Safety and efficacy of active blood-pressure reduction to the recommended thresholds for intravenous thrombolysis in patients with acute ischaemic stroke in the Netherlands (TRUTH): a prospective, observational, cluster-based, parallel-group study.

BACKGROUND: Intravenous thrombolysis is contraindicated in patients with ischaemic stroke with blood pressure higher than 185/110 mm Hg. Prevailing guidelines recommend to actively lower blood pressure with intravenous antihypertensive agents to allow for thrombolysis; however, there is no robust evidence for this strategy. Because rapid declines in blood pressure can also adversely affect clinical outcomes, several Dutch stroke centres use a conservative strategy that does not involve the reduction of blood pressure. We aimed to compare the clinical outcomes of both strategies. METHODS: Thrombolysis and Uncontrolled Hypertension (TRUTH) was a prospective, observational, cluster-based, parallel-group study conducted across 37 stroke centres in the Netherlands. Participating centres had to strictly adhere to an active blood-pressure-lowering strategy or to a non-lowering strategy. Eligible participants were adults (≥18 years) with ischaemic stroke who had blood pressure higher than 185/110 mm Hg but were otherwise eligible for intravenous thrombolysis. The primary outcome was functional status at 90 days, measured using the modified Rankin Scale and assessed through telephone interviews by trained research nurses. Secondary outcomes were symptomatic intracranial haemorrhage, the proportion of patients treated with intravenous thrombolysis, and door-to-needle time. All ordinal logistic regression analyses were adjusted for age, sex, stroke severity, endovascular thrombectomy, and baseline imbalances as fixed-effect variables and centre as a random-effect variable to account for the clustered design. Analyses were done according to the intention-to-treat principle, whereby all patients were analysed according to the treatment strategy of the participating centre at which they were treated. FINDINGS: Recruitment began on Jan 1, 2015, and was prematurely halted because of a declining inclusion rate and insufficient funding on Jan 5, 2022. Between these dates, we recruited 853 patients from 27 centres that followed an active blood-pressure-lowering strategy and 199 patients from ten centres that followed a non-lowering strategy. Baseline characteristics of participants from the two groups were similar. The 90-day mRS score was missing for 15 patients. The adjusted odds ratio (aOR) for a shift towards a worse 90-day functional outcome was 1·27 (95% CI 0·96-1·68) for active blood-pressure reduction compared with no active blood-pressure reduction. 798 (94%) of 853 patients in the active blood-pressure-lowering group were treated with intravenous thrombolysis, with a median door-to-needle time of 35 min (IQR 25-52), compared with 104 (52%) of 199 patients treated in the non-lowering group with a median time of 47 min (29-78). 42 (5%) of 852 patients in the active blood-pressure-lowering group had a symptomatic intracranial haemorrhage compared with six (3%) of 199 of those in the non-lowering group (aOR 1·28 [95% CI 0·62-2·62]). INTERPRETATION: Insufficient evidence was available to establish a difference between an active blood-pressure-lowering strategy-in which antihypertensive agents were administered to reduce blood pressure below 185/110 mm Hg-and a non-lowering strategy for the functional outcomes of patients with ischaemic stroke, despite higher intravenous thrombolysis rates and shorter door-to-needle times among those in the active blood-pressure-lowering group. Randomised controlled trials are needed to inform the use of an active blood-pressure-lowering strategy. FUNDING: Fonds NutsOhra.

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 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.

The Association of Ancillary Diagnostic Tests With Outcome in Dementia.

