2022 Brain Health Updates with Dr. Annie Fenn
Curious what the latest research in brain health in 2022 shows? NeuroReserve founder Dr. Ed Park recently sat down with Dr. Annie Fenn, physician, chef, and founder of the Brain Health Kitchen. They discussed the latest developments in brain health research this year in an Instagram Live.
Their conversation covered 4 main topics:
- Advancements in Mediterranean/MIND diet research (skip to 04:24)
- Dissecting the controversy around amyloid beta and Alzheimer’s disease (skip to 21:09)
- The latest breakthroughs in women’s dementia risk (skip to 26:46)
- Omega-3 Developments (skip to 41:25)
Ed and Annie reviewed the major studies published in 2022 in each area and addressed what the results mean for the overall field. Here, we summarize the highlights of their conversation and offer the main takeaways on each topic.
MIND/Mediterranean Diet Research Made Big Strides This Year
It’s been a banner year for MIND (Mediterranean-DASH Intervention for Neurodegenerative Delay) diet research, as it deepens its evidence in brain health outcomes. Researchers have also begun to show positive outcomes from the MIND diet in other areas of health, including breast cancer and frailty.
The MIND diet is like the Mediterranean diet but with extra brain healthy foods like leafy greens and berries. The initial MIND diet study conducted at Rush University found a 53% reduction in risk for Alzheimer’s disease.1 We await results from the MIND diet trial, anticipated to be released in early 2023. However, there were several exciting studies published on the MIND diet in 2022:
- The first fully reported randomized control trial (RCT) on the MIND diet published its results this year in the Journal Nature Scientific Reports. This study type is highly regarded due to its design of comparing the effects of an experimental diet (in this case the MIND diet), and a standard controlled diet. Researchers measured how the MIND diet affected the cognition and brain structure of obese women. Metabolic dysfunction and obesity lead to an increased risk for neurodegenerative disorders, but we don’t know why, so this study is useful to see changes in cognition in healthy obese women. Participants who were assigned to the MIND diet performed better on cognitive tests of memory and attention after 3 months compared to a group that did not follow a MIND diet. The MIND diet group also had increased surface area in part of the frontal lobe of the brain involved in producing language and decision making. Interestingly, they substituted grapes and grape juice to obtain the same nutrients as wine. This is a good trick for people who don’t want alcohol but want the beneficial antioxidants in wine. The results of this rigorous RCT study show that the MIND diet may counteract some of the harmful effects of obesity on the brain and cognition.2
- Another study looks at a Mediterranean diet that is high in polyphenols (Green-MED). Polyphenols are plant-based pigments that have strong antioxidant and anti-inflammatory properties. Like the MIND diet, researchers in Israel added brain specific polyphenols to the Mediterranean diet. In this study, they added in walnuts, green tea, and a super green called Mankai as the source of extra polyphenols. Researchers aimed to assess changes in brain volume and cognition over an 18-month period in people following either a reduced calorie healthy diet, a traditional Mediterranean diet, or a Green-MED diet. All participants were also told to decrease their processed meat consumption and were given gym memberships and guidance for physical activity. The results suggest that the Mediterranean and Green-MED diets slowed brain shrinkage and better overall cognitive function compared to a standard healthy diet. Additionally, the Green-MED diet had an even greater effect on reducing shrinkage than the regular Mediterranean diet. In particular, a reduced change in the hippocampus was observed, which is a key part of the brain involved in memory formation and Alzheimer’s disease. These observations were even more evident in participants over the age of 50, which is an age where we start to see more decline in brain volume. This study shows a direct effect of a Mediterranean diet, especially one that is high in polyphenols, on reducing brain shrinkage and supporting cognitive function. The importance of polyphenols is illuminated by the difference in effect between a Mediterranean diet and a Green-MED diet.3
- A different approach to the MIND diet includes a study evaluating how the MIND diet impacts risk of open-angle glaucoma, a neurodegenerative eye disease that causes blindness. In this study, participants were followed for about 10 years and their adherence to a MIND diet was assessed by questionnaires which record types and amounts of foods consumed and the frequency of consumption. Researchers determined which participants followed a MIND diet more closely based on the food frequency questionnaires and gave each participant a MIND diet adherence score. Participants that had a higher MIND diet adherence score had a lower risk of developing glaucoma. This study helped form a connection between the MIND diet and glaucoma, but it does not prove that following a MIND diet prevents glaucoma. Further research, specifically randomized controlled trials, need to be conducted to better understand the relationship between the MIND diet and glaucoma.4
Many researchers are exploring the MIND diet for a wide range of health benefits, including topics like longevity and physical strength with aging. This was a great year for MIND diet studies, and we expect the trend to continue as nutritional research study designs improve.
