ABSTRACT Background Treatment of locally‐advanced head and neck cancer (HNC) involves multiple therapeutic exposures that may directly or indirectly impact cognition. Purpose To describe long‐term cognitive impairment in a cohort of HNC survivors and to identify the cognitive domains most commonly affected. Methods and Materials This study enrolled patients with locally advanced or recurrent HNC who received radiation therapy (RT) and survived at least 2 years without recurrence. Participants completed a cognitive battery and quality of life measures. Performance in a cognitive domain was considered impaired if T < 35. Logistic regression was used to assess the relationship between treatment exposures and other variables with impairment in each cognitive domain. Results The final cohort consisted of 185 participants. The proportion of patients classified with cognitive impairment by domain was 36.8% for fine motor, 32.7% for verbal memory, 27.0% for executive function, 7.6% for vocabulary, and 7.0% for working memory. In the final model for impaired verbal memory, only radiation dose to the medial temporal lobe (OR = 1.06, 95% CI: 1.00–1.12) was significant. Time from RT (OR = 1.12, 95% CI: 1.01–1.24) and fatigue (OR = 3.45, 95% CI: 1.02–11.59) were associated with impaired working memory. Non‐white race (OR = 8.44, 95% CI: 3.23–22.05) and fatigue (OR = 2.68, 95% CI: 1.24–5.81) were associated with impaired executive function. Impaired emotional function and fatigue, but not cognitive battery performance, were associated with perceived cognitive impairment. Conclusions This study supports the hypothesis that many long‐term HNC survivors experience cognitive impairment. Higher radiation dose to the medial temporal lobe was associated with lower verbal memory performance, and fatigue was associated with impaired executive function, perceived cognitive abilities, and overall role functioning.
McDonald et al. (2026) studied this question.