OBJECTIVES: Dementia is a clinical diagnosis without curative treatment. It is uncertain whether ancillary testing is beneficial for patients. This study investigates the association between use of diagnostic tests and time to poor outcome and health care costs. DESIGN: Nationwide register-based cohort study using health care reimbursement data in the Netherlands. SETTING AND PARTICIPANTS: All Dutch hospitals, including 13,312 patients diagnosed with dementia in 2018. METHODS: Diagnostic testing included computed tomography or magnetic resonance imaging (CT/MRI), neuropsychological examination (NPE), nuclear imaging (PET/SPECT), electroencephalography (EEG), and cerebrospinal fluid (CSF) testing. We compared time to poor outcome (institutionalization or death) and costs per month from 2018 to 2021 between those who underwent a specific diagnostic test in previous years to controls, propensity score matched for age, sex, type of hospital, and comorbidity. RESULTS: Time to poor outcome in those who underwent CT/MRI, EEG, or CSF testing was similar to those who did not, but was longer for those who underwent NPE. Time to poor outcome was shorter in patients who underwent PET/SPECT. Patients who underwent CSF testing or PET/SPECT had higher mean total health care costs as compared to controls (CSF €248, 95% CI 64-433; PET/SPECT: €315, 95% CI 179-451). NPE during the diagnostic trajectory was associated with lower total health care cost (-€127, 95% CI -62, -193). CONCLUSION AND IMPLICATIONS: NPE was associated with longer time to poor outcome and lower health care costs, potentially due to confounding by indication. Patients who underwent neuroimaging (CT, MRI, SPECT/PET), CSF testing, or EEG for dementia diagnostics did not experience a longer time to poor outcome or lower health care costs. This emphasizes the importance of clinical examination as anchor for the diagnosis of dementia.

Visit-to-visit blood pressure variability and progression of white matter hyperintensities over 14 years.

Purpose: There is evidence that blood pressure variability (BPV) is associated with cerebral small vessel disease (SVD) and may therefore increase the risk of stroke and dementia. It remains unclear if BPV is associated with SVD progression over years. We examined whether visit-to-visit BPV is associated with white matter hyperintensity (WMH) progression over 14 years and MRI markers after 14 years.Materials and methods: We included participants with SVD from the Radboud University Nijmegen Diffusion tensor Magnetic resonance-imaging Cohort (RUNDMC) who underwent baseline assessment in 2006 and follow-up in 2011, 2015 and 2020. BPV was calculated as coefficient of variation (CV) of BP at all visits. Association between WMH progression rates over 14 years and BPV was examined using linear-mixed effects (LME) model. Regression models were used to examine association between BPV and MRI markers at final visit in participants.Results: A total of 199 participants (60.5 SD 6.6 years) who underwent four MRI scans and BP measurements were included, with mean follow-up of 13.7 (SD 0.5) years. Systolic BPV was associated with higher progression of WMH (ß = 0.013, 95% CI 0.005 - 0.022) and higher risk of incident lacunes (OR: 1.10, 95% CI 1.01-1.21). There was no association between systolic BPV and grey and white matter volumes, Peak Skeleton of Mean Diffusivity (PSMD) or microbleed count after 13.7 years.Conclusions: Visit-to-visit systolic BPV is associated with increased progression of WMH volumes and higher risk of incident lacunes over 14 years in participants with SVD. Future studies are needed to examine causality of this association.

High blood pressure (BP) is very common, especially among older individuals. BP is not constant but tends to go up and down over time.Earlier studies have shown that when your BP fluctuates more, this can give a higher risk of dementia, stroke, cardiovascular events and even mortality. Large BP fluctuations are likely damaging for your brain, but it remains unknown if it leads to progression of brain damage over a longer period of time.This study examined if fluctuations in BP over 14 years are associated with progression of brain damage in older individuals with a mean age of 60.5 years.The results indicate that markers of brain damage progress more in participants with more variation in BP.This suggests that fluctuations in BP can cause damage in your brain to progress more.However, it is difficult to determine based on these results if BP fluctuations are a cause or a result of brain damage. More research is needed to determine what the temporal order of this association is.If variations in BP can indeed damage the brain, we need to focus not only on lowering BP, but also on keeping BP stable when considering treatments.

Blood pressure variability and white matter hyperintensities after ischemic stroke.

