Effect of Antihypertensive Medication on Cerebral Small Vessel Disease: A Systematic Review and Meta-Analysis.

BACKGROUND AND PURPOSE: Hypertension is an important risk factor for cerebral small vessel disease. We aimed to study the effect of antihypertensive medication (AHM) on the progression of cerebral small vessel disease. METHODS: We performed a systematic literature search of electronic databases up to January 30, 2017, for randomized controlled trials on the effect of AHM on ≥1 cerebral small vessel disease magnetic resonance imaging markers (ie, white matter hyperintensities, lacunes, microbleeds, enlarged perivascular spaces, acute small subcortical infarcts, and brain atrophy) after ≥1 year. We performed a random-effects meta-analysis using standardized mean difference. RESULTS: We included 4 trials, including patients with stroke, with diabetes mellitus, and people ≥70 years of age. Patients in the AHM group had less progression of white matter hyperintensity during 28 to 47 months (standardized mean difference, -0.19; 95% confidence interval, -0.32 to -0.06; I2=20%; n=1369). Two trials reported on progression of brain atrophy with conflicting results. None of the trials reported on other cerebral small vessel disease markers. CONCLUSIONS: AHM has a protective effect on the progression of white matter hyperintensities, but no effect on brain atrophy. There are no trials on the effect of AHM on lacunes, microbleeds, enlarged perivascular spaces, or acute small subcortical infarcts.

Development and Validation of an Interactive Internet Platform for Older People: The Healthy Ageing Through Internet Counselling in the Elderly Study.

BACKGROUND: A myriad of Web-based applications on self-management have been developed, but few focus on older people. In the face of global aging, older people form an important target population for cardiovascular prevention. This article describes the full development of an interactive Internet platform for older people, which was designed for the Healthy Ageing Through Internet Counselling in the Elderly (HATICE) study. We provide recommendations to design senior-friendly Web-based applications for a new approach to multicomponent cardiovascular prevention. METHODS: The development of the platform followed five phases: (1) conceptual framework; (2) platform concept and functional design; (3) platform building (software and content); (4) testing and pilot study; and (5) final product. RESULTS: We performed a meta-analysis, reviewed guidelines for cardiovascular diseases, and consulted end users, experts, and software developers to create the platform concept and content. The software was built in iterative cycles. In the pilot study, 41 people aged ≥65 years used the platform for 8 weeks. Participants used the interactive features of the platform and appreciated the coach support. During all phases adjustments were made to incorporate all improvements from the previous phases. The final platform is a personal, secured, and interactive platform supported by a coach. DISCUSSION: When carefully designed, an interactive Internet platform is acceptable and feasible for use by older people with basic computer skills. To improve acceptability by older people, we recommend involving the end users in the process of development, to personalize the platform and to combine the application with human support. The interactive HATICE platform will be tested for efficacy in a multinational randomized controlled trial (ISRCTN48151589).

Quality of life after surgical decompression for a space-occupying middle cerebral artery infarct: A cohort study.

BACKGROUND: In patients with a space-occupying middle cerebral artery (MCA) infarct surgical decompression reduces the risk of death, but increases the chance of survival with severe disability. We assessed quality of life (QoL), symptoms of depression, and caregiver burden at long-term follow-up. METHODS: Patients treated in two academic centres between 2007 and 2012 were included. Follow-up was at least six months. Patients and caregivers were interviewed separately. QoL was assessed with a visual analogue scale and the 36-item Short-Form health survey (SF-36); depression with the Hospital Anxiety and Depression Scale; and caregiver burden with the Caregiver Strain Index. RESULTS: Twenty five patients were enrolled, of whom seven had an infarct in the dominant hemisphere. After a median follow-up of 26 months (IQR 11-46) the median SF-36 mental component score was 54.4 (IQR 45-60), indicating a mental QoL comparable to that in the general population. The median SF-36 physical component score was 32.7 (IQR 22-38), indicating a worse physical QoL. Dominance of the hemisphere did not influence QoL. 79 % of patients and 65 % of caregivers would, in retrospect, again choose for surgery. 26 % of patients had signs of depression and 64 % of caregivers were substantially burdened in their daily life. CONCLUSIONS: Mental QoL after surgical decompression for space-occupying MCA infarct is comparable to that in the general population, whereas physical QoL is worse. Dominance of the hemisphere did not influence QoL. The majority of caregivers experience substantial burden. Most patients and caregivers stand by their decision for hemicraniectomy.

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.

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.

Patients' view on gene therapy development for lysosomal storage disorders: a qualitative study.

