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Arlt, Friederike A. ORCID logoORCID: https://orcid.org/0000-0002-0112-8685; Sperber, Pia S. ORCID logoORCID: https://orcid.org/0000-0002-9534-2374; Rennenberg, Regina von; Gebert, Pimrapat; Teegen, Bianca; Georgakis, Marios K. ORCID logoORCID: https://orcid.org/0000-0003-3507-3659; Fang, Rong ORCID logoORCID: https://orcid.org/0000-0002-5663-9407; Dewenter, Anna ORCID logoORCID: https://orcid.org/0000-0002-5636-196X; Görtler, Michael; Petzold, Gabor C.; Wunderlich, Silke; Zerr, Inga ORCID logoORCID: https://orcid.org/0000-0002-6722-2463; Dichgans, Martin ORCID logoORCID: https://orcid.org/0000-0002-0654-387X; Prüss, Harald ORCID logoORCID: https://orcid.org/0000-0002-8283-7976; Endres, Matthias ORCID logoORCID: https://orcid.org/0000-0001-6520-3720; Endres, Matthias ORCID logoORCID: https://orcid.org/0000-0001-6520-3720; Liman, Thomas; Nolte, Christian H.; Kerti, Lucia; Wittenberg, Tatjana; Scheitz, Jan F.; Sperber, Pia S.; Nave, Alexander H.; Kufner, Anna Ibaroule; Bode, Felix; Stösser, Sebastian; Meißner, Julius N.; Ebrahimi, Taraneh; Nordsiek, Julia; Beckonert, Niklas; Hermann, Peter; Schmitz, Matthias; Goebel, Stefan; Schütte-Schmidt, Julia; Nuhn, Sabine; Volpers, Corinna; Dechent, Peter; Bähr, Matthias; Glanz, Wenzel ORCID logoORCID: https://orcid.org/0000-0002-5865-4176; Georgakis, Marios K. ORCID logoORCID: https://orcid.org/0000-0003-3507-3659; Tiedt, Steffen ORCID logoORCID: https://orcid.org/0000-0002-8817-8457; Waegemann, Karin; Janowitz, Daniel ORCID logoORCID: https://orcid.org/0009-0003-4090-547X; Ikenberg, Benno; Bermkopf, Kathleen; Huber, Christiane; Wagner, Michael ORCID logoORCID: https://orcid.org/0000-0003-2589-6440; Neumann, Katja; Spottke, Annika ORCID logoORCID: https://orcid.org/0000-0001-9854-2972; Stöcker, Tony; Dühring, Marco; Speck, Oliver; Duezel, Emrah und Bartenstein, Peter (2024): Serum anti-NMDA receptor antibodies are linked to memory impairment 12 months after stroke. In: Molecular Psychiatry [Forthcoming]

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Abstract

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)

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