Lay summary by Grace Denton, reviewed by Dr Scott Allen and a Dementia lay panel
Background
Alzheimer’s disease (AD) and vascular dementia (VaD) are two brain conditions that have similar symptoms, such as memory loss and cognitive decline. However, they differ in their underlying causes: AD is primarily associated with brain cell death, while VaD results from reduced blood flow to the brain. It is common for individuals to have both conditions at the same time, known as “mixed dementia.” This overlap is challenging to treat.
Why is the study important?
Currently, there is no effective treatment available for people living with mixed dementia This is a growing concern as diagnoses of mixed dementia continue to rise. Existing treatments are typically designed to target either AD or VaD separately, and in some cases, treatment for one condition may worsen the other. This creates a major challenge in treating mixed dementia effectively. This study is important because the researchers aim to develop a single drug that can treat both AD and VaD at the same time, without causing harm to either condition. Their goal was to offer a more holistic and safer treatment option for people with mixed dementia.
What did the authors do and how did they do it?
The biochemical nitric oxide (NO) helps blood vessels widen so that blood can flow more easily, supports the growth of brain cells, and aids in forming brain cells that are essential for thinking and memory. A shortage of NO contributes to the development of AD and VaD. The authors overall aims were to boost NO levels using a new drug called MN-08 which restores NO levels in the blood when administered. In this study, the authors tested MN-08 in rat models of both AD and VaD. They assessed its effects on brain blood flow, behaviour, and brain activity to determine whether MN-08 could be an effective treatment for mixed dementia.
What are the results?
The results demonstrated that MN-08 significantly increased blood flow to the brain in both AD and VaD models. Since reduced blood flow is a key feature of early-stage VaD, this finding suggested that MN-08 could be a promising treatment option for addressing one of the root causes of the disease.
In addition, MN-08 also enhanced memory, learning, and overall brain function in both AD and VaD models. The researchers assessed these improvements using behavioural tests, such as object recognition and maze navigation. Treated models performed noticeably better compared to untreated models, indicating that MN-08 had a positive effect on cognitive ability. MN-08 effectively acted as a NO donor, promoting brain cell growth and activating key pathways involved in brain repair and function, particularly in the VaD models. This NO-donating property also helped maintain proper oxygen and nutrient delivery to the brain. These cellular effects support the idea that MN-08 provides both protective and restorative benefits. Overall, the author concludes that MN-08 offers strong potential as a treatment for patients with mixed dementia.
What do the findings mean going forward for people with the disease?
The results of this study highlight MN-08 as a potential therapeutic drug for both AD and VaD. However, further research is needed to fully understand how MN-08 affects different regions of the brain independently. Gaining a deeper understanding of MN-08’s broader effects will be essential before moving into human trials. Once this foundation is established, human studies can begin to optimise MN-08 for mixed dementia treatment.
This study can be found at
www.sciencedirect.com/science/article/abs/pii/S0028390825001169?via%3Dihub
Paper title
Multi-functional memantine nitrate attenuated cognitive impairment in models of vascular dementia and Alzheimer’s disease through neuroprotection and increased cerebral blood flow
Lead author
Guangying Chen, Yuqiang Wang et. al.
Publication details including date of publication
Neuropharmacology 2025 Jul 1:272:110410. doi: 10.1016/j.neuropharm.2025.110410 Date: 07/2025