Association of body weight and serum uric acid with Alzheimer's disease biomarkers and cognitive impairment

J Alzheimers Dis. 2025 Mar;104(1):255-268. doi: 10.1177/13872877251315011. Epub 2025 Feb 9.

Abstract

BackgroundGiven the limited effective treatments for Alzheimer's disease (AD), obesity and serum uric acid (SUA) levels which are considered modifiable risk factors for dementia are of interest. However, research indicates conflicting results.ObjectiveWe aimed to further investigate the association of body weight (BW) and SUA with AD biomarkers and cognitive impairment.MethodsClinical data were collected from 139 adults (mean age 66.9 years) with chronic cognitive impairment. Cerebrospinal fluid (CSF) biomarkers and PET imaging were used to assess amyloid-β (A) and Tau (T) tangles load, classifying participants into AT profiles based on the results. The association of BW and SUA with AT profiles was evaluated using multivariable logistic regression, and their relationship with cognitive function (Mini-Mental State Examination (MMSE) scores) were analyzed using multivariable linear regression.ResultsLower BW levels significantly influenced the presence of Aβ positive state (A+) (p = 0.007), while SUA levels did not (p = 0.263). Higher dementia proportion (p = 0.021), lighter BW (p = 0.019), and lower mean arterial pressure (MAP) levels (p = 0.025) were associated with AD pathological progress (A-T-→A+T-→A+T+), but SUA was not observed statistically significant. Among all participants regardless of Aβ state, high education levels (p < 0.001), high BW (p = 0.010), and high SUA (p=0.036) were associated with high MMSE scores, and high serum creatinine (p = 0.003) was associated with low MMSE scores.ConclusionsLower BW may accelerate AD pathology and cause cognitive impairment, while SUA is not linked to AD pathological progression but protects cognitive function.

Keywords: Alzheimer's disease pathology; biomarkers; body weight; cognitive function; serum uric acid.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease* / blood
  • Alzheimer Disease* / cerebrospinal fluid
  • Alzheimer Disease* / diagnostic imaging
  • Amyloid beta-Peptides / cerebrospinal fluid
  • Biomarkers / blood
  • Biomarkers / cerebrospinal fluid
  • Body Weight* / physiology
  • Cognitive Dysfunction* / blood
  • Cognitive Dysfunction* / cerebrospinal fluid
  • Cognitive Dysfunction* / diagnostic imaging
  • Female
  • Humans
  • Male
  • Mental Status and Dementia Tests
  • Middle Aged
  • Positron-Emission Tomography
  • Uric Acid* / blood
  • tau Proteins / cerebrospinal fluid

Substances

  • Uric Acid
  • Biomarkers
  • Amyloid beta-Peptides
  • tau Proteins