From,
Dr. Jayakrishnan S.
Preliminary M.D.(AYU) Scholar,
Dept. of P.G. Studies in Manasa Roga,
S.D.M.College of Ayurveda & Hospital,
Hassan – 573201.
To,
The Registrar,
RajivGandhiUniversity of Health Sciences, Karnataka,
Bangalore.
Through,
The Principal and Head of Department of Manasa Roga,
S.D.M.College of Ayurveda,Hassan.
Respected Sir,
Sub: Submission of completed proforma for Registration of subject for Dissertation.
I hereby request you kindly to register the mentioned subject against my name for the submission of Dissertation to the Rajiv Gandhi University of Health Sciences, Karnataka, Bangalore for partial fulfillment of M.D.(Ayu).
Title of the dissertation:
“A PHARMACO -CLINICALSTUDY ON THE EFFECT OF BRAHMYADI YOGA IN THE MANAGEMENT OF DEMENTIA IN ALZHEIMER'S DISEASE”
Here with I am enclosing completed proforma of synopsis for Registration of subject for Dissertation.
Thanking you.
Date: Yours faithfully,
Place: Hassan ( Dr. Jayakrishnan S. )
RajivGandhiUniversity of Health Sciences, Karnataka, Bangalore.
ANNEXURE – 11
PROFORMA FOR REGISTRATION OF SUBJECT FOR DISSERTATION
1. Name of the candidate:Dr. JAYAKRISHNAN S.
and Address1st YEAR M.D.
Dept. of P.G. Studies in Manasa Roga
S.D.M.College of Ayurveda and Hospital,
Hassan – 573201.
Permanent address: S/o Shri. N. N. SUBRAHMANYAN
NAMBOOTHIRI,
“KARTHIKA ”,
SOUTH GATE,
KUMARANALLOOR P.O.,
DIST. KOTTAYAM,
KERALA – 686016.
2. Name of Institution:S.D.M.COLLEGE OF AYURVEDA AND HOSPITAL, HASSAN, KARNATAKA.
3.Course of study in subject: M.D.(Ayu) in MANASA ROGA
4.Date of admission of course: 25 October 2010
5. TITLE OF THE TOPIC:
“A PHARMACO -CLINICAL STUDY ON THE EFFECT OF BRAHMYADI
YOGA IN THE MANAGEMENT OF DEMENTIA IN ALZHEIMER'S DISEASE.”
6. BRIEF RESUME OF INTENDED WORK:
6.1 NEED FOR THE STUDY:
Dementia is a chronic or persistent disorder of behavior and higher intellectual function due to organic brain disease. It is marked by Memory disorder, changes in personality, deterioration in personal care, impaired reasoning ability and disorientation.
``Dementia'' originally meant ``out of one's mind'', from the Latin de (out of) and mens (the mind). Early in the nineteenth century, Esquirol [1] gave a succinct definition of dementia as a cerebral affection characterized by a weakening of the sensibility, understanding, and will'' (cited by Caine et al [2]).
The term ``senile dementia of the Alzheimer type'' (SDAT) is used to describe elderly cases with Alzheimer brain changes based on the Clinical Descriptions and Diagnostic Guidelines of the ICD-10 [3].Alzheimer’s Disease (AD has characteristic neuro pathological and neuro chemical features. It is usually insidious in onset and develops slowly but steadily over a period of years. The onset can be in middle adult life or even earlier (AD with early onset), but the incidence is higher in later life (AD with late onset). In cases with onset before the age of 65±70, there is the likelihood of a family history of a similar dementia. The hippocampal atrophy is an early and sensitive feature of AD, the hippocampus being important for memory function.
The statistical meta-analyses using logistic model shows that the odds of having AD increases by 18% for every year of age.[14][15]The dementias are progressive disorders. There are four known risk factors for AD: age, family history of dementia, Down's syndrome, and apoE "4 genotype.
An individual can lead a normal happy life only if he has a sound intellectual capacity with a good memory.Any impairment to his/her memory will have a direct destructiveeffect on the quality of his living standards, thus this condition has been chosen for thepresent study.
In Ayurveda Aacharyas explained this diseases under ‘ Jara vyadhi’. Charaka explained the Smriti Nasa in the context of‘Vardhakya Janya Vikaras’. In old age people they will lose Grahana, Dharana, and Smarana because there is gradual diminution in the qualities of dhatus and dominance of Vata during this age.[22]
Aacharya Susrutha explained Smriti Nasa in the context of Vayas. He explained after seventy years is called Vardhakya. That time people decreased the strength, power, enthusiasam and Memory also.[23]
Primarily, Shankhapushpi is used as a brain tonic. It is one of thebest and prominent natural medicines that help in improving memory and prevents memory loss.
Brahmi is useful for improving mental clarity, confidence and memory recall. According to Ayurveda, it is tikta, katu, ushna, vamaka and virecaka.
