Does serum uric acid act as a modulator of cerebrospinal fluid Alzheimer's disease biomarker related cognitive decline?

Eur J Neurol. 2016 May;23(5):948-57. doi: 10.1111/ene.12969. Epub 2016 Feb 24.

Abstract

Background and purpose: The association of serum uric acid, cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD) and longitudinal cognitive decline was evaluated using the AD Neuroimaging Initiative database.

Methods: In 271 healthy subjects, 596 mild cognitive impairment patients and 197 AD patients, serum uric acid and CSF AD biomarkers were measured at baseline, and Mini-Mental State Examination and AD Assessment Scale - Cognitive Subscale (ADAS-cog) were assessed serially (mean duration, 2.9 years). The effect of uric acid on longitudinal cognitive decline was evaluated using linear mixed effect models for Mini-Mental State Examination and ADAS-cog scores in female and male subjects separately, with possible confounders controlled (model 1). To determine the effects of uric acid independent of CSF biomarker (Aβ1-42 or tau) and to test whether the detrimental effects of CSF biomarker differ according to uric acid, CSF biomarker and its interaction with uric acid were further included in model 1 (model 2).

Results: Higher levels of uric acid were associated with slower cognitive decline, particularly in the mild cognitive impairment and dementia subgroups, and more prominently in female subjects. Model 2 with CSF Aβ1-42 showed that higher levels of uric acid were associated with a slower cognitive decline and alleviated the detrimental effect of Aβ1-42 on cognitive decline. Model 2 with CSF tau showed that higher levels of uric acid alleviated the detrimental effect of tau on cognitive decline in female subjects but not in male subjects.

Conclusion: Higher levels of uric acid had protective effects on longitudinal cognitive decline independent of and interactively with CSF AD biomarkers.

Keywords: Alzheimer's disease; antioxidant; cerebrospinal fluid; cognitive decline; mild cognitive impairment; uric acid.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / blood
  • Alzheimer Disease / cerebrospinal fluid
  • Alzheimer Disease / complications
  • Alzheimer Disease / diagnosis*
  • Biomarkers / blood
  • Biomarkers / cerebrospinal fluid
  • Cognition Disorders / blood
  • Cognition Disorders / cerebrospinal fluid
  • Cognition Disorders / diagnosis*
  • Cognition Disorders / etiology
  • Cognitive Dysfunction / blood
  • Cognitive Dysfunction / cerebrospinal fluid
  • Cognitive Dysfunction / diagnosis*
  • Cognitive Dysfunction / etiology
  • Databases, Factual
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neuropsychological Tests
  • Uric Acid / blood*

Substances

  • Biomarkers
  • Uric Acid