Molecular Psychiatry ( IF 9.6 ) Pub Date : 2024-10-30 , DOI: 10.1038/s41380-024-02744-w
Friederike A Arlt 1, 2 , Pia S Sperber 1, 3, 4, 5 , Regina von Rennenberg 1, 2 , Pimrapat Gebert 6 , Bianca Teegen 7 , Marios K Georgakis 8 , Rong Fang 8 , Anna Dewenter 8 , Michael Görtler 9, 10 , Gabor C Petzold 11, 12 , Silke Wunderlich 13 , Inga Zerr 14, 15 , Martin Dichgans 8, 16, 17, 18 , Harald Prüss 1, 2 , Matthias Endres 1, 2, 5, 19, 20 ,
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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,NMDAR1-abs 与 6 至 12 个月随访中 GEE 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)