|Year : 2021 | Volume
| Issue : 1 | Page : 30-33
A retrospective chart analysis of 34 cases with the use of oral cerebroprotein hydrolysate in dementia in a tertiary general hospital
Sagar Karia, Avinash Desousa, Nilesh Shah
Department of Psychiatry, Lokmanya Tilak Municipal Medical College and General Hospital, Mumbai, Maharashtra, India
|Date of Submission||24-Mar-2020|
|Date of Decision||16-May-2020|
|Date of Acceptance||16-Jan-2021|
|Date of Web Publication||05-Aug-2021|
Dr. Avinash Desousa
Carmel, 18, St. Francis Road, Off S.V. Road, Santacruz West, Mumbai - 400 005, Maharashtra
Source of Support: None, Conflict of Interest: None
Background: Cerebroprotein hydrolysate (cerebrolysin) is a nootropic and neurotrophic drug used widely in the management of various forms of dementia, stroke and head injury. A number of case series and anecdotal case reports on its efficacy exist. This study is a retrospective chart review of 34 patients with dementia treated at a tertiary general hospital psychiatry department that were given oral cerebroprotein as add on to their existing treatment for dementia. Methodology: 34 patients were administered twice daily oral cerebroprotein 90 mg tablets for 90 consecutive days. The cognitive assessment was done before the first injection and after the last dose using the Adenbrook's Cognitive Examination-Revised (ACER) and the Mini Mental Status Examination (MMSE). Results: Changes on cognitive assessment were minimal and no major improvements were seen though isolated areas of improvement were reported by many patients. The scores on the ACER and MMSE remained in the dementia range though improvement in scores were noted. None of the patients experienced any major side effects with the drug. Conclusions: Oral cerebroprotein is a useful agent in the management of dementia and must be tried as an add-on to regular dementia treatment. Larger studies in prospective cohorts with further stringent assessments warrant exploration.
Keywords: Adenbrook's Cognitive Examination-Revised, cerebrolysin, dementia, Mini Mental Status Examination, oral cerebroprotein
|How to cite this article:|
Karia S, Desousa A, Shah N. A retrospective chart analysis of 34 cases with the use of oral cerebroprotein hydrolysate in dementia in a tertiary general hospital. J Geriatr Ment Health 2021;8:30-3
|How to cite this URL:|
Karia S, Desousa A, Shah N. A retrospective chart analysis of 34 cases with the use of oral cerebroprotein hydrolysate in dementia in a tertiary general hospital. J Geriatr Ment Health [serial online] 2021 [cited 2021 Dec 9];8:30-3. Available from: https://www.jgmh.org/text.asp?2021/8/1/30/323101
| Introduction|| |
Dementia is one of the most common conditions encountered in geriatric psychiatry where patients present with memory loss, cognitive dysfunction, and behavioral symptoms due to age related, neuropathological, and vascular neurodegenerative processes in the brain. Its prevalence worldwide is on the rise and dementia has become a huge public health problem. Dementia affects the quality of life of the patient and his or her caregivers immensely and has huge psychological ramifications for the entire family. Most pharmacological intervention studies show mild to moderate efficacy for the use of anticholinesterases and other similar drugs recommended to halt the progress of the illness as finally dementia is a progressive disorder which has its own course and prognosis. Many newer drugs for dementia are being developed and currently in the pipeline and undergoing clinical trials at various stages. Cerebroprotein hydrolysate (Cerebrolysin) is a pharmacological agent which is reported to be nootropic and neuroprotective and is manufactured in the laboratory by the enzymatic breakdown of lipid-free porcine brain proteins. It has multifold mechanisms of action which include enhancement of neurogenesis, improved neuronal survival, enhancement of neuronal plasticity, and generalized neuro-immunotrophic mechanisms. There are anecdotal case reports where the injectable form of the drug has been reported to be beneficial in the improvement of patients with traumatic brain injury, dementia, extrapontine myelinolysis, and stroke. We have also published a case series of 25 patients where injectable cerebroprotein has been used successfully with minimal side effects and modest improvement in patients with dementia. In this case series, we present a retrospective chart review of 34 patients with dementia from our center that were treated with oral cerebroprotein without major side effects and showed minimal improvements.