Background: High blood pressure variability (BPV) may be a risk factor for stroke and dementia in patients with ischemic stroke, but the underlying mechanism is unknown. We aimed to investigate whether high BPV is associated with presence and progression of white matter hyperintensities (WMH). Methods: We performed a post-hoc analysis on the MRI substudy of the PRoFESS trial, including 771 patients with ischemic stroke who underwent MRI at baseline and after a median of 2.1 years. WMH were rated with a semi-quantitative scale. Visit-to-visit BPV was expressed as the coefficient of variation (interval 3-6 months, median number of visits 7). The association of BPV with WMH burden and progression was assessed with linear and logistic regression analyses adjusted for confounders. Results: BPV was associated with burden of periventricular WMH (ß 0.36 95%CI 0.19-0.53, per one SD increase in BPV) and subcortical (log-transformed) WMH (ß 0.25, 95%CI 0.08-0.42). BPV was not associated with periventricular (OR 1.09, 95%CI 0.94-1.27) and subcortical WMH progression (OR 1.15, 95%CI 0.99-1.35). Associations were independent of mean BP. Conclusion: High visit-to-visit BPV was associated with both subcortical and periventricular WMH burden in patients with ischemic stroke, but not with WMH progression in this study.

Apathy Symptoms, Physical and Cognitive Function, Health-Related Quality of Life, and Mortality in Older Patients With CKD: A Longitudinal Observational Study.

RATIONALE & OBJECTIVE: Apathy reflects diminished motivation, goal-directed behavior, and emotions, as well as less engagement in social interactions. Apathy overlaps with depression and is associated with cognitive decline. In the older individuals with chronic kidney disease (CKD), both depression and cognitive impairments are common, but apathy symptoms have been underreported. We investigated the occurrence of apathy symptoms and their associations with physical and cognitive functioning, health-related quality of life (HRQoL), and mortality in older patients with CKD. STUDY DESIGN: Prospective observational cohort study. SETTING & PARTICIPANTS: 180 outpatients aged≥65 years with estimated glomerular filtration rate≤20mL/min/1.73m2 from 5 Dutch nephrology centers. EXPOSURE: Apathy symptoms at baseline were considered present when a Geriatric Depression Scale's 3-item apathy subscale score was≥2 points. OUTCOME: Physical and cognitive functioning, HRQoL (assessed in annual geriatric assessments), and 4-year mortality. ANALYTICAL APPROACH: Linear regression for cross-sectional associations, linear regression models for longitudinal associations, and Cox regression models for mortality over 4 years of observation. RESULTS: Apathy symptoms were present in 64 patients (36%; 67% men; median age 75.5 years), of whom 32 (50%) had no depressive symptoms. At baseline, the presence of apathy symptoms was associated with significantly more frailty, more functional dependence, less physical capacity, lower visuoconstructive performance, worse delayed recall, and lower HRQoL scores. The presence of apathy symptoms at baseline was also associated with a higher mortality risk (hazard ratio, 2.3 [95% CI, 1.3-4.2], P=0.005 adjusted for age, sex, and high education level), but not with changes in physical and cognitive functioning or HRQoL during the follow-up period. LIMITATIONS: Risk of selection bias and residual confounding. CONCLUSIONS: Apathy symptoms were highly prevalent and associated with concurrent lower physical and cognitive status, lower HRQoL, and increased mortality. These findings highlight apathy as a potentially important clinical phenotype in older CKD patients. PLAIN-LANGUAGE SUMMARY: We observed that older kidney patients often present apathy symptoms, such as less motivation, fewer goal-directed behaviors, fewer emotions, and less social engagement. Prior research has not extensively described apathy in kidney disease. We investigated the link between apathy symptoms and poor outcomes. We measured physical functioning, cognitive functioning, and quality of life. We learned that one-third of our older kidney patients showed symptoms of apathy, only half of whom had symptoms of depression. Patients with apathy symptoms showed lower quality of life and lower physical and cognitive performance. They also had a higher risk of death. These findings highlight the need for awareness of apathy symptoms in older kidney patients.

Evaluation of clinical benefits of treatments for Alzheimer's disease.

The need for regulatory approval of new therapies for the treatment of Alzheimer's disease-a progressive neurodegenerative condition-has made the assessment of treatment efficacy an urgent priority for discussion and investigation in the field. In the first part of this Personal View, we summarise current views on what constitutes a clinically meaningful benefit from treatment for Alzheimer's disease, including the concept of a minimum treatment effect against which to compare trial outcomes and its limitations. Considering existing and divergent definitions of clinically meaningful change, we define this concept in the second part of the Personal View by proposing a new approach that consecutively considers whether a treatment benefit for Alzheimer's disease is noticeable, valuable, and worthwhile in the context of costs and risks. This approach could be a useful foundation from which the field can move forwards on this issue and address existing gaps in understanding.

