Serum uric acid level and association with cognitive impairment and dementia: systematic review and meta-analysis

Abstract

Serum uric acid (sUA) level may be associated with cognitive impairment/dementia. It is possible this relationship varies with dementia subtype, particularly between vascular dementias (VaD) and Alzheimer's (AD) or Parkinson's disease (PDD)-related dementia. We aimed to present a synthesis of all published data on sUA and relationship with dementia/cognition through systematic review and meta-analysis. We included studies that assessed the association between sUA and any measure of cognitive function or a clinical diagnosis of dementia. We pre-defined subgroup analyses for patients with AD, VaD, PDD, mild cognitive impairment (MCI), and mixed or undifferentiated. We assessed risk of bias/generalizability, and where data allowed, we performed meta-analysis to describe pooled measures of association across studies. From 4811 titles, 46 papers (n = 16,688 participants) met our selection criteria. Compared to controls, sUA was lower in dementia (SDM -0.33 (95%CI)). There were differences in association by dementia type with apparent association for AD (SDM -0.33 (95%CI)) and PDD (SDM -0.67 (95%CI)) but not in cases of mixed dementia (SDM 0.19 (95%CI)) or VaD (SDM -0.05 (95%CI)). There was no correlation between scores on Mini-Mental State Examination and sUA level (summary r 0.08, p = 0.27), except in patients with PDD (r 0.16, p = 0.003). Our conclusions are limited by clinical heterogeneity and risk of bias in studies. Accepting this caveat, the relationship between sUA and dementia/cognitive impairment is not consistent across all dementia groups and in particular may differ in patients with VaD compared to other dementia subtypes.

Hyperuricemia as a Protective Factor for Mild Cognitive Impairment in Non-Obese Elderly

“…(Khan et al 2016). In the present study, we showed a more than 30% decreased risk of MCI in non-obese subjects with serum UA levels of ≥ 420μmol/L.…”

“…Previous studies revealed that blood glucose regulation disorder and hyperlipemia contributed to increased risk of dementia in patients with type 2 diabetes mellitus (Yaffe et al 2006;Kloppenborg et al 2008;Whitmer et al 2009). Several hypoglycemic and blood lipid lowering drugs, such as metformin and statins, had preventive and treatment effects on dementia in both epidemiological and animal studies (Risner et al 2006;Li et al 2012;Hendrie et al 2015).…”

“…Blood uric acid (UA), as well as albumin and total bilirubin, is an important non-enzymatic antioxidant in peripheral circulation, and might play a protective role in the development of MCI (Chen et al 2016;Yang et al 2016). Therefore, the relationship between serum UA levels and MCI risk is complicated and diverse, and a firm conclusion could not be drawn (Khan et al 2016).…”

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

“…For treating gout, the European League Against Rheumatism and American College of Rheumatology recommend lowering serum uric acid (SUA) level below 360 µmol/L and below 300 µmol/L in some cases 4 5. However, maintaining too low SUA levels is a concern because uric acid (UA) is thought to be neuroprotective 6. UA might have important antioxidant properties,7 and some studies have reported increased risk of several neurodegenerative diseases such as Parkinson’s disease8 or amyotrophic lateral sclerosis with a low SUA level 9…”

Long-Term Subclinical Hyperglycemia and Hypoglycemia as Independent Risk Factors for Mild Cognitive Impairment in Elderly People

“…A published meta-analysis in 2016 has reported a significant relationship between lower serum level of UA and development of Alzheimer's disease and Parkinsonism dementia (Khan et al 2016).…”