Association of regular use of ibuprofen and paracetamol, genetic susceptibility, and new-onset dementia in the older population

Abstract

ObjectiveAlthough the possible efficacy and adverse effects of paracetamol and ibuprofen on dementia are of global clinical and public health importance, to date, the relationship of the use of paracetamol and ibuprofen with incident dementia remains uncertain. We aimed to assess the prospective association of regular use of ibuprofen and paracetamol with new-onset dementia in an older population. MethodsThis study included 212,968 participants from the UK Biobank, aged ≥60 years, with available data of ibuprofen, paracetamol use and without dementia at baseline. The primary outcome was new-onset all-cause dementia. The secondary outcomes included new-onset Alzheimer's disease and new-onset vascular dementia. ResultsDuring a median follow-up of 12.3 years, 6407 (3.0%) participants developed new-onset all-cause dementia. Participants who regularly used paracetamol had a significantly higher risk of new-onset all-cause dementia (adjusted HR, 1.18; 95%CI: 1.10–1.26), compared with non-users. However, there was no significant association between regular use of ibuprofen and new-onset all-cause dementia (users vs. non-users; adjusted HR, 1.06; 95%CI: 0.97–1.16). Furthermore, APOE ε4 dosage and genetic risk scores (GRS) of Alzheimer's disease calculated by 25 single nucleotide polymorphisms did not significantly modify the relationship of regular use of paracetamol and ibuprofen with new-onset all-cause dementia (Both P-interactions >0.05). Similar results were found in the propensity score analysis. Similar findings were also observed for new-onset Alzheimer's disease and new-onset vascular dementia. ConclusionsRegular use of paracetamol, but not ibuprofen, was associated with a significantly higher risk of new-onset dementia in the old population, regardless of genetic risks of dementia.