Synergistic Increase of Serum BDNF in Alzheimer Patients Treated with Cerebrolysin and Donepezil: Association with Cognitive Improvement in ApoE4 Cases

Abstract

Background:Low circulating brain derived neurotrophic factor may promote cognitive deterioration, but the effects of neurotrophic and combination drug therapies on serum brain derived neurotrophic factor were not previously investigated in Alzheimer’s disease.Methods:We evaluated the effects of Cerebrolysin, donepezil, and the combined therapy on brain derived neurotrophic factor serum levels at week 16 (end of Cerebrolysin treatment) and week 28 (endpoint) in mild-to-moderate Alzheimer’s disease patients.Results:Cerebrolysin, but not donepezil, increased serum brain derived neurotrophic factor at week 16, while the combination therapy enhanced it at both week 16 and study endpoint. Brain derived neurotrophic factor responses were significantly higher in the combination therapy group than in donepezil and Cerebrolysin groups at week 16 and week 28, respectively. Brain derived neurotrophic factor increases were greater in apolipoprotein E epsilon-4 allele carriers, and higher brain derived neurotrophic factor levels were associated with better cognitive improvements in apolipoprotein E epsilon-4 allele patients treated with Cerebrolysin and the combined therapy.Conclusion:Our results indicate a synergistic action of Cerebrolysin and donepezil to increase serum brain derived neurotrophic factor and delaying cognitive decline, particularly in Alzheimer’s disease cases with apolipoprotein E epsilon-4 allele.

Effects of Cerebrolysin on Hippocampal Neuronal Death After Pilocarpine-Induced Seizure

“…Several previous studies have demonstrated that under head trauma and ischemic conditions, the administration of cerebrolysin attenuates brain damage (Zhang L. et al, 2013;Zhang Y. et al, 2013). In addition, previous studies have shown that cerebrolysin increases the level of the BDNF by inhibiting the activity of glycogen synthase kinase-3 beta (GSK-3β) (Alvarez et al, 2016). It has also been shown that enhancing BDNF expression decreases neuronal damage and inflammation and increases neurogenesis (Wada et al, 2003;Chen et al, 2013;Rockenstein et al, 2015).…”

“…In another study, cerebrolysin was confirmed to reduce neuronal cell death and increase neurogenesis and brain functions in diverse brain diseases, such as mouse closed head injury (mCHI) and stroke (Zhang L. et al, 2013;Zhang Y. et al, 2013). In addition, it has been shown in many previous studies that cerebrolysin promotes neuroprotection and neurogenesis by increasing the expression of factors such as NGF and brain-derived neurotrophic factor (BDNF) (Rockenstein et al, 2015;Shishkova et al, 2015;Alvarez et al, 2016). In this way, cerebrolysin has shown positive effects in several brain diseases.…”

Pregnancies alters spine number in cortical and subcortical limbic brain regions of old rats

“…Consequently, many of the therapies to reduce cognitive deficits due to aging aim to increase the levels of these two neurotrophins. For example, cerebrolysin is a drug used in the treatment of Alzheimer's disease, but it has been shown in experimental studies to reduce the cognitive deficit of elderly rats, since it increases the levels of BDNF and NGF in limbic regions such as the hippocampus (Alvarez et al, ; Flores & Atzori, , Stepanichev et al, ; Ubhi et al, ). Accordingly, recent studies show that cerebrolysin possesses procognitive actions, which correlate to an increase in the arborization of the PFC (Pourmemar et al, ; Sadigh‐Eteghad et al, ) underlying the importance of this brain region in cognitive processes.…”

Combination and mutual effect of Alzheimer’s disease and cerebrovascular disease

“…В случае деменции церебролизин используется в дополнении к приему противодементных средств (ингибиторы ацетилхолинэстеразы, мемантин). Применение церебролизина у пациентов с БА повышает содержание мозгового нейротрофического фактора, что может способствовать замедлению прогрессирования заболевания и темпам когнитивного снижения [26]. Важно отметить, что высокое содержание мозгового нейротрофического фактора ассоциируется со снижением риска развития БА [27].…”

“…Важно отметить, что высокое содержание мозгового нейротрофического фактора ассоциируется со снижением риска развития БА [27]. Применение комбинации церебролизина и донепезила у пациентов с БА легкой и средней степени показало, что использование церебролизина, но не донепезила ассоциируется с повышением мозгового нейротрофического фактора [26].…”