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
Department of Neurology and Experimental Neurology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität and Humboldt-Universität zu Berlin, Berlin, Germany.
German Center for Neurodegenerative Diseases (DZNE) Berlin, Berlin, Germany.
Mol Psychiatry. 2025 Apr;30(4):1359-1368. doi: 10.1038/s41380-024-02744-w. Epub 2024 Oct 30.
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).
中风患者患中风后痴呆症的风险增加。血清抗N-甲基-D-天冬氨酸受体自身抗体（NMDAR1抗体）与中风后不良预后相关。然而，它们对特定认知领域的影响仍不清楚。我们使用了来自前瞻性多中心中风后DZNE机制（DEMDAS）队列的数据，并在基线时测量了血清中的NMDAR1抗体。在6个月和12个月的随访中，使用综合神经心理测试组评估认知功能。我们采用了粗线性和逐步混杂因素调整的线性和逻辑回归模型以及广义估计方程模型（GEE）来确定NMDAR1抗体血清阳性与中风后认知功能的相关性。10.2%（58/569）的DEMDAS患者NMDAR1抗体血清呈阳性（IgM：n = 44/Iga：n = 21/IgG：n = 2）。血清阳性与中风后的整体认知障碍无关。然而，与血清阴性患者相比，中风后12个月，NMDAR1抗体血清阳性患者在记忆领域的表现较低（β = -0.11；95%CI = -0.57至-0.03），且记忆障碍风险增加（OR = 3.8；95%CI = 1.33 - 10.82）。此外，在6至12个月的随访中按GEE分析，NMDAR1抗体随时间与记忆障碍相关（OR = 2.41；95%CI = 1.05 - 5.49）。我们的数据表明，NMDAR1抗体在中风1年后导致记忆功能障碍，而不影响其他认知子领域。因此，抗神经元自身免疫可能参与了中风后记忆障碍的不同机制。临床试验名称和注册号：中风后痴呆的决定因素（DEMDAS；临床试验.gov上的研究标识符：NCT01334749）。
