Serum anti-NMDA-receptor antibodies and cognitive function after ischemic stroke (PROSCIS-B)

ObjectiveWe aimed to investigate whether serum anti-N-Methyl-D-Aspartate-receptor GluN1 antibodies (NMDAR1-abs) are associated with worse cognitive function over three years after first ischemic stroke.MethodsData were used from the PROSpective Cohort with Incident Stroke-Berlin (PROSCIS-B;NCT01363856). NMDAR1-abs (IgM/IgA/IgG) were measured with cell-based assays from serum obtained within seven days after first-ever stroke. Seropositivity was defined as titers ≥1:10, low titers as ≤1:100 and high titers as >1:100. We assessed cognitive status annually up to three years after stroke with the Telephone Interview for Cognitive Status – modified (TICS–m) and used crude and adjusted linear mixed models to estimate the impact of NMDAR1-abs exposure on TICS-m over time.ResultsData on NMDAR1-abs (median day of sampling=4[IQR=2–5]) were available in 583 of 621 PROSCIS-B patients (39% female; median NIHSS=2[IQR=1–4]; median MMSE=28[IQR:26–30]; median mRS=2[IQR=1–3]) of whom 76(13%) were seropositive (IgM:n=48/IgA:n=43/IgG:n=2). TICS-m over time was not different in NMDAR1-abs seropositive compared to seronegative patients (βCrude=0.38[95%CI=-1.00 to 1.76]; adjusted βModel3=0.30[95%CI=-1.14 to 1.73]). In subgroups, TICS-m over time was not different in patients with low titers (βCrude=1.53[95%CI=-0.06 to 3.11]; adjusted βModel3=1.42[95%CI=-0.23 to 3.08]), however, in patients with high titers TICS-m was lower in the crude model (β=-2.54[95%CI=-4.99 to -0.08]), with a similar effect size after confounder adjustment (βModel3=-2.30[95%CI=-4.82 to 0.21]). All groups were compared to seronegative patients, respectively.ConclusionOverall NMDAR1-abs seropositivity was not associated with cognitive function over time after first-ever mild-to-moderate ischemic stroke. Our data suggest that high titers associate with impaired cognitive function after stroke, warranting larger studies.