Mild Cognitive Impairment (MCI) is the pre-clinical phase between healthy aging and dementia; it is characterized by mild alteration in the cognitive functions, which do not interfere with the daily life and usual activities. It is estimated that 19% of the over-65 is affected and 46% of these cases evolve in dementia in the following three years; 4% of these will be Alzheimer disease.

MCI is considered a phase in which it is possible to act to delay the worsening toward a more serious disease, reducing its incidence and costs related to dementia diagnosis.

The strongest risk factors for MCI is increasing age, but also other factors are considered, such as: specific genetic mutation, diseases as High blood pressure, elevated cholesterol, diabetes, but also factors related to lifestyle, as smoking, obesity, lack of physical exercise, infrequent participation in mentally or socially stimulating activities.

The first symptoms are loss of short term memory, difficulty in orienting in time and space, loss of the train of thoughts and conversations. Difficulty in speaking and planning activities may rise. Anyway, all these alterations do not interfere with the daily life and usual activities, as opposed to dementia, when these alterations are so bad that compromise the quality of life.

Nicotinamide mononucleotide (NMN)

Nicotinamide mononucleotide (NMN) is a nucleotide derived from ribose and nicotinamide, it is a NAD⁺ precursor. NAD⁺ is a coenzyme associated to many redox reactions in cellular metabolism, especially related to energetic metabolism, DNA repair, mitochondrial homeostasis, protection to oxidative stress and signal transduction.

Il was observed that NAD⁺ decreases with age and its levels are significantly lower in neurodegenerative diseases and cognitive impairment. So, the restoration of NAD⁺ levels can be a strategy to prevent and slow down the neurodegenerative diseases (Lautrup et al., 2019).

However, NAD⁺ supplementation is not a good way, since its low intestinal absorption: NMN, instead, is able to cross the blood-brain-barrier and easily reach the target tissue, the nervous system, and it is the direct NAD⁺ precursor, so the chemically closest molecule.

In literature, we find many preclinical studies supporting the use of NMN in the treatment of neurodegenerative diseases, Alzheimer disease included, which represents the most serious type of dementia. Wang and colleagues (2016) show that the NMN administration to rats with Alzheimer disease model improves the cognitive impairment, in terms of learning and memory.

This benefit is related to the increased survival of neurons: NMN, indeed, decreases the neuronal death in hippocampal cultures, improves the energetic metabolism and reduces the ROS accumulation.

In the research of Yao and colleagues (2017) it was demonstrated the NMN ability to reduce the number of amyloids plaques in rats with Alzheimer disease model, as shown in the figure. Amyloids plaques are accumulation of misfolded proteins in the nervous cells and are considered fundamental in the disease’s development. In MCI’s patients, density and distribution of amyloids plaques is intermediate between a healthy and an Alzheimer disease brain.

We can conclude that NMN is an innovative compound with interesting neuroprotective effects.

References 

Lautrup, S., Sinclair, D. A., Mattson, M. P., & Fang, E. F. (2019). NAD+ in brain aging and neurodegenerative disorders. Cell metabolism, 30(4), 630-655.

Wang, X., Hu, X., Yang, Y., Takata, T., & Sakurai, T. (2016). Nicotinamide mononucleotide protects against β-amyloid oligomer-induced cognitive impairment and neuronal death. Brain research, 1643, 1-9.

Yao, Z., Yang, W., Gao, Z., & Jia, P. (2017). Nicotinamide mononucleotide inhibits JNK activation to reverse Alzheimer disease. Neuroscience letters, 647, 133-140