Uric Acid and Cognitive Impairment in Patients with Acute Ischemic Stroke: A Meta-Analysis

Abstract

Serum uric acid (UA) has been suggested to be correlated with outcomes after stroke. We performed a meta-analysis to evaluate the association between serum UA and post-stroke cognitive impairment (PSCI) in patients with acute ischemic stroke (AIS). Relevant observational studies were identified by search of electronic databases including PubMed, Embase, and Web of Science. A randomized-effect model incorporating the possible between-study heterogeneity was used to pool the results. Overall, eleven studies with 4246 patients of AIS were included, 2073 (48.8%) of them had PSCI. Pooled results showed that patients with PSCI had significantly higher level of serum UA as compared to those without PSCI (mean difference: 35.70 μmol/l, 95% confidence interval (CI): 8.36 to 63.01, p=0.01; I2=95%). Subgroup analysis showed significant higher level of serum UA in patients with PSCI evaluated during follow-up of 3 months to 3 years, but not for those evaluated during hospitalization (p for subgroup difference=0.01). In addition, results of meta-analysis also showed that compared to patients with lower serum UA, AIS patients with higher serum UA had increased risk of PSCI (odds ratio: 1.33, 95% CI: 1.02 to 1.73, p=0.04; I2=72%). Higher level of serum UA after disease onset may be a marker of increased risk of PSCI in patients with AIS. Although these findings need to be validated in large-scale prospective studies, the possible mechanisms underlying the association between UA and PSCI should be also investigated.

Key words

uric acid - post-stroke cognitive impairment - cognitive function - acute ischemic stroke - meta-analysis

