Health and science journalist Max Lugavere has always been close with his mom. When she began to show signs of dementia in her early fifties, it shook him to his core. Wasn’t dementia an old person’s disease? And with drug trials having a near 100% failure rate, what was there to do? In 2017, a leading Alzheimer’s organization recognized for the first time that one third of dementia cases may be preventable. And so Max decided to devote himself to figuring out how he and his peers could best avoid the disease. In this illuminating talk, Max discusses the fascinating diet and lifestyle changes associated with significant risk reduction for Alzheimer’s disease and dementia, and what that means.
For more, pick up his New York Times bestselling book, GENIUS FOODS. Max Lugavere is a filmmaker, author, and TV personality. He is the director of the upcoming film BREAD HEAD, the first-ever documentary about dementia prevention through diet and lifestyle, and is publishing his first book in early 2018 documenting his findings on how to optimize focus, productivity, mood, and long-term brain health with food. Lugavere is a regularly-appearing “core expert” on The Dr. Oz Show, has been featured on NBC Nightly News, in the Wall Street Journal, and has contributed as a health journalist to Medscape, Vice/Munchies, the Daily Beast, and others. He is a highly sought-after speaker and has been invited to keynote events such as the Biohacker Summit in Stockholm Sweden, and esteemed academic institutions like the New York Academy of Sciences.
Increased levels of blood glucose (green) after food intake trigger insulin (blue) secretion from islet β cells. This glucose-triggered insulin secretion is accompanied with Aβ (red) secretion from the same β cells, a phenomenon the research team calls ‘the primary secretion’ of Aβ. Secreted insulin acts on insulin-targeted organs to promote glucose uptake by adipose tissues and muscles and glycogen synthesis in muscles and the liver. These tissues release their own endocrine factors, i.e. organokines, including adipokines, myokines, and hepatokines, upon insulin stimulation to maintain glucose and lipid homeostasis and insulin sensitivity in an autocrine, paracrine, and endocrine manner. This insulin-dependent secretion of organokines coincides with Aβ secretion from the same cells, a phenomenon they called ‘the secondary secretion’ of Aβ. The secreted Aβ acts on β cells in an autocrine and endocrine manner to negatively modulate insulin secretion. CREDITTakami Tomiyama @ Osaka City University
Researchers have identified amyloid beta (Aβ) detected in blood to originate from peripheral tissues, and that the peptide acts on pancreaticβ-cells to suppress insulin secretion, thereby regulating blood glucose levels. The study, which urges us to be careful when using blood Aβ levels as a diagnostic marker for Alzheimer’s disease (AD), was published in The Proceedings of the National Academy of Sciences (PNAS), the official journal of the National Academy of Sciences.
“This work was finally published after about 11 years,” says Professor Takami Tomiyama of the Department of Translational Neuroscience, Osaka City University Graduate School of Medicine. “It is not only an academic discovery, but also has implications in how we diagnose AD.”
Based on what is known, this study sought to explore some unknowns. First, as AD is caused by the accumulation of Aβ in the brain, it is thought that Aβ levels in the blood reflect the pathology in the brain and are currently used as a diagnostic marker. However, Aβ is generated from the amyloid precursor protein (APP) through the function of two enzymes, β- and γ-secretases, and this mechanism is expressed in many of the body’s peripheral tissues, not only in the brain, causing the origin of blood Aβ to remain unknown. Second, epidemiological studies have shown type 2 diabetes to be a strong risk factor for the development of AD, yet the mechanism linking these two diseases has eluded researchers as well.
“In our previous studies on mice injected with glucose,” Professor Tomiyama explains, “we showed a transient increase in glucose and insulin to peak at 15 minutes, but blood Aβ levels to peak some 30-120 minutes later.” In addition, previous studies have shown the oral administration of glucose to increase blood Aβ levels in patients with AD. These findings led the professor and his research team to explore the hypothesis that blood Aβ is secreted from peripheral tissues (pancreas, adipose tissue, skeletal muscle, liver, etc.) and it may contribute to the metabolism of glucose and insulin.
First, they examined the effects of glucose and insulin on blood Aβ levels of mice fasted for 16 hours. Collected blood samples from the tail vein at 0, 15, 30, 45, 60, 120, and 180 min intervals after the injection showed a transient increase in glucose, insulin, and Aβ, confirming previous studies.
Next, they explored the effect of Aβ on blood insulin levels by administering Aβ and glucose to fasted mice that cannot produce Aβ, called APP knock out mice. Measuring insulin in blood samples over time found that Aβ suppressed the glucose-stimulated rise in insulin.
Given that blood Aβ levels changed immediately upon introduction of glucose and insulin, the team focused on the mice pancreas, adipose tissue, skeletal muscle, liver, and kidneys to determine the origin of blood Aβ. They added glucose and insulin to isolated live peripheral tissues and measured the secreted Aβ. Results showed that Aβ was secreted from the pancreas upon glucose stimulation and from adipose tissue, skeletal muscle, and liver upon insulin stimulation. The kidneys, which is not involved in glucose or insulin metabolism, did not secrete Aβ upon either stimulus. They also found that when glucose and Aβ were added to pancreas tissue, levels of secreted insulin were suppressed.