Year-by-Year Blood Pressure Variability From Midlife to Death and Lifetime Dementia Risk.

Importance: High visit-to-visit blood pressure variability (BPV) in late life may reflect increased dementia risk better than mean systolic blood pressure (SBP). Evidence from midlife to late life could be crucial to understanding this association. Objective: To determine whether visit-to-visit BPV at different ages was differentially associated with lifetime incident dementia risk in community-dwelling individuals. Design, Setting, and Participants: This cohort study analyzed data from the Adult Changes in Thought (ACT) study, an ongoing population-based prospective cohort study in the US. Participants were 65 years or older at enrollment, community-dwelling, and without dementia. The study focused on a subset of deceased participants with brain autopsy data and whose midlife to late-life blood pressure data were obtained from Kaiser Permanente Washington medical archives and collected as part of the postmortem brain donation program. In the ACT study, participants underwent biennial medical assessments, including cognitive screening. Data were collected from 1994 (ACT study enrollment) through November 2019 (data set freeze). Data analysis was performed between March 2020 and September 2023. Exposures: Visit-by-visit BPV at ages 60, 70, 80, and 90 years, calculated using the coefficient of variation of year-by-year SBP measurements over the preceding 10 years. Main Outcomes and Measures: All-cause dementia, which was adjudicated by a multidisciplinary outcome adjudication committee. Results: A total of 820 participants (mean [SD] age at enrollment, 77.0 [6.7] years) were analyzed and included 476 females (58.0%). A mean (SD) of 28.4 (8.4) yearly SBP measurements were available over 31.5 (9.0) years. The mean (SD) follow-up time was 32.2 (9.1) years in 27 885 person-years from midlife to death. Of the participants, 372 (45.4%) developed dementia. The number of participants who were alive without dementia and had available data for analysis ranged from 280 of those aged 90 years to 702 of those aged 70 years. Higher BPV was not associated with higher lifetime dementia risk at age 60, 70, or 80 years. At age 90 years, BPV was associated with 35% higher dementia risk (hazard ratio [HR], 1.35; 95% CI, 1.02-1.79). Meta-regression of HRs calculated separately for each age (60-90 years) indicated that associations of high BPV with higher dementia risk were present only at older ages, whereas the association of SBP with dementia gradually shifted direction linearly from being incrementally to inversely associated with older ages. Conclusions and Relevance: In this cohort study, high BPV indicated increased lifetime dementia risk in late life but not in midlife. This result suggests that high BPV may indicate increased dementia risk in older age but might be less viable as a midlife dementia prevention target.

Assessing the Effectiveness of mHealth Interventions for Diabetes and Hypertension Management in Africa: Systematic Review and Meta-Analysis.

Background: Mobile health (mHealth) interventions are effective in improving chronic disease management, mainly in high-income countries. However, less is known about the efficacy of mHealth interventions for the reduction of cardiovascular risk factors, including for hypertension and diabetes, which are rapidly increasing in low- and middle-income countries. Objective: This study aimed to assess the efficacy of mHealth interventions for diabetes and hypertension management in Africa. Methods: We searched PubMed, Cochrane Library, Google Scholar, African Journals Online, and Web of Science for relevant studies published from inception to July 2022. The main outcomes of interest were changes in hemoglobin A1c (HbA1c), systolic blood pressure, and diastolic blood pressure. The random or fixed effect model was used for the meta-analysis, and the I2 statistic was used to gauge study heterogeneity. Z tests and P values were used to evaluate the effect of mHealth interventions on HbA1c and blood pressure levels. Results: This review included 7 studies (randomized controlled trials) with a total of 2249 participants. Two studies assessed the effect of mHealth on glycemic control, and 5 studies assessed the effect of mHealth on blood pressure control. The use of mHealth interventions was not associated with significant reductions in HbA1c levels (weighted mean difference [WMD] 0.20, 95% CI -0.40 to 0.80; P=.51) among patients with diabetes and systolic blood pressure (WMD -1.39, 95% CI -4.46 to 1.68; P=.37) and diastolic blood pressure (WMD 0.36, 95% CI -1.37 to 2.05; P=.69) among patients with hypertension. After conducting sensitivity analyses using the leave-one-out method, the Kingue et al study had an impact on the intervention, resulting in a 2 mm Hg reduction in systolic blood pressure (WMD -2.22, 95% CI -3.94 to -0.60; P=.01) but was nonsignificant for diastolic blood pressure and HbA1c levels after omitting the study. Conclusions: Our review provided no conclusive evidence for the effectiveness of mHealth interventions in reducing blood pressure and glycemic control in Africa among persons with diabetes and hypertension. To confirm these findings, larger randomized controlled trials are required.

