Are Inflammation and Related Therapy Associated with All-Cause Dementia in a Primary Care Population?

Background: There is limited primary-care based evidence for an association between chronic inflammation and related therapy with all-cause dementia. Objective: To estimate the association between several chronic inflammatory disorders and related drug therapy and all-cause dementia. Methods: The study population included a cohort of patients diagnosed with inflammatory conditions and matching controls (ratio 1:2) from the Clinical Practice Research Datalink, a database or primary care records in the UK. Inflammation patients and controls were matched on age, gender, and family practice. The study outcome measure was all-cause dementia. Chronic inflammation diagnosis and anti-inflammatory drugs represented the exposure variables of interest. Competing risks analyses were used to estimate the risk of dementia associated with exposure variables. Results: There were 1,378 (1%) and 2,805 (1%) dementia events recorded for chronic inflammation patients and their matched controls, respectively. Systemic vasculitis was associated with increased hazard ratios of dementia (1.75, 95% confidence interval (CI) 1.35-2.27, p < 0.001). The analyses revealed increased risk of dementia for systemic vasculitis (1.64, 95% CI 1.24-2.18), Crohn's diseases (2.08, 95% CI 1.16-3.74), bullous skin diseases (1.55, 95% CI 1.11-2.18), and inflammatory arthritis (1.33, 95% CI1.06-1.63) among treated patients. Combined glucocorticoids and NSAID therapy suggested reduced risk of dementia across most conditions, particularly systemic autoimmune disorders (0.41, 95% CI 0.18-0.95). Conclusion: The association between chronic inflammation and dementia varied across inflammatory disorders, being stronger for systemic vasculitis. There was evidence that combined therapy was associated with lower risk of dementia across most disorders. These data highlight potential avenues for future mechanistic and intervention investigations.