P21 (P021), Alzheimer's, Cerebrolysin, Cognition, Neurogenesis

​Cerebrolysin and Vascular Dementia

Cerebrolysin and Vascular Dementia

A Look into the Research:

Vascular dementia (VaD) is the second most common form of dementia after Alzheimer’s disease (AD). The term ‘vascular dementia’ refers to a constellation of cognitive and functional impairments all caused by disordered blood flow to the brain. Vascular dementia can be considered a subset of the larger syndrome of vascular cognitive impairment (VCI), that is all cognitive syndromes associated with a cerebrovascular brain injury. VaD includes dementia caused by ischemic or hemorrhagic cerebrovascular diseases (CVD) or by ischemic hypoxic brain lesions of cardiovascular origin.

Vascular dementia and stroke disease are closely linked, but the terms VaD and poststroke dementia (PSD) are not synonymous. Although most PSD cases are pathologically confirmed as VaD, some have been reported to be other dementia related pathologies, such as AD.

Vascular dementia has traditionally received less attention than AD, yet international epidemiological data suggest a substantial global burden from VaD. The prevalence rate of VaD has been estimated to double every 5.3 years, compared with every 4.5 years for AD. In North America, AD accounts for 44% to 70% of all dementia, while VaD accounts for 14.5% to 20%. Studies in the UK have estimated the incidence rate of AD as 1.59/1000 person years, whilst the incidence rate of VaD was 0.99 cases/1000 person years. The prevalence of VaD among individuals aged 65 years and older was 1.50% in China between 2008 and 2009, while AD was the leading cause of dementia (3.21%). Although earlier studies in Japanese populations demonstrated a greater prevalence of VaD than AD, recent studies have shown that the trend has shifted with no changes in VaD prevalence and increases in AD prevalence over time.

Why does this all matter? Despite its prevalence and societal impact, there is no definitive, proven treatment for VaD. Potential interventions may be considered at a few levels: primary prevention, secondary prevention, symptomatic treatments, and disease modifying or curative approaches. The currently available data on the treatment of vascular risk factors does not prove a benefit in primary and secondary prevention. Trials of monotherapies such as antiplatelet agents or statins for the prevention or treatment of VaD are also questionable. Thus, there has been a constant search for such therapy to improve clinical outcomes in vascular dementia.

In a recent study, researchers evaluated the safety and efficacy of Cerebrolysin in patients with VaD. This was a 24-week, randomized, double-blind, placebo-controlled clinical trial. The trial was conducted in accordance with the Recommendations Guiding Physicians in Biomedical Research Involving Human Subjects in the 1989 Declaration of Helsinki, and the protocol and consent forms were approved by independent ethics committees.

Cerebrolysin is a neuropeptide preparation produced by standardized enzymatic breakdown of porcine brain proteins. It is a mixture of 80% low molecular weight peptides and 20% free amino acids. Cerebrolysin is said to have potential neurotrophic and neuroprotective properties. The peptide has also been reported as having beneficial effects on cognitive and physical function in various other neurological conditions, including stroke, AD, and traumatic brain injury.

In the study, a total of 260 patients were screened, and 242 entered the study and were randomized to receive either placebo (n = 121) or Cerebrolysin (n = 121). A total of 217 patients (89.7 %) completed the study. The number of patients who discontinued the study early was similar in the 2 groups, 14 (5.8 %) in the Cerebrolysin arm and 11 (4.5 %) in the placebo arm. The combined outcome of ADAS-cogþ and CIBICþ was assessed 24 weeks after baseline. 20ml IV Cerebrolysin were given OD during two treatment-cycles as add- on therapy to basic treatment with acetylsalicylic acid.

The therapy with Cerebrolysin resulted in significant improvement of both primary parameters. At week 24, cognition (ADAS-cogþ) improved by -10,628 points in the Cerebrolysin group (LS mean difference -6.17; p<.0001 vs. placebo) and the overall clinical functioning (CIBICþ) showed a mean difference of -0.84 (p<.0001 vs. placebo).

These findings were confirmed by responder analyses with higher rates in the Cerebrolysin group (ADAS-cogþ improvement of 4 points from baseline: 82.1% vs. 52.2%; CIBICþ score of <4 at week 24: 75.2% vs. 37.4%; combined response in ADAS-cogþ and CIBICþ: 67.5% vs. 27.0).

For Cerebrolysin, the odds ratios for achieving a favorable CIBICþ response was 5.081 (p<0.05) and 5.633 (p<0.05) for the combined response. Cerebrolysin was significantly superior over placebo also in the MMSE, the activities of daily living (ADCS-ADL) and in the executive function (Trail-making test, Clock-drawing test).

So, how may this intervention work?


There are four very well studied mechanisms:

Various in vitro and in vivo studies have shown that Cerebrolysin has pharmacodynamic properties similar to those of endogenous neurotrophic factors. For example, it exerts nerve growth factor (NGF) like activity on neurons and increases levels of NGF Various animal models have been established to demonstrate the neurotrophic and pro-cognitive effects of Cerebrolysin.

Pleiotropic properties include promotion of neuroprotection, neuroplasticity, and neurogenesis. Suggested underlying mechanisms for these actions include the following:

1. Reduced amyloid plaque formation by regulating amyloid precursor protein (APP).

2. Inhibition of calpain, caspase-3, Bcl-2 and upregulation of Bax, thus protecting neurons from apoptosis and degeneration.

3. Induction of modifications in dendritic morphology by increasing the dendritic length, density, and spine density, ameliorating dendritic pathology and spine loss, whilst increasing the levels of plasticity-related synaptic proteins, thereby improving structural synaptic plasticity.

4. Attenuating the physiological apoptosis of neuroblasts, augmenting the survival of neural progenitor cells, and enhancing neural progenitor cell proliferation and neuronal differentiation, thus stimulating neurogenesis.

In conclusion, cerebrolysin significantly improved the clinical outcome and these benefits lasted for at least six months. Cerebrolysin was safe and well tolerated and is a product that works well for vascular dementia according to the research.



Guekht AB, Moessler H, Novak PH, Gusev EI; Cerebrolysin Investigators. Cerebrolysin in vascular dementia: improvement of clinical outcome in a randomized, double-blind, placebo-controlled multicenter trial. J Stroke Cerebrovasc Dis. 2011 Jul-Aug;20(4):310-8. Doi: 10.1016/j.jstrokecerebrovasdis.2010.01.012. Epub 2010 Jul 24. PMID: 20656516.

Allegri, R.F.; Guekht, A. “Cerebrolysin Improves Symptoms and Delays Progression in Patients With Alzheimer’s Disease and Vascular Dementia.” Drugs of Today 2012, 48 (supplement A), pp. 25-4., DOI: 10.1258/dot.2012.48

Cui S, Chen N, Yang M, Guo J, Zhou M, Zhu C, He L. Cerebrolysin for vascular dementia. Cochrane Database Syst Rev. 2019 Nov 11;2019(11):CD008900. doi: 10.1002/14651858.CD008900.pub3. PMID: 31710397; PMCID: PMC6844361.

Muresanu DF, Alvarez XA, Moessler H, Novak PH, Stan A, Buzoianu A, et al. Persistence of the effects of Cerebrolysin on cognition and qEEG slowing in vascular dementia patients: results of a 3-month extension study. Journal of the Neurological Sciences 2010;299(1-2):179-83


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