Dissecting the Controversy and Questions Regarding Amyloid Beta and Alzheimer's
It’s been a roller coaster year for research science regarding Alzheimer’s disease. There are a lot of big questions being addressed in the field of Alzheimer’s, down to what approach should scientists be taking to address it? A lot of time and money has been focused on amyloid beta plaques over the last several years, and it’s yielded mixed results.
- The Initial Controversy: You may have heard about the controversy of potential scientific fraud regarding a key hypothesis for Alzheimer’s. In July of 2022, an investigation revealed that some of the evidence from a landmark study on Alzheimer’s disease that was originally published in 2006 was fraudulent. The study looked at amyloid beta plaques, which are sticky aggregates or globs of a protein called amyloid. These plaques build up in the space between neurons in Alzheimer’s disease, interfering with brain signaling. In particular, the initial study looked at a form of amyloid called oligomers, and claimed that this form played a key role in the development of Alzheimer’s disease. If this research was fraudulent, you may be wondering how does that affect other research? And what should we believe about the latest headlines regarding recent failures and successes of anti-amyloid drugs? Are amyloid plaques the linchpin or not?
- A recent failure fueled doubts: Over the summer, Roche released results from their study with an anti-amyloid drug called crenezumab. This drug aimed to reduce amyloid levels in patients before they developed symptoms of Alzheimer’s, in the hopes that it would prevent them from becoming symptomatic. People at high risk for Alzheimer’s disease due to genetic mutations were given either crenezumab or a placebo for up to 8 years to see if the drug could slow cognitive impairment and memory loss. Unfortunately, this trial was unsuccessful and crenezumab was deemed another failure of anti-amyloid drugs. This was an especially disappointing result since patients in the study were those with very high risk of Alzheimer’s.
- And then positive news renewed hopes: Just recently in September 2022, pharmaceutical companies Eisai and Biogen released good news of promising results from a trial with their anti-amyloid drug lecanemab. Lecanemab also targets plaques of the amyloid protein building up in the brain. The phase III clinical trial included almost 1,800 people with mild Alzheimer’s disease and found those who took lecanemab had slowed cognitive decline by 27%. This decreased rate of decline equates to about 4 years to reach a degree of decline that would take only 3 years without the drug, which is a significant yet modest result. The outcome of this trial has given many researchers in the Alzheimer’s field a lot to be hopeful for. The FDA is expected to grant accelerated approval of lecanemab in January 2023 as a treatment for Alzheimer’s disease.
While some results are promising, big questions remain about the overall mechanisms involved in Alzheimer’s disease. Are amyloid plaques the root cause or not? Recent developments show that amyloid plaques are part of the problem, but they aren’t the whole problem. This is inspiring researchers to branch out into other areas like other problematic proteins such as tau, dysfunction with glucose metabolism, and neuroinflammation.
Overall conclusion at this time: amyloid is real and important, but we expect new research into other fields and factors to help us see the bigger picture more clearly.
Latest Breakthroughs in Women's Risk of Dementia
It has been established that women are at higher risk of Alzheimer’s than men, in fact, almost two-thirds of Alzheimer’s patients are women, but questions remain about why. We now know that estrogen seems to be protective on the brain, and taking hormones after menopause may reduce risk of Alzheimer’s. Earlier this year, we spoke about the research Dr. Lisa Mosconi and team summarized on women’s risk of Alzheimer’s here, and today we follow up and look at new developments across the field since then.
