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Alzheimer’s expert on bridging the gap between ‘bench’ research and the community

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“Imagine it’s construction season in Michigan. Normally, it might take you 10 to 15 minutes to get from point A to point B.

“But when there is construction, it slows you down, now taking 15 to 20 minutes. And if the highway is closed, it might take you even longer.”

Irving Vega is describing what happens when cells in the central nervous system stop working or die.

More commonly known as neurodegeneration, its devastating consequences affect countless millions of people worldwide.

Alzheimer’s and Parkinson’s are perhaps the two best-known neurodegenerative diseases. But the disorder is also responsible for Huntington’s disease, Amyotrophic lateral sclerosis (ALS), and motor neuron disease, amongst others.

Expanding on his building analogy and how such work can slow down the flow of traffic, Dr Vega says: “That’s what happens in a brain that is undergoing neurodegeneration. The streets start to close, and it takes longer and longer to reach that memory to a point that you don’t have any alternative route to get from point A to point B, and that memory is completely gone.

“For some individuals, they can live all their life with those pathological hallmarks in their brain and never have clinical presentation. For others, they have the clinical presentation at 70.

“But it’s not because they developed it when they were 70. They probably were developing that since they were in their 40s.”

The likelihood of developing a neurodegenerative disease rises dramatically with age. And as life expectancy increases, more people than ever are predicted to be affected by such diseases in the coming decades.

Improving our understanding of what causes neurodegenerative diseases and developing new approaches to understanding, treating and hopefully one day preventing them, has been Dr Vega’s life work.

Dr Irving Vega. Image: MSU College of Human Medicine

A neuroscientist at Michigan State University (MSU) in the US, he spends much of his time in his laboratory studying the impact of certain proteins on the development of neurodegenerative disorders, most notably Alzheimer’s.

But when he’s not conducting research, Dr Vega makes time to engage with students about their interest in science. and to go out into the community to talk about Alzheimer’s, a cruel and insidious disease which currently affects around 55 million worldwide and mercilessly robs patients of their memories, social skills, independence, and eventually their life.

He says: “I’ll go to the Hispanic Centre. I’ll go to the school system in Grand Rapids. I’ll go anywhere they invite me.”

The associate professor in the Department of Translational Neuroscience at MSU, adds: “I believe it’s important to build that bridge of communication between researchers and members of the community so that we can provide access to the new knowledge that we develop.”

While that outreach often happens in West Michigan, Dr Vega also collaborates with institutions elsewhere.

“I want to bring attention to the importance of building a bridge of communication between researchers and the community so that, in a way, we are actually better informed on what the important questions are that are relevant for the community so that we can go back to the bench and then do our research,” he explains.

Dr Vega obtained his undergraduate degree from the University of Puerto Rica at Mayagüez on the Caribbean island where he was born and raised. He was a National Institutes of Health Maximising Access to Research Careers, or MARC, fellow.

He then earned a doctorate from Rutgers University in New Jersey, and completed his postdoctoral fellowship in the Department of Neuroscience at the Mayo Clinic in Jacksonville, Florida, where he developed his research career focusing on the pathobiology of Alzheimer’s disease.

Dr Vega developed his interest in working with the community during his time at the University of Puerto Rico’s Rio Piedras campus, where he rose through the academic ranks from assistant professor to assistant dean of research.

In addition to his analysis work, Dr Vega grew an undergraduate training programme to enhance diversity in neuroscience and after joining MSU in 2014, he continued with both his research and his interest in mentoring students and reaching out to the community.

In 2022, Dr Vega was recognised as a Red Cedar Distinguished Faculty for his community-engaged research.

Located on MSU’s Grand Rapids campus, Dr Vega’s laboratory focuses on three main areas.

First, the researchers study the mechanisms that cause tau proteins – which help stabilise the internal structure of neurons in the brain – to clump together, leading to toxicity within the cells that house them.

