Navigating Advancements in Brain Health: Key Takeaways from AAIC and ASN 2023
Every July is an exciting time for the brain nutrition community because the Alzheimer’s Association International Conference in Amsterdam and American Society for Nutrition Conference (ASN) in Boston conferences reveal the latest discoveries and breakthroughs in cognitive health, Alzheimer’s, and dementia research, moving the bar forward for better prevention and treatment.
And this year did not disappoint!
AAIC Delivers Three Important Learnings
1. A new treatment for people diagnosed with Alzheimer’s disease: donanemab.
One exciting development revealed at AAIC were clinical study results of a new Alzheimer’s drug called donanemab. Donanemab works by removing the amyloid “plaques” that form in the brains of most people with Alzheimer’s disease. It was a large study, involving 1700 patients in the early stages of Alzheimer’s. What it showed was that donanemab slowed down cognitive decline in Alzheimer’s patients by 35% over 18 months. In a group of patients in the earliest stages of Alzheimer’s, it appeared to slow down the disease by 60% over the same 18 months. While not a cure, those findings are a major accomplishment, roughly equivalent to slowing progression by 4 to 7 months; and the developer of the drug, Eli Lilly, has announced it will apply to the FDA for approval.1
Experts are calling these results an important first step in a new era of Alzheimer’s drugs. Insights from the donanemab study:
- Removing amyloid plaques appears to help people with Alzheimer’s: The donanemab study is a second confirmation of the anti-amyloid strategy, coming hard on the heels of the lecanemab clinical study results from last November (learn more about that here), which was the first Alzheimer’s drug to clearly show such benefit.
- It’s a long, long road for progress like this: Researching and testing the idea of removing amyloid plaques from Alzheimer’s patients has taken almost 30 years, marked by decades of failures, only in the last year showing positive results in major studies. Along the way, each failure contributed to new lessons that were applied to the next study – persistence and learning are the key!
- Anti-amyloid drugs help slow things down, but they are not a cure: We’re also seeing that anti-amyloid drugs like donanemab and lecanemab, though helpful, are probably not the full solution; Alzheimer’s disease and dementias are complex, and amyloid is only one aspect of it. There are many others, such as tangled tau proteins, neuroinflammation, neuronal insulin resistance, and cerebrovascular aspects that play a role, among many others.
- Donanemab and lecanemab apply to a specific group of Alzheimer’s patients: Keep in-mind that these new drugs were tested in people who were early in the disease, and they had confirmed the presence of amyloid plaques. For Alzheimer’s patients in the late stages of the disease and who do not have amyloid plaques, it is unclear whether these drugs will work.
- There is still more to learn on safety and sustainability: Since the clinical study was only 18 months, more research is required to determine if its benefits are sustained. Also, side effects, such as brain swelling and bleeding occurred in 37% of patients. Although in many cases these events were mild or asymptomatic, there is some concern, since three patients died, and assessing their long-term effects will be important. For any drug, patients and doctors must weigh the benefits against the risks before making a decision to treat.
2. Prevention strategies and non-drug approaches, particularly in hearing and nutrition, are making big advances.
As you know, our favorite topic is brain preventive nutrition, and we were delighted to see more interest, growth, and a very high volume of research in this field. New results continue to build upon the benefits of neuroprotective dietary patterns (like the Mediterranean diet) and specific nutrients for long-term brain health, including:
- Mediterranean diet reducing inflammation related to Alzheimer’s disease when compared to Western diet;
- FINGER (Finnish geriatric study) trial showing that adherence to recommendations on vegetables, fruit, berries, fish, fiber, while reducing saturated fat is linked to better cognitive performance over 2 years;
- Mediterranean diet as a key dietary approach to prevent dementia, regardless of genetic predisposition;
- Polyphenols (potent plant-based nutrients) significantly associated with lower inflammation and better logical problem-solving;
- Importance of vitamin B12 for people over 60, where deficiencies show lower cognitive performance; and
- Another large study (378,000 participants in the UK) showing that tea consumption was significantly associated with reduced risk of dementia.
- MIND diet study: Also, the results from the first multi-year clinical trial of the MIND diet were presented, providing surprising and insightful learnings. In this study, 600 participants from Chicago and Boston areas were split into two groups (about 300 each), each encouraged to follow a different type of diet: (1) the MIND diet, with focus on reducing calories (you can learn more about it by clicking here); and (2) a generalized mild caloric restriction diet. Over the course of 3 years, each participant’s cognitive abilities were measured.
- MIND results show cognitive gains and weight loss: Both group’s cognitive scores increased over the 3 years, with the MIND diet group showing slightly better performance, though it was not statistically significant. The surprising result was that the mild caloric restriction group kept pace with the MIND group on cognitive tests, and both groups lost about 11 lbs on average in weight.2
- What does this all mean? Is general calorie reduction just as good as the MIND diet? Is cognitive health strongly related to weight loss? How did the COVID pandemic affect the results of the trial? No matter what the questions, researchers are agreeing on a few things:
- There is much to learn: Since this is the first major, multi-year randomized controlled trial of the MIND, there is likely much to optimize regarding how to design and execute a trial as complex as a dietary intervention. Researchers are already asking questions regarding:
- Was the trial too short to show long-term effects?