- Data regarding preeclampsia, high blood pressure condition during pregnancy, was presented at the Alzheimer’s Association International Conference in August 2022. Researchers found that a history of preeclampsia was associated with a higher risk of vascular dementia later in life. Vascular dementia differs from Alzheimer’s disease in that the cognitive decline results from reduced or blocked blood flow to the brain. Additionally, women with severe preeclampsia had higher amyloid beta levels and inflammation, both of which contribute to the development of Alzheimer’s disease. This newly released data has sparked interest in learning more about how preeclampsia may have long lasting effects on the brain and what we can do to mitigate these effects. This is another reminder of how events at any phase of life can impact vulnerability of the brain, and also offer an opportunity to stave off Alzheimer’s.5
- A paper from the well-regarded journal Cell suggests an explanation for the increased aggregation of a protein call tau in women. Tau, like amyloid, is a protein that builds up in the brains of Alzheimer’s patients. Experiments were conducted at Case Western Reserve University in Ohio focused on a protein called ubiquitin specific peptidase 11 (USP11). The study confirmed that USP11 is found in higher amounts in females than males. The researchers revealed a complex mechanism by which USP11 contributes to tau forming harmful tangles inside brain cells which make it difficult for cells to function normally. In fact, they discovered that removing USP11 from female mice protected them from excess tau in the brain and cognitive impairment. This study opens up a major area for more research into how women become more susceptible to Alzheimer’s disease than men. Fundamental science experiments like this lead us in new directions to help us better understand women’s risk. This could be the start of a new area of research that could be looked back on years later as a great discovery towards women’s prevention and treatment strategies. Further research in this area may lead to targeted treatments that help reduce the effects of this gene.6
There are many biological differences between males and females that may contribute to differences in susceptibility to a variety of diseases. There remain many questions as to why women are more susceptible to Alzheimer’s disease than men, but researchers continue to explore different factors on many levels, from cellular models to clinical studies in humans.
These clinical studies are key to making progress in science. In fact, Dr. Annie Fenn participated in Dr. Mosconi’s current clinical study and had brain scans, blood work, and cognitive tests done. If you may be interested in participating in a clinical study, email Annie at firstname.lastname@example.org.
Developments in Omega-3s for Neuroprotection
Omega-3s are a type of fatty acid called PUFAs for polyunsaturated fatty acids, and they are mainly found in fatty fish like salmon and nuts and seeds. Omega-3s are associated with brain benefits because they can enter and exert a direct effect in the brain, and they support proper blood flow and reduce inflammation. As such, they have been studied for a wide range of health benefits.
- Two of the top experts in the field of brain health are doctors Ayesha and Dean Sherzai. They also go by “The Brain Docs” and they recently published a review paper on omega-3s and neuroprotective outcomes. This type of paper looks at all of the existing studies on omega-3 consumption and cognitive measures, and compiles the information into one article. The review acknowledges that due to changing dietary habits, people consume fewer omega-3s today than they did in the past. A total of 42 studies were included in the review, and upon compiling the results from all the studies they found mixed outcomes. Some studies showed clear improvements in cognitive function among those with existing cognitive impairment, while some showed no effect from omega-3 consumption. Overall, omega-3 supplementation appeared more likely to slow progression of disease than improve symptoms. Additionally, omega-3s seemed to have a limited effect in younger and healthier people, which suggests they may have already had enough omega-3s in their diet. This reflects a “threshold effect” in which omega-3 supplementation may only make a difference if you start with lower levels. Lastly, there were a variety of dosages used among the studies, suggesting that more research needs to be conducting to understand what the optimal dose is for certain populations. The Brain Docs conclude that while the results of all the studies combined are inconclusive, there is evidence that omega-3s may be neuroprotective, especially in older adults and those with cognitive decline. They also emphasize the need for more research in this area to have more conclusive results.7
- Another omega-3 study just released in October 2022 looks at the effects of omega-3s in middle-aged participants. This study used data from a large cohort study called the Framingham Heart Study. Researchers were able to measure the levels of omega-3s that were present in red blood cells of over 2,000 cognitively healthy, middle-aged participants. Looking at omega-3s levels in red blood cells is useful because these cells like about 90-120 days which is enough time to see how the omega-3 levels build up. These participants also underwent MRI scans which can measure relative sizes of different parts of the brain. Higher omega-3 levels were associated with a larger volume of the hippocampus, the key brain structure involved in memory formation. Participants also completed tests of cognitive function, and higher omega-3 levels were associated with better abstract reasoning ability. It would be interesting to see more research in this area, particularly in a randomized controlled trial, to see if a stronger relationship between omega-3s and brain volume would be established. This study does offer a new way to more reliably measure omega-3s levels and this technique could be used in future studies to narrow down healthy levels.8
Omega-3s are an important nutrient that exerts a positive effect on the brain. The exact role of omega-3s in preventing or slowing cognitive decline is still being examined, but top researchers in the field believe omega-3s may provide significant benefits to support the aging brain. It will be helpful to further understand the proper forms and dosages of omega-3s that people should be taking, as well as who the optimal target populations are for omega-3 supplementation.