Publication History

Received: 10 February 2022

Accepted after revision: 09 March 2022

Article published online:
09 May 2022

• References

• 1 Tsao CW, Aday AW, Almarzooq ZI. et al. Heart disease and stroke statistics-2022 update: a report from the American heart association. Circulation 2022; 145: e153-e639
• 2 [Anonymous] Global, regional, and national burden of stroke and its risk factors, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet Neurol 2021; 20: 795-820
• 3 Kleindorfer DO, Towfighi A, Chaturvedi S. et al. 2021 Guideline for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline from the American heart association/American stroke association. Stroke 2021; 52: e364-e467
• 4 Zhang X, Bi X. Post-stroke cognitive impairment: a review focusing on molecular biomarkers. J Mol Neurosci 2020; 70: 1244-1254
• 5 Kim KY, Shin KY, Chang KA. Potential biomarkers for post-stroke cognitive impairment: a systematic review and meta-analysis. Int J Mol Sci 2022; 23: 602
• 6 Brainin M, Tuomilehto J, Heiss WD. et al. Post-stroke cognitive decline: an update and perspectives for clinical research. Eur J Neurol 2015; 22: 229-238 e213–e226
• 7 Burton L, Tyson SF. Screening for cognitive impairment after stroke: a systematic review of psychometric properties and clinical utility. J Rehabil Med 2015; 47: 193-203
• 8 Makin SD, Turpin S, Dennis MS. et al. Cognitive impairment after lacunar stroke: systematic review and meta-analysis of incidence, prevalence and comparison with other stroke subtypes. J Neurol Neurosurg Psychiatry 2013; 84: 893-900
• 9 Dros J, Klimkowicz-Mrowiec A. Current view on post-stroke dementia. Psychogeriatrics 2021; 21: 407-417
• 10 Park JH, Kim BJ, Bae HJ. et al. Impact of post-stroke cognitive impairment with no dementia on health-related quality of life. J Stroke 2013; 15: 49-56
• 11 Gaynor E, Rohde D, Large M. et al. Cognitive impairment, vulnerability, and mortality post ischemic stroke: a five-year follow-up of the Action on secondary prevention interventions and rehabilitation in stroke (ASPIRE-S) cohort. J Stroke Cerebrovasc Dis 2018; 27: 2466-2473
• 12 Quinn TJ, Richard E, Teuschl Y. et al. European stroke organisation and european academy of neurology joint guidelines on post-stroke cognitive impairment. Eur J Neurol 2021; 28: 3883-3920
• 13 Saito Y, Tanaka A, Node K. et al. Uric acid and cardiovascular disease: A clinical review. J Cardiol 2021; 78: 51-57
• 14 Qiao T, Wu H, Peng W. The relationship between elevated serum uric acid and risk of stroke in adult: an updated and dose-response meta-analysis. Front Neurol 2021; 12: 674398
• 15 Dong Y, Shi H, Chen X. et al. Serum uric acid and risk of stroke: a dose-response meta-analysis. J Clin Biochem Nutr 2021; 68: 221-227
• 16 Zhong C, Zhong X, Xu T. et al. Sex-specific relationship between serum uric acid and risk of stroke: a dose-response meta-analysis of prospective studies. J Am Heart Assoc 2017; 6: e005042
• 17 Khan AA, Quinn TJ, Hewitt J. et al. Serum uric acid level and association with cognitive impairment and dementia: systematic review and meta-analysis. Age (Dordr) 2016; 38: 16
• 18 Zhou Z, Zhong S, Liang Y. et al. Serum uric acid and the risk of dementia: a systematic review and meta-analysis. Front Aging Neurosci 2021; 13: 625690
• 19 Latourte A, Dumurgier J, Paquet C. et al. Hyperuricemia, gout, and the brain - an update. Curr Rheumatol Rep 2021; 23: 82
• 20 Liu H, Reynolds GP, Wang W. et al. Lower uric acid is associated with poor short-term outcome and a higher frequency of posterior arterial involvement in ischemic stroke. Neurol Sci 2018; 39: 1117-1119
• 21 Weng X, Fu F, Ling Y. et al. Gallstone disease is an independent predictor for poststroke cognitive impairment in young patients with acute ischemic stroke. Eur Neurol 2019; 82: 15-22
• 22 Zeng Q, Huang Z, Wei L. et al. Correlations of serum cystatin C level and gene polymorphism with vascular cognitive impairment after acute cerebral infarction. Neurol Sci 2019; 40: 1049-1054
• 23 Zhu Z, Zhong C, Guo D. et al. Multiple biomarkers covering several pathways improve predictive ability for cognitive impairment among ischemic stroke patients with elevated blood pressure. Atherosclerosis 2019; 287: 30-37
• 24 Huang J, Tang J, Zhang Y. et al. Association between ankle brachial index, brachial-ankle pulse wave velocity, and mild cognitive impairment in patients with acute lacunar infarction. Eur Neurol 2020; 83: 147-153
• 25 Ran F, Liu F, Zhang Y. et al. Serum uric acid and high-sensitivity C-reactive protein as predictors of cognitive impairment in patients with cerebral infarction. Dement Geriatr Cogn Disord 2020; 49: 235-242
• 26 Sun J, Lv X, Gao X. et al. The association between serum uric acid level and the risk of cognitive impairment after ischemic stroke. Neurosci Lett 2020; 734: 135098
• 27 Wu JX, Xue J, Zhuang L. et al. Plasma parameters and risk factors of patients with post-stroke cognitive impairment. Ann Palliat Med 2020; 9: 45-52