It was this team that in 2019 identified the tau protein EFhd2 – a novel amyloid protein associated with pathological tau in Alzheimer’s disease. They are currently evaluating the role this protein plays with Alzheimer’s disease to establish models that could be used to test potential therapeutics against tau aggregation.

The second focus of Dr Vega’s lab is investigating the potential links between intestinal bacteria changes, inflammation, and Alzheimer’s disease.

A third area of focus is the development of better diagnostic tools for Alzheimer’s disease. Dr Vega and his colleagues are currently looking at non-invasive methods to detect biomarkers (such as the tau protein); checking whether race and ethnicity affect those levels; as well as looking to identify new biological molecules that could eventually lead to better diagnostic tools.

Dr Vega and his team never lose sight of the fact that Alzheimer’s disease is more than just a strand of research and that in America alone it affects 6.7 million people. He says that in Michigan alone it’s forecast 220,000 people will be living with the disease by 2050.

He says the illness disproportionately affects communities of colour.

“We know that people in the Latino community are at a higher risk of developing these illnesses, but we don’t know exactly why.”

Dr Irving Vega in his lab at MSU’s Department of Translational Neuroscience. Image: MSU College of Human Medicine

He adds that while there’s consensus on the risk factors – metabolic disorders, diabetes, high cholesterol, hypertension – contextual or social factors related to ethnic and racial health disparities are less clear.

About 13% of Hispanics older than 65 have Alzheimer’s or another type of dementia. And Hispanics are 50% more likely than their peers to develop Alzheimer’s or other types of dementia.

“There are a lot of barriers to access health care. There are barriers to accessing healthy food. There are barriers to quality education. There is discrimination, and there is higher social stress due to discrimination,” he says. “The high levels of stress lead to biological changes in the individual.”

He admits that coming up with solutions is not easy.

“We know what is very good for your brain: exercise, good quality of sleep, a healthy diet. For underserved populations there are things that prevent people from doing exercise. There’s no safety on the roads or at the park. Sometimes they have two jobs and no time to exercise. Maybe they are not eating well or sleeping well. There’s a lot of things that we can do to reduce the risk, but we have a huge fight against us to achieve health equity.”

Dr Vega recently presented his research in front of 35 community members at the request of the Catholic Diocese of Grand Rapids.

He talked about how the brain works, the different regions of the organ that are responsible for different tasks, and how they coordinate with each other to produce an outcome.

Then, he discussed neurodegenerative diseases, their risk factors and how to mitigate them. Hence his drawing on the construction analogy; a relatable comparison highlighting the raw horror of cognitive decline, as patients’ families and friends are forced to watch the comprehensive disintegration of their loved one’s brain.

Dr Vega says: “Once I get to that part of my presentation, people start asking ‘How I can reduce my risk?’

“This is the third part of my talk — explaining how you can reduce your risk of developing these diseases. If you sleep well, this is what happens to your brain. If you eat well, this is what happens to your brain. If you exercise, this is what happens to your brain.”

He says community members enjoy having researchers explain their work to them. He believes researchers stay inside their lab to their own detriment.

“Sometimes by not being connected with the community and people living with the diseases that we’re trying to understand, we miss a lot of points and references on how these diseases affect people in different ways and the risk factors that contribute to them.”

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Certain nutrients may slow brain aging

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A new study from the University of Nebraska–Lincoln’s Center for Brain, Biology and Behavior and the University of Illinois at Urbana-Champaign has shown that people with slower brain aging had a nutrient profile similar to the Mediterranean diet.

Scientists have long been studying the brain with a goal of aiding healthier aging. While much is known about risk factors for accelerated brain aging, less has been uncovered to identify ways to prevent cognitive decline.

There is evidence that nutrition matters, and this new study further signals how specific nutrients may play a pivotal role in the healthy aging of the brain.

