Cerebrolysin in the therapy of mild cognitive impairment and dementia due to Alzheimer's disease: 30 years of clinical use

Alzheimer's disease (AD) is the most common neurocognitive disorder and a global health problem. The prevalence of AD is growing dramatically, especially in low- and middle-income countries, and will reach 131.5 million cases worldwide by 2050. Therefore, developing a disease-modifying therapy capable of delaying or even preventing the onset and progression of AD has become a world priority, and is an unmet need. The pathogenesis of AD, considered as the result of an imbalance between resilience and risk factors, begins many years before the typical clinical picture develops and involves multiple pathophysiological mechanisms. Since the pathophysiology of AD is multifactorial, it is not surprising that all attempts done to modify the disease course with drugs directed towards a single therapeutic target have been unsuccessful. Thus, combined modality therapy, using multiple drugs with a single mechanism of action or multi-target drugs, appears as the most promising strategy for both effective AD therapy and prevention. Cerebrolysin, acting as a multitarget peptidergic drug with a neurotrophic mode of action, exerts long-lasting therapeutic effects on AD that could reflect its potential utility for disease modification. Clinical trials demonstrated that Cerebrolysin is safe and efficacious in the treatment of AD, and may enhance and prolong the efficacy of cholinergic drugs, particularly in moderate to advanced AD patients. In this review, we summarize advances of therapeutic relevance in the pathogenesis and the biomarkers of AD, paying special attention to neurotrophic factors, and present results of preclinical and clinical investigations with Cerebrolysin in AD.