Alzheimer's disease (AD) is the main cause of dementia. At present, AD is incurable. Memantine is recommended for the treatment of moderate and severe AD patients. Sodium oligomannate (GV-971) is a marine-derived oligosaccharide. It is proposed that it can reconstitute the gut microbiota, and inhibit neuroinflammation in the brain as observed in animal models. It reduces Aβ deposition in the brain of Aβ-transgenic mice. The reduction in both Aβ deposition and neuroinflammation may synergistically contribute to the improvement of cognitive impairment and delay the progress of the disease. China Food and Drug Administration（CFDA）approved it for the treatment of mild to moderate AD in 2019. Due to the different mechanism of memantine and GV-971, theoretically, they may synergistically improve cognitive function and delay disease progression. However, there is a lack of data on their effectiveness and safety. Therefore, the purpose of this study is to compare the efficacy and safety of memantine and GV-971 monotherapy and combination therapy in patients with moderate to severe AD, which is of great significance for guiding the treatment of moderate and severe AD.

Inclusion Criteria:

• age of 50-80 years old , either sex;
• met the diagnostic criteria for suspected AD;
• moderate to severe AD patients(5 points ≤Mini-Mental State Examination total score≤14 points);
• total Hachinski ischemic scale (HIS) score ≤4 points;
• memory loss for at least 12 months, with a progressive deterioration;
• brain MRI scan suggesting a significant possibility of AD;
• no obvious physical signs during nervous system examination;
• stable and reliable caregivers;
• elementary school or higher education level;
• signed an informed consent form.

Exclusion Criteria:

• previous nervous system diseases ;
• mental illness;
• unstable or severe heart, lung, liver, kidney, or hematopoietic diseases;
• uncorrectable visual and auditory disorders;
• simultaneous use of cholinesterase inhibitors, memantine or GV-971.