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

OBJECTIVE: Although 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. METHODS: This 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. RESULTS: During 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. CONCLUSIONS: Regular 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.

Variety and Duration of Different Sedentary Behaviors, Inflammation, Genetic Susceptibility, and New-Onset Dementia in the Older Population.

OBJECTIVES: We aimed to evaluate the relationship of the variety and duration of different sedentary behaviors (TV-watching, driving, and nonoccupational computer use) with the risk of dementia in older participants, and examine whether inflammation and genetic susceptibility may modify the relationship. DESIGN: A prospective cohort study. SETTING AND PARTICIPANTS: 173,829 older participants (≥60 years) without prior dementia in the UK Biobank were enrolled. METHODS: A healthy sedentary behavior score was calculated as the number of the 3 major sedentary behaviors with a duration associated with the lowest risk of dementia. The primary outcome was new-onset all-cause dementia. RESULTS: During a median follow-up of 12.4 years, 4965 (2.9%) participants developed new-onset dementia. There were U-shaped associations for TV-watching and driving time, and a reversed J-shaped association for nonoccupational computer use time with new-onset all-cause dementia, with the lowest dementia risk at >0-<2 hours/day for all the 3 sedentary behaviors. Moreover, a higher healthy sedentary behavior score was significantly associated with a lower risk of all-cause dementia (per 1 score increment: hazard ratio 0.78, 95% CI 0.75-0.81), with a stronger inverse association in those with higher levels of high-sensitivity C-reactive protein and monocytes (both P-interactions <.05). Genetic risks of dementia did not significantly modify the association. Similar trends were found for new-onset Alzheimer's disease and vascular dementia. CONCLUSIONS AND IMPLICATIONS: The associations between the duration of different sedentary behaviors and new-onset dementia were different in the older population. Moreover, the variety of sedentary behavior was inversely associated with new-onset dementia, especially among those with higher levels of inflammation.

Risk of New-Onset Dementia in Patients with Chronic Kidney Disease on Statin Users: A Population-Based Cohort Study.

Patients with chronic kidney disease (CKD) are at a higher risk for developing dementia than the general population. Clinical studies have investigated the effects of statin use on new-onset dementia (NOD) in patients with CKD; however, the findings are inconsistent. This study examines the association between the use of statins and NOD in patients with CKD. We conducted a nationwide retrospective cohort study using the Taiwan Health Insurance Review and Assessment Service database (2003-2016). The primary outcome assessed the risk of incident dementia by estimating the hazard ratios and 95% confidence intervals. Therefore, multiple Cox regression models were conducted to analyse the association between statin use and NOD in patients with CKD. There were 24,090 participants with statin use and 28,049 participants without statin use in patients with new-diagnosed CKD; the NOD event was 1390 and 1608, respectively. There was a trend of reduction association between statin users and NOD events after adjusted sex, age, comorbidities, and concurrent medication (adjusted HR 0.93, 95% CI 0.87 to 1.00) in the 14 years of the follow-up. Sensitivity test for the propensity score 1:1 matched analyses showed similar results (adjusted HR 0.91, 95% CI 0.81 to 1.02). The subgroup analysis also identified the use of statins as having a trend against developing NOD in patients with hypertension. In conclusion, statin therapy may effectively reduce the risk of NOD in patients with CKD. More studies are needed to credibly evaluate the effects of statin therapy on the prevention of NOD in patients with CKD.