2026 American Academy of Neurology Abstract Website

Objective:

Determine if memantine improves objective neuropsychological function in individuals with systemic lupus erythematosus (SLE).

Background:

Neuropsychological dysfunction is a common, functionally disabling manifestation of SLE and often persists despite immunomodulatory treatment. Memantine is an N-methyl-D-aspartate (NMDA) receptor antagonist mediating glutamate excitotoxicity that may be amplified by autoantibodies and/or neuroinflammation in SLE.

Design/Methods:

ClearMEMory (NCT03527472) was a phase II, multi-site, randomized, double-blind, placebo-controlled trial. Potential participants meeting pre-screening criteria were screened for objective dysfunction using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Individuals scoring one age-adjusted standard deviation below population norms were eligible for the study and randomized to memantine or placebo stratified by NMDA receptor antibodies. Participants underwent a weekly dose escalation to identify the maximum tolerated dose 10-40 mg/d. The primary outcome was change in RBANS from baseline to endpoint (week 12). Other measures included RBANS subscales and measures of lupus disease activity, fibromyalgia, depression/anxiety, and global impression of change (PGIC).

Results:

Of 257 prescreened and 131 screened, 56 were randomized to either memantine (n=26) or placebo (n=30). Failure to meet the eligibility threshold on the RBANS (≤85 out of 100) accounted for 96% of screen failures. Premature discontinuations after randomization due to AE were the same (5 per group), but fewer in the memantine group tolerated maximum dose (42% vs 70%). We observed significantly greater improvement of RBANS total score in memantine (baseline:75.3) compared to placebo (baseline:77.1) groups (+10.4 vs +4.2, p= 0.032). Responders were higher in the memantine than placebo groups (+8: 67% vs 36%, NNT=3.3; +5 MCID: 78% vs 56%, NNT=4.6). The RBANS immediate memory subscale was also improved (P=0.023). More participants taking memantine were improved or much improved on PGIC. There were no significant differences in other outcome measures.

Conclusions:

In SLE, treatment with memantine meaningfully improved objective neuropsychological performance without significant effects on other domains.