Association between urate-lowering therapies and cognitive decline in community-dwelling older adults

Abstract

Long-term use of urate-lowering therapies (ULT) may reduce inflammaging and thus prevent cognitive decline during aging. This article examined the association between long-term use of ULT and cognitive decline among community-dwelling older adults with spontaneous memory complaints. We performed a secondary observational analysis using data of 1673 participants ≥ 70 years old from the Multidomain Alzheimer Preventive Trial (MAPT Study), a randomized controlled trial assessing the effect of a multidomain intervention, the administration of polyunsaturated fatty acids (PUFA), both, or placebo on cognitive decline. We compared cognitive decline during the 5-year follow-up between three groups according to ULT (i.e. allopurinol and febuxostat) use: participants treated with ULT during at least 75% of the study period (PT ≥ 75; n = 51), less than 75% (PT < 75; n = 31), and non-treated participants (PNT; n = 1591). Cognitive function (measured by a composite score) was assessed at baseline, 6 months and every year for 5 years. Linear mixed models were performed and results were adjusted for age, sex, body mass index (BMI), diagnosis of arterial hypertension or diabetes, baseline composite cognitive score, and MAPT intervention groups. After the 5-year follow-up, only non-treated participants presented a significant decline in the cognitive composite score (mean change - 0.173, 95%CI - 0.212 to - 0.135; p < 0.0001). However, there were no differences in change of the composite cognitive score between groups (adjusted between-group difference for PT ≥ 75 vs. PNT: 0.144, 95%CI - 0.075 to 0.363, p = 0.196; PT < 75 vs. PNT: 0.103, 95%CI - 0.148 to 0.353, p = 0.421). Use of ULT was not associated with reduced cognitive decline over a 5-year follow-up among community-dwelling older adults at risk of dementia.

Figure 1

Evolution of the cognitive composite score (Z-Score) in the groups with participants not treated (PNT) with urate-lowering therapies (ULT), participants treated with ULT less than 75% of the study follow-up (PT < 75) and participants treated with ULT more than 75% of the study follow-up (PT ≥ 75) during a 5-year follow-up, among the participants of the MAPT study. PNT: patients not treated with urate-lowering therapies. PT < 75 : participants treated with urate-lowering therapies less than 75% of the study follow-up. PT ≥ 75 : participants treated with urate-lowering therapies more than 75% of the study follow-up.