Longevity Briefs: Lose Fat, Gain Brain?

Longevity briefs provides a short summary of novel research in biology, medicine, or biotechnology that caught the attention of our researchers in Oxford, due to its potential to improve our health, wellbeing, and longevity.

The problem:

There’s a large amount of evidence showing that having more adipose (fat) tissue correlates with an increased risk of cognitive decline and neurodegenerative disease. Visceral fat tissue (the fat that surrounds the organs, as opposed the subcutaneous fat that lies beneath the skin) is particularly problematic.

Having some visceral fat tissue is vital as it is the main storage location for excess energy. It also fulfils other important and beneficial functions, such as cushioning our internal organs and in the production of certain hormones. However, having too much visceral fat leads to a variety of problems including increased inflammation and risk of cardiovascular disease, which have a knock-on impact on the brain. Fortunately, visceral adipose tissue can be reduced through diet and exercise. Yet while we know that more visceral fat correlates with worse cognitive function, there is less research investigating whether losing visceral fat specifically leads to better cognitive outcomes. In this study, which is still in preprint, researchers set out to help fill that gap.

The discovery:

Researchers looked at data from four previous randomized trials of lifestyle interventions aimed at achieving weight loss. The data analysed included a total of 533 adults, with an average (mean) age of 52 at the start of the interventions, which typically lasted 18-24 months. Most participants were men and had a body mass index (BMI) of 30 on average, which is on the borderline between being overweight and obese. Participants underwent abdominal and brain Magnetic Resonance Imaging (MRIs) (to assess visceral vs subcutaneous fat mass and brain structure) and Montreal Cognitive Assessment (MoCA) testing (which is a standard tool for screening cognitive function). These measurements were repeated at various times depending on the study, up to 16 years later.

Using this information, the researchers calculated each participant’s cumulative visceral adipose tissue exposure over time using a method called “area-under-the-curve” for a subset of 295 individuals. This is essentially an estimate of long term visceral adipose tissue as opposed to a snapshot at a specific time. For example, a person who maintained a certain amount of visceral fat for 5 years would have equivalent exposure to someone who maintained half that amount of fat for 10 years. The researchers found that maintaining a lower visceral fat exposure was associated with significantly better cognitive performance and a slower rate of brain atrophy (loss of brain tissue). Meanwhile, people with higher visceral fat exposure lost more grey matter (which is the brain matter involved in information processing) and lost more hippocampal tissue (involved in memory).

The implications:

This study suggests that exposure to visceral adipose tissue specifically is associated with brain atrophy and cognitive decline, but that this can be avoided if you are able to lose visceral adipose tissue and maintain it at a lower level.

Given that the visceral fat loss was achieved through lifestyle interventions like diet and exercise, it is possible that the improved cognitive outcomes were partly due to the fact that some participants maintained their lifestyle changes while others did not. The researchers tried to control for this by adjusting for adherence to lifestyle interventions. However, if one person successfully maintains their weight loss while another does not, there is presumably a reason for this, perhaps genetic or perhaps lifestyle differences that are not picked up, so differences in outcome could still be explained by other factors. The researchers also found that those with more visceral fat exposure still had poorer cognitive outcomes after controlling for BMI and body weight, but this isn’t a perfect control since muscle mass factors in to both measurements. In other words, if you have more visceral fat than someone else but weigh the same, it is quite likely the other person has more muscle than you, which could contribute to their lower risk of cognitive decline.

That said, given what we already know about visceral adipose tissue, it is likely to be at least partly responsible for worse cognitive outcomes. Visceral adipose tissue is involved in the disruption of blood sugar control, which was observed in this study among those with higher visceral fat exposure and is known to contribute to neurodegeneration. Visceral adipose tissue is also associated with atherosclerosis (narrowing of the arteries) which can reduce blood supply to the brain and accelerate cognitive decline and dementia. Regardless of the mechanisms involved, the take-home from this study is that by adopting and maintaining a healthy lifestyle long-term, you can significantly improve your cognitive health in older age.