ABSTRACT NUMBER: ESOC2026A160 IMPROVED COGNITIVE TRAJECTORY AFTER ACUTE ISCHEMIC STROKE: INSIGHTS FROM C-REGS2 TRIAL

Abstract Background and aims *on behalf of the C-REGS2-investigators Pre-stroke cognitive impairment (PCI) is common in patients with acute ischemic stroke (AIS), affecting 9–14% of all cases. PCI is associated with greater comorbidity and poorer functional outcomes. Recent real-world data suggest that specific neuropeptides (Cerebrolysin), as an adjunct treatment, may protect from cognitive decline in AIS patients with PCI. Methods C-REGS2 was a prospective, multinational, comparative-effectiveness research study in patients with moderate AIS (NIHSS 8–15). PCI was defined according to the IQCODE. Treatment effects in patients with and without PCI were evaluated using a severity-adjusted ANCOVA based on baseline NIHSS, comparing patients with low and high IQCODE scores. Cognition after 90 days was assessed using the Montreal Cognitive Assessment test (MoCA). Results Of the 1769 patients in the target population, 1021 received Cerebrolysin (verum group) and 748 received standard stroke treatment (control group). Verum group achieved significant superiority in the MoCA score among patients with PCI at day 90 (MoCA +3.24 in favor of verum group; p<0.0001) and a significant, less-pronounced effect in patients with no previous cognitive impairment (MoCA +0.8; p<0.0001). In thrombolysed patients, effects were again stronger in those with PCI (MoCA +3.25, p=0.0311) than without PCI (IQCODE MoCA ES +1.25, p=0.0696). No group differences in safety or adverse events were observed. Conclusions In C-REGS2, a specific neuropeptide compound (Cerebrolysin) was associated with significantly better 90-day cognitive outcomes, with greatest benefit in patients with PCI; this effect was seen in thrombolysed, as well as in non-thrombolysed patients. Conflict of interest M.R.V., D.S., J.C.V. and M.B. have received honoraria from EVER Neuro Pharma. M.R.V. and D.S. were PIs in one of the participating sites of C-REGS2.