- Was the mild caloric restriction group the right “control group” for a trial like this; or were they making big enough changes to their diet and lifestyle to “keep up” with the MIND group?
- Was the patient population too different from the original MIND studies (e.g. in age and other health conditions), and were the patients in both groups representative of health-conscious people who would have lower risk of decline anyway?
- Did the MIND diet group increase their MIND adherence enough to show a big difference?
- It’s a long road: Much like the anti-amyloid drugs mentioned earlier, dietary interventions for cognitive health will take a long time to fully evaluate. It took almost 30 years for researchers to hone their study of anti-amyloid drugs and clearly show their ability to make a difference. Dietary studies are more complex, including numerous food types and nutrients (not just a single drug) and requiring longer time to show preventive benefit. So, patience is required as researchers optimize and hone the design for dietary clinical studies for dementia prevention.
- Stick with the MIND and similar brain-healthy diets: Given the overwhelming evidence supporting the MIND and Mediterranean diets for long-term brain health in other studies, researchers are still big advocates of the MIND diet and other Mediterranean-like diets for brain health. The benefits of a healthy diet are very evident, including in this latest MIND trial. The interesting thing is that they may have uncovered other dietary and lifestyle mechanisms for long-term brain health through this study!
In addition to diet and nutrition, hearing made a loud statement at AAIC.
- Hearing loss has emerged as a risk factor for dementia, which motivated the Aging and Cognitive Health Evaluation in Elders (ACHIEVE) trial. Over 3 years, ACHIEVE studied the effect of hearing aids and audiological counseling on cognitive performance in older people with mild-to-moderate hearing loss. The results showed that these hearing interventions slowed the rate of cognitive decline by 48%. It was the largest study to-date on hearing aids and cognition, and it underscores the importance of monitoring our hearing as we age and making sure we get the right treatment before it affects our brain health!3
3. Blood-based “biomarkers” could be the key to getting the proper treatment and making the right changes for prevention.
Although not as appealing as drugs and diet, the concept of a simple finger prick blood test to diagnose a person’s stage of dementia or identify if the person is at-risk for dementia could be transformative. For those who have family experiences with Alzheimer’s, the frustration of misdiagnoses is all too common, and simple ways to confirm or complement current cognitive tests can be extremely helpful.
- A blood test could tell what stage of Alzheimer’s a person is in, helping physicians determine whether current (and future drugs) could be more or less helpful.
- For those who don’t show any symptoms, a blood test can serve as an early warning for risk of dementia, motivating people to change their lifestyle, diets, and behavior to change course to delay or even completely avoid disease.
Researchers at University of Gothenburg and Lund University in Sweden are looking for substances called neurofilament light (NfL), glial fibrillary acidic protein (GFAP), and tau (p-tau181 and 217) circulating in the blood as disease and prevention markers – and they are showing that their blood test is accurate in diagnosing Alzheimer’s 85% of the time (compared to 55% with a standard doctor’s diagnosis).4
One could imagine a future where an Alzheimer’s blood test would be just as effective as A1C for diabetes or HDL and LDL for cardiovascular health, where people could monitor their readings as they make proactive changes in their brain health regimen!
A few words on the American Society for Nutrition (ASN) conference.
In addition to presenting our own research at ASN on the Mediterranean diet (click here for more details), a striking development there was its focus on bioactive nutrients, which are those found in vegetables and fruit, yet are not considered vitamins and minerals. Researchers are advocating that certain bioactives, such as flavonoids, lutein, and zeaxanthin be given official RDAs (recommended daily allowances) and taking steps to establish minimum consumption levels. Also, the microbiome and gut health sessions were standing room only, which is a harbinger of where most of the discoveries and focus will be for the foreseeable future in nutritional research. Coincidentally, the above bioactives and the microbiome are both heavily implicated in brain and cognitive health.
The big picture.
Stepping back from these highlights gives us the bigger picture. Researchers are making a coordinated effort to attack dementia from three important and interrelated angles: through drugs, through prevention (including diet, nutrition, and lifestyle), and through more convenient (and more accurate) diagnostics – helping people wherever they are in the course of life and making sure that diagnostics can tell us when and how we can help.
So, the final results of this year’s AAIC and ASN conferences: more hope and more motivation for taking care of our brains!
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- Sims JR, Zimmer JA, Evans CD, et al. Donanemab in Early Symptomatic Alzheimer Disease: The TRAILBLAZER-ALZ 2 Randomized Clinical Trial. JAMA. Published online July 17, 2023. doi:10.1001/jama.2023.13239.
- Barnes, L. L., Dhana, K., et al. (2023). Trial of the MIND Diet for Prevention of Cognitive Decline in Older Persons. New England Journal of Medicine, 7.
- Lin, F. R., et al. ACHIEVE Collaborative Research Group. (2023). Hearing intervention versus health education control to reduce cognitive decline in older adults with hearing loss in the USA (ACHIEVE): a multicentre, randomised controlled trial. The Lancet, 0(0). https://doi.org/10.1016/S0140-6736(23)01406-X
- Huber Hanna, et al. Finger Prick Blood Test for Alzheimer’s Brings Promise | alz.org. Retrieved July 26, 2023, from https://aaic.alz.org/releases_2023/finger-prick-blood-test-alzheimers-disease.asp