Manduka parni is mildly antibacterial, anti-viral, antiinflammatory, anti-ulcerogenic, anxiolytic, a cerebral tonic, a circulatory stimulant, a diuretic and nervine.[1][2]In addition, preliminary evidence suggests that it may have nootropic effects.[3]It is used to re-vitalize the brain and nervous system, increase attention span and concentration.[4] It is Tikta, Laghu, Shita, Rasayanam, medhyam, mutra Virecana .[5]
All these 3 drugs are “Medhya” and act as brain tonic and improve memory and intellectualcapacity so these drugs have been selected for this particular studyto assess their combined effect in memory disorder. The Pharmacological study has been taken in order to assess the effect of the drug, their toxic effects and to determine the safety levels of these drugs.
6.2 REVIEW OF LITERATURE:
Charaka has mentioned about Smrti as rememberence of things directly perceived, heard or experienced earlier. The memory goes astray due to the person being overcome by rajas and tamas.this state is explained as Smrti Bhramsha.[18]. He has mainly explained about Smrtinasha in Unmada and Apasmara.[16][17]
The diagnostic criteria for dementia are essentially similar in the Diagnostic and Statistical Manual (4th edition) of the American Psychiatric Association (DSM-IV) [5], although the two systems may give somewhat different prevalence estimates, even when they are applied to the same data from the same population. The evidence so far is that the ICD-10 criteria are more strict and therefore identify fewer cases [6,7].Various terms have emerged to describe such states. The term ``benign senescent forgetfulness'' was introduced by Kral [8] to describe one group of such states. ``Age-associated memory impairment'' [9] has been shown to be an unsatisfactory construct. Christensen et al [10,11] showed that the ICD-10 experimental entity called``mild cognitive disorder'' is not really a syndrome in its own right, there is surely some face validity in the proposition that there is a state of progressive cognitive decline which people traverse on their way to eventually fulfilling the diagnostic criteria for a dementia. For this reason, it will be important to assess the validity and natural history of the entities called ``mild neuro-cognitive disorder'' and ``age-related cognitive decline'' proposed in the DSM-IV. A useful review of this important issue has been provided by Ritchie et al [12].
Dementia results from distruction of brain tissue by a series of small strokes. It is important to distinguish these organicconditions from psychological disorders that cause the same symptom.
Brahmi - Bacopa monniera is bitter in taste; has been used in the Ayurvedic system of medicine for centuries. Brahmi which occurs naturally in India and has a long history of use in the Ayurvedic medicine tradition in the treatment of a number of disorders, particularly those involving anxiety, intellect and poor memory. Traditionally, it was used as a brain tonic to enhance memory development, learning, and concentration.
Shankapuspi-Convolvulus pluricaulis. Primarily, shankhapushpi is used as a brain tonic. It is one of the best and prominent natural medicines that help in improving memory. The whole plant of shankhapushpi is used in medical treatment. Its consumption also prevents memory loss.
Mandookaparni - Centella asiatica Rasa is Tikta, Vipaka is laghu, Veeya Shita , Karma- Rasayanam, medhyam, mutra virecana
Prabhava- Rasayanam, medhyam.
Previous research works done:
- Dubey GP, Pathak SR, Gupta BS. Combined effect of Brahmi (Bacopa monniera) and Shankhpushpi (Convolvulus pluricaulis) on cognitive functions. Pharmacopsychoecologia 1994;7(3):249-51.
- Sharma R, Chaturvedi C, Tewari PV. Efficacy of Bacopa monniera in revitalizing intellectual functions in children. J Res Edu Indian Med 1987;1:12.
- Singh RH, Singh L. Studies on the anti-anxiety effect of the medyha rasayana drug Brahmi (Bacopa monniera Wettst.). Res Ayur Siddha 1980;1:133-48.
- A clinical study on the management of generalized anxiety disorder with Centella asiatica U Jana, 1 TK Sur, 2 LN Maity, 3 PK Debnath 4 and D Bhattacharyya Nepal Med Coll J 2010; 12(1): 8-1
- Cataldo, A., Gasbarro, V., et al., "Effectiveness of the Combination of Alpha Tocopherol, Rutin, Melilotus, and Centella asiatica in The Treatment of Patients With Chronic Venous Insufficiency", Minerva Cardioangiology, 2001, Apr; 49(2):159-63
- Afr J Tradit Complement Altern Med. 2009; 6(1): 9–16. Published online 2008 October 25. PMCID: PMC2816528 Copyright © Afr. J. Traditional, Complementary and Alternative Medicines 2009 Apoptosis Induction of Centella Asiatica on Human Breast Cancer Cells Suboj Babykutty,1 Jose Padikkala,2 Priya Prasanna Sathiadevan, Vinod Vijayakurup, Thasni Karedath Abdul Azis,3 Priya Srinivas,3 and Srinivas Gopala
- Khare, C. P. (2003). Indian Herbal Remedies: Rational Western Therapy, Ayurvedic, and Other Traditional Usage, Botany. Springer. pp.89. ISBN9783540010265.
