MTR: The Cochrane review of Cerebrolysin is high quality, however the included studies are not. I accept that most of the studies included in the review report beneficial changes in cognition. However, the available studies are limited in number and have potential biases. Do small trials Clinical trials are research studies involving people who use healthcare services. They often compare a new or different treatment with the best treatment currently available. This is to test whether the new or different treatment is safe, effective and any better than what is currently used. No matter how promising a new treatment may appear during tests in a laboratory, it must go through clinical trials before its benefits and risks can really be known. of very selected populations have relevance to the majority of people living with vascular dementia in the UK? It seems odd to me that a treatment that has international traction has such a modest evidence base. Statistical assessment of publication bias Any factor, recognised or not, that distorts the findings of a study. For example, reporting bias is a type of bias that occurs when researchers, or others (e.g. drug companies) choose not report or publish the results of a study, or do not provide full information about a study. was not possible in the Cochrane review and I wonder if selective publication of positive results could be a factor here. i] Plosker, G. L., & Gauthier, S. (2009). Cerebrolysin: a review of its use in dementia. Drugs & aging, 26(11), 893–915. https://doi.org/10.2165/11203320-000000000-00000 Asghari M, Meshkini A, Salehpoor F, Agazadeh J, Shakeri M, Shokohi G, Ebrahimi N, Bazzazi A, Pourhajshokr N (2014) Investigation of the effect of cerebrolysin on patients with head trauma and diffuse axonal injury. Int J Curr Res Acad Rev 2:62–69 Liang S, Li Z, Yan H, Pei X (2001) The efficacy of Cerebrolysin in multi-infarct dementia. Heilongjiang Med Pharm 24(5):75

vii) hereditary vascular dementia (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)). Z. Liu et al., “Cerebrolysin alleviates cognitive deficits induced by chronic cerebral hypoperfusion by increasing the levels of plasticity-related proteins and decreasing the levels of apoptosis-related proteins in the rat hippocampus,” Neurosci. Lett., vol. 651, pp. 72–78, Jun. 2017, doi: 10.1016/j.neulet.2017.04.022. Xiao S, Xue H, Li G et al. (2012) Therapeutic effects of cerebrolysin added to risperidone in patients with schizophrenia dominated by negative symptoms. Aust N Z J Psychiatry 46, 153-160. While Cerebrolysin offers numerous benefits, it's important to note that individual responses may vary. Some users might experience mild side effects such as headaches or dizziness initially; however, these typically subside as the body adjusts to the supplement. G. L. Plosker and S. Gauthier, “Cerebrolysin: a review of its use in dementia,” Drugs Aging, vol. 26, no. 11, pp. 893–915, 2009, doi: 10.2165/11203320-000000000-00000.Gavrilova SI, Alvarez A (2020) Cerebrolysin in the therapy of mild cognitive impairment and dementia due to Alzheimer’s disease: 30 years of clinical use. Med Res Rev. https://doi.org/10.1002/med.21722

Similar pain-reducing effects have been seen in rat models of neuropathic (nerve) pain. Administration of Cerebrolysin in this setting helps to reduce mechanical pain, but not inflammatory pain[20]. However, the study was not carried out long enough to fully rule out an effect on inflammatory pain. What makes this finding significant is that it shows a reduction in pain that likely results from the neurotrophic (nerve plasticity) properties of Cerebrolysin as well as from its neurogenic (nerve growth) properties. Cerebrolysin Summary Hartbauer M, Hutter-Paie B, Windisch M (2001) Effects of Cerebrolysin on the outgrowth and protection of processes of cultured brain neurons. Journal of neural transmission 108, 581-592.Alvarez XA, Alvarez I, Iglesias O et al. (2016) Synergistic Increase of Serum BDNF in Alzheimer Patients Treated with Cerebrolysin and Donepezil: Association with Cognitive Improvement in ApoE4 Cases. Int J Neuropsychopharmacol. Alvarez XA, Cacabelos R, Sampedro C, Couceiro V, Aleixandre M, Vargas M, Linares C, Granizo E, Garcia-Fantini M, Baurecht W, Doppler E, Moessler H (2011) Combination treatment in Alzheimer’s disease: results of a randomized, controlled trial with cerebrolysin and donepezil. Curr Alzheimer Res 8(5):583–591. https://doi.org/10.2174/156720511796391863 Our source of Cerebrolysin is from an EU Ever Pharma registered distributor - so the box is in German Yao PJ, Manor U, Petralia RS, Brose RD, Wu RT, Ott C, Wang YX, Charnoff A, Lippincott-Schwartz J, Mattson MP (2017) Sonic hedgehog pathway activation increases mitochondrial abundance and activity in hippocampal neurons. Mol Biol Cell 28(3):387–395. https://doi.org/10.1091/mbc.E16-07-0553 Sharma HS, Zimmermann-Meinzingen S, Johanson CE (2010) Cerebrolysin reduces blood-cerebrospinal fluid barrier permeability change, brain pathology, and functional deficits following traumatic brain injury in the rat. Ann N Y Acad Sci 1199:125–137. https://doi.org/10.1111/j.1749-6632.2009.05329.x