Now that the origin of blood Aβ had been clarified, the team wanted to localize Aβ in the periphery tissues studied. “This would elucidate the cells involved with Aβ,” adds Professor Tomiyama. “In addition to providing further validation to our findings, this would give us a more detailed picture from which we could draw conclusions to possible mechanisms connecting type 2 diabetes and AD.”
Using immunohistochemistry to exploit the fact that antibodies bind to certain proteins, the team started with the pancreas tissue, detecting Aβonly in insulin (β cells). The team also found the β cells of mice with glucose injections to have less immunoreactions to Aβand insulin, suggesting during periods of fast, Aβ and insulin are stored in β cells and then released into circulation when stimulated with glucose. Similarly, tissue sections of each insulin-targeted organ were prepared and immunostained for Aβ and the bioactive substances specific to each tissue, called organokines. Aβ was found with the organokines of all the organ tissues tested, with less immunoreactions when stimulated with insulin.
“Our findings suggest that Aβ and organokines are stored during periods of fast and released into circulation when stimulated with insulin,” adds Prof. Tomiyama. “A comprehensive understanding of the organokine action of peripheral Aβ is something we hope to develop in future work.”
In addition to an explanation for the origin of Aβ in the blood, the research findings suggest a mechanism by which type 2 diabetes is a strong risk factor for the development of AD. In diabetes, Aβ levels in the blood are constantly elevated due to high levels of glucose and insulin. This inhibits Aβ to leave the brain to the periphery (transport through the blood-brain barrier and by body fluid flow through the brain parenchyma called the glymphatic system), causing Aβ to accumulate in the brain and develop into AD.
“Other more practical suggestions can be gleaned from this study,” concludes Prof. Tomiyama, “our data suggest that as blood Aβ levels fluctuate significantly with diet, special care should be taken when diagnosing AD with blood Aβ.”
“Drinking tea and red wine with plenty of kale could slash the risk of Alzheimer’s disease,” reports the Mail Online.
If you think this claim sounds familiar, that’s because it is. For decades, scientists have been investigating the possible effects of chemicals called flavonols, which are found in tea, red wine, fruit and green vegetables.
We know that foods such as fruit and vegetables are an important part of a healthy diet as there is strong evidence they can reduce the risk of heart disease, stroke and some types of cancer. But we do not know if we could replicate the health effects if we just consumed flavonols separately, as supplements.
Previous research found that the evidence about red wine is inconsistent. Plus, any possible benefit does not outweigh the risks if you drink alcohol above the recommended limit.
This study looked at the diets of 921 people in the US, with an average age of 81, and followed them up for 6 years, on average, with annual checks. During the study almost 24% developed Alzheimer’s disease. The researchers found that those who ate diets highest in flavonols had a 40% lower chance of developing Alzheimer’s disease compared to those with diets lowest in flavonols.
The study cannot prove that flavonols have specifically contributed to disease risk, as other health or lifestyle factors or other nutrients in the foods may still be having an influence. But regardless of this, it adds weight to what we previously knew – that eating plenty of fruits and vegetables may help protect against dementia. Other things that may decrease your risk of dementia include being active, not smoking, and (despite headlines to the contrary) not drinking too much alcohol.
Where did the story come from?
The researchers who carried out the study were from Rush University Medical Center and Tufts University, both in the US. The study was funded by the US National Institutes for Health and the USDA Agricultural Research Service. It was published in the peer-reviewed journal Neurology, on an open-access basis, so it’s free to read online.
Despite the usual headline extolling the virtues of red wine, the Mail Online’s coverage does include commentary from experts making it clear that the study is not conclusive.
What kind of research was this?
This was a cohort study. Like other observational studies, cohort studies are a good way to look for links between factors, such as diet, and outcomes, such as Alzheimer’s disease. However, they cannot demonstrate that dietary factors directly lead to the outcomes. Other factors (such as other chemicals found in the foods studied, or people’s general lifestyle) may be involved.
What did the research involve?
This analysis, beginning in 2004, included 921 volunteers from the Rush Memory and Aging Project, an ongoing study of older adults living in retirement communities and public housing in Chicago, US, that’s been running since 1997. None of the participants had Alzheimer’s disease at recruitment and all had completed questionnaires about their diet over the previous 12 months and attended at least 2 annual follow-up assessments. Their average age was 81.2 years and the majority (75%) were women.
The food questionnaire looked at what people ate, then calculated the average number of flavonols they ate each week. The researchers looked at 4 types of flavonols:
kaempferol – found in kale, beans, tea and spinach
quercetin – found in tomatoes, kale, apples and tea
myricetin – found in tea, wine, kale, oranges and tomatoes
isorhamnetin – found in pears, olive oil, wine and tomato sauce
People were followed up for an average of 6.1 years and had at least 2 clinical assessments during that time where Alzheimer’s disease was assessed. This included having their brain function assessed using 19 cognitive tests and being assessed by specialist doctors who made the diagnosis according to standard criteria.
