Serum Uric Acid Levels in Patients with Alzheimer's Disease: A Meta-Analysis

Abstract

BackgroundSerum uric acid (UA) could exert neuro-protective effects against Alzheimer's disease (AD) via its antioxidant capacities. Many studies investigated serum UA levels in AD patients, but to date, results from these observational studies are conflicting.MethodsWe conducted a meta-analysis to compare serum UA levels between AD patients and healthy controls by the random-effects model. Studies were identified by searching PubMed, ISI Web of Science, EMBASE, and the Cochrane library databases from 1966 through July 2013 using the Medical Subject Headings and keywords without restriction in languages. Only case-control studies were included if they had data on serum UA levels in AD patients and healthy controls. Begg's funnel plot and Egger's regression test were applied to assess the potential publication bias. Sensitivity analyses and meta-regression were conducted to explore possible explanations for heterogeneity.ResultsA total of 11 studies met the inclusion criteria including 2708 participants were abstracted. Serum UA levels were not significantly different in AD patients compared to healthy controls (standardized mean difference (SMD) = −0.50; 95% confidence interval (CI): −1.23 to 0.22). Little evidence of publication bias was observed. Sensitivity analyses showed that the combined SMD was consistent every time omitting any one study, except only one study which greatly influenced the overall results. Meta-regression showed that year of publication, race, sample size, and mean age were not significant sources of heterogeneity.ConclusionOur meta-analysis of case-control studies suggests that serum UA levels do not differ significantly in AD patients, but there may be a trend toward decreased UA in AD after an appropriate interpretation. More well-designed investigations are needed to demonstrate the potential change of serum UA levels in AD patients.

Uric acid and incident dementia over 12 years of follow-up: a population-based cohort study

“…Chen et al , in a meta-analysis of case–control studies (n=2708 participants), found no significant difference between patients with AD and healthy controls in SUA level 10. Another recent meta-analysis found lower SUA level in AD but not vascular nor mixed dementia 6.…”

“…Furthermore, given the putative adverse effect of UA on cardiovascular outcomes, UA may contribute to cognitive impairment and dementia risk via increased risk of cerebrovascular disease 13. Most studies that investigated the link between SUA level and dementia were cross-sectional, with risk of bias (review in refs 6 and 10), and longitudinal studies are scarce. Thus, more longitudinal population-based cohort studies are needed to better unravel the complex link between UA and cognitive impairment.…”

A Human-Based Integrated Framework forAlzheimer’s Disease Research

“…Elevated HCys in brain microvessels may be implicated in the disruption of the blood-brain barrier [51] and induction of excitotoxicity in cells expressing glutamate receptors of the N-methyl-D-aspartate class [52]. Other biomarkers considered relevant to AD are: low levels of plasma uric acid [53,54], high levels of serum 3,4-dihydroxybutanoic acid (C 4 H 8 O 4 ), docosapentaenoic acid (C22:5) [55], and hexacosanoic acid (C26:0) [56], the presence of insulin resistance and high insulin-like growth factor expression [57][58][59], impaired glycemic levels [60], mitochondrial damage and increased mitochondrial O-linked N-acetylglucosamine transferase activity [61], the presence of a dyslipidemic profile [31,[62][63][64][65][66], deregulation of plasma orexin [67][68][69][70], and high levels of the secreted heparin-binding glycoprotein YKL-40 [71,72] (Table 2). Additionally, the CSF milieu is altered in subjects presenting AD.…”

Role of serum urate in neurocognitive function and dementia: new evidence contradicts old thinking

“…Another systematic review assessed the association of sUA with Alzheimer’s dementia 12. Based on 11 case–control studies including 2,708 participants, the sUA levels were not significantly different between patients with Alzheimer’s dementia and healthy controls, and the standardized mean difference (SMD; same as the effect size) for sUA was −0.50 (95% CI −1.23 to 0.22), not statistically significant 12.…”