Although the pathogenesis of Alzheimer's disease (AD) is unclear, neuroinflammation appears to play a role in its development. Psoriasis is a chronic inflammatory skin disease that has recently been found to genetically overlap with AD. We aimed to investigate the risk of AD in patients with psoriasis. Subjects with psoriasis (n = 535,927) and age- and sex-matched controls without psoriasis (at a 5:1 ratio; n = 2,679,635) who underwent ≥3 health examinations between 2008 and 2014 were included, drawn from the Korean National Health Insurance System database. There were 50,209 cases of AD (1.87%) in controls without psoriasis and 11,311 cases (2.11%) in patients with psoriasis, and the median follow-up was 3.35 years. In a multivariable-adjusted model, patients with psoriasis showed a significantly increased risk of AD (hazard ratio, 1.09; 95% CI, 1.07-1.12, p < 0.0001) compared to controls without psoriasis. Among patients with psoriasis, the risk of AD was significantly increased in psoriasis patients not receiving systemic therapy compared to those receiving systemic therapy (hazard ratio, 1.10; 95% CI, 1.08-1.12 vs. hazard ratio, 0.99; 95% CI: 0.90-1.09, p < 0.0001). The incidence of AD was significantly increased in patients with psoriasis compared to control subjects without psoriasis. Of note, systemic treatment for psoriasis was associated with a reduced risk of AD.