Researchers adjusted their results to take account of several factors known to affect the risk of Alzheimer’s disease, including:
age
sex
education level
participation in activities that stimulate the brain
physical activity
presence of a genetic mutation APOE4, which raises the risk of Alzheimer’s disease
What were the basic results?
Of the 921 people recruited, 220 developed Alzheimer’s disease (24%) during the average follow-up of 6.1 years.
The amount of flavonols in people’s diet varied from an average 5.3mg a day for those eating least, to an average 15.3mg for those eating most. An expert quoted in the Mail Online report said most UK adults consume around 30mg a day.
The researchers found that people eating the most flavonols in their study had the lowest chance of developing Alzheimer’s disease.
people eating diets with the most flavonol content had a 48% lower risk of Alzheimer’s disease (hazard ratio (HR) 0.52, 95% confidence interval (CI) 0.33 to 0.84) compared to those eating diets with the least flavonol content
the results did not change much when the researchers also adjusted the figures for whether people had cardiovascular disease, or for the presence of other nutrients linked with Alzheimer’s (such as omega-3 fatty acids)
How did the researchers interpret the results?
The researchers said the findings “suggest that dietary intake of flavonols may reduce the risk of developing Alzheimer’s dementia”.
They added: “Although there is more work to be done, the associations that we observed are promising and deserve further study.”
Conclusion
We know that eating a healthy, balanced diet with plenty of fruits and vegetables helps to keep the body and brain healthy as we age. Whether flavonols are the key to this, or other chemicals found in food, or combinations of foods, perhaps does not matter, as long as we continue to eat a balanced diet.
The study has some limitations. Firstly, as it is an observational study it cannot show cause and effect. Many different health and lifestyle factors may influence the risk of Alzheimer’s disease and it’s not possible to take account of them all.
The people who volunteered to take part in the study were mostly white, college-educated and from one area of the US. We do not know if the same results would be found in other groups of people. People reported their diet through food questionnaires, which means they may not be wholly accurate. This may lead to inaccuracy in estimating flavonol intake.
Also, as the study included people who were already in old age, we cannot conclude that a higher intake of flavonols, or fruit and vegetables in general throughout life, decreases dementia risk.
The study adds weight to previous findings that a healthy diet containing plenty of plant-based foods is good for general health and may also reduce dementia risk. However, as the cause of Alzheimer’s is not completely clear (aside from age and certain genetic factors), there are no guarantees.
Other things that may reduce the risk of dementia include:
keeping your cardiovascular system healthy through regular exercise, not smoking, keeping alcohol to a minimum and having regular blood pressure checks
staying mentally active through reading, learning foreign languages or playing musical instruments
staying socially active through volunteering in your local community, taking part in group activities, trying new hobbies and maintaining an active social life
Living a healthy lifestyle may help offset a person’s genetic risk of dementia, according to new research.
The study was led by the University of Exeter – simultaneously published today in JAMA and presented at the Alzheimer’s Association International Conference 2019 in Los Angeles. The research found that the risk of dementia was 32 per cent lower in people with a high genetic risk if they had followed a healthy lifestyle, compared to those who had an unhealthy lifestyle.
Participants with high genetic risk and an unfavourable lifestyle were almost three times more likely to develop dementia compared to those with a low genetic risk and favourable lifestyle.
Joint lead author Dr El?bieta Ku?ma, at the University of Exeter Medical School, said: “This is the first study to analyse the extent to which you may offset your genetic risk of dementia by living a healthy lifestyle. Our findings are exciting as they show that we can take action to try to offset our genetic risk for dementia. Sticking to a healthy lifestyle was associated with a reduced risk of dementia, regardless of the genetic risk.”
The study analysed data from 196,383 adults of European ancestry aged 60 and older from UK Biobank. The researchers identified 1,769 cases of dementia over a follow-up period of eight years. The team grouped the participants into those with high, intermediate and low genetic risk for dementia.
To assess genetic risk, the researchers looked at previously published data and identified all known genetic risk factors for Alzheimer’s disease. Each genetic risk factor was weighted according to the strength of its association with Alzheimer’s disease.
To assess lifestyle, researchers grouped participants into favourable, intermediate and unfavourable categories based on their self-reported diet, physical activity, smoking and alcohol consumption. The researchers considered no current smoking, regular physical activity, healthy diet and moderate alcohol consumption as healthy behaviours. The team found that living a healthy lifestyle was associated with a reduced dementia risk across all genetic risk groups.
Joint lead author Dr David Llewellyn, from the University of Exeter Medical School and the Alan Turing Institute, said: “This research delivers a really important message that undermines a fatalistic view of dementia. Some people believe it’s inevitable they’ll develop dementia because of their genetics. However it appears that you may be able to substantially reduce your dementia risk by living a healthy lifestyle.”
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