The team of scientists, led by Aron Barbey, director of the Center for Brain, Biology and Behavior, with Jisheng Wu, a doctoral student at Nebraska, and Christopher Zwilling, research scientist at UIUC, performed the multimodal study — combining state-of-the-art innovations in neuroscience and nutritional science — and identified a specific nutrient profile in participants who performed better cognitively.

The cross-sectional study enrolled 100 cognitively healthy participants, aged 65-75. These participants completed a questionnaire with demographic information, body measurements and physical activity. Blood plasma was collected following a fasting period to analyse the nutrient biomarkers. Participants also underwent cognitive assessments and MRI scans.

The efforts revealed two types of brain aging among the participants — accelerated and slower-than-expected. Those with slower brain aging had a distinct nutrient profile.

The beneficial nutrient blood biomarkers were a combination of fatty acids (vaccenic, gondoic, alpha linolenic, elcosapentaenoic, eicosadienoic and lignoceric acids); antioxidants and carotenoids including cis-lutein, trans-lutein and zeaxanthin; two forms of vitamin E and choline. This profile is correlated with nutrients found in the Mediterranean diet, which research has previously associated with healthy brain aging.

“We investigated specific nutrient biomarkers, such as fatty acid profiles, known in nutritional science to potentially offer health benefits. This aligns with the extensive body of research in the field demonstrating the positive health effects of the Mediterranean Diet, which emphasizes foods rich in these beneficial nutrients,” Barbey, Mildred Francis Thompson Professor of Psychology, said.

“The present study identifies particular nutrient biomarker patterns that are promising and have favourable associations with measures of cognitive performance and brain health.”

Barbey noted that previous research on nutrition and brain aging has mostly relied on food frequency questionnaires, which are dependent on participants’ own recall. This study is one of the first and the largest to combine brain imaging, blood biomarkers and validated cognitive assessments.

“The unique aspect of our study lies in its comprehensive approach, integrating data on nutrition, cognitive function, and brain imaging,” Barbey said.

“This allows us to build a more robust understanding of the relationship between these factors. We move beyond simply measuring cognitive performance with traditional neuropsychological tests. Instead, we simultaneously examine brain structure, function, and metabolism, demonstrating a direct link between these brain properties and cognitive abilities. Furthermore, we show that these brain properties are directly linked to diet and nutrition, as revealed by the patterns observed in nutrient biomarkers.”

The researchers will continue to explore this nutrient profile as it relates healthy brain aging. Barbey said it’s possible, in the future, that the findings will aid in developing therapies and interventions to promote brain health.

“An important next step involves conducting randomized controlled trials. In these trials, we will isolate specific nutrients with favourable associations with cognitive function and brain health, and administer them in the form of nutraceuticals,” Barbey said.

“This will allow us to definitively assess whether increasing the levels of these specific nutrient profiles reliably leads to improvements in cognitive test performance and measures of brain structure, function, and metabolism.”

Barbey is also co-editing an upcoming special collection for the Journal of Nutrition, “Nutrition and the Brain — Exploring Pathways to Optimal Brain Health Through Nutrition,” which is currently inviting submissions for consideration, and articles will begin publishing next year.

“There’s immense scientific and medical interest in understanding the profound impact of nutrition on brain health,” Barbey said. “Recognising this, the National Institutes of Health recently launched a ten-year strategic plan to significantly accelerate nutrition research. Our work directly aligns with this critical initiative, aiming to contribute valuable insights into how dietary patterns influence brain health and cognitive function.”

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Extreme exercise doesn’t curb lifespan, according to longevity of under 4-minute miler’s

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Extreme exercise doesn’t seem to shorten the lifespan as is widely believed, suggest the findings of a study on the longevity of the first 200 athletes to run a mile in under four minutes.

They outlive the general population by several years, shows the study, published online in the British Journal of Sports Medicine, which marks the 70th anniversary of the seminal achievement of Roger Bannister, who was the first person to run a mile in under 4 minutes in May 1954.

