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• A link exists between NPC treated with RT and dementia development. • A 1.97-fold higher risk of dementia exists in NPC patients than in controls. • The occurrence of dementia seems earlier in NPC patients than in the controls. We evaluated the risk of dementia in patients with nasopharyngeal cancer (NPC) after undergoing radiation therapy (RT). Between January 1, 2000, and December 31, 2015, 594 patients newly diagnosed with NPC and treated with RT (NPC cohort) were identified from the Longitudinal Health Insurance Database (LHID) for this nationwide population-based matched cohort study. LHID is a subset of the National Health Insurance Research Database of Taiwan. We selected 2376 controls (non-NPC comparison cohort) using a four-fold propensity score-matched by sex, age, comorbidities, education level, tobacco abuse, and index date (the date when the patient received first RT). After adjusting for confounding factors, Fine and Gray's competing risk analysis compared dementia development between the NPC study cohort and non-NPC comparison cohort over the observation period from 2000 to 2015. Dementia development was 6.57% (39 of 594) and 4.42% (105 of 2376) in the NPC study cohort and non-NPC comparison cohort, respectively. Patients with NPC receiving RT were more likely to develop dementia than the comparison cohort, with a crude hazard ratio (HR) of 1.63 [95% confidence interval (CI) = 1.25–2.13, P < 0.001]. After adjusting for age, sex, education level, tobacco abuse, comorbidity, geographic area, urbanization level of the residence, and care level, the adjusted HR was 1.91 (95% CI = 1.42–2.51, P < 0.001). Patients with NPC receiving RT had a 1.91-fold higher risk of dementia than the non-NPC comparison controls. [ABSTRACT FROM AUTHOR]