NAD+ For Preventing and Treating Cognitive Impairment
As we age, we often expect that some of our brain function will begin to weaken. In fact, for many people, the mental and cognitive effects of aging worry them much more than the physical effects of aging.
The worries around mental and brain health as we age are related to our ability to carry out daily tasks. Many people experience memory loss, brain fog, problems concentrating, and others as we age.
Researchers are highly interested in finding ways to optimize and prolong mental health as we age. Unsurprisingly, the role of NAD+ in optimal brain function, and the potential NAD+ has to prevent cognitive decline and even reduce symptoms of several age-related mental illnesses, is at the forefront of anti-aging research.
In this article we summarize the most recent research around the role of NAD+ in supporting cognitive health throughout your lifetime.
The Role of NAD+ in Cognitive Health
On the most basic level, cognitive impairment, is the result of a slowing or damaging of the processes in the brain the support memory, rational thinking, motor control, and higher cognitive processes like problem-solving and analysis. Severe cognitive impairment can result in the development of neurodegenerative diseases and disorders like Parkinson’s disease, Alzheimer’s disease, Huntington’s disease, and amyotrophic lateral sclerosis.
NAD+ has an essential role in the metabolism of all cells in the body, including brain cells. The difference is that the brain has multiple complex functions that require a constant high demand of energy. NAD+ is a key component in a series of chemical processes that allows cells to gain access to energy and carry out its normal functions (1).
More specifically, to quote a recent ground-breaking study on the role of “NAD+ in Brain Aging and Neurodegenerative Disorders”:
NAD+ is a pivotal metabolite involved in cellular bioenergetics, genomic stability, mitochondrial homeostasis, adaptive stress responses, and cell survival. Multiple NAD+-dependent enzymes are involved in synaptic plasticity and neuronal stress resistance (2).
As humans age, so does the cell’s ability to produce and use NAD+ efficiently. At the same time, NAD+ demands increase as cells and tissues are damaged, immunity is impaired, and illnesses arise (3).
Keeping cellular NAD+ supplies up through leading a healthy lifestyle and NAD+ supplementation are some ways to give the brain what it needs all throughout life.
How NAD+ Helps Prevent Cognitive Impairment
The key to helping prevent cognitive impairment is reducing the speed at which the brain ages, and potentially reversing some effects of brain aging.
Research has shown that supplementation with NAD+ precursors nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN). NR has been shown to help to maintain and improve neurogenesis, which is the growth and development of tissue and cells of the nervous system, including the brain. It also helps to maintain and increase the proliferation of neural stem cells and increase lifespan in lab models.
NMN has been shown to directly increase NAD+ and SIRT1/SIRT2 cells and promote neurogenesis.
How NAD+ May Treat Cognitive Impairment and Neurodegenerative Diseases
Lab research has made great strides in understanding the role of NAD+ supplementation as therapeutic treatment for neurological diseases. The primary diseases studied include Alzheimer’s Disease, Parkinson’s Disease, amyotrophic lateral sclerosis (ALS), and Huntington’s Disease.
It is important to note that most research is focused on the role of supplements that are precursors to NAD+ and NAD+ itself, notably:
- NAD+, nicotinamide adenine dinucleotide
- NADPH, NAD phosphate
- NAM, nicotinamide
- NLRP3, NLR family pyrin domain-containing
- NMN, nicotinamide mononucleotide; NR, nicotinamide riboside
The below results were reported and summarized in the article published by researchers from the department of Genetics at Harvard University and the University of Oslo (2).
With regards to Alzheimer’s Disease, NAM has been found to increase SIRT1 expressions, antioxidant levels, and maintain or increase oxidative stress resistance and neuronal plasticity and cognitive function. NR has been shows to directly increase NAD levels, lower DNA damage, increase neurogenesis, lower neuroinflammation, and increase fitness, memory and lifespan.
NAD+ precursors have also had an important role in the treatment of Parkinson’s Disease. NAM has increased mitochondrial function and reduced oxidative stress and DNA damage, in addition to reducing the loss of dopaminergic neurons. Supplementation with pure NAD+ was shown to increase sensitivity toward MeHg, which reduced MeGH-induced neuronal damage.
There are vital advancements in treatment for ALS, where supplementation with NR or NMN saw increases in NAD+ and increase in oxidative stress resistance, mitochondrial function, and a reduction in toxicity toward cocultured neurons.
Finally, laboratory research has demonstrated important advancements in treatment for Huntington Disease. NAM supplementation reversed toxic effects of mHTT , increased neuroprotection, and saw an increase in motor function. NR helped to increase overall NAD+, an increase in oxidative metabolism and neuroprotection, and a decrease in HD-related motor dysfunction and related pathways.
Main Takeaways
NAD+ research has made important strides in helping us understand the role of NAD in cognitive impairment. It is also paving the way for understanding how NAD+ supplementation can help to prevent neurodegeneration and even form part of the treatment for neurodegenerative diseases.
References:
1. Camandola, S., & Mattson, M. P. (2017). Brain metabolism in health, aging, and neurodegeneration. The EMBO Journal, 36(11), 1474–1492. https://doi.org/10.15252/embj.201695810
2. 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. https://doi.org/10.1016/j.cmet.2019.09.001
3. Cell Metabolism. (2009, July 20). NAD+ Metabolism and Signaling. Cell Metabolism Voices. Retrieved December 7, 2021, from https://www.cell.com/cell-metabolism/pdf/S1550-4131(19)30316-X.pdf