users. Adjusted for dementia risk factors including blood pressure and medical history, angiotensin II–stimulating antihypertensive users had a 45% lower incident dementia rate (hazard ratio [HR], 0.55; 95% CI, 0.34–0.89) without excess mortality (HR, 0.86; 95% CI, 0.64–1.16), and individuals using both types had a nonsignificant 20% lower dementia rate (HR, 0.80; 95% CI,0.53–1.20) without excess mortality (HR, 0.97; 95% CI, 0.76–1.24), compared to angiotensin II–inhibiting antihypertensive users. Results were consistent for subgroups based on diabetes and stroke history, but may be specific for individuals without a history of cardiovascular disease.ConclusionsUsers of angiotensin II–stimulating antihypertensives had lower dementia rates compared to angiotensin II–inhibiting antihypertensive users, supporting the angiotensin hypothesis. Confounding by indication must be examined further, although subanalyses suggest this did not influence results. If replicated, dementia prevention could become a compelling indication for older individuals receiving antihypertensive treatment.

Consistent cerebral blood flow (CBF) is fundamental to brain function. Cerebral autoregulation ensures CBF stability. Chronic hypertension can lead to disrupted cerebral autoregulation in older people, potentially leading to blood pressure levels interfering with CBF. This study tested whether low BP and AHD use are associated with contemporaneous low CBF, and whether longitudinal change in BP is associated with change in CBF, using arterial spin labelling (ASL) MRI, in a prospective longitudinal cohort of 186 community-dwelling older individuals with hypertension (77 ± 3 years, 53% female), 125 (67%) of whom with 3-year follow-up. Diastolic blood pressure, systolic blood pressure, mean arterial pressure, and pulse pressure were assessed as blood pressure parameters. As additional cerebrovascular marker, we evaluated the ASL signal spatial coefficient of variation (ASL SCoV), a measure of ASL signal heterogeneity that may reflect cerebrovascular health. We found no associations between any of the blood pressure measures and concurrent CBF nor between changes in blood pressure measures and CBF over three-year follow-up. Antihypertensive use was associated with lower grey matter CBF (−5.49 ml/100 g/min, 95%CI = −10.7|−0.27, p = 0.04) and higher ASL SCoV (0.32 SD, 95%CI = 0.12|0.52, p = 0.002). These results warrant future research on the potential relations between antihypertensive use and cerebral perfusion.

Background: Systemic infection is an important risk factor for delirium, associated with neurodegeneration and subsequent cognitive impairment in older people. Microglial cell response is a known key player in this process and we hypothesize that the triggering receptor expressed on myeloid cells 2 (TREM2) plays an important role in the regulation of this response. Methods: 8- to 10-week old male wild-type (WT) and TREM2 knock-out (Trem2-/-) mice were intraperitoneally inoculated with live Escherichia coli (E. coli) or saline. After inoculation, all mice were treated with ceftriaxone (an antimicrobial drug) at 12 and 24 hours and were sacrificed after 2 and 3 days. Microglial response was determined by immunohistochemical staining with an ionized calcium-binding adaptor molecule 1 (Iba-1) antibody and flow cytometry. mRNA expression of pro- and anti-inflammatory mediators was measured to quantify the inflammatory response.Results: We observed increased Iba-1 positive cells number in thalamus of Trem2-/- mice at 3d after inoculation compared to WT mice (mean 120 cell/mm2 [SD 8] vs. 105 cell/mm2 [SD 11]; p=0.03). Flow cytometry showed no differences in forward scatter or expression of CD11b, CD45 and CD14 between WT and Trem2-/- mice. The brain mRNA expression levels of tumor necrosis factor alpha (TNF-α) of Trem2-/- mice at 2d were higher compared to WT mice (p=0.003). Higher mRNA expression of interleukin 1 beta (IL-1β), Iba-1, CD11b and mitogen-activated protein kinase 1 (MAPK-1) was found in brain of WT mice at 2d compared to Trem2-/- mice (respectively p=0.02; p=0.001; p=0.03 and p=0.02). In spleen there were no differences in inflammatory mediators, between WT and Trem2-/- mice.Interpretation: Although the loss of function of TREM2 during systemic infection led to an increased number of activated microglia in the thalamus, we did not observe a consistent increase in expression of inflammatory genes in the brain. The role of TREM2 in the neuro-inflammatory response following systemic infection therefore appears to be limited.

Bestaande predictiemodellen geven een slechte voorspelling van het cardiovasculair risico bij ouderen. Een nieuw model laat zien dat op hogere leeftijd systolische bloeddruk, totaal cholesterol en HDL-cholesterol als voorspellers minder belangrijk worden, maar polyfarmacie en apathie steeds belangrijker.

