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      Association of Blood Pressure Lowering With Incident Dementia or Cognitive Impairment : A Systematic Review and Meta-analysis

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          Abstract

          Is there an association between blood pressure lowering with antihypertensive therapy and the incidence of dementia or cognitive impairment? In this meta-analysis that included 12 trials with 92 135 participants for the primary outcome measure, blood pressure lowering with antihypertensive agents, compared with control, was associated with the development of a composite dementia or cognitive impairment outcome in 7.0% vs 7.5% of patients over a mean trial follow-up of 4.1 years, a difference that was statistically significant. Lowering blood pressure may be associated with a lower risk of dementia or cognitive impairment. The benefit of blood pressure lowering for the prevention of dementia or cognitive impairment is unclear. To determine the association of blood pressure lowering with dementia or cognitive impairment. Search of PubMed, EMBASE, and CENTRAL for randomized clinical trials published from database inception through December 31, 2019, that evaluated the association of blood pressure lowering on cognitive outcomes. The control groups consisted of either placebo, alternative antihypertensive agents, or higher blood pressure targets. Data were screened and extracted independently by 2 authors. Random-effects meta-analysis models were used to report pooled treatment effects and CIs. The primary outcome was dementia or cognitive impairment. The secondary outcomes were cognitive decline and changes in cognitive test scores. Fourteen randomized clinical trials were eligible for inclusion (96 158 participants), of which 12 reported the incidence of dementia (or composite of dementia and cognitive impairment [3 trials]) on follow-up and were included in the primary meta-analysis, 8 reported cognitive decline, and 8 reported changes in cognitive test scores. The mean (SD) age of trial participants was 69 (5.4) years and 40 617 (42.2%) were women. The mean systolic baseline blood pressure was 154 (14.9) mm Hg and the mean diastolic blood pressure was 83.3 (9.9) mm Hg. The mean duration of follow-up was 49.2 months. Blood pressure lowering with antihypertensive agents compared with control was significantly associated with a reduced risk of dementia or cognitive impairment (12 trials; 92 135 participants) (7.0% vs 7.5% of patients over a mean trial follow-up of 4.1 years; odds ratio [OR], 0.93 [95% CI, 0.88-0.98]; absolute risk reduction, 0.39% [95% CI, 0.09%-0.68%]; I 2  = 0.0%) and cognitive decline (8 trials) (20.2% vs 21.1% of participants over a mean trial follow-up of 4.1 years; OR, 0.93 [95% CI, 0.88-0.99]; absolute risk reduction, 0.71% [95% CI, 0.19%-1.2%]; I 2  = 36.1%). Blood pressure lowering was not significantly associated with a change in cognitive test scores. In this meta-analysis of randomized clinical trials, blood pressure lowering with antihypertensive agents compared with control was significantly associated with a lower risk of incident dementia or cognitive impairment. This systematic review and meta-analysis examines whether blood pressure lowering is associated with a reduced risk of dementia or cognitive impairment.

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          Incident dementia and blood pressure lowering in the Hypertension in the Very Elderly Trial cognitive function assessment (HYVET-COG): a double-blind, placebo controlled trial.

          Observational epidemiological studies have shown a positive association between hypertension and risk of incident dementia; however, the effects of antihypertensive therapy on cognitive function in controlled trials have been conflicting, and meta-analyses of the trials have not provided clear evidence of whether antihypertensive treatment reduces dementia incidence. The Hypertension in the Very Elderly trial (HYVET) was designed to assess the risks and benefits of treatment of hypertension in elderly patients and included an assessment of cognitive function. Patients with hypertension (systolic pressure 160-200 mm Hg; diastolic pressure <110 mm Hg) who were aged 80 years or older were enrolled in this double-blind, placebo-controlled trial. Participants were randomly assigned to receive 1.5 mg slow release indapamide, with the option of 2-4 mg perindopril, or placebo. The target systolic blood pressure was 150 mm Hg; the target diastolic blood pressure was 80 mm Hg. Participants had no clinical diagnosis of dementia at baseline, and cognitive function was assessed at baseline and annually with the mini-mental state examination (MMSE). Possible cases of incident dementia (a fall in the MMSE score to <24 points or a drop of three points in 1 year) were assessed by standard diagnostic criteria and expert review. The trial was stopped in 2007 at the second interim analysis after treatment resulted in a reduction in stroke and total mortality. Analysis was by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00122811. 3336 HYVET participants had at least one follow-up assessment (mean 2.2 years) and were included: 1687 participants were randomly assigned to the treatment group and 1649 to the placebo group. Only five reports of adverse effects were attributed to the medication: three in the placebo group and two in the treatment group. The mean decrease in systolic blood pressure between the treatment and placebo groups at 2 years was systolic -15 mm Hg, p<0.0001; and diastolic -5.9 mm Hg, p<0.0001. There were 263 incident cases of dementia. The rates of incident dementia were 38 per 1000 patient-years in the placebo group and 33 per 1000 patient-years in the treatment group. There was no significant difference between treatment and placebo groups (hazard ratio [HR] 0.86, 95% CI 0.67-1.09); however, when these data were combined in a meta-analysis with other placebo-controlled trials of antihypertensive treatment, the combined risk ratio favoured treatment (HR 0.87, 0.76-1.00, p=0.045). Antihypertensive treatment in elderly patients does not statistically reduce incidence of dementia. This negative finding might have been due to the short follow-up, owing to the early termination of the trial, or the modest effect of treatment. Nevertheless, the HYVET findings, when included in a meta-analysis, might support antihypertensive treatment to reduce incident dementia.
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            Population attributable fractions for risk factors for dementia in low-income and middle-income countries: an analysis using cross-sectional survey data

