Memory Deficits in Cancer Patients With Serum NMDA Receptor Autoantibodies

Neuronal autoantibodies are linked to cognitive impairment in neurologic diseases and can be associated with tumors. In patients with cancer, IgA/IgM N-Methyl-D-Aspartate receptor (NMDAR) autoantibodies are most common, yet their clinical relevance is unclear. We assessed cognitive function in cancer patients with serum NMDAR autoantibodies and compared the results with matched controls.

For this cross-sectional case-control study in Germany, we recruited 1,055 patients with cancer and tested for neuronal serum autoantibodies. Cognitive assessment was performed blinded to antibody status and after excluding patients with potential confounders of cognitive dysfunction. The tests included verbal memory (Rey Auditory Verbal Learning Test), visuospatial memory (Rey-Osterrieth Complex Figure), and working memory.

Fifty-six patients with IgA/IgM NMDAR autoantibodies (median age 61.0 years [28.0-86.0], 35.7% female) were matched 1:1 to autoantibody-negative patients by age, sex, cancer type, and stage. Autoantibody-positive patients showed impairments in verbal memory (mean score ± SD: 9.7 ± 3.6 vs 11.4 ± 3.2; p = 0.01; Cohen d = 0.49), visuospatial memory (19.4 ± 7.0 vs 22.6 ± 5.6; p = 0.01; d = 0.50), and working memory (6.2 ± 1.9 vs 7.0 ± 2.1; p = 0.04; d = 0.40). Memory function decreased with increasing IgA NMDAR autoantibody levels. Both groups performed similarly on measures of attention, executive function, and verbal fluency.

Serum NMDAR autoantibodies are associated with isolated memory deficits in patients with cancer and might serve as a potential biomarker for cancer-related cognitive impairment.