Background and ObjectivesLow 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.MethodsThis 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.ResultsDuring 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.DiscussionOlder 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 InformationISRCTN registry preDIVA: ISRCTN29711771. Date of study submission to ISRCTN registry: February 14, 2006. Recruitment start date: January 1, 2006. doi.org/10.1186/ISRCTN29711771.

Summary 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.

Contains fulltext : 248846.pdf (Publisher’s version ) (Closed access) IMPORTANCE: The optimal systolic blood pressure (SBP) to minimize the risk of dementia in older age is unknown. OBJECTIVE: To investigate whether the association between SBP and dementia risk is U-shaped and whether age and comorbidity play a role in this association. DESIGN, SETTING, AND PARTICIPANTS: This cohort study used an individual participant data approach to analyze 7 prospective, observational, population-based cohort studies that were designed to evaluate incident dementia in older adults. These studies started between 1987 and 2006 in Europe and the US. Participants had no dementia diagnosis and had SBP and/or diastolic blood pressure (BP) data at baseline and incident dementia status during follow-up. Data analysis was conducted from November 7, 2019, to October 3, 2021. EXPOSURES: Baseline systolic BP. MAIN OUTCOMES AND MEASURES: All-cause dementia (defined using Diagnostic and Statistical Manual of Mental Disorders [Third Edition Revised] or Diagnostic and Statistical Manual of Mental Disorders [Fourth Edition] and established at follow-up measurements or in clinical practice), mortality, and combined dementia and mortality were the outcomes. Covariates included baseline antihypertensive medication use, sex, educational level, body mass index, smoking status, diabetes, stroke history, myocardial infarction history, and polypharmacy. Cox proportional hazards regression models were used, and nonlinear associations were explored using natural splines. RESULTS: The study analyzed 7 cohort studies with a total of 17 286 participants, among whom 10 393 were women (60.1%) and the mean (SD) baseline age was 74.5 (7.3) years. Overall, dementia risk was lower for individuals with higher SBP, with the lowest risk associated with an SBP of approximately 185 mm Hg (95% CI, 161-230 mm Hg; P = .001). Stratified by overlapping 10-year baseline age groups, the lowest dementia risk was observed at somewhat lower systolic BP levels in those older than 75 years (158 [95% CI, 152-178] mm Hg to 170 [95% CI, 160-260] mm Hg). For mortality, there was a clear U-shaped association, with the lowest risk at 160 mm Hg (95% CI, 154-181 mm Hg; P

Background Biomarkers for delirium could increase diagnostic accuracy and may help to identify pathological pathways. Until now study findings concerning cytokine levels have been inconsistent. Aims Systematic review and meta-analysis investigating the association between peripheral levels of Insulin-like Growth Factor-1 (IGF-1), C-Reactive Protein (C-RP) and Interleukin-6 (IL-6) and delirium in surgical patients, and to explore if there are distinct/specific patterns that may potentially explain inconsistent results. Methods PubMed, Scopus, CINAHL, Cochrane, and EMBASE databases were searched. Inclusion criteria were: prospective studies, surgical populations excluding preoperative delirium, available data. The following were collected: type of operation (orthopaedic, abdominal, etc), the timing of operation (acute, elective, both), demographics, number of participants with delirium, time of preoperative blood withdrawal, and preoperative levels of each biomarker. Results Low levels of IGF-1 (n = 7 studies) are significantly associated with post-operative delirium in abdominal surgical samples. High levels of C-RP (n = 9) are associated with delirium in acute orthopaedic and elective abdominal operations. IL-6 (n = 14) is a significant predictor of post-operative delirium in a variety of surgical conditions (elective or acute). Discussion A common pattern exists in the otherwise conflicting reported findings. This similarity may reflect different underling mechanisms and predisposing factors like cachexia and catabolic stages. It seems that delirium in abdominal surgery is triggered by IGF-1 disturbances, while in other surgeries by an inflammatory reaction. Conclusions Despite the contradictory results concerning the association of IGF-1, C-RP and IL-6 with postoperative delirium, the present meta-analysis shows that there are certain patterns. IL-6 seems a consistent predictor for delirium in surgical samples.

IntroductionProfiles 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 analysisThe 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 disseminationThe 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 numberISRCTN15986016.

Background:Studies on the association between depression and dementia risk mostly use sum scores on depression questionnaires to model symptomatology severity. Since individual items may contribute differently to this association, this approach has limited validity.Methods:We used network analysis to investigate the functioning of individual Geriatric Depression Scale (GDS-15) items, of which, based on studies that used factor analysis, 3 are generally considered to measure apathy (GDS-3A) and 12 depression (GDS-12D). Functional disability and future dementia were also included in our analysis. Data were extracted from 3229 participants of the Prevention of Dementia by Intensive Vascular care trial (preDIVA), analyzed as a single cohort, yielding 20,542 person-years of observation. We estimated a sparse network by only including connections between variables that could not be accounted for by variance in other variables. For this, we used a repeated L1 regularized regression procedure.Results:This procedure resulted in a selection of 59/136 possible connections. GDS-3A items were strongly connected to each other and with varying strength to several GDS-12D items. Functional disability was connected to all three GDS-3A items and the GDS-12D items “helplessness” and “worthlessness”. Future dementia was only connected to the GDS-12D item “memory problems”, which was in turn connected to the GDS-12D items “unhappiness” and “helplessness” and all three GDS-3A items.Conclusion:Network analysis reveals interesting relationships between GDS items, functional disability and dementia risk. We discuss what implications our results may have for (future) research on the associations between depression and/or apathy with dementia.