While regular moderate exercise is considered a pillar of healthy ageing, it has long been thought that exposing the body to bouts of extreme endurance exercise may push it too far and shorten life expectancy, say the researchers.

The repeated bouts of near maximal to maximal exercise performed by mile runners makes them a unique group in which to test the potential impact of extreme intense exercise on longevity, they explain.

They therefore scrutinised the compendium of 1,759 athletes who had run a mile in under 4 minutes as of June 2022, and extracted the details of the first 200 to do so, on the grounds that they would be at an age that would either match or exceed the typical life expectancy for their generation.

The runners’ longevity was tracked, using publicly available information, from the exact date of their first successful attempt at breaking the four-minute mile to either the age of 100, the end of 2023, or death, to find out the average difference in life expectancy between them and the general population, matched for age, sex, and nationality.

This difference was calculated as the observed life years for a runner minus their population-matched life expectancy. This number was then averaged across all 200.

The first 200 runners to break the 4-minute mile spanned a period of 20 years from 1954 to 1974. They came from 28 different countries across Europe (88), North America (78), Oceania (22) and Africa (12).

They were born between 1928 to 1955, and were aged 23, on average, when they ran the mile in under 4 minutes, with times ranging between 3:52.86 and 3:59.9 minutes.

Of the total, 60 (30%) had died and 140 were alive at the time of the analysis. The average age at death was 73, but ranged from 24 to 91, while the average age of the surviving runners was 77, ranging from 68 to 93.

Information on cause of death wasn’t known for most of the athletes, but of the seven who died before the age of 55, six were due to trauma or suicide and one was due to pancreatic cancer.

The analysis revealed that the under four-minute milers lived nearly 5 years beyond their predicted life expectancy, on average, based on sex, age, year of birth, age at achievement, and nationality.

When factoring in the decade of completion, those whose first successful attempt was in the 1950s, lived an average of 9 years longer than the general population during an average tracking period of 67 years.

And those whose first successful attempt was in the 1960s and 1970s lived 5.5 years and nearly 3 years longer during an average tracking period of 58 and 51 years, respectively.

General improvements in life expectancy secondary to advances in the diagnosis and treatment of several major diseases might explain this particular trend, suggest the researchers.

They acknowledge that they didn’t have any information on the lifelong exercise habits (or other health behaviours) of the 200 athletes included in the study, so weren’t able to determine the precise relationship between lifelong exercise dose and longevity.

And comparison against the general population precluded assessment of how other lifestyle factors, such as diet and smoking, cardiometabolic risk factors, and other potentially influential medical factors, such as high blood pressure and high cholesterol, might affect longevity. Finally, the study included only men as no woman has yet to run a mile in under 4 minutes.

Nevertheless, they say: “This finding challenges the upper ends of the U-shaped exercise hypothesis (as it relates to longevity) and, once again, reiterates the benefits of exercise on the lifespan, even at the levels of training required for elite performance.”

Although the effort required in this group might seem to be less than that of endurance athletes, the high aerobic and anaerobic requirements of middle distance events, such as the mile, necessitate putting in relatively high training volumes of around 9–12 hours or 120–170 km a week, they explain.

While all this raises the possibility of pushing the body beyond its limits, particularly from an intensity perspective, this doesn’t seem to affect lifespan, and if anything seems to prolong it, they add.

The physiological explanations for the extended lifespan are yet to be fully identified, say the researchers, but suggest that these likely reflect the positive adaptations of endurance exercise on cardiovascular, metabolic, and immune-related health and function.

A healthy lifestyle and genes may also have a role, they point out, as 20 sets of brothers, including six sets of twins and father and son combinations, were among the first 200 runners to break the 4-minute mile.

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Ultra-processed food linked to higher risk of early death – study

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A 30-year study from researchers in the US has linked ultra-processed food to a slightly higher risk of early death.

