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Cosmos Study

Low Uric Acid Levels Associated with Increased Risk of Degenerative Neurologic Conditions

January 2, 2024
Dual-Team Study
Team A:Dave Little, MDAlex Piff
Team B:Kersten Bartelt, RNBrendan Joyce

Key Findings

  • Uric acid levels below 3.5 mg/dL are correlated with increased rates of being diagnosed with non-vascular and vascular dementia, as well as other degenerative neurologic conditions. 
  • Uric acid levels above 7.5 mg/dL are correlated with marginally decreased rates of being diagnosed with non-vascular dementia and other degenerative neurologic conditions. 

Uric acid levels are measured through a lab test of a patient’s blood or urine and are commonly used to diagnose conditions such as gout or to monitor patients undergoing chemotherapy.1 While some studies have found no correlation between uric acid levels and increased risk of dementia, others have suggested that uric acid has antioxidant properties and may offer protective benefits against neurologic conditions.2,3 

To better understand the relationship between uric acid levels and degenerative neurologic conditions, we studied 131,552 patients over the age of 50 who had at least one serum uric acid lab result between January 1, 2017, and November 1, 2021. We adjusted for various factors, including obesity, sex, age, ethnicity, and comorbidities. We calculated the risk of being diagnosed with a degenerative neurologic condition within the two years following a patient’s randomly selected serum uric acid reading. Our findings indicate that patients with a uric acid level below 3.5 mg/dL have increased rates of vascular and non-vascular dementia and other degenerative neurologic conditions compared to those with a high normal uric acid level (at 3.5-7.5 mg/dL), as seen in Figure 1. Conversely, those with a uric acid level above normal range (at 7.5-10 mg/dL) have a slightly decreased rates of non-vascular dementia and other degenerative neurologic conditions. We did not find consistent evidence of a correlation between Alzheimer’s disease and uric acid levels. 

Figure 1
Relative Rate of Degenerative Neurologic Conditions by Serum Uric Acid Level
Relative Rate of Degenerative Neurologic Conditions by Serum Uric Acid Level
Figure 1. The relative likelihood of being diagnosed with a degenerative neurologic condition by serum uric acid (SUA) level. High SUA is defined as greater than 10 mg/dL, slightly elevated is defined as 7.5 – 10 mg/dL, high normal is defined as 3.5 – 7.5 mg/dL, low normal is defined as 2.5 – 3.5 mg/dL, and below normal is defined as less than 2.5 mg/dL.

A sensitivity analysis using a Cox proportional hazards model that adjusted for obesity, sex, age, social vulnerability, race, ethnicity, and comorbidities showed similar results for the relationship between uric acid levels and degenerative neurologic conditions. 

These data come from Cosmos, a collaboration of 236 Epic health systems representing over 227 million patient records from 1,301 hospitals and more than 28,600 clinics from all 50 states and Lebanon. This study was completed by two teams that worked independently, each composed of a clinician and research scientists. The two teams came to similar conclusions. Graphics by Brian Olson. Kyle Fitzpatrick helped identify outcome codes.

References

  1. Uric Acid Test. MedlinePlus. Published December 15, 2022. https://medlineplus.gov/lab-tests/uric-acid-test/. Accessed November 30, 2023. 
  2. Alam AB, Wu A, Power MC, West NA, Alonso A. Associations of serum uric acid with incident dementia and cognitive decline in the ARIC-NCS cohort. J Neurol Sci. 2020;414:116866. doi:10.1016/j.jns.2020.116866 
  3. Tana C, Ticinesi A, Prati B, Nouvenne A, Meschi T. Uric Acid and Cognitive Function in Older Individuals. Nutrients. 2018; 10(8):975. https://doi.org/10.3390/nu10080975