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Serum anti-NMDA receptor antibodies are linked to memory impairment 12 months after stroke
Molecular Psychiatry ( IF 9.6 ) Pub Date : 2024-10-30 , DOI: 10.1038/s41380-024-02744-w
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

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)



中文翻译:


血清抗 NMDA 受体抗体与中风后 12 个月的记忆障碍有关



中风患者患中风后痴呆的风险增加。血清抗 NMDA 受体自身抗体 (NMDAR1-abs) 与卒中后不良结局相关。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 DZNE—卒中机制 (DEMDAS) 队列的数据,并测量了基线时血清中的 NMDAR1-abs。在 6 个月和 12 个月的随访中,使用综合神经心理学测试组合评估认知功能。我们采用粗略和逐步混杂调整的线性和 logistic 回归模型以及广义估计方程模型 (GEE) 来确定 NMDAR1-abs 血清阳性与中风后认知功能的相关性。10.2% (58/569) 的 DEMDAS 患者为 NMDAR1-abs 血清阳性 (IgM:n = 44/IgA:n = 21/IgG:n = 2)。血清阳性与卒中后整体认知障碍无关。然而,与血清阴性患者相比,NMDAR1-abs 血清阳性患者在记忆领域的表现较低 (β调整 = -0.11;95%CI = -0.57 至 -0.03),并且记忆障碍的风险增加 (OR调整 = 3.8;95%CI = 1.33-10.82) 与血清阴性患者相比,在中风后 12 个月。此外,从 6 到 12 个月的随访中,NMDAR1-abs 与 GEE 中随时间推移的记忆障碍有关 (OR调整 = 2.41;95% CI = 1.05-5.49)。我们的数据表明,NMDAR1-abs 会导致中风后 1 年出现记忆功能障碍,而不会影响其他认知子域。因此,抗神经元自身免疫可能参与中风后记忆障碍的不同机制。临床试验名称和注册号:卒中后痴呆的决定因素 (DEMDAS;临床 trials.gov 上的研究标识符:NCT01334749)

更新日期:2024-10-30
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