OBJECTIVE Cognitive functions, including working memory, attention, word fluency, and information processing speed, are known to be impaired in persons with multiple sclerosis (pwMS). Despite the clinical similarity of cognitive symptoms between persons with neuromyelitis optica (pwNMO) and pwMS, there is a dearth of research addressing cognitive impairment (CI) in NMO-related literature. This study aimed to examine the potential link between the age of initial symptom onset (ISO) and the presence of CI in pwNMO. Materials and Methods This study comprised two groups of pwNMO: eleven patients with age at ISO between 18 and 29, and 15 with age at ISO between 30 and 50. To mitigate the confounding effects on CI, pwNMO with matched education levels and ages were included in the study. A cohort of 467 healthy controls was assessed using the Brief International Cognitive Assessment for Multiple Sclerosis battery with a predefined cut-off value for CI set at 1.5 standard deviations below the mean. Participants with scores below this threshold value were classified as exhibiting CI in the respective domains. The severity of CI was stratified based on the number of impacted domains: participants exhibiting impairment in one domain were classified as experiencing moderate-to-severe impairment, those with impairment in two domains as severe, and those with impairment across all three domains as very severe. RESULTS None of the pwNMO who developed ISO between the ages of 18-29 exhibited CI. However, among those with ISO between the ages of 30 and 50, three demonstrated moderate-to-severe CI, one experienced severe CI, and one showed very severe CI. CONCLUSION The study results indicate a potential link between the age at ISO and the development of CI in pwNMO. Specifically, none of the pwNMO who experienced ISO between the ages of 18 and 29 exhibited signs of CI, whereas a significant percentage of those who experienced ISO between the ages of 30 and 50 showed signs of CI to varying degrees. These findings indicated that the onset of NMO symptoms at a later age may raise the risk of developing CI. Therefore, an early initiation of treatment could be vital in preventing and managing CI in pwNMO. Additional research is warranted to validate these findings and clarify the underlying mechanisms causing this connection.