Combination treatment in Alzheimer's disease: results of a randomized, controlled trial with cerebrolysin and donepezil.

Treatment with neurotrophic agents might enhance and/or prolong the effects of cholinesterase inhibitors (ChEIs) in Alzheimer's disease (AD). We compared the safety and efficacy of the neurotrophic compound Cerebrolysin (10 ml; n=64), donepezil (10 mg; n=66) and a combination of both treatments (n=67) in mild-to-moderate (mini-mental state examination-MMSE score 12-25) probable AD patients enrolled in a randomized, double-blind trial. Primary endpoints were global outcome (Clinician's Interview-Based Impression of Change plus caregiver input; CIBIC+) and cognition (change from baseline in AD Assessment Scale-cognitive subscale+; ADAS-cog+) at week 28. Changes in functioning (AD Cooperative Study-Activities of Daily Living scale, ADCS-ADL) and behaviour (Neuropsychiatric Inventory, NPI) were secondary endpoints. Treatment effects in cognitive, functional and behavioral domains showed no significant group differences; whereas improvements in global outcome favored Cerebrolysin and the combination therapy. Cognitive performance improved in all treatment groups (mean±SD for Cerebrolysin: -1.7±7.5; donepezil: -1.2±6.1; combination: -2.3±6.0) with best scores in the combined therapy group at all study visits. Cerebrolysin was as effective as donepezil, and the combination of neurotrophic (Cerebrolysin) and cholinergic (donepezil) treatment was safe in mild-to-moderate AD. The convenience of exploring long-term synergistic effects of this combined therapy is suggested.

Efficacy and safety of Cerebrolysin in moderate to moderately severe Alzheimer's disease: results of a randomized, double-blind, controlled trial investigating three dosages of Cerebrolysin.

BACKGROUND: cerebrolysin is a neuropeptide preparation mimicking the effects of neurotrophic factors. This subgroup analysis assessed safety and efficacy of Cerebrolysin in patients with moderate to moderately severe Alzheimer's disease (AD) (ITT data set: N = 133; MMSE: 14-20) included in a dose-finding study (ITT data set: N = 51; MMSE: 14-25). Results of the mild AD subgroup (ITT data set: N = 118; MMSE: 21-25) are also presented. METHODS: patients with AD received 100 ml IV infusions of Cerebrolysin (10, 30 or 60 ml diluted in saline; N = 32, 34 and 35, respectively) or placebo (saline; N = 32) over twelve weeks (5 days per week for 4 weeks and 2 days per week for another 8 weeks). Primary efficacy criteria ADAS-cog+ (Alzheimer's Disease Assessment Scale Cognitive Subpart Modified) and CIBIC+ (Clinical Interview-based Impression of Change with Caregiver Input) were assessed 24 weeks after baseline. RESULTS: at week 24, Cerebrolysin improved the global clinical function significantly with all three dosages and induced significant improvements in cognition, initiation of activities of daily living (ADL) and neuropsychiatric symptoms at 10-, 30- and 60-ml doses, respectively. Treatment effects on total ADL and other secondary parameters (MMSE, Trail-making test) were not significant. Cerebrolysin was safe and well tolerated. CONCLUSIONS: these results demonstrate the efficacy of Cerebrolysin in moderate to moderately severe AD, showing dose-specific effects similar to those reported for patients with mild to moderate AD. The benefits of Cerebrolysin in advanced AD need to be confirmed in larger trials.

A 24-week, double-blind, placebo-controlled study of three dosages of Cerebrolysin in patients with mild to moderate Alzheimer's disease.

Cerebrolysin (Cere) is a compound with neurotrophic activity shown to be effective in Alzheimer's disease in earlier trials. The efficacy and safety of three dosages of Cere were investigated in this randomized, double-blind, placebo-controlled, study. Two hundred and seventy-nine patients were enrolled (69 Cere 10 ml; 70 Cere 30 ml; 71 Cere 60 ml and 69 placebo). Patients received iv infusions of 10, 30, 60 ml Cere or placebo 5 days/week for the first 4 weeks and thereafter, two iv infusions per week for 8 weeks. Effects on cognition and clinical global impressions were evaluated 4, 12 and 24 weeks after the beginning of the infusions using the CIBIC+ and the modified Alzheimer's Disease Assessment Scale (ADAS)-cog. At week 24, significant improvement of cognitive performance on the ADAS-cog (P=0.038) and global function (CIBIC+; P>0.001) was observed for the 10 ml dose. The 30 and 60 ml doses showed significant improvement of the global outcome but failed to show significant improvement of cognition. The results are consistent with a reversed U-shaped dose-response relationship for Cere. The percentage of patients reporting adverse events was similar across all study groups. Cere treatment was well tolerated and led to significant, dose-dependent improvement of cognition and global clinical impression.