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      Hypertension, dietary salt and cognitive impairment

      1 , 1
      Journal of Cerebral Blood Flow & Metabolism
      SAGE Publications

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          Abstract

          <p class="first" id="d272484e114">Dementia is growing at an alarming rate worldwide. Although Alzheimer disease is the leading cause, over 50% of individuals diagnosed with Alzheimer disease have vascular lesions at autopsy. There has been an increasing appreciation of the pathogenic role of vascular risk factors in cognitive impairment caused by neurodegeneration. Midlife hypertension is a leading risk factor for late-life dementia. Hypertension alters cerebrovascular structure, impairs the major factors regulating the cerebral microcirculation, and promotes Alzheimer pathology. Experimental studies have identified brain perivascular macrophages as the major free radical source mediating neurovascular dysfunction of hypertension. Recent evidence indicates that high dietary salt may also induce cognitive impairment. Contrary to previous belief, the effect is not necessarily associated with hypertension and is mediated by a deficit in endothelial nitric oxide. Collectively, the evidence suggests a remarkable cellular diversity of the impact of vascular risk factors on the cerebral vasculature and cognition. Whereas long-term longitudinal epidemiological studies are needed to resolve the temporal relationships between vascular risk factors and cognitive dysfunction, single-cell molecular studies of the vasculature in animal models will provide a fuller mechanistic understanding. This knowledge is critical for developing new preventive, diagnostic, and therapeutic approaches for these devastating diseases of the mind. </p>

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          Most cited references103

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          Interleukin 17 promotes angiotensin II-induced hypertension and vascular dysfunction.

          We have shown previously that T cells are required for the full development of angiotensin II-induced hypertension. However, the specific subsets of T cells that are important in this process are unknown. T helper 17 cells represent a novel subset that produces the proinflammatory cytokine interleukin 17 (IL-17). We found that angiotensin II infusion increased IL-17 production from T cells and IL-17 protein in the aortic media. To determine the effect of IL-17 on blood pressure and vascular function, we studied IL-17(-/-) mice. The initial hypertensive response to angiotensin II infusion was similar in IL-17(-/-) and C57BL/6J mice. However, hypertension was not sustained in IL-17(-/-) mice, reaching levels 30-mm Hg lower than in wild-type mice by 4 weeks of angiotensin II infusion. Vessels from IL-17(-/-) mice displayed preserved vascular function, decreased superoxide production, and reduced T-cell infiltration in response to angiotensin II. Gene array analysis of cultured human aortic smooth muscle cells revealed that IL-17, in conjunction with tumor necrosis factor-alpha, modulated expression of >30 genes, including a number of inflammatory cytokines/chemokines. Examination of IL-17 in diabetic humans showed that serum levels of this cytokine were significantly increased in those with hypertension compared with normotensive subjects. We conclude that IL-17 is critical for the maintenance of angiotensin II-induced hypertension and vascular dysfunction and might be a therapeutic target for this widespread disease.
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            Association Between Midlife Vascular Risk Factors and Estimated Brain Amyloid Deposition.

            Midlife vascular risk factors have been associated with late-life dementia. Whether these risk factors directly contribute to brain amyloid deposition is less well understood.
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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.
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                Author and article information

                Journal
                Journal of Cerebral Blood Flow & Metabolism
                J Cereb Blood Flow Metab
                SAGE Publications
                0271-678X
                1559-7016
                July 18 2018
                December 2018
                October 08 2018
                December 2018
                : 38
                : 12
                : 2112-2128
                Affiliations
                [1 ]Feil Family Brain and Mind Research Institute Weill Cornell Medicine, New York, NY, USA
                Article
                10.1177/0271678X18803374
                6282225
                30295560
                58acbe41-a7aa-42c8-a275-f29568b81249
                © 2018

                http://journals.sagepub.com/page/policies/text-and-data-mining-license

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