The effect of cardiovascular risk on disease progression in de novo Parkinson's disease patients: An observational analysis.

Background: Currently available treatment options for Parkinson's disease are symptomatic and do not alter the course of the disease. Recent studies have raised the possibility that cardiovascular risk management may slow the progression of the disease. Objectives: We estimated the effect of baseline cardiovascular risk factors on the progression of Parkinson's disease, using measures for PD-specific motor signs and cognitive functions. Methods: We used data from 424 de novo Parkinson's disease patients and 199 age-matched controls from the observational, multicenter Parkinson's Progression Markers Initiative (PPMI) study, which included follow-up of up to 9 years. The primary outcome was the severity of PD-specific motor signs, assessed with the MDS-UPDRS part III in the "OFF"-state. The secondary outcome was cognitive function, measured with the Montreal Cognitive Assessment, Symbol Digit Modalities Test, and Letter-Number Sequencing task. Exposures of interest were diabetes mellitus, hypertension, body mass index, cardiovascular event history and hypercholesterolemia, and a modified Framingham risk score, measured at baseline. The effect of each of these exposures on disease progression was modeled using linear mixed models, including adjustment for identified confounders. A secondary analysis on the Tracking Parkinson's cohort including 1,841 patients was performed to validate our findings in an independent patient cohort. Results: Mean age was 61.4 years, and the average follow-up was 5.5 years. We found no statistically significant effect of any individual cardiovascular risk factor on the MDS-UPDRS part III progression (all 95% confidence intervals (CIs) included zero), with one exception: in the PD group, the estimated effect of a one-point increase in body mass index was 0.059 points on the MDS-UPDRS part III per year (95% CI: 0.017 to 0.102). We found no evidence for an effect of any of the exposures on the rate of change in cognitive functioning in the PD group. Similar results were observed for the Tracking Parkinson's cohort (all 95% CIs overlapped with PPMI), but the 95% CI of the effect of body mass index on the MDS-UPDRS part III progression included zero. Conclusions: Based on this analysis of two large cohorts of de novo PD patients, we found no evidence to support clinically relevant effects of cardiovascular risk factors on the clinical progression of Parkinson's disease.

Effect of long-term antihypertensive treatment on cerebrovascular structure and function in hypertensive rats.

Midlife hypertension is an important risk factor for cognitive impairment and dementia, including Alzheimer's disease. We investigated the effects of long-term treatment with two classes of antihypertensive drugs to determine whether diverging mechanisms of blood pressure lowering impact the brain differently. Spontaneously hypertensive rats (SHR) were either left untreated or treated with a calcium channel blocker (amlodipine) or beta blocker (atenolol) until one year of age. The normotensive Wistar Kyoto rat (WKY) was used as a reference group. Both drugs lowered blood pressure equally, while only atenolol decreased heart rate. Cerebrovascular resistance was increased in SHR, which was prevented by amlodipine but not atenolol. SHR showed a larger carotid artery diameter with impaired pulsatility, which was prevented by atenolol. Cerebral arteries demonstrated inward remodelling, stiffening and endothelial dysfunction in SHR. Both treatments similarly improved these parameters. MRI revealed that SHR have smaller brains with enlarged ventricles. In addition, neurofilament light levels were increased in cerebrospinal fluid of SHR. However, neither treatment affected these parameters. In conclusion, amlodipine and atenolol both lower blood pressure, but elicit a different hemodynamic profile. Both medications improve cerebral artery structure and function, but neither drug prevented indices of brain damage in this model of hypertension.

