Data regarding the association between psoriasis and dementia are inconclusive. The aim of this study was to evaluate this association in the database of Clalit Health Services, Israel. A comparative analysis for the association between psoriasis, dementia and its risk factors was performed for the entire study population and in the subgroup of patients with moderate-to-severe psoriasis. The study included 121,801 patients with psoriasis, of whom 16,947 were diagnosed with moderate-to-severe psoriasis, and 121,802 controls. Psoriasis was associated with a lower prevalence of dementia relative to control subjects (1.6% vs 1.8%; odds ratio (OR) 0.85; 95% confidence interval (95% CI) 0.80–0.91; p < 0.001). Multivariate analysis adjus-ting for demographic variables, cardiovascular-related risk factors, and healthcare utilization demonstrated a significant inverse association between psoriasis and dementia in the entire study population (adjusted OR 0.86; 95% CI 0.76–0.96; p = 0.009), but not in the subgroup of patients with moderate-to-severe psoriasis (adjusted OR 0.91; 95% CI 0.81–1.02; p = 0.113). In conclusion, these data support the hypothesis that psoriasis is inversely associated with dementia.