Combination Treatment in Alzheimers Disease: Results of a Randomized, Controlled Trial with Cerebrolysin and Donepezil

X.      A. Alvarez; R.      Cacabelos; C.      Sampedro; V.      Couceiro; M.      Aleixandre; M.      Vargas; C.      Linares; E.      Granizo; M.      Garcia-Fantini; W.      Baurecht; E.      Doppler; H.      Moessler

Abstract

Treatment with neurotrophic agents might enhance and/or prolong the effects of cholinesterase inhibitors (ChEIs) in Alzheimers 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 (Clinicians 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.

Keywords: Alzheimer's disease, randomized controlled trial, cerebrolysin, combination therapy, neurotrophic factor, donepezil, cholinesterase inhibitors, trophic factor, ApoE genotyping