            Nine potentially modifiable risk factors (less childhood education, midlife hearing loss, hypertension, and obesity, and later-life smoking, depression, physical inactivity, social isolation, and diabetes) account for 35% of worldwide dementia, but most data to calculate these risk factors come from high-income countries only. We aimed to calculate population attributable fractions (PAFs) for dementia in selected low-income and middle-income countries (LMICs) to identify potential dementia prevention targets in these countries.
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              Effects of blood pressure lowering with perindopril and indapamide therapy on dementia and cognitive decline in patients with cerebrovascular disease.

              High blood pressure and stroke are associated with increased risks of dementia and cognitive impairment. This study aimed to determine whether blood pressure lowering would reduce the risks of dementia and cognitive decline among individuals with cerebrovascular disease. The Perindopril Protection Against Recurrent Stroke Study (PROGRESS) was a randomized, double-blind, placebo-controlled trial conducted among 6105 people with prior stroke or transient ischemic attack. Participants were assigned to either active treatment (perindopril for all participants and indapamide for those with neither an indication for nor a contraindication to a diuretic) or matching placebo(s). The primary outcomes for these analyses were dementia (using DSM-IV criteria) and cognitive decline (a decline of 3 or more points in the Mini-Mental State Examination score). During a mean follow-up of 3.9 years, dementia was documented in 193 (6.3%) of the 3051 randomized participants in the actively treated group and 217 (7.1%) of the 3054 randomized participants in the placebo group (relative risk reduction, 12% [95% confidence interval, -8% to 28%]; P =.2). Cognitive decline occurred in 9.1% of the actively treated group and 11.0% of the placebo group (risk reduction, 19% [95% confidence interval, 4% to 32%]; P =.01). The risks of the composite outcomes of dementia with recurrent stroke and of cognitive decline with recurrent stroke were reduced by 34% (95% confidence interval, 3% to 55%) (P =.03) and 45% (95% confidence interval, 21% to 61%) (P<.001), respectively, with no clear effect on either dementia or cognitive decline in the absence of recurrent stroke. Active treatment was associated with reduced risks of dementia and cognitive decline associated with recurrent stroke. These findings further support the recommendation that blood pressure lowering with perindopril and indapamide therapy be considered for all patients with cerebrovascular disease.
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                Author and article information

                Journal
                JAMA
                JAMA
                American Medical Association (AMA)
                0098-7484
                May 19 2020
                May 19 2020
                : 323
                : 19
                : 1934
                Affiliations
                [1 ]HRB Clinical Research Facility, NUI Galway and Saolta University Hospital Group, Galway, Ireland
                [2 ]Translational Medical Device Lab, NUI Galway, Galway, Ireland
                [3 ]Wellcome Trust-HRB, Irish Clinical Academic Training, Dublin, Ireland
                [4 ]Centre for Clinical Brain Sciences, The University of Edinburgh, Edinburgh, Scotland
                [5 ]Population Health Research Institute, Hamilton, Canada
                Article
                10.1001/jama.2020.4249
                7237983
                32427305
                74d468c2-690d-4082-8f80-2a9a9e18e3ef
                © 2020
                History

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