Global cognitive and verbal episodic memory impairment in the post-acute phase of anti-nmdar encephalitis: a systematic review and meta-analysis with narrative synthesis.

BACKGROUND

Cognitive impairment is a recognized long-term complication of anti-NMDAR encephalitis, but its pooled magnitude, domain specificity, and time course have not been systematically quantified.

OBJECTIVE

To quantify pooled global cognitive and verbal episodic memory impairment in convalescent anti-NMDAR encephalitis relative to healthy comparators, and to assess whether impairment magnitude changes with time since disease onset.

METHODS

We systematically reviewed observational studies assessing standardized cognitive outcomes in adults with cell-based-assay-confirmed anti-NMDAR encephalitis during the post-acute/convalescent phase. PubMed, Embase, Scopus, and CENTRAL were searched from inception to 20 June 2026. Random-effects meta-analyses were performed for cognitive domains with at least three independent cohorts, while other domains were synthesized narratively according to SWiM principles.

RESULTS

Fourteen independent cohorts comprising 439 patients were included. Six cohorts (191 patients, 182 controls) contributed to the confirmed primary global-cognition analysis, showing substantial impairment (Hedges' g - 1.26, 95% CI - 1.49 to - 1.04; I²=0%). Verbal episodic memory was also impaired (g - 0.88, 95% CI - 1.13 to - 0.63; 5 cohorts). Recognition was impaired alongside recall in the two cohorts reporting recognition trials. Narrative synthesis identified frequent executive and working-memory impairment, impaired speeded processing, and deficits in visual episodic memory and language, whereas visuospatial findings were less consistent.

CONCLUSIONS

Post-acute anti-NMDAR encephalitis is associated with substantial global cognitive and verbal episodic memory impairment, with additional deficits across several cognitive domains. Comprehensive longitudinal neuropsychological assessment, including social cognition and psychiatric symptoms, is needed to clarify recovery trajectories and mechanisms.