Department of Psychiatry and Psychotherapy, University Medical Center of Göttingen, University of Goettingen, Von-Siebold-Str. 5, 37075, Goettingen, Germany.
Department of Neurology, University of Goettingen, Robert-Koch Str. 40, 37075, Goettingen, Germany.
J Neural Transm (Vienna). 2021 Mar;128(3):357-369. doi: 10.1007/s00702-021-02316-0. Epub 2021 Mar 6.
Autoantibody-associated cognitive impairment is an expanding field in geriatric psychiatry. We aim to assess the association between the presence of specific neural autoantibodies and cognitive performance in a memory clinic cohort. 154 patients with cognitive impairment were included between 2019 and 2020 presenting initially in a memory clinic. We evaluated their patient files retrospectively applying epidemiologic parameters, psychopathology, neuropsychology, intracellular and membrane-surface autoantibodies in serum and cerebrospinal fluid (CSF) and markers of neurodegeneration in CSF. In 26 of 154 patients, we searched for neural autoantibodies due to indicators for autoimmunity. In 15/26 (58%) of patients we detected serum and/or CSF autoantibodies. We identified autoantibodies against intracellular or cell-surface antigens in 7 of all 26 (27%) patients with cognitive dysfunction, although we cannot exclude patients with potential specific autoantibodies lacking autoimmune indicators. There were no significant differences between psychopathological and neuropsychological profiles in groups of patients with cognitive impairment comprising patients with autoantibodies (ABS + COG), no autoantibodies (ABS - COG), and Alzheimer's disease (ADCOG). Concerning our CSF parameters, we detected intrathecal IgG synthesis in 14% of ABS + COG and in 13% of ABS - COG patients, whereas no intrathecal IgG synthesis was found in ADCOG patients. Furthermore, CSF Aß42 was significantly diminished in the ADCOG compared to the ABS + COG group (p < 0.05). In addition, the Aß42/40 ratio was lower in ADCOG patients than in the ABS + COG or ABS - COG group (p < 0.05). Our findings reveal the underestimated occurrence and autoantibodies' potential role in patients presenting cognitive impairment. Furthermore, the patients with possible Alzheimer's disease might be differentiated from autoantibody-positive patients via a reduced Aß42 and Aß42/40 ratio in the CSF. The antibody-type varies between patients to a relevant degree, thus demonstrating the need for more research to identify subgroup-specific phenotypes. These pilot study results open an avenue for improving diagnosis and treatment in a memory clinic.
自身抗体相关性认知障碍是老年精神病学中一个不断扩展的领域。我们旨在评估特定神经自身抗体的存在与记忆门诊队列中认知表现之间的关联。2019 年至 2020 年间，我们共纳入了 154 名认知障碍患者，这些患者最初在记忆门诊就诊。我们回顾性地评估了他们的病历，应用了流行病学参数、精神病理学、神经心理学、血清和脑脊液（CSF）中的细胞内和膜表面自身抗体以及 CSF 中的神经退行性标志物。由于自身免疫的指标，我们在 154 名患者中的 26 名患者中寻找神经自身抗体。在 26 名患者中的 15 名（58%）检测到血清和/或 CSF 自身抗体。我们在所有 26 名认知功能障碍患者中的 7 名患者中发现了针对细胞内或细胞表面抗原的自身抗体，尽管我们不能排除潜在具有特异性自身抗体但缺乏自身免疫指标的患者。在包含自身抗体（ABS+COG）、无自身抗体（ABS-COG）和阿尔茨海默病（ADCOG）的认知障碍患者组中，自身抗体（ABS+COG）和无自身抗体（ABS-COG）的患者在精神病理学和神经心理学特征方面没有显著差异。在 ABS+COG 和 ABS-COG 患者中，14%和 13%分别检测到鞘内 IgG 合成，而在 ADCOG 患者中未检测到鞘内 IgG 合成。此外，ADCOG 患者的 CSF Aß42 显著低于 ABS+COG 组（p<0.05）。此外，ADCOG 患者的 Aß42/40 比值低于 ABS+COG 或 ABS-COG 组（p<0.05）。我们的研究结果揭示了在表现出认知障碍的患者中，自身抗体的发生和潜在作用被低估了。此外，通过 CSF 中 Aß42 和 Aß42/40 比值的降低，可能可以将患有阿尔茨海默病的患者与自身抗体阳性患者区分开来。抗体类型在患者之间存在显著差异，因此需要进一步研究以确定亚组特异性表型。这些初步研究结果为改善记忆门诊的诊断和治疗开辟了道路。