INTRODUCTION: Several new treatment modalities are being developed for lysosomal storage disorders (LSDs), including gene therapy. As the currently available treatment options and their influence on disease progression differ greatly within the spectrum of LSDs, willingness to undergo gene therapy might vary among patients with LSDs and/or their representatives. The width of the LSD spectrum is illustrated by the differences between type 1 Gaucher disease, Fabry disease and Mucopolysaccharidosis type III (MPS III). For type 1 Gaucher and Fabry disease several therapies are available, resulting in a near normal or improved, but individually varying, prognosis. No treatment options are available for MPS III. AIM: To identify factors influencing patients' and/or their representatives' decisions regarding undergoing gene therapy. METHODS: Focus group discussions and semi-structured interviews were conducted with patients with type 1 Gaucher disease, Fabry disease and MPS III. Parents of MPS III patients were included as patients' representatives. RESULTS: Nine Gaucher patients, 23 Fabry patients, two adult MPS III patients and five parents of MPS III patients participated in the study. The five main themes that arose were: outcome of gene therapy, risks and side effects, burden of gene therapy treatment, current situation and ethical aspects. Participants' views ranged from hesitance to eagerness to undergo gene therapy, which seemed to be mostly related to disease severity and currently available treatment options. Severe disease, limited treatment options and limited effectiveness of current treatment augmented the willingness to choose gene therapy. Gaucher and Fabry patients deemed the burden of treatment important. Fabry and MPS III patients and parents considered outcome important, suggesting hope for improvement. When asked to rank the factors discussed in the focus group discussions, Gaucher patients ranked outcome low, which could indicate a more cautious attitude towards gene therapy. CONCLUSION: This study underlines the importance of exploring patients' needs and expectations before using limited resources in the development of therapies for patient groups of which a significant subset may not be willing to undergo that specific therapy.

Antihypertensive Medication Classes and the Risk of Dementia: A Systematic Review and Network Meta-Analysis.

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.

Patient and proxies' attitudes towards deferred consent in randomised trials of acute treatment for stroke: A qualitative survey.

Introduction: Deferral of consent for participation in a clinical study is a relatively novel procedure, in which informed consent is obtained after randomisation and study treatment. Deferred consent can be used in emergency situations, where small therapeutic time windows limit possibilities for patients to provide informed consent. We aimed to investigate patients' or their proxies' experiences and opinions regarding deferred consent in acute stroke randomised trials. Patients and methods: For this qualitative study, Dutch Collaboration for New Treatments of Acute Stroke (CONTRAST) trial participants were selected. Study participants were either patients or their proxies who provided consent and were selected with theoretical sampling based on patient characteristics. Semi-structured interviews were conducted face-to-face or by telephone. Themes and subthemes were iteratively defined. Results: Twenty of the 23 interviewed participants (16 patients and 7 proxies) considered deferred consent acceptable. The received study treatment and consent conversation were remembered by 18 participations, although the concept of randomisation and treatment comparison were generally not well understood. Sixteen participants felt capable of overseeing the decision to give deferred consent. Distress in the first days after stroke, lack of understanding and neurological deficits were reasons for feeling incapable of providing consent. Four participants would have preferred a different timing of the consent conversation, of whom two prior to treatment. Conclusion: Our study found that deferred consent was considered acceptable by most study participants who provided consent for acute stroke randomised trials. Though they felt capable, the recall and comprehension of consent were overall limited.

Outcome After Decompressive Craniectomy for Middle Cerebral Artery Infarction: Timing of the Intervention.

BACKGROUND: Based on randomized controlled trials (RCTs), clinical guidelines for the treatment of space-occupying hemispheric infarct employ age (≤60 yr) and time elapsed since stroke onset (≤48 h) as decisive criteria whether to perform decompressive craniectomy (DC). However, only few patients in these RCTs underwent DC after 48 h. OBJECTIVE: To study the association between the timing of DC and (un)favorable outcome in patients with space-occupying middle cerebral artery (MCA) infarct undergoing DC. METHODS: We performed a single-center cohort study from 2007 to 2017. Unfavorable outcome at 1 yr was defined as a Glasgow outcome scale 1 to 3. Additionally, we systematically reviewed the literature up to November 2018, including studies reporting on the timing of DC and other predictors of outcome. We performed Firth penalized likelihood and random-effects meta-analysis with odds ratio (OR) on unfavorable outcome. RESULTS: A total of 66 patients were enrolled. A total of 26 (39%) patients achieved favorable and 40 (61%) unfavorable outcomes (13 [20%] died). DC after 48 h since stroke diagnosis did not significantly increase the risk of unfavorable outcome (OR 0.8, 95% CI 0.3-2.3). Also, in the meta-analysis, DC after 48 h of stroke onset was not associated with a higher risk of unfavorable outcome (OR 1.11; 95% CI 0.89-1.38). CONCLUSION: The outcome of DC performed after 48 h in patients with malignant MCA infarct was not worse than the outcome of DC performed within 48 h. Contrary to current guidelines, we, therefore, advocate not to set a restriction of ≤48 h on the time elapsed since stroke onset in the decision whether to perform DC.

