Cognitive dysfunction may be a sequelae of N-Methyl-D-Aspartate receptor encephalitis (NMDAR encephalitis) with working memory commonly affected. This study examined cognitive outcomes in patients treated for NMDAR encephalitis using a neurocognitive test battery and a working memory paradigm, compared with healthy controls & patients with schizophrenia.

Adult patients previously treated for NMDAR encephalitis were assessed using the Cambridge Automated Neuropsychological Test Battery (CANTAB) for working memory & episodic memory. Patients completed the N-back task during functional MRI (fMRI) scanning. Results were compared to patients with schizophrenia and healthy controls from a prior study.

Twelve patients were recruited [11 women; mean (SD) age 37(12) years; Mean (SD) duration until immunotherapy treatment 7.09 (2.43) weeks]. Data were compared to 14 patients with schizophrenia [10 women; mean (SD) age 39 (12) years] and 14 healthy controls [7 women; mean (SD) age 30 (6) years]. Significant differences in letter number sequencing, spatial working memory, logical memory I, 1-back, and 2-back performance were observed (Cohen's d = 0.766 to 1.254, p< 0.05), driven by poorer performance by patients with schizophrenia. While patients with NMDAR encephalitis exhibited slightly lower performance compared with healthy controls, none of these differences were statistically significant. No significant differences in neural activation during 1-back or 2-back performance were observed.

Study findings suggest cognitive performance in patients treated for NMDAR encephalitis approaches normal over time. Prompt treatment with immunotherapy is associated with improved cognitive outcomes. Psychiatric services should be aware of the clinical features of autoimmune encephalitis.

Autoimmune encephalitis

NMDAR encephalitis

First episode psychosis

Neurocognitive function

Working memory

Functional MRI

© 2025 The Authors. Published by Elsevier B.V.