A Randomized open label controlled clinical study to evaluate the efficacy of Yasti Madhu (Glycyrrhiza glabra Linn.) churna with milk in Mild Cognitive Impairment.

Mild Cognitive Impairment is a neurological disorder in older adults characterized by slight but noticeable deficits in memory or other thinking skills with minimal impacts on daily living functioning.The term ‘Mild Cognitive Impairment’ (MCI) is commonly being used to refer a stage of cognitive impairment prior to attaining clinical dementia in Alzheimer disease (AD) and related disorders. It is considered as a prior condition to senile dementia.MCI has been conceptualized as an intermediate phase between normal aging and dementia.It may often progress leading to dementia, may remain static or may improve. The criteria for MCI include subjective memory problems, objective memory decline, absence of other cognitive disorders or repercussions on daily life, normal general cognitive function and absence of dementia. Being an alarming problem, it needs effective and safe treatment. Therefore, there is wide scope of research to find out a remedy in Ayurveda for the management of this disease. Yasti madhu is one of the important medicinal plants mentioned in Ayurveda classics having more than 1250 preparations indicated for various disease conditions. Yasti madhu is also mentioned as one of the *Medhya Rasayanas.*Recent experimental studies have proven its efficacy in enhancing learning and memory. Hence the current study is planned to clinically evaluate efficacy of Yasti madhu in Mild cognitive impairment. The drug Mandukaparni (Centella asiatica), which is proven for its Medhya action and Rasayana properties is taken as the control drug.

The trail drug yasti madhu(Glycyrrhiza glabra) stem and roots are procured and authenticated using standard protocol. The control drug Mandukaparni(Centella asiatica) leaf extract capsules will be procured from the GMP certified Pharmacy. Thirty human subjects, fulfilling the inclusion criteria visiting outpatient departments (OPD) and in patient departments (IPD) of Sri Sri College of Ayurvedic Science and Research Hospital, Kanakapura road, Bengaluru will be selected for the present study. Subjects will also be selected from referral sources and special camps conducted at old age homes. Subjects willing to participate with written informed consent, which is conveyed in the language which the subject can understand. Inclusion criteria: Subjects who aged more than 40 years irrespective of Gender and get score less than 26 in Montreal cognitive assessment scale (MoCA) and less than 24 in Mini mental status (MMSE) scale will be taken for study. Exclusion criteria: Subjects who have lost cognitive function as a result of trauma. Subjects diagnosed with Tumor, Types of Dementia like Alzheimer’s dementia, Vascular dementia, Lewy body dementia etc. and lost cognitive function as a result of these. Subjects under Anti-psychotic drugs, Anti-epileptic drugs will be excluded. Subjects having any other conditions which can interfere with the treatment will be excluded. The selected participants are randomly (lottery method) assigned into 2 groups (without masking), Group A(trail) and Group B(control). Subjects will be equally assigned into 2 groups of 15 each: Group A: A sachet of 500mg of Trail drug (yastimadhu churna) with boiled and cooled cow’s milk(150ml) is administered after breakfast and dinner for 90 days. Group B: 500mg of Control drug (mandukaparni leaf extract) with water (150ml) will be administered after breakfast and dinner for 90 days. Follow-up will be done alternative days through phone and follow-up assessment will be carried on 0th day,45th day, 90th day and drug free follow-up on 120th day. Data will be collected through special case sheet proforma and adopted for the study. Diagnostic criteria: Montreal cognitive assessment scale (MoCA) and Mini mental status (MMSE) scale. Assessment Criteria: Scoring pattern will be adopted for both subjective and objective criteria, through Montreal cognitive assessment scale (MoCA) and Mini mental status (MMSE) scale. Withdrawal criteria: Subjects who develop any acute adverse reaction due to intervention or any serious disease during the study period, will be withdrawn from the study and necessary steps will be taken for management. Monitoring adverse events: Any adverse events during the study will be monitored, recorded and reported to the Pharmacovigilance cell of Sri Sri College of Ayurvedic Science and Research Center. The adverse events will be managed as per standard treatment protocol of SSCASR, Bengaluru. Confidentiality of the data would be maintained, and the original raw data would be preserved for at least 5 years from the date of completion of the study. Statistical Analysis: The collected data will be presented in the form of Mean + SD (Standard Deviation), SEM (Standard Error of Mean) or Range Whichever is applicable. For objective data, paired ‘t’ test & Repeated period ANOVA would be employed to assess before and after treatment differences within the groups and Un paired ‘t’ test would be employed for assessing the difference between the treated and reference control groups. For subjective data Wilcoxon signed rank test would be employed to assess before and after treatment differences within the groups and Mann-Whitney U test would be employed for assessing the difference between the treated and reference control groups. P< 0.05 would be considered statistically significant. In addition, Clinical effect size will be calculated based on calculation of Cohen’s ‘d.’ IBM SPSS Software version 26 will be used for analysis. Also standardized effect size would be calculated to ascertain the significance of the difference observed in the clinical evaluation.