Researchers around the globe are dedicated to studying the brain and finding ways to prevent or treat Alzheimer’s disease and other forms of dementia. All of the research we discuss here was just published in 2022. There’s still a lot to learn but we are making strides towards a better brain health future for everyone. We’ll catch-up again on the biggest highlights in brain health research after the holidays!
About Dr. Annie Fenn: Annie is a physician and chef who is dedicated to Alzheimer’s disease prevention. She is the founder of Brain Health Kitchen, an online resource providing innovative whole foods-based recipes and dietary recommendations that equip people to cultivate resilient, healthy, and nourished brains for themselves and their families. She’s also founder of the Brain Health Kitchen Cooking School, the only school of its kind entirely devoted to teaching how to cook through the lens of brain health. Annie is a frequent lecturer on the leading evidence regarding foods and dietary patterns that reduce the risk of dementia and cognitive decline. She believes that cooking is the best way she knows how, as a physician, to radically improve health. Stay tuned for her first cookbook, coming out in early 2023!
- Morris, M. C., Tangney, C. C., Wang, Y., Sacks, F. M., Bennett, D. A., and Aggarwal, N. T., MIND diet associated with reduced incidence of Alzheimer’s disease. Alzheimer’s Dement., 2015, 11, 1007–1014.
- Arjmand, G., Abbas-Zadeh, M., and Eftekhari, M. H., Effect of MIND diet intervention on cognitive performance and brain structure in healthy obese women: a randomized controlled trial. Sci. Rep., 2022, 12, 2871.
- Kaplan, A., Zelicha, H., Yaskolka Meir, A., et al., The effect of a high-polyphenol Mediterranean diet (Green-MED) combined with physical activity on age-related brain atrophy: the Dietary Intervention Randomized Controlled Trial Polyphenols Unprocessed Study (DIRECT PLUS). Am. J. Clin. Nutr., 2022, 115, 1270–1281.
- Vergroesen, J. E., de Crom, T. O. E., van Duijn, C. M., Voortman, T., Klaver, C. C. W., and Ramdas, W. D., MIND diet lowers risk of open-angle glaucoma: the Rotterdam Study. Eur. J. Nutr., 2022.
- Schliep, K., FROM THE ALZHEIMER ’ S ASSOCIATION INTERNATIONAL CONFERENCE 2022 HISTORY OF HYPERTENSIVE DISORDERS DURING PREGNANCY LINKED TO INCREASED RISK OF DEMENTIA. 2022.
- Yan, Y., Wang, X., Chaput, D., et al., X-linked ubiquitin-specific peptidase 11 increases tauopathy vulnerability in women. Cell, 2022, 1–18.
- Sherzai, A. Z., Sherzai, A. N., and Sherzai, D., A Systematic Review of Omega-3 Consumption and Neuroprotective Cognitive Outcomes. Am. J. Lifestyle Med., 2022, 0, 155982762211171.
- Satizabal, C. L., Himali, J. J., Beiser, A. S., et al., Association of Red Blood Cell Omega-3 Fatty Acids With MRI Markers and Cognitive Function in Midlife : The Framingham Heart Study. Neurology, 2022.