Globally, there is a rise in dementia including Alzheimer’s disease (AD), which affects over 36 million people. According to estimates, by 2050, the number could double to 115 million, which could become a significant burden on society. There has been no effective drug approved for Alzheimer’s disease for many years despite decades of research. Although Aducanumab (an anti-amyloid monoclonal antibody) is the only disease-modifying treatment approved for Alzheimer’s disease (recent accelerated approval, awaiting phase 4 trial results), and the scientific question of whether it works is still open. It is well known that mild cognitive impairment (MCI) precedes AD. Approximately 10% of patients with MCI progress to Alzheimer’s disease every year. Mild cognitive impairment (MCI) refers to significant impairment in memory or in other cognitive domains but the impairment is not severe enough to affect everyday life. It is believed that treatment designed to slow or stop the progression of MCI to Alzheimer’s disease and preserve brain function will be most effective when applied early in the disease continuum and conserving brain function. Considering that conventional drug therapy is not enough to treat MCI and AD, herbs that are traditionally used in Indian system of Medicine i.e. Ayurveda are in popular demand worldwide. Thus, taking leads from Ayurvedic classical texts, there is an increasing interest for “medhya rasayanas” which may act as memory and learning enhancers, and have significant potential in improving cognitive disorders. Brahmi (Bacopa monnieri) is one such herb that has been frequently used for the treatment of anxiety, intellect, and poor memory for ages. Clinical and preclinical studies have shown that Brahmi enhances the retention of information and is safe for clinical use. But there is a paucity of studies, available in patients with MCI and AD. Additionally,  the evidence for the beneficial effect of Brahmi (Bacopa monnieri), its mechanism of action in humans is not fully known. To the best of our knowledge, no study has explored the effect of the administration of Brahmi (Bacopa monnieri) on metabolomics among MCI patients. Metabolites are the side products of cellular regulatory or biochemical pathways and hence have the potential to provide minute details of biological pathways. Untargeted metabolomics helps in understanding broad metabolomic profiles which includes novel metabolites that can be later used as a biomarker. Thus, it is important to explore not only the clinical efficacy of Brahmi (Bacopa monnieri) in patients with MCI and early AD but also the plasma metabolite alterations with Brahmi administration through the metabolomics approach.

The current study aims to assess the efficacy of Brahmi (Bacopa monnieri Linn.) on cognitive functions in patients with amnestic mild cognitive impairment(MCI) and early Alzheimer Disease (AD)through a double-blind, randomized placebo-controlled trial, and perform untargeted metabolomics to identify the global changes and canonical pathways after administration of Brahmi. It is hypothesized that administration of Brahmi (Bacopa monnieri Linn.) in MCI and early AD patients for 12 weeks would lead to improvement in memory and other cognitive domains and alteration in metabolomics profile.