Objectives: Important precipitating risk factors for delirium such as infections, vascular disorders, and surgery are accompanied by a systemic inflammatory response. Systemic inflammatory mediators can induce delirium in susceptible individuals. Little is known about the trajectory of systemic inflammatory markers and their role in the development and outcome of delirium. Methods: This is a prospective cohort study of older patients undergoing acute surgery for hip fracture. Baseline characteristics were assessed preoperatively. During hospital admission, presence of delirium was assessed daily according to the Confusion Assessment Method criteria. This study compared the trajectory of serum levels of the C-reactive protein (CRP) between people with and without postoperative delirium. Blood samples were taken at baseline and at postoperative day 1 through postoperative day 5. Results: Forty-one out of 121 patients developed postoperative delirium after hip fracture surgery. Longitudinal analysis of the trajectory of serum CRP levels using the Generalized Estimating Equations (GEE) method identified that higher CRP levels were associated with postoperative delirium. CRP levels were higher from postoperative day 2 through postoperative day 5. No significant differences in serum CRP levels were found when we compared patients with short (1-2 days) and more prolonged delirium (3 days or more). Conclusions: Delirium is associated with an increased systemic inflammatory response, and our results suggest that CRP plays a role in the underlying (inflammatory-vascular) pathological pathway of postoperative delirium.

Inleiding Het is niet duidelijk of cardiovasculaire interventies in de eerste lijn het risico op cardiovasculaire ziekten bij ouderen daadwerkelijk verlagen. Methode Deelnemers waren 2254 thuiswonende ouderen (70-78 jaar) zonder cardiovasculaire ziekten in de voorgeschiedenis, die afkomstig waren uit het preDIVA-onderzoek (Preventie van Dementie door Intensieve VAatzorg). De interventiegroep kreeg elke vier maanden vasculaire zorg in de huisartsenpraktijk. De controlegroep ontving standaardzorg. De onderzoekers keken naar het effect van de interventie op de intermediaire uitkomst SCORE-OP (‘Systematic COronary Risk Evaluation in Older Persons’), een maat voor het tienjaarsrisico op cardiovasculaire sterfte, die gebaseerd is op zes cardiovasculaire risicofactoren. Resultaten De interventie bleek geen effect te hebben op cardiovasculaire morbiditeit en mortaliteit (in gemiddeld ruim zes jaar). De SCORE-OP steeg 0,60% (95%-BI -0,01 tot 1,20) minder in de interventiegroep vergeleken met de controlegroep. In de interventiegroep was er een grotere daling in systolische bloeddruk van 2,4 mmHg (95%-BI 0,9 tot 3,9) en een sterkere afname van het aantal rokers met 1,9% (95%-BI 0,4 tot 3,4) vergeleken met de controlegroep. Conclusie Intensieve vaatzorg door de praktijkondersteuner voor thuiswonende ouderen zonder cardiovasculaire voorgeschiedenis resulteerde in een grotere daling in de bloeddruk en het rookgedrag dan de standaardzorg. Deze interventie leidde echter niet tot een gunstiger cardiovasculair risicoprofiel volgens de SCORE-OP of tot een reductie van de cardiovasculaire morbiditeit of mortaliteit.

Delirium is a common serious complication in dementia that is associated with poor prognosis and a high burden on caregivers and healthcare professionals. Appropriate care is therefore important at an early stage for patients with delirium superimposed on dementiaTo gain insight into the care of six patients with delirium superimposed on dementia, 19 semi-structured interviews were conducted focused on the experiences of caregivers and professionals. The interviews revealed four themes that appeared to play a role: 1. experiences with and views on behavioral problems of these patients, 2. recognition and diagnosis of delirium in dementia, 3. views on good care and 4. organizational aspects. Knowledge gaps about delirium in dementia, as well as ethical considerations, play an important role in organizing timely and adequate care for patients with delirium superimposed on dementia.Delier is een veel voorkomende ernstige complicatie bij dementie, die gepaard gaat met een slechte prognose en grote belasting van zowel mantelzorger als professionele zorgverleners. Tijdige en goede zorg voor patiënten met delier bij dementie is daarom van belang. Om inzicht te verkrijgen in de zorgverlening van zes patiënten met een delier bij dementie werden 19 semigestructureerde interviews afgenomen gericht op de ervaringen van mantelzorgers en professionele zorgverleners. Uit de interviews kwamen vier thema’s naar voren die een rol speelden: 1. ervaringen met en opvattingen over gedragsproblemen van deze patiënten, 2. herkenning en diagnose van delier bij dementie, 3. opvattingen over goede zorg en 4. organisatorische aspecten. Kennislacunes over delier bij dementie, evenals zorg-ethische overwegingen, spelen een belangrijke rol bij de start van tijdige en goede zorg voor patiënten met delier bij dementie.

