Brain protein may be key link between obesity, aging & memory loss

US researchers have received a US$410,000 grant from the National Institute on Aging to investigate whether obesity speeds up brain aging and its impact on memory loss and brain-related diseases, including Alzheimer’s. 

Nutrition Insight sits down with the study lead researcher, Timothy Jarome, professor at the College of Agriculture and Life Sciences’ School of Animal Sciences at Virginia Tech, to discuss what drove him to research this issue and its importance amid an increasingly obese population.

“There is strong evidence that obesity is associated with memory decline, and it is a risk factor for developing dementia and Alzheimer’s disease. However, despite this well-established relationship, little is known about how obesity accelerates brain aging and leads to the increased risk of memory decline and dementia.”

He shares that the lack of knowledge about obesity and the mechanisms by which it accelerates memory loss with age is due to a limited number of longitudinal, mechanistic studies that directly test this relationship. 

“Considering that the number of people with obesity or dementia continues to increase worldwide, we need a greater understanding of the mechanisms by which obesity can increase the risk of memory decline if we are going to develop effective therapeutic treatments for dementia and memory loss late in life.”

Obesity and the brain

Obesity is a risk factor for dementia and Alzheimer’s disease, as well as many other brain-associated disorders, says Jarome.

Obesity is a risk factor for dementia, Alzheimer’s disease, and other brain-associated disorders, says Jarome.“We often lack longitudinal studies that track how developing obesity leads to these disorders, though, especially those that occur late in life. While we are focusing on the K63 protein and memory loss, we hope that this study will expand into future investigations on how obesity leads to short-term and lasting impacts on the brain and how this increases the risk for memory loss and other disorders.”

He explains that K63 is a form of a specific protein called ubiquitin, which is found in essentially all organisms on Earth. 

“This K63 protein binds to other proteins in the brain and changes their function in a variety of ways. My lab recently found that too much of this K63 protein in the hippocampus, the part of the brain that forms and stores most memories, is bad for memory.” 

“We also found that this K63 protein increases in levels in the hippocampus as we age and during the early stages of obesity. Considering that too much of this K63 protein is bad for memory, having increased levels with obesity and aging suggests that it could be the mechanism that links obesity to accelerated brain aging and memory decline, which is what we will be investigating in our study.”

He says it is known that obesity affects memory, and that aging affects memory. “What we don’t know is whether they’re driven by the same process in the brain.” 

Reversible brain function?

When asked if weight loss could be beneficial for memory loss or cognitive ability, Jarome shares that this is something that the research team plans to examine soon.

He points to prior studies, which have shown that obesity-induced changes in the brain often persist even after weight is lost. “However, evidence suggests that the memory loss from obesity could be reversible. This is something we intend to examine further in our study.”

Novo Nordisk, the pharmaceutical company behind Ozempic and Wegovy, conducted a trial that finished late last year on the relationship between weight loss using GLP-1 medications and Alzheimer’s disease, without finding any statistical significance. 

Another US study found a link between having more lean muscle mass, less hidden belly fat, and having a younger and healthier brain. The researchers behind this paper said that this, in turn, lowers the risk for future brain diseases, including Alzheimer’s disease.

According to the US Department of Health and Human Services, over 70% of US citizens are overweight or obese. The US teen obesity rate reached 16% earlier this year, with Black and Hispanic adolescents at the highest risk.

Furthermore, Jarome says it is difficult to know if the US has a higher number of people with memory loss compared to countries with less obesity, because there are many conditions or disorders that can also lead to memory loss. 

“Dementia is high in the US, but other countries have higher rates, including some that do not see the prevalence of obesity that we do in the US. This is important because obesity is not the only factor that can lead to memory loss, especially as we age. However, it could be a major factor contributing to memory loss and increasing rates of dementia in countries that have high obesity rates, such as the US.”

Nutrition as a tool

Jarome explains that if obesity increases the risk of memory decline and the development of dementia, then reducing the risk of becoming obese, such as through nutrition, would be a good preventative approach.

Proper nutrition is critical in preventing obesity, especially when combined with exercise and other important lifestyle factors.“Nutrition and eating a well-balanced, healthy diet is obviously important, though it may not be sufficient for all individuals. Regardless, even if the goal is not focused on body weight, the part of the brain that controls memory and is heavily impacted in dementia and Alzheimer’s disease is also extremely sensitive to nutrients, especially sugars and saturated fats. Eating the proper nutrients can help support healthy brain function,” he suggests.

“While our work suggests that obesity is driving increases in this K63 protein, which may be leading to memory loss, it is likely that the protein changes are caused by the nutrients in the diet that lead to obesity rather than the increase in weight or body fat.”

He stresses that proper nutrition is critical in preventing obesity, especially when combined with exercise and other important lifestyle factors. 

“Obesity and how it relates to memory loss also emphasize the gut-brain connection. While calories are an important factor, the nutrients we are ingesting require special attention.”