General practitioners' views on cardiovascular prevention for ethnic minorities-a qualitative study in the Netherlands.

OBJECTIVES: While ethnic minorities in Europe are disproportionally affected by cardiovascular disease (CVD), little is known about how general practitioners (GPs) perceive differences in risk or care needs across ethnic minority groups. Therefore, we explored GPs' views on whether ethnicity influences cardiovascular risk, whether a culturally sensitive approach is warranted, on potential barriers in the provision of such care, and to find potential opportunities to improve cardiovascular prevention for these groups. METHODS: We conducted a qualitative study by interviewing GPs practising in The Netherlands. The interviews were semistructured, audio-recorded, and analysed by 2 researchers using thematic analysis. RESULTS: We interviewed 24 Dutch GPs (50% male). GPs' views on the impact of ethnicity on CVD risk varied widely, yet it was generally recognized as a relevant factor in cardiovascular prevention for most minority groups, prompting earlier case-finding of high-risk patients. While GPs were aware of sociocultural differences, they emphasized an individualized approach. Perceived limitations were language barriers and unfamiliarity with sociocultural customs, leading to a need for continuing medical education on culturally sensitive care and reimbursement of telephone interpreting services. CONCLUSION: Dutch GPs have differing views on the role of ethnicity in evaluating and treating cardiovascular risk. Despite these differences, they emphasized the importance of a personalized and culturally sensitive approach during patient consultations and expressed a need for continuing medical education. Additional research on how ethnicity influences CVD risk may strengthen cardiovascular prevention in increasingly diverse primary care populations.

The challenge of dementia prevention trials and the role of quasi-experimental studies.

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.

[Which blood pressure target for the frail older patient?] / Welke bloeddruk bij kwetsbare oudere patiënten?

Recent guidelines, including the ESC, have moved towards lower targets (<140 mmHg, 130 if tolerated systolic, < 80 mmHg diastolic) for antihypertensive treatment in older adults. The evidence for clinically relevant benefit against limited risk of side effects applies to relatively fit older adults, representing less than 30 % of older patients in clinical practice. We discuss that formal evidence of treatment benefit for frail older adults is absent, although there is limited evidence that this benefit is similar for frail and non-frail participants in clinical trials (e.g. SPRINT). On the other hand, we discuss that the evidence for harm associated with antihypertensive treatment in frail older adults is weak when critically appraised. This applies to the risk of cerebral hypoperfusion, orthostatic hypotension, coronary hypoperfusion, and renal hypoperfusion. The frequently cited J-curve reflects patient characteristics, but is not evidence of harm induced by treatment-induced blood pressure lowering. In this context of absent solid evidence for both benefit and harm, we provide practical treatment advice for hypertension in frail older adults.

What would a population-level approach to dementia risk reduction look like, and how would it work?

Dementia is a leading global public health challenge. Prevention approaches have traditionally focused on individual-level strategies. However, such approaches have limited potential, particularly for resource-constrained populations in which exposure to risk factors is greatest, and exposure to protective factors is lowest. A population-level approach to dementia risk reduction is therefore essential to meet the scale of the challenge and to tackle global inequalities in risk and incidence of disease. Such approaches can be highly cost effective. In this viewpoint article, we describe what such an approach should look like, barriers and facilitators to success, and how we should go about achieving it. We include 10 strategic goals to achieve population-level dementia risk reduction and protection enhancement, targeted at researchers, professionals, funders, science communicators, governments, businesses, and policy makers. If we are to significantly reduce the prevalence of dementia there must be increased emphasis on population-level approaches. HIGHLIGHTS: Dementia risk reduction is a global public health priority Population-level approaches change societal conditions to make them less conducive to dementia's modifiable risk factors, and increase exposure to protective factors. Urgent development of population-level approaches is required to reduce the prevalence of, and inequalities in, dementia Action is required from researchers, governments and business, funders, public health professionals, and science communicators.

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.