Systemic infection is an important risk factor for the development cognitive impairment and neurodegeneration in older people. Animal experiments show that systemic challenges with live bacteria cause a neuro-inflammatory response, but the effect of age on this response in these models is unknown. Young (2 months) and middle-aged mice (13&ndash, 14 months) were intraperitoneally challenged with live Escherichia coli (E. coli) or saline. The mice were sacrificed at 2, 3 and 7 days after inoculation, for all time points, the mice were treated with ceftriaxone (an antimicrobial drug) at 12 and 24 h after inoculation. Microglial response was monitored by immunohistochemical staining with an ionized calcium-binding adaptor molecule 1 (Iba-1) antibody and flow cytometry, and inflammatory response by mRNA expression of pro- and anti-inflammatory mediators. We observed an increased microglial cell number and moderate morphologically activated microglial cells in middle-aged mice, as compared to young mice, after intraperitoneal challenge with live E. coli. Flow cytometry of microglial cells showed higher CD45 and CD11b expressions in middle-aged infected mice compared to young infected mice. The brain expression levels of pro-inflammatory genes were higher in middle-aged than in young infected mice, while middle-aged infected mice had similar expression levels of these genes in the systemic compartment. We conclude that systemic challenge with live bacteria causes an age-dependent neuro-inflammatory and microglial response. Our data show signs of an age-dependent disconnection of the inflammatory transcriptional signature between the brain and the systemic compartment.

Objectives Drugs with anticholinergic properties are associated with an increased prevalence of delirium, especially in older persons. The aim of this study was to evaluate the association between the use of this class of drugs in nursing home (NH) patients and prevalence of delirium, particularly in people with dementia. Design Cross-sectional multicenter study. Setting and participants 3924 nursing home patients of 57 nursing homes in 7 European countries participating in the Services and Health for Elderly in Long TERmcare (SHELTER) project. Methods Descriptive statistics, calculation of percentage, and multivariable logistic analysis were applied to describe the relationship between anticholinergic drug use and prevalence of delirium in NH patients. The Anticholinergic Risk Scale (ARS) and the Anticholinergic Burden Scale (ACB) were used to calculate the anticholinergic load. Results 54% of patients with dementia and 60% without dementia received at least 1 anticholinergic drug according to the ACB. The prevalence of delirium was higher in the dementia group (21%) compared with the nondementia group (11%). Overall, anticholinergic burden according to the ACB and ARS was associated with delirium both in patients with and without dementia, with odds ratios ranging from 1.07 [95% confidence interval (CI) 0.94-1.21] to 1.26 (95% CI 1.11-1.44). These associations reached statistical significance only in the group of patients with dementia. Among patients with dementia, delirium prevalence increased only modestly with increasing anticholinergic burden according to the ACB, from 20% (with none or minimal anticholinergic burden) to 25% (with moderate burden) and 27% delirium (with strong burden scores). Conclusions and Implications The ACB scale is relatively capable to detect anticholinergic side effects, which are positively associated with prevalence of delirium in NH patients. Given the modest nature of this association, strong recommendations are currently not warranted, and more longitudinal studies are needed.

Contains fulltext : 235592.pdf (Publisher’s version ) (Open Access) Numerous clinical trials of anti-amyloid beta (Aβ) immunotherapy in Alzheimer's disease have been performed. None of these have provided convincing evidence for beneficial effects. Using traditional frequentist meta-analysis, the conclusion is that there is absence of evidence for a therapeutic effect, with a point estimate effect size of 0.05 (95% confidence interval -0.00 to 0.10, P = .055). In addition, this non-significant effect equates to 0.4 points per year on the cognitive subscale of the Alzheimer's Disease Assessment Scale. This is well below the minimally clinically important difference. Bayesian meta-analysis of these trial data provides strong evidence of absence of a therapeutic effect, with a Bayes factor of 11.27 in favor of the null hypothesis, opposed to a Bayes factor of 0.09 in favor of a treatment effect. Bayesian analysis is particularly valuable in this context of repeatedly reported small, non-significant effect sizes in individual trials. Mechanisms other than removal of Aβ from the brain may be probed to slow progression of Alzheimer's disease.

