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

• Published in: Molecular psychiatry
• Main Authors: Arlt, Friederike A, Sperber, Pia S, von Rennenberg, Regina, Gebert, Pimrapat, Teegen, Bianca, Georgakis, Marios K, Fang, Rong, Dewenter, Anna, Görtler, Michael, Petzold, Gabor C, Wunderlich, Silke, Zerr, Inga, Dichgans, Martin, Prüss, Harald, Endres, Matthias
• Format: Journal Article
• Language: English
• Published: England 30.10.2024
• ISSN: 1359-4184; 1476-5578; 1476-5578
• DOI: 10.1038/s41380-024-02744-w

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 (β  = -0.11; 95%CI = -0.57 to -0.03) and were at increased risk for memory impairment (OR = 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 (OR = 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).