Gout, Hyperuricemia Linked to Decreased Likelihood of Alzheimer Disease

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An analysis of data from more than half a dozen studies has concluded presence of gout or hyperuricemia could signal a reduced risk of developing Alzheimer disease in older adults.

A systematic review and meta-analysis of prospective and retrospective cohort studies on the topic, results of the study suggest a diagnosis of gout or hyperuricemia was associated with a 31% reduction in risk of Alzheimer disease, with investigators noting a high level of heterogeneity driven by regional distribution of the studies.¹

“The findings suggested that gout or hyperuricemia might have a protective effect against [Alzheimer disease]. This negative correlation should be verified by more cohort studies due to the existence of substantial heterogeneity,” wrote investigators.¹

The most common cause of dementia and impacting more than 6 million adults in the US, Alzheimer disease poses a significant threat to individual- and population-level health, with the National Institute on Aging suggesting it is the 7th leading cause of death in the US.² Citing previous drawing contradictory conclusion on the role of hyperuricemia on development of cognitive disorders, a team representing the Anhui Medical University and Second People’s Hospital of Hefei China launched the current study to provide clinicians with further clarity on the subject.¹

With this in mind, investigators designed the current research endeavor as a systematic review and meta-analysis of published cohort studies that measured the risk of Alzheimer disease in people with gout/ hyperuricemia up to May 20, 2023. Through a search of the PubMed and EMBASE databases, investigators planned to calculate the relative ratio or hazard ratio for included studies, with additional plans for subgroup analyses to assess the sources of heterogeneity.¹

The investigators’ initial search yielded more than 500 records. Of these, 12 underwent full-text assessment for eligibility. After exclusion of noncohort studies, studies reporting from the same cohort, and those where risk of Alzheimer disease was not reported, a group of 7 studies was identified for inclusion in the meta-analysis.¹

Of the 7 studies included, 4 were conducted in Europe and 3 were conducted in Asia. When examining population sizes, 3 studies included more than 100,000 individuals and the remaining 4 contained fewer than 50,000 individuals. Investigators pointed out 4 studies had follow-up greater than 10 years in length and all studies were considered to be of high quality, which was defined as a Newcastle-Ottawa Scale score of 7 or greater.¹

Results of the pooled analysis indicated those with gout or hyperuricemia had a reduced risk of developing Alzheimer disease relative to their counterparts without gout or hyperuricemia, with 93% heterogeneity (P <.001). Further analysis suggested these results were consistent across subgroups defined by sample size, study design, location, and after adjustment for confounding factors (P >.05 for all).¹

Subgroup analyses determined the elevated level of heterogeneity could not be explained by study design or sample size, but assessments using regional distribution as a subgroup suggested studies from Asia had lower heterogeneity (I² = 28%). Based on this finding, investigators purported regional distribution was the source of the elevated heterogeneity.¹

“The role of gout or hyperuricemia in the pathogenesis of [Alzheimer disease] has often been described as controversial,” investigators noted.² “As mentioned above, our study showed a negative correlation between gout/hyperuricemia and [Alzheimer disease]. However, there were some previous studies with totally different conclusion: reporting that gout or hyperuricemia had no correlation with [Alzheimer disease] or even a positive association.”

References:

1. Wang L, Tan Z, Wang FY, Wu WP, Wu JC. Gout/hyperuricemia reduces the risk of Alzheimer's disease: A meta-analysis based on latest evidence [published online ahead of print, 2023 Sep 4]. Brain Behav. 2023;e3207. doi:10.1002/brb3.3207
2. Alzheimer’s disease fact sheet. National Institute on Aging. Accessed September 7, 2023. https://www.nia.nih.gov/health/alzheimers-disease-fact-sheet.