Delirium is a common serious complication in dementia that is associated with poor prognosis and a high burden on caregivers and healthcare professionals. Appropriate care is therefore important at an early stage for patients with delirium superimposed on dementia To gain insight into the care of six patients with delirium superimposed on dementia, 19 semi-structured interviews were conducted focused on the experiences of caregivers and professionals. The interviews revealed four themes that appeared to play a role: 1. experiences with and views on behavioral problems of these patients, 2. recognition and diagnosis of delirium in dementia, 3. views on good care and 4. organizational aspects. Knowledge gaps about delirium in dementia, as well as ethical considerations, play an important role in organizing timely and adequate care for patients with delirium superimposed on dementia.

ObjectiveHigh blood pressure is one of the main modifiable risk factors for dementia. However, there is conflicting evidence regarding the best antihypertensive class for optimizing cognition. Our objective was to determine whether any particular antihypertensive class was associated with a reduced risk of cognitive decline or dementia using comprehensive meta-analysis including reanalysis of original participant data.MethodsTo identify suitable studies, MEDLINE, Embase, and PsycINFO and preexisting study consortia were searched from inception to December 2017. Authors of prospective longitudinal human studies or trials of antihypertensives were contacted for data sharing and collaboration. Outcome measures were incident dementia or incident cognitive decline (classified using the reliable change index method). Data were separated into mid and late-life (>65 years) and each antihypertensive class was compared to no treatment and to treatment with other antihypertensives. Meta-analysis was used to synthesize data.ResultsOver 50,000 participants from 27 studies were included. Among those aged >65 years, with the exception of diuretics, we found no relationship by class with incident cognitive decline or dementia. Diuretic use was suggestive of benefit in some analyses but results were not consistent across follow-up time, comparator group, and outcome. Limited data precluded meaningful analyses in those ≤65 years of age.ConclusionOur findings, drawn from the current evidence base, support clinical freedom in the selection of antihypertensive regimens to achieve blood pressure goals.Clinical trials registrationThe review was registered with the international prospective register of systematic reviews (PROSPERO), registration number CRD42016045454.

Supplemental Digital Content is available in the text., Background. Several studies have reported improved cognitive outcomes after kidney transplantation, but most studies either did not include controls or lacked extensive neuroimaging. In addition, there is uncertainty whether kidney donation is a safe procedure in terms of cognitive outcomes. Methods. We prospectively studied neurocognitive function in kidney transplant recipients. The primary outcome was change in neurocognitive function after 1 year compared with baseline, which was evaluated using the Amsterdam Neuropsychological Task battery and verbal fluency tests. Secondary outcomes included changes in depression and anxiety (measured by the Hospital Anxiety and Depression scale) and changes in fatigue (measured by the Checklist for Individual Strength). We included kidney donors to control for learning effects, socioeconomic status, and surgery. In addition, kidney transplant recipients were evaluated with MRI scans at baseline and at year 1. The MRI protocol included conventional MRI, automated volumetric measurement, diffusion tensor imaging, magnetic resonance spectroscopy, arterial spin labeling, and a resting state functional MRI. Results. Twenty-seven recipients and 24 donors were included. For both recipients and donors, neuropsychologic testing scores improved 1 year after transplantation (donation). Recipient improvement significantly exceeded donor improvement on tasks measuring attention and working memory. These improvements were associated with increases in white matter volume and N-acetylaspartate/creatine (a marker for neuronal integrity). Conclusions. Attention and working memory improve significantly 1 year after kidney transplantation. Learning effects do not account for these improvements because recipient improvement in these areas exceeds donor improvement and correlates with an improvement in white matter integrity after transplantation. Kidney donation appears to be a safe procedure in terms of cognitive outcomes.

Background Research links blood pressure variability ( BPV ) with stroke; however, the association with cerebral small‐vessel disease ( CSVD ) remains unclear. As BPV and mean blood pressure are interrelated, it remains uncertain whether BPV adds additional information to understanding cerebrovascular morphological characteristics. Methods and Results A systematic review was performed from inception until March 3, 2019. Eligibility criteria included population, adults without stroke (BPV quantified by any metric over any duration; comparison, (1) low versus high or mean BPV and (2) people with versus without CSVD ; and outcomes, (1) CSVD as subcortical infarct, lacunae, white matter hyperintensities, cerebral microbleeds, or enlarged perivascular spaces; and (2) standardized mean difference in BPV . A total of 27 articles were meta‐analyzed, comprising 12 309 unique brain scans. A total of 31 odds ratios ( OR s) were pooled, indicating that higher systolic BPV was associated with higher odds for CSVD ( OR, 1.27; 95% CI, 1.14–1.42; I 2 =85%) independent of mean systolic pressure. Likewise, higher diastolic BPV was associated with higher odds for CSVD ( OR, 1.30; 95% CI, 1.14–1.48; I 2 =53%) independent of mean diastolic pressure. There was no evidence of a pairwise interaction between systolic/diastolic and BPV /mean OR s ( P =0.47), nor a difference between BPV versus mean pressure OR s ( P =0.58). Fifty‐four standardized mean differences were pooled and provided similar results for pairwise interaction ( P =0.38) and difference between standardized mean differences ( P =0.70). Conclusions On the basis of the available studies, BPV was associated with CSVD independent of mean blood pressure. However, more high‐quality longitudinal data are required to elucidate whether BPV contributes unique variance to CSVD morphological characteristics.