6.3 OBJECTIVE OF THE STUDY:
1. To clinically evaluate the effect of Brahmyadi yoga in the management of Dementia (Smriti nasha)
2. To evaluate the psychoneuropharmacoligical effect of madukaparni, brahmi and shankhapushpi in animal models with primary focus on memory related protocols.
7. MATERIAL AND METHODS
I- Experimental study:
A: Primary tests for assessing memory and learning
1.Elevated plus maze test with protocol for testing effect on memory in mice
2.Assessment of effect on memory and learning behavior of rats in Morris water maze
3.Assessment of effect of learning linked conditioned avoidance response (CAR) establishment
Secondary tests :
- Gross behavior study ( Morpurgo’s C 1972- protocol)
- Assessment of effect on Muscle tone and balance using Rota-rod instrument
- Assessment for anti-anxiety activity using elevated plus maze
- Assessment for anti-depressant activity using behavioral ‘despair’ test ( Porsolt et al 1977 method)
- Assessment for anti-psychotic activity employing d-amphetamine stereotypy test
- Any other test depending up on the results of the primary tests
Mice weighing between 22-35g body weight, healthy and of either sex
Rats of either sex, healthy, between the weight of 150 to 250 g body weight
Assessment criteria:
Primary tests:
Elevated plus maze and Morris water maze- reversal of amnesic agent caused memory loss.
Conditioned avoidance test- faster establishment of CAR.
Individual test based.
Observation of CNS parameter changes in gross behavior study.
Modulation of the rat performance on rota rod.
Elevated plus maze – decrease in the time spent in closed tunnels.
Behavioural despair test- decrease the duration of mouse immobility.
Decrease in the d-amphetamine stereotypy
Other relevant end points as per the test protocol
II. Clinical study
7.2 SOURCE OF DATA:
Patients will be selected from OPD and IPD of SDM College of Ayurveda & Hospital, Hassan.
- CRITERIA OF DIAGNOSIS :
A summary of the ICD-10 Diagnostic Guidelines for dementia [3] is that each of the following should be present:
1. A decline in memory to an extent that it interferes with everyday activities, or makes independent living either difficult or impossible.
2. A decline in thinking, planning and organizing day-to-day things, again to the above extent.
3. Initially, preserved awareness of the environment, including orientation in space and time.
4. A decline in emotional control or motivation, or a change in social behaviour, as shown in one or more of the following: emotional liability, irritability, apathy or coarsening of social behaviour, as in eating, dressing and interacting with others.
B. Inclusion Criteria:
- Patients will be selected between the age group of 45 – 75 yrs.
2. Mild type of dementia as per clinical dementia rating.
C. Exclusion Criteria:
1. Diabetes Mellitus
2. Endocrinal Dysfunction
3. Dementia due to trauma.
4. Cerebro vascular disease.
5.Parkinson’s disease.
6. Brain tumour.
7. Sub dural haematoma.
D. Plan to study the effect of the treatment:
30 patients who fulfill the criteria for inclusion for memory impairment will be selected. 4 gms of Brahmyadi yoga will be administered twice a day after food with warm water for 1 month.
E. Criteria of Assessment:
Improvement in signs and symptoms according to the standard Dementia rating scale.
The Clinical Dementia Rating is a five-point scale in which CDR-0 connotes no cognitive impairment, and then the remaining four points are for various stages of dementia:
CDR-0.5 = very mild dementia
CDR-1 = mild
CDR-2 = moderate
CDR-3 = severe
The CDR is constructed over the six domains viz. Memory, Orientation, Judgment and Problemsolving,Community Affairs, Home and Hobbies, and Personal Care. In rating each of thesedomains, the assessment is made on the patient’s cognitive ability to function in these areas.
F. Follow up Study:
After completion of the treatment the patients’ follow – up will be done at an interval of 15 days for the period of 3 months.
7.3 Laboratory Investigation:
Routine Blood and Urine.
7.4 Has ethical clearance obtained from institution ---
Yes
8. List of references:
1. Esquirol J.E. (1845) A treatise on insanity. In Documentary History of Psychiatry. A Source Book on Historical Principles (Ed. C.E. Goshen), pp. 314±369, Lea and Blanchard, New York.
2. Caine E.D., Grossman H., Lyness J.M. (1995) Delirium, dementia, and amnestic and other cognitive disorders and mental disorders due to a general medical condition. In Comprehensive Textbook of Psychiatry (Eds H.I. Kaplan, B.J. Sadock), pp. 705±754, Williams and Wilkins, Baltimore.
