Association of homocysteine (Hcy) metabolism with cognitive dysfunction in AD pathogenesis has been revealed by many studies. The aim of this study was to investigate serum levels of vitamin B12 (VB12) and Hcy with response to donepezil and VB12 supplement therapy in AD treatment. Methods: Study comprised of 71 AD patients and 70 healthy controls above 60 years of age. Blood serum samples were analyzed for VB12 and Hcy levels by the chemiluminescence method. AD patients were treated with

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... il (5mg/day) and nutritional supplement containing VB12 (1.5mg/day) and was observed at intervals of 3 and 6 months. Statistical evaluation was done by using IMB SPSS statistics version 25. Results: The serum levels of Hcy were significantly higher and VB12 were significantly low in AD patients as compared to baseline. The therapy did not show any improvement at 3 months interval but after 6 months the serum levels of VB12 increased and Hcy decreased as compared to 3 months. Hcy and VB12 show a negative correlation with each other in AD groups. (p < 0.01) Conclusion: We conclude that the combination of donepezil and VB12 not only render symptomatic reliefs in AD patients, but also helps to revive from the metabolic consequences caused due to HHcy. It lowers the serum Hcy levels in AD, thereby reducing the progressive neurodegeneration and further vascular complications of AD. Research on efficacy of this combination therapy for a longer duration will help in better understanding of the disease pathogenesis and thus develop novel therapeutic target drugs.