Introduction Older adults undergoing elective surgery have a high risk of developing postoperative delirium (POD). Validated models predicting POD are scarce. This study investigated whether preoperative impairment of attentional function predicts POD in older adults without previously diagnosed cognitive impairment. Methods In this prospective cohort study we recruited patients aged ≥70 years preceding major elective surgery. Preoperatively a visual vigilance test was administered to determine intra‐individual reaction‐time variability. Postoperatively, presence of delirium was screened daily. Results We recruited 152 patients, 25 (16.4%) developed POD. Intra‐individual reaction‐time variability was not significantly different between patients with or without POD (0.18 ± 0.08 ms vs 0.22 ± 0.11 ms; P = 0.087). Receiver operating characteristic analyses indicated a poor accuracy for POD (area under the curve 0.609 ± 0.63). Except for surgery duration, no clinically significant between‐group differences were found for secondary outcome parameters. Discussion Preoperative intra‐individual reaction time variability does not predict the incidence of POD in older patients undergoing major elective surgery.

Contains fulltext : 218833.pdf (Publisher’s version ) (Open Access) 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/m(2) ), the risk of all-cause dementia was higher among underweight individuals but lower among those with upper-normal (22.5-24.9 kg/m(2) ) 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.

Background High visit-to-visit variability (VVV) in blood pressure (BP) is associated with cerebrovascular lesions on neuroimaging. Objective Our primary objective was to investigate whether VVV is associated with incident all-cause dementia. As a secondary objective, we studied the association of VVV with cognitive decline and cardiovascular disease (CVD). Methods We included community-dwelling people (age 70-78 year) from the 'Prevention of Dementia by Intensive Vascular Care' (preDIVA) trial with three to five 2-yearly BP measurements during 6-8 years follow-up. VVV was defined using coefficient of variation (CV; SD/mean×100). Cognitive decline was assessed using the Mini-Mental State Examination (MMSE). Incident CVD was defined as myocardial infarction or stroke. We used a Cox proportional hazard regression and mixed-effects model adjusted for sociodemographic factors and cardiovascular risk factors. Results In 2,305 participants (aged 74.2±2.5), mean systolic BP over all available visits was 150.1 mmHg (SD 13.6), yielding a CV of 9.0. After 6.4 years (SD 0.8) follow-up, 110 (4.8%) participants developed dementia and 140 (6.1%) CVD. Higher VVV was not associated with increased risk of dementia (hazard ratio [HR] 1.00 per point CV increase; 95% confidence interval [CI] 0.96-1.05), although the highest quartile of VVV was associated with stronger decline in MMSE (β -0.09, 95% CI -0.17 to -0.01). Higher VVV was associated with incident CVD (HR 1.07; 95% CI 1.04-1.11). Conclusion In our study among older people, high VVV is not associated with incident all-cause dementia. It is associated with decline in MMSE and incident CVD.

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.

Contains fulltext : 238505.pdf (Publisher’s version ) (Open Access) OBJECTIVES: To systematically review and synthesize the evidence on differential associations between antihypertensive medication (AHM) classes and the risk of incident dementia. DESIGN: Systematic review and random effects frequentist network meta-analysis. Embase, MEDLINE, and the Cochrane library were searched from origin to December 2019. SETTING AND PARTICIPANTS: Randomized controlled trials (RCTs) and prospective cohort studies that compared associations of different AHM classes with incident all-cause dementia and/or Alzheimer's disease over at least 1 year of follow-up. MEASURES: All cause dementia and/or Alzheimer's disease. RESULTS: Fifteen observational studies and 7 RCTs were included. Data on AHM classes were available for 649,790 participants and dementia occurred in 19,600 (3.02%). Network meta-analysis showed that in observational studies, treatment with either calcium channel blockers (CCBs) or angiotensin II receptor blockers (ARBs) was associated with lower dementia risks than treatment with other antihypertensives: CCBs vs angiotensin converting enzyme inhibitors (ACE inhibitors) (HR=0.84, 95% CI 0.74-0.95), beta blockers (HR=0.83, 95% CI 0.73-0.95) and diuretics (HR=0.89, 95% CI 0.78-1.01) and ARBs vs ACE inhibitors (HR=0.88, 95% CI 0.81-0.97), beta blockers (HR=0.87, 95% CI 0.77-0.99), and diuretics (HR=0.93, 95% CI 0.83-1.05). There were insufficient RCTs to create a robust network based on randomized data alone. CONCLUSIONS AND IMPLICATIONS: Recommending CCBs or ARBs as preferred first-line antihypertensive treatment may significantly reduce the risk of dementia. If corroborated in a randomized setting, these findings reflect a low-cost and scalable opportunity to reduce dementia incidence worldwide.

