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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.

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., (© Pearl Aovare, Kasim Abdulai, Amos Laar, Eva L van der Linden, Nicolaas Moens, Edo Richard, Eric P Moll van Charante, Charles Agyemang. Originally published in JMIR mHealth and uHealth (https://mhealth.jmir.org).)

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.

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., (© 2023. The Author(s).)

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., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

Hypertension is an important risk factor for Alzheimer's disease (AD) and all-cause dementia. The mechanisms underlying this association are unclear. Hypertension may be associated with AD neuropathological changes (ADNC), but reports are sparse and inconsistent. This systematic review included 15 autopsy studies (n = 5879) from observational cohorts. Studies were highly heterogeneous regarding populations, follow-up duration, hypertension operationalization, neuropathological methods, and statistical analyses. Hypertension seems associated with higher plaque and tangle burden, but results are inconsistent. Four studies (n = 3993/5879; 68%), reported clear associations between hypertension and ADNC. Another four suggested that antihypertensive medication may protect against ADNC. Larger studies with longer follow-up reported the strongest relationships. Our findings suggest a positive association between hypertension and ADNC, but effects may be modest, and possibly attenuate with higher hypertension age and antihypertensive medication use. Investigating interactions among plaques, tangles, cerebrovascular pathology, and dementia may be key in better understanding hypertension's role in dementia development., (© 2022 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

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 < .001). This U-shape occurred across all age groups, with the lowest dementia risk associated with an SBP of 134 mm Hg (95% CI, 102-149 mm Hg; P = .03) in those aged 60 to 70 years and increasing to between 155 mm Hg (95% CI, 150-166 mm Hg; P < .001) and 166 mm Hg (95% CI, 154-260 mm Hg; P = .02) for age groups between 70 and 95 years. Combined dementia and mortality risk curves closely resembled those for mortality. Associations of diastolic BP with dementia risk were generally similar but were less distinct., Conclusions and Relevance: This cohort study found that dementia risk was lower for older individuals with higher SBP levels and that more distinctly U-shaped associations appeared for those older than 75 years, but these associations cannot be explained by SBP-associated changes in mortality risk. The findings may warrant future trials on tailored BP management in older age groups that take life expectancy and health context into consideration.

Objective: High blood pressure and blood pressure variability are potential, modifiable risk factors of poststroke dementia. We aimed to investigate the association between achieved blood pressure, blood pressure variability and poststroke dementia., Methods: We studied 17 064 patients with noncardioembolic ischemic stroke included in the Prevention Regimen for Effectively avoiding Second Strokes (PRoFESS) trial. We analysed the data as a single observational cohort. We studied mean achieved SBP and DBP and blood pressure variability defined as coefficient of variation (SD/mean∗100). The association between blood pressure and dementia was investigated with logistic regression analysis, correcting for sociodemographic factors and cardiovascular risk factors., Results: During 39 818 person-years of follow-up, 817 patients were diagnosed with dementia (2.1 per 100 person-years). We found a significant nonlinear association between mean SBP and the risk of dementia, implying a U-shaped association between mean SBP and dementia. Mean SBP of 120-129 mmHg was associated with a significantly higher risk of dementia than 130-139 mmHg [odds ratio (OR) 1.28; 95% confidence interval (95% CI) 1.03-1.58]. There was no indication of a U-shaped association between mean DBP and dementia, and no significant association between mean DBP categories and dementia. Higher blood pressure variability was associated with an increased risk of dementia (OR 1.06 per point increase, 95% CI 1.02-1.04), independent of mean SBP., Conclusion: Among patients with a recent noncardioembolic ischemic stroke, there appears to be a U-shaped association between achieved SBP and dementia. High blood pressure variability is associated with an increased risk of poststroke dementia., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

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.

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., (Copyright © 2020 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

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., (© 2019 American Academy of Neurology.)

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., (Copyright © 2019 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Objectives: Sixty-five per cent of older people have hypertension, but little is known about their preferences and concerns regarding hypertension management. Guidelines on hypertension lack consensus on how to treat older people without previous cardiovascular disease (CVD). This asks for explicit consideration of patient preferences in decision making. Therefore, the aim of this study was to explore older peoples' experiences, preferences, concerns and perceived involvement regarding hypertension management., Design: Qualitative interview study., Setting: Participants were selected from 11 general practitioner (GP) practices in the Netherlands and purposively sampled until data saturation was achieved. Semistructured interviews were conducted, audio recorded and analysed by two researchers using thematic analysis., Participants: Fifteen community dwelling older people aged 74-93 years with hypertension and without previous CVD participated., Results: Interviewees rarely started the conversation about hypertension management with their GP, although they did have concerns. Reasons for not discussing the subject included low priority of hypertension concerns, reliance on GPs or trust in GPs to make the right decision on their behalf. Also, interviewees anticipated regret of reducing medication, fearing vascular incidents. Interviewees would like to discuss tailoring treatment to their needs, deprescription of medication and ways to reduce side effects. They expected GPs to be more transparent on treatment effects., Conclusion: Older people describe having little involvement in hypertension management, although they have several concerns. Since GPs are also known to be hesitant to bring up this subject, we signal a conspiracy of silence about antihypertensive medication. Through breaking this silence, GPs can facilitate shared decision-making on hypertension management and better tailored care., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.)

