Department of Old Age Psychiatry (Gibson, Hye, Aarsland) and Department of Psychosis Studies, Neuropsychiatry Research and Education Group (Pollak, Nicholson), Institute of Psychiatry, Psychology and Neuroscience, King's College London; Neuroimmunology and CSF Laboratory, Queen Square Institute of Neurology, National Hospital for Neurology and Neurosurgery, London (Hart, Church, Lakdawala); Departments of Neuroinflammation (Hart) and Neurodegenerative Disease (Heslegrave, Zetterberg), Institute of Neurology, University College London; UK Dementia Research Institute, University College London (Heslegrave, Zetterberg); Department of Basic and Clinical Neuroscience, Parkinson Foundation International Centre of Excellence, King's College Hospital and King's College London (Batzu, Rota, Trivedi, Chaudhuri); Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Sweden (Zetterberg); Centre for Age-Related Medicine, Stavanger University Hospital, Stavanger, Norway (Aarsland).
J Neuropsychiatry Clin Neurosci. 2023 Summer;35(3):236-243. doi: 10.1176/appi.neuropsych.20220107. Epub 2023 Jan 30.
-methyl-d-aspartate receptor (NMDAR) encephalitis is an autoantibody-mediated neurological syndrome with prominent cognitive and neuropsychiatric symptoms. The clinical relevance of NMDAR antibodies outside the context of encephalitis was assessed in this study.
Plasma from patients with Parkinson's disease (PD) (N=108) and healthy control subjects (N=89) was screened at baseline for immunoglobulin A (IgA), IgM, and IgG NMDAR antibodies, phosphorylated tau 181 (p-tau181), and the neuroaxonal injury marker neurofilament light (NfL). Clinical assessment of the patients included measures of cognition (Mini-Mental State Examination [MMSE]) and neuropsychiatric symptoms (Hospital Anxiety and Depression Scale; Non-Motor Symptoms Scale for Parkinson's Disease). A subgroup of patients (N=61) was followed annually for up to 6 years.
Ten (9%) patients with PD tested positive for NMDAR antibodies (IgA, N=5; IgM, N=6; IgG, N=0), and three (3%) healthy control subjects had IgM NMDAR antibodies; IgA NMDAR antibodies were detected significantly more commonly among patients with PD than healthy control subjects (χ=4.23, df=1, p=0.04). Age, gender, and disease duration were not associated with NMDAR antibody positivity. Longitudinally, antibody-positive patients had significantly greater decline in annual MMSE scores when the analyses were adjusted for education, age, disease duration, p-tau181, NfL, and follow-up duration (adjusted R=0.26, p=0.01). Neuropsychiatric symptoms were not associated with antibody status, and no associations were seen between NMDAR antibodies and p-tau181 or NfL levels.
NMDAR antibodies were associated with greater cognitive impairment over time in patients with PD, independent of other pathological biomarkers, suggesting a potential contribution of these antibodies to cognitive decline in PD.
-甲基-D-天冬氨酸受体（NMDAR）脑炎是一种自身抗体介导的神经综合征，以明显的认知和神经精神症状为特征。本研究评估了 NMDAR 抗体在脑炎背景之外的临床相关性。
在基线时，对帕金森病（PD）患者（N=108）和健康对照者（N=89）的血浆进行免疫球蛋白 A（IgA）、IgM 和 IgG NMDAR 抗体、磷酸化 tau181（p-tau181）和神经轴突损伤标志物神经丝轻（NfL）的筛查。对患者的临床评估包括认知（简易精神状态检查[MMSE]）和神经精神症状（医院焦虑和抑郁量表；帕金森病非运动症状量表）的评估。对一组患者（N=61）进行了长达 6 年的每年随访。
10 名（9%）PD 患者的 NMDAR 抗体检测呈阳性（IgA，N=5；IgM，N=6；IgG，N=0），3 名（3%）健康对照者的 IgM NMDAR 抗体呈阳性；PD 患者中 IgA NMDAR 抗体的检出率明显高于健康对照组（χ=4.23，df=1，p=0.04）。年龄、性别和疾病持续时间与 NMDAR 抗体阳性无关。纵向分析显示，在校正教育、年龄、疾病持续时间、p-tau181、NfL 和随访时间后，抗体阳性患者的 MMSE 评分每年下降幅度明显更大（调整后的 R=0.26，p=0.01）。神经精神症状与抗体状态无关，也没有发现 NMDAR 抗体与 p-tau181 或 NfL 水平之间存在相关性。
NMDAR 抗体与 PD 患者随时间推移认知功能下降有关，与其他病理生物标志物无关，提示这些抗体可能对 PD 的认知下降有一定的贡献。
