Relationship Between Serum Uric Acid and Cognitive Function, Dementia

Researchers explored the association between midlife serum uric acid and the risk for cognitive decline and dementia.

Higher serum uric acid levels are related to a faster cognitive decline, while the association with dementia is inconclusive, according to study results published in the Journal of the Neurological Sciences.

Serum uric acid is a product of purine metabolism and previous studies have reported mixed results on the association between serum uric acid levels and cognitive decline and dementia and there is no consensus on this subject. While uric acid has antioxidant properties that may protect against cognitive decline, there are data showing it may induce cognitive dysfunction.

The goal of this study was to explore the association between midlife serum uric acid and the risk for cognitive decline and dementia over the course of 25 years and characterize the influence of race and sex on this association.

The study included 11,169 subjects free of dementia and cardiovascular disease from the Atherosclerosis Risk in Communities (ARIC) cohort, an ongoing, community-based cohort study in the US with first study visit in 1987-1989. Baseline cognitive function assessment was done at visit 2 (1990-92). Serum uric acid was measured in blood samples collected at that time.

Diagnosis of incident dementia was based on clinical assessments in 2011-12 and 2016-17, according to the criteria recommended by the National Institute of Aging – Alzheimer’s Association work groups. Assessment of cognitive decline was based on 3 neurocognitive exams administered at baseline and the follow-up visits. The Delayed Word Recall Test (DWRT), Digit Symbol Substitution Test (DSST), and Word Fluency Test (WFT) evaluate verbal learning and short-term memory, executive functioning, and expressive language, respectively.

The participants were followed for a median of 24.1 years, during which time, 2005 (18.0%) of 11,169 participants developed dementia. Those who developed dementia were slightly older, more likely to be female, black and less educated, compared to participants with intact cognitive function.

While following adjustment for sociodemographic variables there was an association between serum uric acid with risk for dementia, and the highest quartile of serum uric acid was associated with a 29% increased risk for dementia (hazard ratio [HR] 1.29, 95% CI, 1.12-1.47), this association disappeared after adjustment for cardiovascular risk factors (HR 1.03, 95% CI, 0.88-1.21). The association between serum uric acid and incident dementia was stronger in whites than blacks and in women compared to men, but these also disappeared following adjustments for cardiovascular risk factors.

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As for cognitive decline, there was an association between elevated serum uric acid with poorer cognitive function at baseline and faster 25-year cognitive decline in all neurocognitive domains following adjustment for sociodemographic variables. While the association between serum uric acid and incident dementia disappeared following accounting to cardiovascular risk factors, the association between elevated baseline serum uric acid with faster decline in each cognitive domain remained significant after full adjustment (25-year global z-score difference, -0.149; 95% CI, -0.246 to -0.052), except in the DSST. Overall, global cognitive decline seemed to be driven mainly by decline in DWRT scores.

The researchers acknowledged several study limitations, including one time measurement of serum uric acid, potential estimations error, and possible bias as participants with elevated serum uric acid could have died from cardiovascular disease in conjunction with dementia thus masking the real burden of dementia and cognitive decline.

“We have substantiated previous reports claiming an association between elevated SUA [serum uric acid] and increased cognitive decline in whites and women, but have found the evidence for a relationship between SUA and formally diagnosed dementia to be inconclusive,” concluded the researchers.


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 (published online 28 April, 2020). J Neurol Sci.  doi: 10.1016/j.jns.2020.116866