3. World Health Organization (1992) The ICD-10 Classification of Mental and Behavioural Disorders. Clinical Descriptions and Diagnostic Guidelines, World Health Organization, Geneva.
4. World Health Organization (1993) The ICD-10 Classification of Mental and Behavioural Disorders. Diagnostic Criteria for Research, World Health Organization, Geneva.
5. American Psychiatric Association (1994) Diagnostic and Statistical Manual of Mental Disorders, 4th edn, American Psychiatric Association, Washington,DC.
6. Henderson A.S., Easteal S., Jorm A.F., Mackinnon A.J., Korten A.E., Christensen H., Croft L., Jacomb P.A. (1995) Apolipoprotein E allele e4, dementia and cognitive decline in a population sample. Lancet, 346: 1387±1390.
7. Erkinjuntti T., Ostbye T., Steenhuis R., Hachinski V. (1997) The effect of
different diagnostic criteria on the prevalence of dementia. N. Engl. J. Med.,
337: 1667±1674.
8. Kral V.A. (1962) Senescent forgetfulness, benign and malignant. Can. Med. Assoc. J., 86: 257±260.
9. Crook T., Bartus R.T., Ferris S.H., Whitehouse P., Cohen G.D., Gershon S. (1986) Age-associated memory impairment: proposed diagnostic criteria and measures of clinical changeÐReport of a National Institute of Mental Health Work Group. Develop. Neuropsychol., 2: 261±276.
10. Christensen H., Henderson A.S., Jorm A.F., Mackinnon A.J., Scott R., Korten A.E. (1995) ICD-10 mild cognitive disorder: epidemiological evidence of its validity. Psychol. Med., 25: 105±120.
11. Christensen H., Henderson A.S., Korten A.E., Jorm A.F., Jacomb P.A., Mackinnon A.J. (1997) ICD-10 mild cognitive disorder: its outcome three years later. Int. J. Geriatr. Psychiatry, 12: 581±586.
12. Ritchie K., Touchon J. (2000) Mild cognitive impairment: conceptual basis and current nosological status. Lancet, 355: 225±228.
13. McKhann G., Drachman D., Folstein M., Katzman R., Price D., Stadlan E.M.(1984) Clinical diagnosis of Alzheimer's disease: Report of the NINCDS± ADRDA work group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease. Neurology, 34: 939±944.
14. Rocca W.A., Hofman A., Brayne C., Breteler M.M., Clarke M., Copeland J.R.M., Dartigues J.-F., Engedal K., Hagnell O., Heeren T.J. et al (1991) Frequency and distribution of Alzheimer's disease in Europe: a collaborative study of 1980± 1990 prevalence findings. Ann. Neurol., 30: 381±390.
15. Corrada M., Brookmeyer R., Kawas C. (1995) Sources of variability in prevalence rates of Alzheimer's disease. Int. J. Epidemiol., 24: 1000±1005.
16) Charaka samhita with Ayurveda Dipika Commentary,
Chaukhamba Sanskrit Sansthan, Varanasi, 1994, Nidana Sthana, 9:5.
17) Charaka samhita with Ayurveda Dipika Commentary,
Chaukhamba Sanskrit Sansthan, Varanasi, 1994, Nidana Sthana,10:5.
18) Charaka samhita with Ayurveda Dipika Commentary,
Chaukhamba Sanskrit Sansthan, Varanasi, 1994,Sareera sthana,1/101
19) Sushruta Samhita with Ayurveda Tattva Sandipika Commentary, Chaukhamba Sanskrit Sansthan, Varanasi 2000, Uttara tantra, 61:14
20) Sushruta Samhita with Ayurveda Tattva Sandipika Commentary, Chaukhamba Sanskrit Sansthan, Varanasi 2000, Uttara tantra, 62:3
21) Ashtanga Hrudaya Samhita, Nidana Sthana, 6:9.
22) Charaka Samhitha, Vimana Sthana 8; 122 sloka.
23) Susrutha Sutra Sthana 35;29 sloka
9. SIGNATURE OF CANDIDATE:
10. REMARKS OF GUIDE :
11. NAMES AND DESIGNATION OF
11.1 GUIDE : DR. SUHAS KUMAR SHETTY
READER
DEPT. OF MANASA ROGA,
SDMCA&H, HASSAN.
11.2 SIGNATURE :
11.3 CO-GUIDE : DR. NARAYANA PRAKASH B,
PROFFESOR &HOD,
DEPT. OF MANASA ROGA,
SDMCA & H, HASSAN
SIGNATURE
11.4. H.O.D. :DR. NARAYANA PRAKASH B,
PROFFESOR &HOD,
DEPT. OF MANASA ROGA,
SDMCA & H, HASSAN
12 SIGNATURE :
12.1 REMARK OF CHAIRMAN:
& PRINCIPAL
12.2 SIGNATURE :