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OBJECTIVE	The enigmatic etiology of neurodegenerative diseases poses a challenge for the development of novel and efficient drugs .
OBJECTIVE	The objective of the present study was to evaluate the efficacy of a polyherbal ( test ) formulation on cognitive functions , inflammatory markers and oxidative stress in healthy elderly as well as senile dementia of Alzheimer 's type ( SDAT ) patients .
METHODS	A randomized double-blind placebo - and active-controlled clinical trial was performed in healthy elderly subjects and SDAT patients with an age range of 60-75 years .
METHODS	The polyherbal test formulation along with a placebo was given to healthy elderly subjects while the SDAT patients received either the test formulation containing extracts of Bacopa monnieri ( whole plant ) , Hippophae rhamnoides ( leaves and fruits ) and Dioscorea bulbifera ( bulbils ) at a dose of 500 mg or donepezil drug ( Aricept ) at a dose of 10 mg , twice daily , for a period of 12 months .
METHODS	After every three months , cognitive functions were assessed by determining the mini mental state examination ( MMSE ) score , digital symbol substitution ( DSS ; subtest of the Wechsler Adult Intelligence Scale-Revised ) , immediate and delayed word recall ( digital memory apparatus-Medicaid systems , Chandigarh , India ) , attention span ( Attention Span Apparatus-Medicaid systems , Chandigarh , India ) , functional activity questionnaire ( FAQ ) and depression ( geriatric depression scale ) scores .
METHODS	Further inflammatory markers and level of oxidative stress were analyzed using standard biochemical tests .
RESULTS	The trial was performed in 109 healthy subjects and 123 SDAT patients of whom 97 healthy subjects and 104 SDAT patients completed the study .
RESULTS	Administration of the test formulation for a period of 12 months was effective in improving cognitive functions in the SDAT patients , when compared to the donepezil-treated group , as determined by the DSS ( 38.984 3.016 vs 35.852 4.906 , P = 0.0001 ) , word recall immediate ( 3.594 1.003 vs 2.794 0.593 , P < 0.0001 ) and attention span ( 4.918 1.239 vs 4.396 0.913 , P = 0.0208 ) scores .
RESULTS	A significant improvement in the FAQ ( 11.873 2.751 vs 9.801 1.458 , P < 0.0001 ) and depression ( 16.387 2.116 vs 21.006 2.778 , P < 0.0001 ) scores was also observed , whereas no significant differences were observed in the MMSE and word recall delayed scores .
RESULTS	The level of inflammation and oxidative stress was markedly reduced in the SDAT patients treated with the test formulation when compared to the donepezil-treated group indicating a likely mechanism of action of the test formulation ( homocysteine 30.22 3.87 vs 44.73 7.11 nmol/L , P < 0.0001 ; C-reactive protein [ CRP ] 4.751 1.149 vs 5.887 1.049 mg/L , P < 0.0001 ; tumour necrosis factor alpha [ TNF - ] 1139.45 198.87 vs 1598.77 298.52 pg/ml , P < 0.0001 ; superoxide dismutase [ SOD ] 1145.92 228.75 vs 1296 225.72 U/g Hb , P = 0.0013 ; glutathione peroxidase [ GPx ] 20.78 3.14 vs 25.99 4.11 U/g Hb , P < 0.0001 ; glutathione [ GSH ] 9.358 2.139 vs 6.831 1.139 U/g Hb , P < 0.0001 ; thiobarbituric acid reactive substances [ TBARS ] 131.62 29.68 vs 176.40 68.11 nmol/g Hb , P < 0.0001 ) .
RESULTS	Similarly , when healthy elderly subjects treated with the test formulation for 12 months were compared to the placebo group , a significant ( P < 0.001 ) improvement in cognitive measures ( MMSE , DSS , word recall delayed but not immediate , attention span , FAQ and depression scores ) and a reduction in inflammation ( reduction in homocysteine , CRP , IL-6 and TNF - levels ) and oxidative stress levels ( reduction in SOD , GPx and TBARS and increase in GSH ) was observed .
RESULTS	This indicated a protective effect of the test formulation in managing cognitive decline associated with the ageing process .
CONCLUSIONS	The results of this study demonstrate the therapeutic potential of this novel polyherbal formulation for the management and treatment of SDAT .

