- Aging can cause cognitive decline due to changes that happen in our brain cells; however, it is not clear how much of this is intrinsic or due to diseases such as Alzheimer’s.
- In order to improve energy metabolism in the brain, a group of scientists looked at the effect of supplementing a group of adults with a form of vitamin B3.
- The researchers found that the supplement nicotinamide riboside was converted into a molecule involved in energy metabolism in neurons.
- They also observed a small but significant decrease in the levels of amyloid beta protein in neurons, following supplementation.
Age isn’t just a number, and aging mechanisms affect us at a cellular level. The reason why some people age faster than others has been the focus of much recent research.
One condition for which age is a risk factor is dementia. About one-third of people who are over the age of 85 have some form of dementia.
As humans are living longer, the number of people with dementia in the population is also growing, and the World Health Organisation reports there are currently more than 55 million people living with dementia worldwide, and nearly 10 million new cases every year.
Despite this high prevalence, the mechanisms and risk factors underlying dementia are poorly understood.
The prevailing understanding is that Alzheimer’s disease is thought to be underpinned by the presence of clumps of certain forms of a protein called beta-amyloid between neurons, or nerve cells, in the brain. This is thought to affect their ability to signal, causing the cognitive decline seen in individuals with the condition.
However, it is important to note there is still significant debate over this mechanism, and how much of an impact it has on the development of Alzheimer’s disease, as well as its suitability as a potential target for treatment.
One theory is that the decline in cognition observed in people with Alzheimer’s disease is due to the disruption of typical energy production and metabolism in the brain.
A recent paper published in Aging Cellon the subject explores whether vitamin B could help offset this disruption.
Alzheimer’s and energy disruption in the brain
The brain is hugely energy dependent, and uses up to 20% of oxygen and therefore calories, of those used by the whole body, despite making up just 2% of its mass. This energy metabolism is understood to be disrupted in the brains of people with Alzheimer’s disease.
One way this can be disrupted is when nerve cells in the brain become insulin resistant. Insulin resistance means that the cells do not take up glucose for energy as they should. When this occurs in the brain energy metabolism, signalling and immune response functions are all affected negatively.
This can occur in individuals who have type 2 diabetes, which is characterised by insulin resistance, and there is a correlation between the condition and Alzheimer’s disease, though it is unclear why.
Dr. Kellie Middleton, orthopaedic surgeon at Northside Hospital, Atlanta, Georgia, who was not involved in the study, explained to Medical News Today:
“Neurodegeneration is a term used to describe the progressive loss of nerve cells in the brain and spinal cord, leading to problems with memory, cognition, movement, and other neurological functions. It can be caused by genetic or [underlying medical conditions including] aging, diabetes, stroke, Parkinson’s disease, Alzheimer’s disease, or traumatic brain injury.”
“Biochemical pathways are known to be associated with various forms of neurodegeneration, and research into these pathways is ongoing. For example, studies have highlighted connections between imbalances in energy metabolism, oxidative stress, inflammation, and mitochondrial dysfunction with the development of neurological diseases,” she continued.
If the brain cells can’t produce the energy they need to be able to function, then they can’t signal, and if nerve cells in the brain can’t signal effectively then cognition will be affected. Whether this is a cause of the disease or a symptom is unclear, said Dr. Christopher Martens, director of the Delaware Center for Cognitive Aging Research, and lead author of the current study.
“One of the main challenges with Alzheimer’s disease is the disruption of energy metabolism in the brain, which may actually contribute to the development of the disease.”
— Dr. Christopher Martens
Dr. Martens and his team looked at the role of a particular molecule involved in energy metabolism, called nicotinamide adenine dinucleotide, or NAD+.
“NAD+ is essential for cells to create energy and there is strong evidence from animal studies that aging and metabolic dysfunction results in a depletion of NAD+ within cells. Therefore, there is strong rationale that replenishing the NAD+ within the brain could have a positive effect on brain function,” he explained to MNT.
In order to do this a cohort of 10 adults were given a form of vitamin B3 called nicotinamide riboside as a supplement, as this molecule is a precursor for NAD+. This means that the body converts it into NAD+.
A group of 12 other adults received a placebo. Neither group knew whether they were receiving the supplement or a placebo.
In order to measure whether or not taking 500mg of the supplement twice a day for six weeks actually increased NAD+ in neurons, researchers measured the NAD+ in extracellular vesicles that are present in the neurons and end up in the blood. They extracted these from blood samples and found a small, but significant difference.
These results were previously published in 2018 in Nature.
In addition to this finding, the team have now published data showing that changes in levels of NAD+ and its precursors were correlated with changes in the presence of insulin-signalling proteins and molecules involved in inflammation, also thought to play a role in the development of Alzheimer’s and dementia.
While decreases in the tau and amyloid proteins, thought to be involved in the development of Alzheimer’s disease, were not significant when comparing all supplemented participants to placebo, a small but significant change was observed in the levels of these marker proteins in the extracellular vesicles of a sub-set of the supplemented participants who responded.
Can vitamins cross the blood-brain barrier?
Still, it is unclear if the supplement had crossed the blood-brain barrier and that these changes took place in brain cells.
“We don’t have definitive proof that the supplement itself crosses the blood-brain barrier, especially not from our data. What we do know is that taking the supplement results in an increase in NAD+ within tiny vesicles that likely originated in the brain and other neural tissue,” Dr. Martens told MNT.
“This is one of the big challenges in the field [d]etermining whether the compound can reach its intended target. [A]lthough we do not have direct evidence, the results of our study suggest that it is having an effect on the brain and also changing the metabolism of molecular pathways known to be involved in Alzheimer’s disease,” he added.
Next steps in research
This was the next step for the team said Dr. Martens.
“This is something we are actively testing now in my laboratory in a follow-up trial in older adults with mild cognitive impairment, but first we wanted to understand whether we could detect an increase in NAD+ in brain tissue after taking the supplement,” he said.
“We did this using small vesicles found in the blood that we are quite confident originated in neurons. What’s really interesting is that we also found changes in more established markers of Alzheimer’s disease (e.g., amyloid beta) after taking the supplement,” he added.
“While there are some promising therapeutic strategies being explored for neurodegenerative diseases, more research is needed to fully understand their potential benefit.”
— Dr. Kellie Middleton
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