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      Hypertension and cognitive dysfunction in elderly: blood pressure management for this global burden

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          Abstract

          Arterial hypertension and stroke are strong independent risk factors for the development of cognitive impairment and dementia. Persistently elevated blood pressure (BP) is known to impair cognitive function, however onset of new cognitive decline is common following a large and multiple mini strokes. Among various forms of dementia the most prevalent include Alzheimer’s disease (AD) and vascular dementia (VaD) which often present with similar clinical symptoms and challenging diagnosis. While hypertension is the most important modifiable vascular risk factor with antihypertensive therapy reducing the risk of stroke and potentially slowing cognitive decline, optimal BP levels for maintaining an ideal age-related mental performance are yet to be established. Cognition has improved following the use of at least one representative agent of the major drug classes with further neuroprotection with renin angiotensin inhibitors and calcium channel blockers in the hypertensive elderly. However, a reduction in BP may worsen cerebral perfusion causing an increased risk of CV complications due to the J-curve phenomenon. Given the uncertainties and conflicting results from randomized trials regarding the hypertension management in the elderly, particularly octogenarians, antihypertensive approaches are primarily based on expert opinion. Herein, we summarize available data linking arterial hypertension to cognitive decline and antihypertensive approach with potential benefits in improving cognitive function in elderly hypertensive patients.

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          Cerebral microvascular pathology in aging and Alzheimer's disease.

          The aging of the central nervous system and the development of incapacitating neurological diseases like Alzheimer's disease (AD) are generally associated with a wide range of histological and pathophysiological changes eventually leading to a compromised cognitive status. Although the diverse triggers of the neurodegenerative processes and their interactions are still the topic of extensive debate, the possible contribution of cerebrovascular deficiencies has been vigorously promoted in recent years. Various forms of cerebrovascular insufficiency such as reduced blood supply to the brain or disrupted microvascular integrity in cortical regions may occupy an initiating or intermediate position in the chain of events ending with cognitive failure. When, for example, vasoconstriction takes over a dominating role in the cerebral vessels, the perfusion rate of the brain can considerably decrease causing directly or through structural vascular damage a drop in cerebral glucose utilization. Consequently, cerebral metabolism can suffer a setback leading to neuronal damage and a concomitant suboptimal cognitive capacity. The present review focuses on the microvascular aspects of neurodegenerative processes in aging and AD with special attention to cerebral blood flow, neural metabolic changes and the abnormalities in microvascular ultrastructure. In this context, a few of the specific triggers leading to the prominent cerebrovascular pathology, as well as the potential neurological outcome of the compromised cerebral microvascular system are also going to be touched upon to a certain extent, without aiming at total comprehensiveness. Finally, a set of animal models are going to be presented that are frequently used to uncover the functional relationship between cerebrovascular factors and the damage to neural networks.
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            Brain infarction and the clinical expression of Alzheimer disease. The Nun Study.

            To determine the relationship of brain infarction to the clinical expression of Alzheimer disease (AD). Cognitive function and the prevalence of dementia were determined for participants in the Nun Study who later died. At autopsy, lacunar and larger brain infarcts were identified, and senile plaques and neurofibrillary tangles in the neocortex were quantitated. Participants with abundant senile plaques and some neurofibrillary tangles in the neocortex were classified as having met the neuropathologic criteria for AD. Convents in the Midwestern, Eastern, and Southern United States. A total of 102 college-educated women aged 76 to 100 years. Cognitive function assessed by standard tests and dementia and AD assessed by clinical and neuropathologic criteria. Among 61 participants who met the neuropathologic criteria for AD, those with brain infarcts had poorer cognitive function and a higher prevalence of dementia than those without infarcts. Participants with lacunar infarcts in the basal ganglia, thalamus, or deep white matter had an especially high prevalence of dementia, compared with those without infarcts (the odds ratio [OR] for dementia was 20.7, 95% confidence interval [95% CI], 1.5-288.0). Fewer neuropathologic lesions of AD appeared to result in dementia in those with lacunar infarcts in the basal ganglia, thalamus, or deep white matter than in those without infarcts. In contrast, among 41 participants who did not meet the neuropathologic criteria for AD, brain infarcts were only weakly associated with poor cognitive function and dementia. Among all 102 participants, atherosclerosis of the circle of Willis was strongly associated with lacunar and large brain infarcts. These findings suggest that cerebrovascular disease may play an important role in determining the presence and severity of the clinical symptoms of AD.
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              15-year longitudinal study of blood pressure and dementia.

              Vascular causes of dementia may be more common than supposed. Vascular factors may also have a role in late-onset Alzheimer's disease, but the role of hypertension in the development of dementia is unclear. As part of the Longitudinal Population Study of 70-year-olds in Göteborg, Sweden, we analysed the relation between blood pressure and the development of dementia in the age intervals 70-75, 75-79, and 79-85 years in those non-demented at age 70 (n = 382). The sample was followed up for 15 years and examined repeatedly with a comprehensive investigation, including a psychiatric and physical examination. a Participants who developed dementia at age 79-85 had higher systolic blood pressure at age 70 (mean 178 vs 164 mm Hg, p = 0.034) and higher diastolic blood pressure at ages 70 (101 vs 92, p = 0.004) and 75 (97 vs 90, p = 0.022) than those who did not develop dementia. For subtypes of dementia, higher diastolic blood pressure was recorded at age 70 (101, p = 0.019) for those developing Alzheimer's disease and at age 75 (101, p = 0.015) for those developing vascular dementia than for those who did not develop dementia. Participants with white-matter lesions on computed tomography at age 85 had higher blood pressure at age 70 than those without such lesions. Blood pressure declined in the years before dementia onset and was then similar to or lower than that in non-demented individuals. Previously increased blood pressure may increase the risk for dementia by inducing small-vessel disease and white-matter lesions. To what extent the decline in blood pressure before dementia onset is a consequence or a cause of the brain disease remains to be elucidated.
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                Author and article information

                Contributors
                marijana_tadic@hotmail.com
                cesare.cuspidi@unimib.it
                dagmara.hering@uw.edu.au
                Journal
                BMC Cardiovasc Disord
                BMC Cardiovasc Disord
                BMC Cardiovascular Disorders
                BioMed Central (London )
                1471-2261
                3 November 2016
                3 November 2016
                2016
                : 16
                : 208
                Affiliations
                [1 ]University Clinical Hospital Centre “Dr. Dragisa Misovic”, Heroja Milana Tepica 1, 11000 Belgrade, Serbia
                [2 ]University of Milan-Bicocca and Istituto Auxologico Italiano, Clinical Research Unit, Viale della Resistenza 23, 20036 Meda, Italy
                [3 ]Dobney Hypertension Centre, School of Medicine and Pharmacology-Royal Perth, Hospital Unit, The University of Western Australia, Rear 50 Murray Street, 6000 Perth, Australia
                Article
                386
                10.1186/s12872-016-0386-0
                5093934
                27809779
                688f3c2e-c834-4782-81c7-56006e8ba7e1
                © The Author(s). 2016

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 2 August 2016
                : 26 October 2016
                Categories
                Review
                Custom metadata
                © The Author(s) 2016

                Cardiovascular Medicine
                arterial hypertension,cognitive decline,dementia,antihypertensive therapy

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