Serum Uric Acid, Alzheimer-Related Brain Changes, and Cognitive Impairment

Abstract

Background: Despite known associations of lower serum uric acid (UA) with Alzheimer's disease (AD) dementia or AD-related cognitive impairment, little is known regarding the underlying patho-mechanisms. We aimed to examine the relationships of serum UA with in vivo AD pathologies including cerebral beta-amyloid (Aβ) and tau deposition, AD-signature region cerebral glucose metabolism (AD-CM), and white matter hyperintensities (WMH). We also investigated the association between serum UA and cognitive performance, and then assessed whether such an association is mediated by the brain pathologies. Methods: A total of 430 non-demented older adults underwent comprehensive clinical assessments, measurement of serum UA level, and multimodal brain imaging, including Pittsburgh compound B-positron emission tomography (PET), AV-1451 PET, fluorodeoxyglucose (FDG)-PET, and magnetic resonance imaging scans. Mini-Mental State Examination (MMSE) and word list recall (WLR) test scores were used to measure cognitive performance. Results: Serum UA level was significantly associated with AD-CM, but not with Aβ deposition, tau deposition, or WMH volume. Serum UA levels also had significant association with WLR and marginal association with MMSE; such associations disappeared when AD-CM was controlled as a covariate, indicating that AD-CM has a mediating effect. Conclusion: The findings of the present study indicate that there is an association of low serum UA with AD-related cerebral hypometabolism, and whether this represents a causal relationship remains to be determined.

Association between serum urate and CSF markers of Alzheimer's disease pathology in a population‐based sample of 70‐year‐olds

“…The different results to our study may partially be explained by the differences in the study populations (i.e., ethnicity, selection, age range); analysis (no sex‐stratified analysis in Kim et al. 24 ); and the methods used for the detection of amyloid deposition, positron emission tomography (PET) scan in Kim et al. 24 and CSF markers by us, which may differ with regard to the timing, sensitivity, and specificity for the detection of Aβ deposition.…”

“… 24 ); and the methods used for the detection of amyloid deposition, positron emission tomography (PET) scan in Kim et al. 24 and CSF markers by us, which may differ with regard to the timing, sensitivity, and specificity for the detection of Aβ deposition.…”

“… 23 To date, only one study has investigated the association between serum urate and cerebral Aβ deposition in non‐demented Korean individuals (age range = 55 to 90 years), indicating no association. 24 However, the relationship between serum urate concentration and CSF markers of preclinical AD in healthy older people has not been examined.…”

The Influence of Serum Uric Acid Level on Alzheimer’s Disease: A Narrative Review

“…AD-CM was the link of UA and cognitive measure scores. A decreased level of SUA was relevant to AD-related cerebral hypometabolism [42]. In previous studies, few studies had included multimodal brain imaging to observe the relationship between uric acid and brain changes.…”

“…Therefore, the two aspects interacted with each other and accelerated the development of AD. Additionally, it has been demonstrated that increasing antioxidative potential correlated with a reduction of white matter injury [42].…”