title: Cerebrolysin in vascular dementia: improvement of clinical outcome in a randomized, double-blind, placebo-controlled multicenter trial.
abstract: No drug to treat vascular dementia (VaD) has yet been approved by the American or European authorities, leaving a large population of patients without effective therapy. Cerebrolysin has a long record of safety and might be efficacious in this condition. We conducted a large, multicenter, double-blind, placebo-controlled study in 242 patients meeting the criteria for VaD. The primary endpoint was the combined outcome of cognition (based on Alzheimer's Disease Assessment Scale Cognitive Subpart, Extended Version [ADAS-cog+] score) and overall clinical functioning (based on Clinician's Interview-Based Impression of Change plus Caregiver Input [CIBIC+] score) assessed after 24 weeks of treatment. Intravenous Cerebrolysin 20 mL was administered once daily over the course of 2 treatment cycles as add-on therapy to basic treatment with acetylsalicylic acid. The addition of Cerebrolysin was associated with significant improvement in both primary parameters. At week 24, ADAS-cog+ score improved by 10.6 points in the Cerebrolysin group, compared with 4.4 points in the placebo group (least squares mean difference, -6.17; P < .0001 vs placebo). CIBIC+ showed a mean improvement of 2.84 in the treatment arm and 3.68 in the placebo arm, a treatment difference of 0.84 (P < .0001 vs placebo). These findings were confirmed by responder analyses demonstrating higher rates in the Cerebrolysin group (ADAS-cog+ improvement of ≥4 points from baseline, 82.1% vs 52.2%; CIBIC+ score of <4 at week 24, 75.3% vs 37.4%; combined response in ADAS-cog+ and CIBIC+, 67.5% vs 27.0%). For Cerebrolysin, the odds ratio for achieving a favorable CIBIC+ response was 5.08 (P < .05), and that for achieving a favorable combined response was 5.63 (P < .05). Our data indicate that the addition of Cerebrolysin significantly improved clinical outcome, and that the benefits persisted for at least 24 weeks. Cerebrolysin was safe and well tolerated.
authors.affiliation: Department of Neurology and Neurosurgery, Russian State Medical University, Moscow, Russia.
authors.forename: Alla B
authors.initials: AB
authors.lastname: Guekht
authors.forename: Herbert
authors.initials: H
authors.lastname: Moessler
authors.forename: Philipp H
authors.initials: PH
authors.lastname: Novak
authors.forename: Evgenyi I
authors.initials: EI
authors.lastname: Gusev
mesh_terms: D000368:Aged; D000596:Amino Acids / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001241:Aspirin / Q000627:therapeutic use; D016009:Chi-Square Distribution; D003071:Cognition / Q000187:drug effects*; D015140:Dementia, Vascular / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005060:Europe; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D018697:Nootropic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016017:Odds Ratio; D015990:Placebo Effect; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000596:Amino Acids; D018697:Nootropic Agents; D010975:Platelet Aggregation Inhibitors; C006952:cerebrolysin; D001241:Aspirin