Background: Stroke is an important cause of death and disability worldwide. Since high blood pressure is an important risk factor for stroke and stroke recurrence, drugs that lower blood pressure might play an important role in secondary stroke prevention., Objectives: To investigate whether blood pressure-lowering drugs (BPLDs) started at least 48 hours after the index event are effective for the prevention of recurrent stroke, major vascular events, and dementia in people with stroke or transient ischaemic attack (TIA). Secondary objectives were to identify subgroups of people in which BPLDs are effective, and to investigate the optimum systolic blood pressure target after stroke or TIA for preventing recurrent stroke, major vascular events, and dementia., Search Methods: In August 2017, we searched the Trials Registers of the Cochrane Stroke Group and the Cochrane Hypertension Group, the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 8), MEDLINE Ovid (1946 to August 2017), Embase Ovid (1974 to August 2017), ClinicalTrials.gov, the ISRCTN Registry, Stroke Trials Registry, Trials Central, and the World Health Organization (WHO) International Clinical Trials Registry Platform Portal., Selection Criteria: Randomised controlled trials (RCTs) of BPLDs started at least 48 hours after stroke or TIA., Data Collection and Analysis: Two review authors independently screened all titles and abstracts, selected eligible trials, extracted the data, assessed risk of bias, and used GRADE to assess the quality of the evidence. If necessary, we contacted the principal investigators or corresponding authors for additional data., Main Results: We included 11 studies involving a total of 38,742 participants: eight studies compared BPLDs versus placebo or no treatment (35,110 participants), and three studies compared different systolic blood pressure targets (3632 participants). The risk of bias varied greatly between included studies. The pooled risk ratios (RRs) of BPLDs were 0.81 (95% confidence interval (CI) 0.70 to 0.93; 8 RCTs; 35,110 participants; moderate-quality evidence), 0.90 (95% CI 0.78 to 1.04; 4 RCTs; 28,630 participants; high-quality evidence) for major vascular event, and 0.88 (95% CI 0.73 to 1.06; 2 RCTs; 6671 participants; high-quality evidence) for dementia. We mainly observed a reduced risk of recurrent stroke in the subgroup of participants using an angiotensin-converting enzyme (ACE) inhibitor or a diuretic (I 2 statistic for subgroup differences 72.1%; P = 0.006). The pooled RRs of intensive blood pressure-lowering were 0.80 (95% CI 0.63 to 1.00) for recurrent stroke and 0.58 (95% CI 0.23 to 1.46) for major vascular event., Authors' Conclusions: Our results support the use of BPLDs in people with stroke or TIA for reducing the risk of recurrent stroke. Current evidence is primarily derived from trials studying an ACE inhibitor or a diuretic. No definite conclusions can be drawn from current evidence regarding an optimal systolic blood pressure target after stroke or TIA.

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; I 2 =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., (© 2018 American Heart Association, Inc.)

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., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

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.

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 β-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.

Hypertension is associated with cognitive decline and various forms of dementia, including Alzheimer's disease. In animal models of hypertension, many of Alzheimer's disease characteristics are recapitulated, including brain atrophy, cognitive decline, amyloid β accumulation and blood brain barrier dysfunction. Removal of amyloid β and other waste products depends in part on clearance via the brain interstitial fluid (ISF). Here we studied the impact of hypertension on ISF drainage, using spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY). At 8 months, high (500 kD) and low (3 kD) fluorescent molecular weight tracers released passively into the hippocampus showed a drastically enhanced spreading in SHR. Tracer spreading was inhomogeneous, with accumulation at ISF-CSF borders, around arteries, and towards the stratum lacunosum moleculare. These locations stained positively for the astrocyte marker GFAP, and aquaporin 4. Despite enhanced dispersion, clearance of tracers was not affected in SHR. In conclusion, these data indicate enhanced bulk flow of ISF in the hippocampus of hypertensive rats. ISF drains along astrocytes towards the cerebrospinal fluid compartment, which leads to sieving of high molecular weight solutes. Sieving may lead to a local increase in the concentration of waste products and potentially promotes the aggregation of amyloid β.

