'NMN' and 'Citicoline' fight against memory loss!
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"Co-administration of NMN and citicoline improved memory, reduced brain inflammation, and reduced damage to the brain's white matter tract in mice with vascular dementia."
vascular dementia, VD
Vascular dementia (VD) is the second most common form of dementia after Alzheimer's disease. Vascular dementia occurs when brain cells are damaged by a blockage in the blood vessels leading to the brain, or by a brain disease such as a cerebral hemorrhage or infarction, leading to dementia. Because the risk of vascular dementia increases with age, it's crucial to take precautions to protect against it.
* Cerebral infarction: A disease in which a part of the brain is damaged due to blockage of a cerebral blood vessel.
NMN and citicoline
According to a report in the journal 'Cellular and Molecular Neurobiology,' researchers at Hangzhou Normal University in China showed that NMN and citicoline alleviated memory loss in mice with vascular dementia. The researchers also found that NMN and citicoline reduced brain inflammation and damage, and that the combination of NMN and citicoline protected the brain more effectively than when taken alone.
In the brain, citicoline maintains a brain fat called phosphatidylcholine (PC) and improves neuron survival. PC and other brain fats are known to contribute to preventing cognitive decline in humans.
Experimental results of NMN and citicoline
The researchers created a "VD mouse model" by blocking blood flow to the brains of mice for their experiments. Without sufficient blood flow to the brain, brain tissue begins to deteriorate, ultimately leading to deficits in learning and memory, key aspects of cognition, and ultimately to vascular dementia. Using VD mice, the researchers will explore the effects of a combination of citicoline and NMN on memory, brain inflammation, and white matter damage .
1- Memory test of VD rats
To determine the effects of NMN and citicoline on vascular dementia, the researchers administered each anti-aging compound (NMN, citicoline) separately to VD mice. They then performed a "novel object recognition test" to test the rodents' memory .
Graph 1. Discriminant index (DI) according to citicoline and NMN treatment
Discrimination index (DI) indicates a rodent's ability to distinguish between novel and familiar objects. A high DI score indicates enhanced learning and memory. The groups administered citicoline at 50 mg/kg, 100 mg/kg, or 200 mg/kg, and NMN at 500 mg/kg, 1,000 mg/kg, or 2,000 mg/kg, respectively, did not show any improvement in D1 scores (left) , whereas the group administered both supplements together showed a significant increase in DI scores compared to the groups administered them individually (right) . Here, Sham refers to the general test rat control group, not the VD rat model, and vehiclei refers to the VD rat control group that did not receive either citicoline or NMN.
Neither NMN nor citicoline alone significantly improved learning or memory in mice. However, co-administration of NMN and citicoline resulted in improved memory.
2- Degree of inflammation in VD rats
Brain inflammation is a key physiological indicator of vascular dementia. This time, we assessed the severity of dementia by measuring the activity of microglia cells . When microglia are activated, they promote inflammation, which can cause brain damage .
* Microglia cells: These are immune cells that exist in the brain and play a key role in the inflammatory response.
Graph 2. Iba-1 cell area (mm) according to citicoline + NMN treatment ²)
Iba-1 (Ionized Calcium-binding Adaptor Molecule 1) is a marker that indicates the degree of microglial activation. The more Iba-1 found in the cell, the more activated the microglial cells are and the more active the inflammatory response is. VD mice administered citicoline and NMN together (orange) showed lower expression of Iba-1 and reduced inflammation in the brain compared to VD mice that were not treated with either (red) .
* Iba-1 (Ionzied Calcium-binding adaptor molecule 1): A marker of microglia. When microglia are activated, the concentration of Iba-1 also increases.
Consequently, when NMN was combined with citicoline, microglial activation was reduced by nearly threefold, suggesting a reduction in brain inflammation.
3- Degree of white matter damage in VD rats
When microglia are activated in the brain, we see increased inflammation in the brain, which damages myelin, the fatty layer that protects neurons. Because myelin manifests itself macroscopically in white matter , damage to myelin compromises the integrity of white matter.
* Myelin: An insulating material that mainly surrounds neurons in multiple layers.
* White matter: Found in the inner part of the brain and contains the axons and myelin of neurons. 
Graph 3. Changes in white matter integrity following citicoline + NMN treatment (% of sham)
To determine the extent of brain damage, we measured the extent of changes in white matter compared to normal mice. Untreated VD mice (red) showed decreased white matter, while VD mice treated with NMN and citicoline (orange) showed less white matter loss. This suggests that NMN and citicoline protect the brain, preventing damage to white matter structures.
Consequently, co-treatment with NMN and citicoline resulted in less white matter loss, suggesting a reduction in brain damage.
[References and Figure Source]
[1] NMN and Citicoline Synergistically Shield Against Memory Decline, Study Finds
[2] Vascular dementia
https://www.amc.seoul.kr/asan/healthinfo/disease/diseaseDetail.do?contentId=32001
[3] Cerebral infarction
https://www.amc.seoul.kr/asan/mobile/healthinfo/disease/diseaseDetail.do?contentId=31996
[4] IBA1 (Ionized calcium-binding adapter molecule 1)
[5] White matter of the brain
https://medlineplus.gov/ency/article/002344.htm
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