Item does not contain fulltext OBJECTIVES: To explore and compare sociodemographic, clinical, and neuropsychiatric determinants of dropout and nonadherence in older people participating in an open-label cluster-randomized controlled trial-the Prevention of Dementia by Intensive Vascular care (preDIVA) trial-over 6 years. DESIGN: Secondary analysis. SETTING: One hundred sixteen general practices in the Netherlands. PARTICIPANTS: Community-dwelling individuals aged 70 to 78 (N = 2,994). INTERVENTION: Nurse-led multidomain intervention targeting cardiovascular risk factors to prevent dementia. MEASUREMENTS: The associations between participant baseline sociodemographic (age, sex, education), clinical (medical history, disability, cardiovascular risk), neuropsychiatric (depressive symptoms (Geriatric Depression Scale-15), and cognitive (Mini-Mental State Examination)) characteristics and dropout from the trial and nonadherence to the trial intervention were explored using multilevel logistic regression models. RESULTS: Older age, poorer cognitive function, more symptoms of depression, and greater disability were the most important determinants of dropout of older people. The presence of cardiovascular risk factors was not associated with dropout but was associated with nonadherence. Being overweight was a risk factor for nonadherence, whereas people with high blood pressure or a low level of physical exercise adhered better to the intervention. The association between poorer cognitive function and symptoms of depression and dropout was stronger in the control group than in the intervention group, and vice versa for increased disability. CONCLUSION: In a large dementia prevention trial with 6-year follow-up, dropout was associated with older age, poorer cognitive function, symptoms of depression, and disability at baseline. These findings can help to guide the design of future dementia prevention trials in older adults. The associations found between cardiovascular risk factors and nonadherence need to be confirmed in other older populations receiving cardiovascular prevention interventions.

Background and Purpose— This study aimed to evaluate the effect of a nurse-led multidomain cardiovascular intervention on white matter hyperintensity (WMH) progression and incident lacunar infarcts in community-dwelling elderly with hypertension. Methods— The preDIVA trial (Prevention of Dementia by Intensive Vascular Care) was an open-label, cluster-randomized controlled trial in community-dwelling individuals aged 70 to 78 years. General practices were assigned by computer-generated randomization to 6-year nurse-led, multidomain intensive vascular care or standard care. Of 3526 preDIVA participants, 195 nondemented participants with a systolic blood pressure ≥140 mm Hg were consecutively recruited to undergo magnetic resonance imaging at 2 to 3 and 5 to 6 years after baseline. WMH volumes were measured automatically, lacunar infarcts assessed visually, blinded to treatment allocation. Results— One hundred and twenty-six participants were available for longitudinal analysis (64 intervention and 62 control). Annual WMH volume increase in milliliter was similar for intervention (mean=0.73, SD=0.84) and control (mean=0.70, SD=0.59) participants (adjusted mean difference, −0.08 mL; 95% confidence interval, −0.30 to 0.15; P =0.50). Analyses suggested greater intervention effects with increasing baseline WMH volumes ( P for interaction=0.03). New lacunar infarcts developed in 6 (9%) intervention and 2 (3%) control participants (odds ratio, 2.2; 95% confidence interval, 0.4–12.1; P =0.36). Conclusions— Nurse-led vascular care in hypertensive community-dwelling older persons did not diminish WMH accumulation over 3 years. However, our results do suggest this type of intervention could be effective in persons with high WMH volumes. There was no effect on lacunar infarcts incidence but numbers were low. Clinical Trial Information— URL: http://www.isrctn.com/ISRCTN29711771 . Unique identifier: ISRCTN29711771.

Item does not contain fulltext OBJECTIVE: Use of antihypertensive medication (AHM) is potentially associated with a reduced risk of dementia. Both calcium channel blockers (CCBs) and angiotensin receptor blockers (ARBs) are suggested to have a more pronounced protective effect. We aimed to study the association between different classes of AHM and dementia in older people. METHODS: A subgroup of community-dwelling older people using AHM included in the 'Prevention of Dementia by Intensive Vascular Care' randomized controlled trial was studied. Incident dementia rates in participants with different AHM classes (mono and combination therapy) were compared with dementia rates in participants with any other AHM. RESULTS: At baseline, 1951 participants (55.3%) used AHM [mean age, 74.4 year (SD 2.5); mean SBP, 156.4 mmHg (SD 21.5)]. In total, 986 participants (50.5%) used beta-blockers, 798 diuretics (40.9%), 623 angiotensin- converting enzyme inhibitors (31.9%), 522 CCBs (26.8%), and 402 ARBs (20.6%). After 6.7 years (interquartile range 6.0-7.3) of follow-up, 136 participants (7.0%) developed dementia. Both use of CCBs [hazard ratio 0.56, 95% confidence interval (95% CI) 0.36-0.87] and ARBs (hazard ratio 0.60, 95% CI 0.37-0.98) were independently associated with a decreased risk of dementia. The association of CCBs with dementia was most apparent in participants without a history of cardiovascular disease (hazard ratio 0.38, 95% CI 0.18-0.81) and with uncontrolled hypertension (hazard ratio 0.26, 95% CI 0.11-0.61). SBP was not significantly lower in participants using CCBs or ARBs. CONCLUSION: Both use of CCBs and ARBs are independently associated with a decreased risk of dementia in older people.

