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

• Published in: Journal of neurology Vol. 268; no. 8; pp. 2769 - 2779
• Main Authors: Gibson, Lucy L., McKeever, Anna, Cullen, Alexis E., Nicholson, Timothy R., Aarsland, Dag, Zandi, Michael S., Pollak, Thomas A.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.08.2021; Springer Nature B.V
• Subjects: Antibodies; Autoantibodies; Cerebrospinal fluid; Cognitive ability; Dementia; Dementia disorders; Encephalopathy; Glutamic acid receptors; Immunoglobulin A; Immunoglobulin G; Immunoglobulin M; Medicin och hälsovetenskap; Medicine; Medicine & Public Health; Meta-analysis; N-Methyl-D-aspartic acid receptors; Neurology; Neuroradiology; Neurosciences; Pathogenicity; Review; Systematic review; Antibodies in dementia; Autoimmune dementia; NMDAR antibody; Atypical dementia
• ISSN: 0340-5354; 1432-1459; 1432-1459
• DOI: 10.1007/s00415-020-09825-0

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.