Background/Purpose: The pursuit of a link between gout/hyperuricemia and dementia has led to contradictory results.  Most observational studies, including population-based studies, showed that hyperuricemia was associated with a higher risk of dementia and less cognitive dysfunction, while a few studies found hyperuricemia to be associated with a lower risk of dementia.  Recently, a large French population-based study in the elderly (65 years or older) showed that hyperuricemia was associated with a higher risk of dementia and with MRI changes of aging in the brain. Our objective was to assess whether gout in the elderly is associated with a risk of incident dementia.

Methods: We used the 5% Medicare claims data for this observational cohort study.  We used multivariable-adjusted Cox proportional hazard models to assess the association of gout with incident dementia, adjusting for potential confounders/covariates including demographics (age, race, gender), comorbidities (Charlson-Romano comorbidity index), and medications commonly used for cardiac diseases (statins, beta-blockers, diuretics, and angiotensin converting enzyme (ACE)-inhibitors) and gout (allopurinol and febuxostat).  

Results: In our cohort of 1.71 million Medicare beneficiaries, 111,656 had incident dementia.  The crude incidence rates in people without and with gout were 10.9 and 17.9 per 1,000 person-years, respectively.  In multivariable-adjusted analyses, gout was independently associated with a significantly higher hazard ratio of incident dementia, with a hazard ratio [HR] of 1.15 (95% CI, 1.12, 1.18); sensitivity analyses confirmed the main findings. Compared to age 65 to <75 years, older age groups were associated with 3.5 and 7.8-fold higher hazards of dementia; hazards were also higher for females, Black race or people with higher medical comorbidity.

Subgroup analyses indicated that gout was significantly associated with dementia in patients without key comorbidities (CAD, hyperlipidemia, CVD, diabetes, hypertension) with HR ranging 1.19-1.52, but not in patients with each of these comorbidities, except CAD, with HR 0.99-1.04 (Table 1). 

Conclusion: Gout was independently associated with 17-20% higher risk of incident dementia in the elderly.  Future studies need to understand the pathogenic pathways involved in this increased risk.