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      Association Between Serum Uric Acid Levels and Cognitive Function in Patients with Ischemic Stroke and Transient Ischemic Attack (TIA): A 3-Month Follow-Up Study

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          Abstract

          Purpose

          Cognitive impairment is a common complication after stroke and transient ischemic attack (TIA). The relationship between serum uric acid (SUA) and post-stroke cognitive impairment (PSCI) is controversial. This study evaluated the association of different SUA levels in the normal range and PSCI at 3 months.

          Patients and Methods

          A total of 1523 patients with ischemic stroke/TIA were recruited from the Impairment of Cognition and Sleep (ICONS) subgroup of the China National Stroke Registry-3 (CNSR-3). SUA concentration was assessed at baseline. Global cognitive status was evaluated using the Montreal Cognitive Assessment (MoCA). The main clinical outcome was the incidence of PSCI assessed at 3 months after stroke/TIA. The association between SUA status and the risk of PSCI was assessed with multiple regression models adjusted for potential covariates.

          Results

          Among the 1523 patients (1391 (91.33%) stroke patients and 132 (8.67%) TIA patients), 747 (49.05%) patients had PSCI at 3 months. Compared to the reference group, there was an increased risk of PSCI in males with SUA levels in the first (OR=1.76) and fourth quartiles (OR=1.47). A U-shaped association between SUA levels and the incidence of PSCI with an inflection point of 297 mmol/L was also found in males. However, there was no association between SUA levels and PSCI in females.

          Conclusion

          The association between SUA and PSCI differed between males and females. In males, both low and high SUA levels were associated with relatively higher incidences of PSCI, supporting a U-shaped association between SUA levels and PSCI.

          Most cited references37

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          The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment.

          To develop a 10-minute cognitive screening tool (Montreal Cognitive Assessment, MoCA) to assist first-line physicians in detection of mild cognitive impairment (MCI), a clinical state that often progresses to dementia. Validation study. A community clinic and an academic center. Ninety-four patients meeting MCI clinical criteria supported by psychometric measures, 93 patients with mild Alzheimer's disease (AD) (Mini-Mental State Examination (MMSE) score > or =17), and 90 healthy elderly controls (NC). The MoCA and MMSE were administered to all participants, and sensitivity and specificity of both measures were assessed for detection of MCI and mild AD. Using a cutoff score 26, the MMSE had a sensitivity of 18% to detect MCI, whereas the MoCA detected 90% of MCI subjects. In the mild AD group, the MMSE had a sensitivity of 78%, whereas the MoCA detected 100%. Specificity was excellent for both MMSE and MoCA (100% and 87%, respectively). MCI as an entity is evolving and somewhat controversial. The MoCA is a brief cognitive screening tool with high sensitivity and specificity for detecting MCI as currently conceptualized in patients performing in the normal range on the MMSE.
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            The pathobiology of vascular dementia.

            Vascular cognitive impairment defines alterations in cognition, ranging from subtle deficits to full-blown dementia, attributable to cerebrovascular causes. Often coexisting with Alzheimer's disease, mixed vascular and neurodegenerative dementia has emerged as the leading cause of age-related cognitive impairment. Central to the disease mechanism is the crucial role that cerebral blood vessels play in brain health, not only for the delivery of oxygen and nutrients, but also for the trophic signaling that inextricably links the well-being of neurons and glia to that of cerebrovascular cells. This review will examine how vascular damage disrupts these vital homeostatic interactions, focusing on the hemispheric white matter, a region at heightened risk for vascular damage, and on the interplay between vascular factors and Alzheimer's disease. Finally, preventative and therapeutic prospects will be examined, highlighting the importance of midlife vascular risk factor control in the prevention of late-life dementia. Copyright © 2013 Elsevier Inc. All rights reserved.
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              Uric acid-induced C-reactive protein expression: implication on cell proliferation and nitric oxide production of human vascular cells.