| Methodology|| |
The patients (if cognitively capable) and relatives in the study were informed and educated about oral cerebroprotein, its pharmacological make up, dosage schedule and role in the management of dementia, along with the probable side effects reported in literature. A written informed consent was taken from every relative before starting the treatment as all our patients were not cognitively fit to consent for treatment. Thirty-four patients who were diagnosed as having dementia of various types based on DSM-IVTR criteria who were following up in outpatient department were prescribed 90 mg oral Cerebroprotein tablets and were told that they have to take the medicine for 90 days. The medication was provided to them at half the cost with the help of the psychiatric social work department. This helped in ensuring compliance as patients would visit regularly to collect their medications. All patients took the medication as outpatients and none were admitted to the hospital. The patient's cognitive assessments were done using the Adenbrook's Cognitive Examination Revised (ACER) and Mini Mental Status Examination (MMSE). The scales were administered twice namely prior to starting oral Cerebroprotein therapy and at the end of the course of 90 days of treatment. These scales are used routinely in our department in the assessment of dementia. Most patients were on concomitant medication for other neuropsychiatric symptoms. Most of the patients were on concomitant medication for dementia as well. The patient continued their psychiatric, anti-hypertensive and oral hypoglycemic and other medical treatments as advised and as done in routine clinical practice. The patients were provided the option of continuing oral Cerebroprotein at half cost even after 90 days of treatment if they wished for another 6 months. They were offered oral Cerebroprotein therapy and they or their caregivers patients had the right to choose or refuse treatment after a full understanding of the treatment. The study was a retrospective chart analysis of the findings in these patients. The patient choice of participation was not compromised in the study. Ethical clearance for the retrospective chart review was obtained from the institutional ethics committee. As this was a retrospective chart review and not a clinical trial, no CTRI registration was sought. No control group was present either. The present study is not a clinical trial and is a retrospective chart analysis. Patients who wished to continue the therapy further were offered medication at the same concessional rate and had the option of doing so. None of the patients in the study had any other psychiatric comorbidity and this was ruled out during their assessment as procured from their case papers. The patients had medical illnesses like blood pressure and diabetes that were under control with oral medical treatments.
| Results|| |
Majority of the patients were male (30 out of 34). All patients were aged above 65 years with the age range being 66–87 years and the mean age being 73.76 ± 5.35 years. A majority of patients had mixed dementia (Alzheimer's + Vascular) (n = 22; 64.71%). Ten patients had pure vascular dementia while 2 had Alzheimer's dementia. All patients had studied up to and/or above the 12th standard. The mean ACER scores at the start of therapy was 15.35 (standard deviation [SD] = 4.35; range 10–24) and at the end of the course of therapy was 37.97 (SD = 6.09; range 26–48) [Table 1]. The mean MMSE scores at the start of therapy was 11.41 (SD = 1.01; range 10–15) and at the end of therapy was 19.67 (SD = 1.69; range 16–24) [Table 1]. The changes in ACER scores (t = 28.273, df = 32, P < 0.0001) and MMSE (t = 24.602, df = 32, P = 0.0001) were statistically significant. It is worthwhile noting that the changes in scores were modest and cannot be said to have a major change in cognitive abilities of the patient but there were certain areas of improvement that were appreciated by the relatives. Six patients regained bladder control and 1 regained bowel control which was a big relief to the caregivers while aggression and anger reduced markedly in 6 patients each. One patient who had pathological laughter improved and one patient with verbal disinhibition showed improvement. No major side effects were noted in any of the patients. None of the patients reported feeling allergic to the drug. Only one patient complained of acidity after starting the medication and he was started on oral Pantoprazole 40 mg once a day and the acidity was fine thereafter.
| Discussion|| |
Cerebroprotein is the first drug that is neurotrophic in nature in the laboratory and promotes neuronal survival and growth. It is peptide in nature just like many endogenous neurotrophic factors. Studies have documented neuroprotective and neurotrophic action with injectable medication but studies with the oral preparation are scarce. This drug is the only medication acting at a neuronal level unlike others that act at neurotransmission and neurotransmitter level in dementia. In the cases mentioned above, we continued the medications that patients were on Cerebroprotein and especially in those where improvement was noted. We were surprised to see improvement in areas of bladder and bowel control, aggressive behavior, pathological laughter, verbal disinhibition, and especially as these areas had shown no improvement so far in these cases. It was difficult to comment whether this improvement was due to oral cerebroprotein or due to other drugs or spontaneous remission. It is worthwhile noting that the improvement was seen however only 7–10 days after oral cerebroprotein was started. We admit that changes in cognition and memory seen with oral cerebroprotein was mild to moderate and yielded scores within the dementia range itself, but still a positive change in scores were noted. No major side effects were seen in our cases. Cerebroprotein is currently available both as an injectable and as an oral preparation. It has been mentioned that the injectable drug works faster than the oral one but patient preference is for an oral dosage. It is worthwhile that the oral drug be tried as an add-on with other current available treatments in dementia. Further longitudinal studies with the oral preparation and comparing it with the injectable preparation in varied cohorts of dementia are warranted. The study had limitations as it was restricted to 34 patients in a retrospective chart analysis. The study was an open one and no blinding was done. There was no control group in the study.