Background: There is little information on the prevalence of hypertension and other modifiable cardiovascular risk factors in community-dwelling elderly in the Netherlands and the potential impact of improving antihypertensive treatment on major cardiovascular events., Design: Cross-sectional analysis of Dutch community-dwelling subjects aged 70-78 years without dementia who were included in the cluster randomized preDIVA trial (Prevention of Dementia by Intensive Vascular care)., Methods: The prevalence of hypertension and other cardiovascular risk factors are described for participants with and without a history of cardiovascular disease (CVD). Projected benefits of blood pressure decrease are calculated using data from a meta-analysis and a large national registry., Results: Of 3534 subjects, more than one-third (n = 1230, 35.2%) have a history of cardiovascular disease. Overall, 63% of subjects have two or more cardiovascular risk factors amenable to treatment. Systolic blood pressure (SBP) is ≥160 mmHg in 37% of patients with CVD, of which 28% is untreated. In subjects without a history of CVD, 41% have a SBP ≥ 160 mmHg of which 52% is untreated. A 5-15 mmHg decrease in SBP is projected to prevent 12-32% of coronary heart disease and 16-41% of strokes, respectively. This corresponds with 14-38 prevented cases within 2 years in our intervention group (n = 1895)., Conclusions: Hypertension and other cardiovascular risk factors are very common in elderly subjects. Current (primary and secondary) prevention programmes appear insufficient. Improved antihypertensive treatment has the potential to prevent a substantial proportion of strokes and coronary heart disease in this population.

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. [ABSTRACT FROM AUTHOR]

Hypertension is an important risk factor for Alzheimer's disease (AD) and all‐cause dementia. The mechanisms underlying this association are unclear. Hypertension may be associated with AD neuropathological changes (ADNC), but reports are sparse and inconsistent. This systematic review included 15 autopsy studies (n = 5879) from observational cohorts. Studies were highly heterogeneous regarding populations, follow‐up duration, hypertension operationalization, neuropathological methods, and statistical analyses. Hypertension seems associated with higher plaque and tangle burden, but results are inconsistent. Four studies (n = 3993/5879; 68%), reported clear associations between hypertension and ADNC. Another four suggested that antihypertensive medication may protect against ADNC. Larger studies with longer follow‐up reported the strongest relationships. Our findings suggest a positive association between hypertension and ADNC, but effects may be modest, and possibly attenuate with higher hypertension age and antihypertensive medication use. Investigating interactions among plaques, tangles, cerebrovascular pathology, and dementia may be key in better understanding hypertension's role in dementia development. [ABSTRACT FROM AUTHOR]

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 (pre DIVA) 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. [ABSTRACT FROM AUTHOR]

To evaluate whether discontinuation of antihypertensive medication in community-dwelling older people is associated with a reduction in memory complaints and/or incident dementia. Prospective observational cohort study within the Prevention of Dementia by Intensive Vascular Care (preDIVA) trial. Community-dwelling participants (aged 70-78 years at baseline) who underwent 2-yearly assessments during 6-8 years of follow-up. Cox regression analyses of the relation between discontinuation of antihypertensive medication during the study and change in subjective memory complaints, incident dementia, and mortality. Dementia occurred more often in participants discontinuing antihypertensive treatment (13.4% vs 6.2%, P =.02); mortality was similar (16.5% vs 13.9%, P =.52). Discontinuation of antihypertensive medication was associated with a double dementia hazard [hazard ratio (HR) (95% confidence interval) = 2.15 (1.15-4.03)], which somewhat attenuated after adjustment for sex, blood pressure, number of antihypertensives and other medications [HR = 1.92 (1.01-3.65)], and additionally for stroke, cardiovascular disease, diabetes, smoking, memory complaints, and MMSE score [HR = 1.79 (0.93-3.44)]. Antihypertensive discontinuation was associated with an approximately 50% higher hazard of dementia and/or mortality combined [HR = 1.58 (1.04-2.40); model 2: HR = 1.64 (1.07-2.51); model 3: HR = 1.49 (0.96-2.30)]. Antihypertensive discontinuation was not associated with change in memory complaints [odds ratio (95% confidence interval) = 0.96 (0.55-1.67)]. Subgroup and sensitivity analyses addressing possible sources of bias and confounding gave similar results. Our results suggest that antihypertensive withdrawal in community-dwelling older people does not preserve cognition and may in fact increase dementia risk. This is not due to reduced mortality as competing risk. Additional analyses suggest results are unlikely to be explainable by confounding, reverse causality, or observational biases. Studies with person-specific reasons for antihypertensive discontinuation may be able to exclude reverse causality completely. Given the beneficial effects of antihypertensive medication on cardiovascular risk, observational data may be the best currently obtainable on the pressing issue of when withdrawal of antihypertensives in older people is acceptable and what consequences need to be weighed. [ABSTRACT FROM AUTHOR]