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Serum anti-NMDA receptor antibodies are linked to memory impairment 12 months after stroke

  • Friederike A. Arlt,
  • Pia S. Sperber,
  • Regina von Rennenberg,
  • Pimrapat Gebert,
  • Bianca Teegen,
  • Marios K. Georgakis,
  • Rong Fang,
  • Anna Dewenter,
  • Michael Görtler,
  • Gabor C. Petzold,
  • Silke Wunderlich,
  • Inga Zerr,
  • Martin Dichgans,
  • Harald Prüss,
  • Matthias Endres,
  • Matthias Endres,
  • Thomas Liman,
  • Christian Nolte,
  • Lucia Kerti,
  • Tatjana Wittenberg,
  • Jan F. Scheitz,
  • Pia S. Sperber,
  • Alexander H. Nave,
  • Anna Ibaroule Kufner,
  • Felix Bode,
  • Sebastian Stösser,
  • Julius N. Meißner,
  • Taraneh Ebrahimi,
  • Julia Nordsiek,
  • Niklas Beckonert,
  • Peter Hermann,
  • Matthias Schmitz,
  • Stefan Goebel,
  • Julia Schütte-Schmidt,
  • Sabine Nuhn,
  • Corinna Volpers,
  • Peter Dechent,
  • Matthias Bähr,
  • Wenzel Glanz,
  • Marios Georgakis,
  • Steffen Tiedt,
  • Karin Waegemann,
  • Daniel Janowitz,
  • Benno Ikenberg,
  • Kathleen Bermkopf,
  • Christiane Huber,
  • Michael Wagner,
  • Katja Neumann,
  • Annika Spottke,
  • Tony Stöcker,
  • Marco Dühring,
  • Oliver Speck,
  • Emrah Duezel,
  • Peter Bartenstein

摘要

Patients suffering from strokes are at increased risk of developing post-stroke dementia. Serum anti-NMDA receptor autoantibodies (NMDAR1-abs) have been associated with unfavorable post-stroke outcomes. However, their effect on specific cognitive domains remains unclear. We used data from the prospective multicenter DZNE—mechanisms after stroke (DEMDAS) cohort, and measured NMDAR1-abs in serum at baseline. Cognitive function was assessed with a comprehensive neuropsychological test battery at 6- and 12-months follow-up. We employed crude and stepwise confounder adjusted linear and logistic regression models as well as generalized estimating equation models (GEE) to determine the relevance of NMDAR1-abs seropositivity on cognitive function after stroke. 10.2% (58/569) DEMDAS patients were NMDAR1-abs seropositive (IgM:n = 44/IgA:n = 21/IgG:n = 2). Seropositivity was not associated with global cognitive impairment after stroke. However, NMDAR1-abs seropositive patients performed lower in the memory domain (βadjusted = −0.11; 95%CI = −0.57 to −0.03) and were at increased risk for memory impairment (ORadjusted = 3.8; 95%CI = 1.33–10.82) compared to seronegative patients, 12 months after stroke. Further, NMDAR1-abs were linked to memory impairment over time in GEE from 6- to 12-months follow-up (ORadjusted = 2.41; 95%CI = 1.05–5.49). Our data suggests that NMDAR1-abs contribute to memory dysfunction 1 year after stroke while not affecting other cognitive subdomains. Hence, antineuronal autoimmunity may be involved in distinct mechanisms of post-stroke memory impairment. Clinical trial name and registration number: The Determinants of Dementia After Stroke (DEMDAS; study identifier on clinical trials.gov: NCT01334749)