LIFO: Strengthening Your Brain’s Weakest Link to Stop Memory Loss

There are many risk factors for dementia, and we’ve previously highlighted the most important ones we can act upon to lower our risk. Many of those are impacting the brain as a whole. Now, Oxford University scientists are pointing to specific regions of the brain that are especially vulnerable to Alzheimer’s disease. And they want you to know what risk factors impact these regions most so you can try to protect them.

It begs the question, where is your brain weakest when it comes to losing your memory and why?

Your Brain’s Biggest Weakness

The team from Oxford University made a remarkable discovery: a brain network that’s particularly vulnerable to neurological diseases. They showed this network of brain regions develops only during adolescence and then shows accelerated degeneration in old age compared with the rest of the brain. They called this the ‘last in, first out’ (LIFO) network hypothesis. It's like that friend who shows up late to the party but is the first to leave. They noticed that how this network develops as we grow up is like a mirror image of how it falls apart as we age. Pretty wild, right?

They published their initial findings back in 2014. [1] Then they dug deeper.

They learned this LIFO network isn't just about normal brain development and aging. It's also the bullseye for two major brain disorders: schizophrenia and Alzheimer's disease.

Schizophrenia tends to rear its head during those tumultuous teen years when this network is just getting established. And Alzheimer's? Well, that likes to target these same areas as we get older.

What does all of this mean? These Oxford researchers have uncovered a hidden map of our brain's vulnerable spots. To follow up this research, they wanted to determine if any specific genetic or modifiable risk factors target these “weak spots” in the brain in the hopes we could use the findings to stop memory loss.

The Oxford Team Examined 161 Risk Factors

Oxford researchers examined brain scans of 40,000 people aged between 44 and 82 who volunteered to be part of the UK Biobank database, which contains comprehensive genetic, health, and lifestyle data on each enrolled participant.

They examined 161 risk factors for dementia (yes, there are that many). They ranked them according to their impact on the LIFO network over and above the effects of normal aging and gender differences. They then divided these modifiable factors, which can all potentially be changed, into 15 broad categories as follows:

1. blood pressure
2. cholesterol
3. diabetes
4. weight
5. alcohol consumption
6. smoking
7. depressive mood
8. inflammation
9. pollution
10. hearing
11. sleep
12. socialization
13. diet
14. physical activity
15. education

In terms of genetic factors, they discovered seven that influence the LIFO network, including some that are already implicated in schizophrenia, Alzheimer’s, and Parkinson’s disease, as well as death from cardiovascular disease.

They also discovered that the LIFO brain network is linked to a “forgotten” blood group system called XG. This was described as “an entirely new and unexpected finding” that requires further research.

XG is a unique classification of human blood. So, you know how we have different blood types, right? XG is based on the presence of Xg antigens on red blood cells. It is the only blood group system located on the X chromosome. Discovered in the 1960s, it has been a valuable tool in genetic mapping that helps scientists understand how certain traits get passed down from parents to kids and how different genes interact with blood.

It's pretty amazing when you think about it - who knew our blood could tell us so much about our genes? But really, that’s another whole article. Back to the key risk factors the researchers found…

The Dangers of Alcohol, Diabetes and Pollution

Among the 15 modifiable risk factors, professor Gwenaëlle Douaud, the lead scientist on their paper published in the journal Nature Communications in March, pointed to the major ones that impact the LIFO network:

“We know that a constellation of brain regions degenerates earlier in aging, and in this new study, we have shown that these specific parts of the brain are most vulnerable to diabetes, traffic-related air pollution − increasingly a major player in dementia − and alcohol, of all the common risk factors for dementia.” [2]

Diabetes and alcohol consumption “have been consistently shown to be associated with both cerebral and cognitive decline,” the researchers wrote.[3]

The existing evidence linking air pollution with dementia was strengthened recently with a new study published by the American Academy of Neurology. It shows that the more often people are exposed to traffic-related air pollution, the more likely they are to develop brain plaques.[4]

So, how bad can these risk factors damage your memory?

The effects of the three top risk factors were about double those of other leading risk factors. The next risk factors of importance in the Oxford study were sleep, weight, smoking, and blood pressure.

What You Can Do To Protect Your Memory

To counter the main risk factors, Dr. Douaud suggested people eat a healthy and varied diet to help reduce blood sugar and protect against diabetes, drink alcohol in moderation, and take protective measures against traffic pollution. We’d also add that it’s essential to take antioxidant-rich supplements to support brain cell communication and health.

Gill Livingston, Professor of Psychiatry of Older People at University College London, who was not involved in the study, told the Washington Post, "[t]here’s quite a lot people can do in their everyday life to maintain cognitive health. This [study] reinforces it.”

She added that meeting up with friends and having conversions can lead to “rapid brain stimulation.” She also emphasized the value of exercise and having stimulating experiences to protect the brain.[5]