Background/Purpose: Previous studies of hyperuricemia and dementia have provided contradictory findings, ranging from reduced to increased risk.  Our objective was to assess the comparative effectiveness of allopurinol vs. febuxostat for preventing incident dementia in elderly.

Methods: In a retrospective cohort study using Medicare claims data, we included patients newly treated with allopurinol or febuxostat (baseline period of 365 days without either medication).  We used 1:5 propensity-matched Cox regression analyses to compare the hazard ratio (HR) of incident dementia with allopurinol vs. febuxostat, assessing use, dose and duration.

Results: We found 42,704 new allopurinol or febuxostat treatment episodes in 35,030 patients, of which 2,591 ended in incident dementia. Crude rates of incident dementia per 100,000 person-days were lower with higher daily dose: allopurinol <200, 200-299 and ³300 mg/day with 12, 9 and 8; and febuxostat 40 mg and 80 mg/day with 9 and 8, respectively.  In propensity-matched analyses, compared to allopurinol <200 mg/day, higher allopurinol doses (200-299 mg/day and ³300 mg/day) and febuxostat 40 mg/day dose were associated with lower HR of dementia, 0.80 (95% CI, 0.64, 0.98), 0.59 (95% CI, 0.50, 0.71) and 0.64 (95% CI, 0.47, 0.86), respectively; febuxostat 80 mg/day was not associated, 0.66 (95% CI, 0.36, 1.19).  Compared to allopurinol use for 1-180 days, longer febuxostat or allopurinol use durations were not significantly associated with differences in HR of dementia, ranging 0.76 to 1.14. 

Conclusion: Higher allopurinol dose and febuxostat were more effective than low-dose allopurinol in preventing dementia in elderly patients.  Future studies need to examine the mechanism of this benefit of febuxostat and higher-dose allopurinol. 

Keywords: Allopurinol; Febuxostat; Dementia; Elderly; Medicare

Comparative Effectiveness of Allopurinol versus Febuxostat in preventing Incident Dementia in the Elderly