NMDA Receptor Antibodies and Neuropsychiatric Symptoms in Parkinson's Disease

Lucy L. Gibson*, Thomas A. Pollak, Melanie Hart, Amanda Heslegrave, Abdul Hye, Andrew J. Church, Neghat Lakdawala, Timothy R. Nicholson, Lucia Batzu, Silvia Rota, Dhaval Trivedi, Henrik Zetterberg, Kallol Ray Chaudhuri, Dag Aarsland

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)


OBJECTIVE: N-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. 

METHODS: 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. 

RESULTS: 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 (χ2=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 R2=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. 

CONCLUSIONS: 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.

Original languageEnglish
Pages (from-to)236-243
Number of pages8
JournalThe Journal of neuropsychiatry and clinical neurosciences
Issue number3
Early online date30 Jan 2023
Publication statusPublished - 1 Jul 2023


  • Immunology (Neuropsychiatric Aspects)
  • Parkinson’s Disease


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