• 28 Chen XY, Fu M, Wan SF. et al. Association between plasma immunoproteasome and 90-day prognosis after first-ever ischemic stroke. Neural Regen Res 2021; 16: 790-795
• 29 Liu Q, Liao X, Pan Y. et al. 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. Neuropsychiatr Dis Treat 2021; 17: 991-999
• 30 Wanggong F, Xiang J, Yang S. et al. Correlation of serum uric acid, cystatin C and high-sensitivity C-reactive protein with cognitive impairment in lacunar cerebral infarction. Am J Transl Res 2021; 13: 6717-6723
• 31 Page MJ, McKenzie JE, Bossuyt PM. et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ 2021; 372: n71
• 32 Page MJ, Moher D, Bossuyt PM. et al. PRISMA 2020 explanation and elaboration: updated guidance and exemplars for reporting systematic reviews. BMJ 2021; 372: n160
• 33 Higgins J, Thomas J, Chandler J. et al. Cochrane handbook for systematic reviews of interventions version 6.2. The Cochrane Collaboration. 2021 www.training.cochrane.org/handbook
• 34 Wells GA, Shea B, O’Connell D. et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. 2010 http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp
• 35 Higgins J, Green S. Cochrane handbook for systematic reviews of interventions version 5.1.0. The Cochrane Collaboration. 2011 www.cochranehandbook.org
• 36 Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med 2002; 21: 1539-1558
• 37 Egger M, Davey Smith G, Schneider M. et al. Bias in meta-analysis detected by a simple, graphical test. BMJ 1997; 315: 629-634
• 38 Zhu Y, Zhao S, Fan Z. et al. Evaluation of the mini-mental state examination and the montreal cognitive assessment for predicting post-stroke cognitive impairment during the acute phase in Chinese minor stroke patients. Front Aging Neurosci 2020; 12: 236
• 39 Shi D, Chen X, Li Z. Diagnostic test accuracy of the Montreal cognitive assessment in the detection of post-stroke cognitive impairment under different stages and cutoffs: a systematic review and meta-analysis. Neurol Sci 2018; 39: 705-716
• 40 Latourte A, Bardin T, Richette P. Uric acid and cognitive decline: a double-edge sword?. Curr Opin Rheumatol 2018; 30: 183-187
• 41 Aliena-Valero A, Baixauli-Martin J, Castello-Ruiz M. et al. Effect of uric acid in animal models of ischemic stroke: a systematic review and meta-analysis. J Cereb Blood Flow Metab 2021; 41: 707-722
• 42 Lei Z, Cai J, Hong H. et al. Serum uric acid level and outcome of patients with ischemic stroke: a systematic review and meta-analysis. Neurologist 2019; 24: 121-131
• 43 Wang Z, Lin Y, Liu Y. et al. Serum uric acid levels and outcomes after acute ischemic stroke. Mol Neurobiol 2016; 53: 1753-1759
• 44 Zhang M, Wang Y, Wang K. et al. Association between uric acid and the prognosis of acute ischemic stroke: a systematic review and meta-analysis. Nutr Metab Cardiovasc Dis 2021; 31: 3016-3023
• 45 Seet RC, Kasiman K, Gruber J. et al. Is uric acid protective or deleterious in acute ischemic stroke? A prospective cohort study. Atherosclerosis 2010; 209: 215-219
• 46 Zhang X, Huang ZC, Lu TS. et al. Prognostic significance of uric acid levels in ischemic stroke patients. Neurotox Res 2016; 29: 10-20
• 47 Yang Y, Zhang Y, Li Y. et al. U-shaped relationship between functional outcome and serum uric acid in ischemic stroke. Cell Physiol Biochem 2018; 47: 2369-2379
• 48 Zhang B, Yang N, Lin SP. et al. Suitable concentrations of uric acid can reduce cell death in models of OGD and cerebral ischemia-reperfusion injury. Cell Mol Neurobiol 2017; 37: 931-939
• 49 Furuhashi M. New insights into purine metabolism in metabolic diseases: role of xanthine oxidoreductase activity. Am J Physiol Endocrinol Metab 2020; 319: E827-E834
• 50 Cherubini A, Polidori MC, Bregnocchi M. et al. Antioxidant profile and early outcome in stroke patients. Stroke 2000; 31: 2295-2300
• 51 Li D, Wang L, Ou J, Wang C. et al. Reactive oxygen species induced by uric acid promote NRK52E cell apoptosis through the NEK7NLRP3 signaling pathway. Mol Med Rep 2021; 24 Article No. 729
• 52 Brouns R, Wauters A, Van De Vijver G. et al. Decrease in uric acid in acute ischemic stroke correlates with stroke severity, evolution and outcome. Clin Chem Lab Med 2010; 48: 383-390
• 53 Gao J, Xu W, Han K. et al. Changes of serum uric acid and total bilirubin in elderly patients with major postischemic stroke depression. Neuropsychiatr Dis Treat 2018; 14: 83-93
• 54 Derosa G, Maffioli P, Reiner Z. et al. Impact of statin therapy on plasma uric acid concentrations: a systematic review and meta-analysis. Drugs 2016; 76: 947-956
• 55 Fan Y, Wei F, Lang Y. et al. Losartan treatment for hypertensive patients with hyperuricaemia in Chinese population: a meta-analysis. J Hypertens 2015; 33: 681-688 discussion 689
• 56 Zhao Y, Xu L, Tian D. et al. Effects of sodium-glucose co-transporter 2 (SGLT2) inhibitors on serum uric acid level: A meta-analysis of randomized controlled trials. Diabetes Obes Metab 2018; 20: 458-462