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      The Age-Dependent Relationship between Blood Pressure and Cognitive Impairment: A Cross-Sectional Study in a Rural Area of Xi'an, China

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          Abstract

          Background

          Hypertension is a modifiable risk factor for cognitive impairment, although the relationship between hypertension and cognitive impairment is not fully understood. The objective of this study was to investigate the effect of age on the relationship between blood pressure and cognitive impairment.

          Methods

          Blood pressure and global cognitive function information was collected from 1799 participants (age 40–85) who lived in a village in the suburbs of Xi'an, China, during in-person interviews. Cognitive impairment was defined as a Mini-Mental State Examination (MMSE) score lower than the cutoff value. The effect of age on the relationship between blood pressure parameters [systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial blood pressure (MABP), and high blood pressure (HBP, SBP≥140 mm Hg and/or DBP≥90 mm Hg)] and cognitive impairment was analyzed by logistic regression models using interaction and stratified analysis. Blood pressure and age were regarded as both continuous and categorical data.

          Results

          A total of 231 participants were diagnosed as having cognitive impairment based on our criteria. Interaction analysis for the total population showed that SBP (when regarded as continuous data) was positively correlated with cognitive impairment (OR = 1.130 [95% CI, 1.028–1.242] per 10mmHg, P = 0.011); however, the age by SBP interaction term was negatively correlated with cognitive impairment (OR = 0.989 [95% CI, 0.982–0.997] per 10mmHg×year, P = 0.006), indicating that the relationship between SBP and cognitive impairment was age-dependent (OR = 1.130×0.989 (age-55.5) per 10mmHg,40 ≤age≤85). When the blood pressure and age were considered as binary data, the results were similar to those obtained when they were considered as continuous variables. Stratified multivariate analysis revealed that the relationship between SBP (when regarded as continuous data) and cognitive impairment was positive for patients aged 40–49 years (OR = 1.349 [95% CI: 1.039–1.753] per 10mmHg, P = 0.025) and 50–59 years (OR = 1.185 [95% CI: 1.028–1.366] per 10mmHg, P = 0.019), whereas it tended to be negative for patients aged 60–69 years (OR = 0.878 [95% CI: 0.729–1.058] per 10mmHg, P = 0.171) and ≥70 years (OR = 0.927 [95% CI: 0.772–1.113] per 10mmHg, P = 0.416). Results similar to those for SBP were obtained for DBP, MABP and HBP as well. Subsequently, SBP, DBP and MABP were transformed into categorical data (SBP<140mmHg, 140mmHg≤SBP<160mmHg, and SBP≥160mmHg; DBP<90mmHg, 90mmHg≤DBP<100mmHg, and DBP≥100mmHg; MABP<100mmHg, 100mmHg≤MABP<110mmHg, and MABP≥110mmHg), and the stratified multivariate analysis was repeated. This analysis showed that the age-dependent association continued to exist and was especially prominent in the SBP≥160 mmHg, DBP≥90 mmHg and MABP≥110 mmHg groups.

          Conclusions

          Elevated blood pressure is positively correlated with cognitive impairment in the middle-aged, but this positive association declines with increasing age. These results indicated that specific blood pressure management strategies for various age groups may be crucial for maintaining cognitive vitality.

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          Most cited references18

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          The overlap between neurodegenerative and vascular factors in the pathogenesis of dementia.

          There is increasing evidence that cerebrovascular dysfunction plays a role not only in vascular causes of cognitive impairment but also in Alzheimer's disease (AD). Vascular risk factors and AD impair the structure and function of cerebral blood vessels and associated cells (neurovascular unit), effects mediated by vascular oxidative stress and inflammation. Injury to the neurovascular unit alters cerebral blood flow regulation, depletes vascular reserves, disrupts the blood-brain barrier, and reduces the brain's repair potential, effects that amplify the brain dysfunction and damage exerted by incident ischemia and coexisting neurodegeneration. Clinical-pathological studies support the notion that vascular lesions aggravate the deleterious effects of AD pathology by reducing the threshold for cognitive impairment and accelerating the pace of the dementia. In the absence of mechanism-based approaches to counteract cognitive dysfunction, targeting vascular risk factors and improving cerebrovascular health offers the opportunity to mitigate the impact of one of the most disabling human afflictions.
            • Record: found
            • Abstract: found
            • Article: not found

            Midlife hypertension and 20-year cognitive change: the atherosclerosis risk in communities neurocognitive study.

            Hypertension is a treatable potential cause of cognitive decline and dementia, but its greatest influence on cognition may occur in middle age.
              • Record: found
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              • Article: not found

              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.

                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                20 July 2016
                2016
                : 11
                : 7
                : e0159485
                Affiliations
                [001]Department of Neurology, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
                Taipei Veterans General Hospital, TAIWAN
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: QQ SS. Performed the experiments: SS PL MD YJ CC. Analyzed the data: SS PL. Contributed reagents/materials/analysis tools: SS PL. Wrote the paper: SS QQ PL.

                [¤]

                Current address: Department of Neurology, the First Affiliated Hospital of Xi’an Jiaotong University, 277 West Yanta Rd, Xi’an, China

                Article
                PONE-D-15-51778
                10.1371/journal.pone.0159485
                4954703
                27438476
                40d4d583-3818-44e8-b8b8-a184ba051239
                © 2016 Shang et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 22 December 2015
                : 4 July 2016
                Page count
                Figures: 4, Tables: 3, Pages: 18
                Funding
                Funded by: National Science and Technology Major Project on Development of Major New Drugs
                Award ID: 2012ZX09303-005-002
                Award Recipient :
                This work was supported by National Science and Technology Major Project on Development of Major New Drugs (NO.2012ZX09303-005-002) URL: http://www.nmp.gov.cn/zxjs/zdxy/201012/t20101208_2128.htm. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology and Life Sciences
                Neuroscience
                Cognitive Science
                Cognitive Neuroscience
                Cognitive Neurology
                Cognitive Impairment
                Biology and Life Sciences
                Neuroscience
                Cognitive Neuroscience
                Cognitive Neurology
                Cognitive Impairment
                Medicine and Health Sciences
                Neurology
                Cognitive Neurology
                Cognitive Impairment
                Medicine and Health Sciences
                Vascular Medicine
                Blood Pressure
                Medicine and Health Sciences
                Vascular Medicine
                Blood Pressure
                Hypertension
                People and Places
                Population Groupings
                Age Groups
                Elderly
                Earth Sciences
                Geography
                Geographic Areas
                Rural Areas
                People and Places
                Population Groupings
                Age Groups
                Medicine and Health Sciences
                Neurology
                Cerebrovascular Diseases
                Stroke
                Medicine and Health Sciences
                Vascular Medicine
                Stroke
                Medicine and Health Sciences
                Neurology
                Brain Damage
                Medicine and Health Sciences
                Critical Care and Emergency Medicine
                Trauma Medicine
                Brain Damage
                Custom metadata
                Due to restrictions imposed by the government of the People's Republic of China, data cannot be made publicly available in relation to the Tort Liability Law and Statistics Law. Data access has also been restricted by ethical approval to protect personal information of participants. Individuals interested in accessing the data must receive ethical approval from the Medical Ethics Committee of the First Affiliated Hospital of Xi’an Jiaotong University ( xm3215@ 123456126.com ). Requests for a de-identified data set from this study may be sent to corresponding author Qiumin Qu ( qiuminqu@ 123456outlook.com ) after achieving ethical approval.

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