Investigation of antihypertensive class, dementia, and cognitive decline: A meta-analysis.

OBJECTIVE: High 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. METHODS: To 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. RESULTS: Over 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. CONCLUSION: Our findings, drawn from the current evidence base, support clinical freedom in the selection of antihypertensive regimens to achieve blood pressure goals. CLINICAL TRIALS REGISTRATION: The review was registered with the international prospective register of systematic reviews (PROSPERO), registration number CRD42016045454.

Visit-to-Visit Blood Pressure Variability and Progression of White Matter Hyperintensities Among Older People With Hypertension.

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 < .01). 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.

Older Adults' Reasons for Participating in an eHealth Prevention Trial: A Cross-Country, Mixed-Methods Comparison.

OBJECTIVES: To explore older adults' reasons for participating in a multinational eHealth prevention trial, and compare motivations between countries. DESIGN: Cross-sectional mixed methods research using quantitative and qualitative approaches (the ACCEPT-HATICE study). SETTING AND PARTICIPANTS: Substudy conducted during the recruitment phase of an 18-month RCT testing the efficacy of an eHealth intervention for self-management of risk factors for cardiovascular disease (CVD) and cognitive decline in older adults in Finland, France, and the Netherlands. Participants were 343 dementia-free community dwellers aged 65+ with basic computer literacy and either ≥2 cardiovascular risk factors or a history of CVD/diabetes. MEASURES: Online questionnaire (quantitative data) and semistructured interviews (qualitative data). RESULTS: Contributing to scientific progress, wanting to improve one's lifestyle, and benefiting from additional medical monitoring were the predominant reasons for participating. Altruistic reasons were particularly relevant among the French, whereas Finnish and Dutch participants mainly emphasized the benefits of lifestyle changes and regular medical checkups. During interviews, preventing functional dependency emerged as a key underlying motivation. Although some trial design features influenced the decision to participate, the use of an eHealth intervention was not an important motivator in this population. CONCLUSIONS/IMPLICATIONS: Altruism and personal benefits motivated older adults to participate in the trial; emphasizing such aspects could facilitate recruitment in future RCTs. Additional medical monitoring may be particularly appealing when access to public health care is considered limited. Furthermore, maintaining autonomy and preventing functional dependency emerged as a key concern in this population of young older adults.

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

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

Engaging older people in an internet platform for cardiovascular risk self-management: a qualitative study among Dutch HATICE participants.

OBJECTIVES: To study older peoples' experiences with an interactive internet platform for cardiovascular self-management, to assess which factors influence initial and sustained engagement. To assess their views on future use within primary care. DESIGN: Qualitative semistructured interview study, with thematic analysis. SETTING: Primary care in the Netherlands. PARTICIPANTS: People ≥65 years with an increased risk of cardiovascular disease who used the 'Healthy Ageing Through Internet Counselling in the Elderly' internet platform with remote support of a coach. Participants were selected using a purposive sampling method based on gender, age, level of education, cardiovascular history, diabetes, duration of participation and login frequency. RESULTS: We performed 17 interviews with 20 participants, including three couples. In the initial phase, platform engagement was influenced by perceived computer literacy of the participants, user-friendliness, acceptability and appropriateness of the intervention and the initial interaction with the coach. Sustained platform use was mainly facilitated by a relationship of trust with the coach. Other facilitating factors were regular automatic and personal reminders, clear expectations of the platform, incorporation into daily routine, social support and a loyal and persistent attitude. Perceived lack of change in content of the platform could work both stimulating and discouraging. Participants supported the idea of embedding the platform into the primary care setting. CONCLUSIONS: Human support is crucial to initial and sustained engagement of older people in using an interactive internet platform for cardiovascular self-management. Regular reminders further facilitate sustained use, and increased tailoring to personal preference is recommended. Embedding the platform in primary healthcare may enhance future adoption. TRIAL REGISTRATION NUMBER: ISRCTN48151589; Pre-results.

