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Long-term cognitive outcomes and persistent executive dysfunction in LGI1 autoimmune encephalitis.

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|February 6, 2026
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Summary

Cognitive function in Leucine-rich glioma-inactivated 1 (LGI1) antibody-associated autoimmune encephalitis improves with treatment, but executive dysfunction often remains. Older age is linked to poorer long-term outcomes in LGI1-AE patients.

Keywords:
Autoimmune encephalitisCognitive assessmentLGI1Outcome

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Area of Science:

  • Neurology
  • Immunology
  • Cognitive Neuroscience

Background:

  • Leucine-rich glioma-inactivated 1 (LGI1) antibody-associated autoimmune encephalitis (AE) causes cognitive and behavioral issues.
  • While immunotherapy aids recovery, long-term cognitive deficits, especially executive dysfunction, are not fully understood.
  • This study investigates long-term cognitive trajectories in LGI1-AE, focusing on executive function.

Purpose of the Study:

  • To evaluate long-term cognitive outcomes in patients with LGI1 antibody-associated autoimmune encephalitis.
  • To specifically examine the persistence and predictors of executive dysfunction following immunotherapy.

Main Methods:

  • Retrospective analysis of 18 LGI1-AE patients with median 44-month follow-up.
  • Cognitive function assessed via Montreal Cognitive Assessment (MoCA) and its executive function subscales (EIS).
  • Longitudinal changes analyzed using Wilcoxon signed-rank test; regression analysis identified outcome predictors.

Main Results:

  • Global cognition significantly improved post-treatment (median MoCA 20 to 24, p=0.001).
  • Executive function and delayed recall also showed significant gains (p=0.001 and p=0.024).
  • Younger patients (≤65 years) had better initial and follow-up cognition and executive scores. Initial MoCA predicted global cognition; initial EIS and age at onset predicted executive outcomes.

Conclusions:

  • Immunotherapy improves cognitive function in LGI1-AE, but executive dysfunction is a common persistent deficit.
  • Older age is an independent predictor of poorer long-term cognitive outcomes in LGI1-AE.
  • Age-related vulnerability may impair cognitive recovery in LGI1-AE patients.