Inleiding De vaak gebruikte Mini-Mental State Examination (MMSE) is weinig sensitief voor het herkennen van vroege symptomen van dementie. Mogelijk kan het toevoegen van de korte Visual Association Test (VAT) de voorspellende waarde van de MMSE voor dementie verbeteren. Methode De onderzoekers analyseerden gegevens van 2690 deelnemers (70 tot 78 jaar) uit het preDIVA-onderzoek. Ze keken hoe MMSE-scores na twee jaar waren veranderd en wat de aanvullende waarde is van de VAT (zes associatieplaatjes), gescoord als perfect of imperfect. Met logistische regressie analyseerden ze de voorspellende waarde van deze tests voor de diagnose dementie in de daaropvolgende vier tot zes jaar. Resultaten Deelnemers met een daling van 2 MMSE-punten of meer hadden een oddsratio (OR) van 3,6 (95%-BI 2,5 tot 5,0) voor het ontwikkelen van dementie. Bij deelnemers die ook een imperfecte VAT hadden, steeg de OR naar 9,6 (95%-BI 5,9 tot 15,4). Bij de combinatie van een daling van 2 tot 3 punten op de MMSE en een perfecte VAT was het risico op dementie niet verhoogd. Conclusie De VAT geeft een substantiele verbetering van de voorspellende waarde van een kleine daling op de MMSE voor dementie. Deze eenvoudige test kan de huisarts helpen om onderscheid te maken tussen ouderen van wie de cognitieve vermogens extra aandacht behoeven en degenen bij wie geruststelling voldoet.

Objectives Visit-to-visit blood pressure (BP) variability is a risk factor for cardiovascular disease and cognitive decline. Our aim was to assess the association between visit-to-visit BP variability and progression of white matter hyperintensities (WMH). Design Post-hoc analysis in the magnetic resonance imaging substudy of the randomized controlled trial prevention of dementia by intensive vascular care. Setting and participants Community-dwelling people age 70–78 years with hypertension. Methods Participants had 3 to 5 twice yearly BP measurements and 2 magnetic resonance imaging scans at 3 and 6 years follow-up. We used linear regression adjusted for age, sex, WMH at scan 1, (change in) total brain volume, and cardiovascular risk factors. Results Among the 122 participants, there was a modest association between visit-to-visit systolic BP variability and WMH progression [beta = 0.03 mL/y per point increase in variability, 95% confidence interval (CI) 0.00–0.05, P = .058]. Additional adjustment for slope in systolic BP reduced the associated P value to .043. Visit-to-visit diastolic BP variability was not associated with WMH progression (beta = 0.01 mL/y, 95% CI −0.02 to 0.03, P = .68). Visit-to-visit pulse pressure variability was associated with WMH progression (beta 0.03 mL/y, 95% CI 0.01–0.05, P Conclusions Higher visit-to-visit systolic BP and pulse pressure variability is associated with more progression of WMH among people age 70–78 years with hypertension. Implications Interventions to reduce visit-to-visit BP variability may be most effective in people with low WMH burden.

Contains fulltext : 209022.pdf (Publisher’s version ) (Open Access) 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.

Contains fulltext : 215579.pdf (Publisher’s version ) (Closed access) PURPOSE: Family physicians need simple yet comprehensive algorithms to discriminate between community-dwelling older persons who are at increased risk of dementia and those who are not. We aimed to investigate associations between incident dementia and responses to a single question regarding subjective memory complaints (SMC) combined with scores on 2 simple memory tests that are easy to use in the primary care setting. METHODS: Analyses were based on data from 3,454 community-dwelling older persons who participated in the 6- to 8-year Prevention of Dementia by Intensive Vascular Care (preDIVA) trial, yielding 21,341 person-years of observation. Participants were considered a single cohort. We used Cox models to assess separate and combined associations of SMC, an imperfect score on the Mini-Mental State Examination delayed recall item (MMSE-5), and an imperfect score on the Visual Association Test (VAT) with future dementia. RESULTS: Subjective memory complaints alone were associated with future dementia (hazard ratio [HR] = 3.01; 95% CI, 2.31-3.94; P