Higher consumption of most ultra-processed foods is linked to a slightly higher risk of death, with ready-to-eat meat, poultry, and seafood based products, sugary drinks, dairy based desserts, and highly processed breakfast foods showing the strongest associations, finds a 30-year US study in The BMJ.

The researchers say not all ultra-processed food products should be universally restricted, but that their findings “provide support for limiting consumption of certain types of ultra-processed food for long term health.”

Ultra-processed foods include packaged baked goods and snacks, fizzy drinks, sugary cereals, and ready-to-eat or heat products. They often contain colours, emulsifiers, flavours, and other additives and are typically high in energy, added sugar, saturated fat, and salt, but lack vitamins and fibre.

Mounting evidence links ultra-processed foods to higher risks of obesity, heart disease, diabetes and bowel cancer, but few long term studies have examined links to all cause and cause specific deaths, especially due to cancer.

To address this knowledge gap, researchers tracked the long-term health of 74,563 female registered nurses from 11 US states in the Nurses’ Health Study (1984-2018) and 39,501 male health professionals from all 50 US states in the Health Professionals Follow-up Study (1986-2018) with no history of cancer, cardiovascular diseases, or diabetes at study enrolment.

Every two years participants provided information on their health and lifestyle habits, and every four years they completed a detailed food questionnaire. Overall dietary quality was also assessed using the Alternative Healthy Eating Index-2010 (AHEI) score.

During an average 34-year follow-up period, the researchers identified 48,193 deaths, including 13,557 deaths due to cancer, 11,416 deaths due to cardiovascular diseases, 3926 deaths due to respiratory diseases, and 6343 deaths due to neurodegenerative diseases.

Compared with participants in the lowest quarter of ultra-processed food intake (average 3 servings per day), those in the highest quarter (average 7 servings per day) had a 4% higher risk of total deaths and a 9% higher risk of other deaths, including an 8% higher risk of neurodegenerative deaths.

No associations were found for deaths due to cardiovascular diseases, cancer, or respiratory diseases.

In absolute numbers, the rate of death from any cause among participants in the lowest and highest quarter of ultra-processed food intake was 1472 and 1536 per 100,000 person years, respectively.

The association between ultra-processed food intake and death varied across specific food groups, with meat, poultry, and seafood based ready-to-eat products showing the strongest and most consistent associations, followed by sugar sweetened and artificially sweetened beverages, dairy based desserts, and ultra-processed breakfast food.

And the association was less pronounced after overall dietary quality was taken into account, suggesting that dietary quality has a stronger influence on long term health than ultra-processed food consumption, note the authors.

This is an observational study, so no firm conclusions can be drawn about cause and effect, and the authors point out that the ultra-processed food classification system does not capture the full complexity of food processing, leading to potential misclassification. In addition, participants were health professionals and predominantly white, limiting the generalizability of the findings.

However, this was a large study with long follow-up, using detailed, validated, and repeated measurements, and results were similar after further analyses, providing greater confidence in the conclusions.

The researchers stress that not all ultra-processed food products should be universally restricted and say oversimplification when formulating dietary recommendations should be avoided.

But they conclude: “The findings provide support for limiting consumption of certain types of ultra-processed food for long term health,” adding that “future studies are warranted to improve the classification of ultra-processed foods and confirm our findings in other populations.”

In a linked editorial, researchers in New Zealand point out that recommendations to avoid ultra-processed food may also give the impression that foods that are not ultra-processed, such as red meat, can be frequently consumed.

They argue that debate about the ultra-processed concept must not delay food policies that improve health, such as restrictions on marketing unhealthy foods to children, warning labels on nutritionally poor food products, and taxes on sugary drinks.

“Our focus should be on advocating for greater global adoption of these and more ambitious interventions and increasing safeguards to prevent policies from being influenced by multinational food companies with vested interests that do not align with public health or environmental goals,” they conclude.

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