We would like to thank the Department of Social Work, Lokmanya Tilak Municipal Medical College for providing medication at half the cost to patients.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Wimo A, Jönsson L, Bond J, Prince M, Winblad B, Alzheimer Disease International. The worldwide economic impact of dementia 2010. Alzheimers Dement 2013;9:1-11.
Miyamoto Y, Tachimori H, Ito H. Formal caregiver burden in dementia: Impact of behavioral and psychological symptoms of dementia and activities of daily living. Geriatr Nurs 2010;31:246-53.
Madhusoodanan S, Ting MB. Pharmacological management of behavioral symptoms associated with dementia. World J Psychiatry 2014;4:72-9.
Ritchie CW, Molinuevo JL, Truyen L, Satlin A, Van der Geyten S, Lovestone S, et al
. Development of interventions for the secondary prevention of Alzheimer's dementia: The European Prevention of Alzheimer's Dementia (EPAD) project. Lancet Psychiatry 2016;3:179-86.
Plosker GL, Gauthier S. Cerebrolysin: A review of its use in dementia. Drugs Aging 2009;26:893-915.
Hartbauer M, Hutter-Paier B, Skofitsch G, Windisch M. Antiapoptotic effects of the peptidergic drug cerebrolysin on primary cultures of embryonic chick cortical neurons. J Neural Transm (Vienna) 2001;108:459-73.
Gupta P, Yadav S, Singal KK. Cerebroprotein hydrolysate: Innovation in the treatment of neurodegenerative disorders. J Indian Acad Clin Med 2014;15:132-3.
Bae CY, Cho CY, Cho K, Hoon Oh B, Choi KG, Lee HS, et al
. A double-blind, placebo-controlled, multicenter study of Cerebrolysin for Alzheimer's disease. J Am Geriatr Soc 2000;48:1566-71.
Karia S, Majlikar R, De Sousa A, Shah N. Cerebroproteinhydrolysate in extra pontine myelinosis-A case report. Int J Sci Res Publ 2014;1:1-2.
Zhang L, Chopp M, Wang C, Zhang Y, Lu M, Zhang T, et al
. Prospective, double blinded, comparative assessment of the pharmacological activity of Cerebrolysin and distinct peptide preparations for the treatment of embolic stroke. J Neurol Sci 2019;398:22-6.
Phirke M, Desousa A, Shah N, Sonavane S, Bharati A. The use of cerebroprotein hydrolysate in dementia: A case series of 25 cases seen in a tertiary general hospital. J Geriatr Ment Health 2014;1:106-9. [Full text]
American Psychiatric Association. Diagnostic and Statistical Manual for Classification of Psychiatric Disorders – 4th
Edition – Text Revised (DSM-IVTR). New York: American Psychiatric Publishing; 2000.
Mioshi E, Dawson K, Mitchell J, Arnold R, Hodges JR. The Addenbrooke's Cognitive Examination Revised (ACE-R): A brief cognitive test battery for dementia screening. Int J Geriatr Psychiatry 2006;21:1078-85.
Folstein MF, Folstein SE, McHugh PR. “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975;12:189-98.
Liu Z, Wang W, Huang T, Wang C, Huang Y, Tang Y, et al
. CH (II), a cerebroprotein hydrolysate, exhibits potential neuro-protective effect on Alzheimer's disease. PLoS One 2019;14:e0222757.
Plosker GL, Gauthier S. Spotlight on cerebrolysin in dementia. CNS Drugs 2010;24:263-6.
Ma W, Wang S, Liu X, Tang F, Zhao P, Cheng K, et al
. Protective effect of troxerutin and cerebroprotein hydrolysate injection on cerebral ischemia through inhibition of oxidative stress and promotion of angiogenesis in rats. Mol Med Rep 2019;19:3148-58.