              Recent experimental and human studies have shown that hyperuricemia is associated with hypertension, systemic inflammation, and cardiovascular disease mediated by endothelial dysfunction and pathologic vascular remodeling. Elevated levels of C-reactive protein (CRP) have emerged as one of the most powerful independent predictors of cardiovascular disease. In addition to being a marker of inflammation, recent evidence suggests that CRP may participate directly in the development of atherosclerotic vascular disease. For investigating whether uric acid (UA)-induced inflammatory reaction and vascular remodeling is related to CRP, the UA-induced expression of CRP in human vascular smooth muscle cells (HVSMC) and human umbilical vein endothelial cells (HUVEC) was examined, as well as the pathogenetic role of CRP in vascular remodeling. It is interesting that HVSMC and HUVEC expressed CRP mRNA and protein constitutively, revealing that vascular cells are another source of CRP production. UA (6 to 12 mg/dl) upregulated CRP mRNA expression in HVSMC and HUVEC with a concomitant increase in CRP release into cell culture media. Inhibition of p38 or extracellular signal-regulated kinase 44/42 significantly suppressed UA-induced CRP expression, implicating these pathways in the response to UA. UA stimulated HVSMC proliferation whereas UA inhibited serum-induced proliferation of HUVEC assessed by 3H-thymidine uptake and cell counting, which was attenuated by co-incubation with probenecid, the organic anion transport inhibitor, suggesting that entry of UA into cells is responsible for CRP expression. UA also increased HVSMC migration and inhibited HUVEC migration. In HUVEC, UA reduced nitric oxide (NO) release. Treatment of vascular cells with anti-CRP antibody revealed a reversal of the effect of UA on cell proliferation and migration in HVSMC and NO release in HUVEC, which suggests that CRP expression may be responsible for UA-induced vascular remodeling. This is the first study to show that soluble UA, at physiologic concentrations, has profound effects on human vascular cells. The observation that UA alters the proliferation/migration and NO release of human vascular cells, mediated by the expression of CRP, calls for careful reconsideration of the role of UA in hypertension and vascular disease.
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                Author and article information

                Journal
                Neuropsychiatr Dis Treat
                Neuropsychiatr Dis Treat
                ndt
                neurodist
                Neuropsychiatric Disease and Treatment
                Dove
                1176-6328
                1178-2021
                31 March 2021
                2021
                : 17
                : 991-999
                Affiliations
                [1 ]Department of Neurology, Beijing Tiantan Hospital, Capital Medical University , Beijing, People’s Republic of China
                [2 ]China National Clinical Research Center for Neurological Diseases, Capital Medical University , Beijing, People’s Republic of China
                [3 ]Department of Rehabilitation Medicine, Beijing Tiantan Hospital, Capital Medical University , Beijing, People’s Republic of China
                Author notes
                Correspondence: Yumei Zhang Department of Rehabilitation Medicine, Beijing Tiantan Hospital, Capital Medical University , 119#Nan Si Huan Xi Lu, Beijing, 100070, People’s Republic of ChinaTel +86 136-9140-4106 Email zhangyumei95@aliyun.com
                Author information
                http://orcid.org/0000-0003-0110-7750
                Article
                300893
                10.2147/NDT.S300893
                8020328
                33833515
                6432b5c3-8a7e-4b71-885a-96db59f6affb
                © 2021 Liu et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                : 08 January 2021
                : 22 February 2021
                Page count
                Figures: 2, Tables: 6, References: 38, Pages: 9
                Funding
                Funded by: National Natural Science Foundation of China, open-funder-registry 10.13039/501100001809;
                This work was granted by National Key R&D Program of China (2018YFC1312903), National Science and Technology Major Project (2017ZX09304018), Beijing Municipal Science & Technology Commission (D171100003017002, Z181100001818001) and National Natural Science Foundation of China (81972144).
                Categories
                Original Research

                Neurology
                uric acid,cognitive impairment,stroke,transient ischemic attack,u-shaped curve
                Neurology
                uric acid, cognitive impairment, stroke, transient ischemic attack, u-shaped curve

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