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

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

Visit-To-Visit Blood Pressure Variability and the Risk of Dementia in Older People.

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 (ß -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.

Blood pressure-lowering interventions to prevent dementia: a systematic review and meta-analysis.

: Our objective was to study the preventive effect of lowering blood pressure (BP) by medication and/or lifestyle changes on incident all-cause dementia, Alzheimer's disease and vascular dementia. In this systematic review, we included randomized controlled trials with a BP-lowering intervention. Of the nine included trials, seven assessed the effect of antihypertensive medication and two of a lifestyle or combined intervention. In the intervention arm, 1041 out of 29 029 (3.6%) participants were diagnosed with dementia compared with 1090 out of 28 653 (3.8%) controls during a median follow-up of 3.9 years [range 2-10], resulting in a pooled risk ratio of 0.93 (95% confidence interval 0.84-1.02; I 16%). Three trials specified dementia subtypes, with no significant effect on Alzheimer's disease or vascular dementia. To conclude, lowering BP by medication and/or lifestyle changes did not lead to a significantly reduced risk of dementia. This appeared independent of dementia subtype.

Prescribing and deprescribing antihypertensive medication in older people by Dutch general practitioners: a qualitative study.

OBJECTIVES: To explore general practitioners' (GPs) routines and considerations on (de)prescribing antihypertensive medication (AHM) in older patients, their judgement on usability of the current guideline and needs for future support. DESIGN: Semistructured interviews. SETTING: Dutch general practice. PARTICIPANTS: Fifteen GPs were purposively sampled based on level of experience and practice characteristics until saturation was reached. RESULTS: GPs appeared reluctant to start AHM, especially in patient >80 years. High systolic blood pressure and history of cardiovascular disease or diabetes were enablers to start or intensify treatment. Reasons to refrain from this were frailty and patient preference. GPs described a tendency to continue AHM regimens unchanged, influenced by daily time constraints, automated prescription routines and anticipating discomfort when disturbing patients' delicate balance. GPs were only inclined to deprescribe AHM in terminally ill patients or after prolonged achievement of target levels in combination with side effects or patient preference. Deprescription was facilitated when GPs had experience with patients showing increased quality of life after deprescription and was withheld by anticipated regret (ie, GPs' fear of a stroke after deprescribing). GPs felt insufficient guidance from current guidelines, especially on deprescription. CONCLUSIONS: GPs are reluctant to start or deprescribe AHM in older people and have a propensity to continue AHM within a daily routine that insufficiently supports critical medication review. (De)prescription is influenced by patient preferences and anticipated regret and current guidelines provide insufficient guidance.

Lower dementia risk with different classes of antihypertensive medication in older patients.

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 ß-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.

Neurologic Outcome After Decompressive Craniectomy: Predictors of Outcome in Different Pathologic Conditions.

OBJECTIVE: Decompressive craniectomy (DC) has been proposed as a lifesaving treatment in patients with elevated intracranial pressure, but its effectiveness on reaching a favorable neurologic outcome remains unclear. We identified predictors of outcome in a large, single-center cohort of patients undergoing DC for different pathologic conditions. METHODS: This retrospective study included all patients undergoing DC from 2006 to 2014. The 1-year outcome, assessed using the Glasgow Outcome Scale (GOS), was dichotomized into favorable (GOS 4-5) and unfavorable (GOS 1-3) outcome. Predictors of outcome were identified by analyzing patient characteristics. RESULTS: DC was performed in 204 patients for ischemic stroke (n = 57), traumatic brain injury (n = 50), aneurysmal subarachnoid hemorrhage (aSAH) (n = 44), intracerebral hemorrhage (ICH) (n = 29), cerebral venous thrombosis (CVT) (n = 14), or other indications (n = 10). Overall, 69 (34%) patients survived favorably, 39 (19%) survived unfavorably, and 96 (47%) died. Higher age, poor Glasgow Coma Scale score, intubated status before DC, bilateral absence of pupillary light reflexes, DC for aSAH, and additional surgeries after DC (excluding cranioplasty) were significant predictors of unfavorable outcome. When patients were sorted for pathologic conditions and predictors of outcome, favorable outcome rates differed remarkably, ranging from 91% for CVT patients undergoing uncomplicated DC to 0% for aSAH patients undergoing DC for secondary infarction or ICH patients with unilateral or bilateral abnormal pupillary light reflexes upon admission. CONCLUSIONS: Long-term neurologic outcome after DC differed remarkably among subpopulations of patients, with favorable outcome rates ranging from 0% to >90%.