Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2021 Aug;268(8):2769-2779.
doi: 10.1007/s00415-020-09825-0. Epub 2020 Apr 18.

Neuronal surface autoantibodies in dementia: a systematic review and meta-analysis

Lucy L Gibson  1 , Anna McKeever  2 , Alexis E Cullen  3 , Timothy R Nicholson  3 , Dag Aarsland  1   4 , Michael S Zandi  5 , Thomas A Pollak  3
Affiliations
Meta-Analysis

Neuronal surface autoantibodies in dementia: a systematic review and meta-analysis

Lucy L Gibson et al. J Neurol. 2021 Aug.

Abstract

Introduction: Neuronal antibodies can cause encephalopathy syndromes often presenting with subacute cognitive impairment, sometimes resembling neurodegenerative dementias.

Methods: We searched Medline and Embase for studies reporting associations between neuronal surface antibodies in all-cause dementia versus controls. Random-effects meta-analysis was used to pool adjusted estimates across studies.

Results: Six studies were included, all reporting frequency of serum NMDAR antibodies in dementia with four also reporting frequency in atypical dementias. Both IgG [OR = 8.09 (1.51; 56.85), p = 0.036] and IgA/IgM NMDAR antibodies [OR = 42.48 (11.39; 158.52), p < 0.001] were associated with atypical dementia, but neither were associated with all-cause dementia.

Discussion: In the first meta-analysis to explore this literature, serum IgG and IgA/IgM NMDAR antibodies were significantly more common in atypical dementias. However, methodological issues and small-sample sizes necessitate caution interpreting this result. Further studies measuring both serum and CSF antibodies are needed to investigate the role of neuronal antibodies in dementia, since evidence of pathogenicity in even a subset of patients could pave the way for novel treatment options.

Keywords: Antibodies in dementia; Atypical dementia; Autoimmune dementia; NMDAR antibody.

PubMed Disclaimer

Conflict of interest statement

MZ has received honoraria for lecturing from Eisai and UCB. DA has received research support and/or honoraria from Astra-Zeneca, H. Lundbeck, Novartis Pharmaceuticals, and GE Health, and served as paid consultant for H. Lundbeck, Eisai, Heptares, Sanofi, and Mentis Cura.

Figures

Fig. 1
Fig. 1
Search process
Fig. 2
Fig. 2
Meta-analysis of IgG NMDAR antibody in atypical dementia vs controls
Fig. 3
Fig. 3
Meta-analysis of IgA or IgM NMDAR antibody in atypical dementia vs controls
See this image and copyright information in PMC

References

    1. Binks SNM, et al. LGI1, CASPR2 and related antibodies: a molecular evolution of the phenotypes. J Neurol Neurosurg Psychiatry. 2018;89(5):526–534. doi: 10.1136/jnnp-2017-315720. - DOI - PMC - PubMed
    1. Hughes EG, et al. Cellular and synaptic mechanisms of anti-NMDA receptor encephalitis. J Neurosci. 2010;30(17):5866–5875. doi: 10.1523/JNEUROSCI.0167-10.2010. - DOI - PMC - PubMed
    1. Moscato EH, et al. Acute mechanisms underlying antibody effects in anti-N-methyl-d-aspartate receptor encephalitis. Ann Neurol. 2014;76(1):108–119. doi: 10.1002/ana.24195. - DOI - PMC - PubMed
    1. Jezequel J, et al. Molecular pathogenicity of anti-NMDA receptor autoantibody from patients with first-episode psychosis. Am J Psychiatry. 2018;175(4):382–383. doi: 10.1176/appi.ajp.2017.17091053. - DOI - PubMed
    1. Irani SR, et al. N-methyl-d-aspartate antibody encephalitis: temporal progression of clinical and paraclinical observations in a predominantly non-paraneoplastic disorder of both sexes. Brain. 2010;133(Pt 6):1655–1667. doi: 10.1093/brain/awq113. - DOI - PMC - PubMed