Another Alzheimer’s Drug Failed Late Stage Trial. Brain Health Is Not Just a Brain Matter

Learning of some recent scientific discoveries and ancient wisdom for brain health and prevention practice

There was an announcement this month that Alzheimer’s drug from Roche failed in the long waited late-stage clinical trial. This added another major setback to the daunting path of developing an effective drug for this devastating neurodegenerative disease.

According to the science news, “Results of phase 3 trials testing gantenerumab are the latest blow to amyloid hypothesis”. Gantenerumab is the name of the drug.

It reminded me of a few conversations I had with researchers at Banner Alzheimer Institute, triggered by a random event about ten years ago. Being a curious outsider, I shared some of my thoughts such as the below from 2010 to 2017.

“Have you and your colleagues planned to include alternative medical approaches as part of the prevention and treatment? For example, in the view of TCM (Traditional Chinese Medicine), Alzheimer’s disease is not just a brain disorder; it’s also linked to the degradation of other organs’ functions… So an integrated approach is likely the effective maybe the only effective way for prevention.”

“The hypothesis on Amyloid plaque and Tau: while they seem like the cause, I think they could just be the pathology symptoms. In other words, these are microscopic changes while the macroscopic symptom is abnormal memory loss, etc. What’s the cause of them, the precursor, seems more critical when it comes to the next level of mechanism. I am afraid treating Amyloid plaque and Tau won’t help much as it is already too late…”

“Somehow I feel the CSF, the environment surrounding neurons, and the cleansing state of microglia are more important and deserve more attention for root cause and prevention research.”

“Healthy lifestyle is important. If we can link what changes they have enabled to the microscopic state inside the brain, that is another perspective for mechanism understanding.”

Perhaps not completely off — I was told some of the thoughts were also on their minds.

Thanks to the advancement of brain imaging techniques in recent years, scientific discoveries have certainly shed new light on brain health and Alzheimer’s disease (AD)

I first came across microglia and its role in removing amyloid beta aka the brain waste from a 2017 TED talk by neuroscientist Lisa Geneva. While a small amount of amyloid beta generated as a by-product at synapses (the tiny space between neurons) is normal when neurons release neurotransmitters, amyloid plaque can be formed when too much waste is piled up at synapses and not cleared away, the typical characteristic of AD.

In her latest 2021 TED talk “, Dr. Geneva illustrated further how memory works and that “most of what we forget is just a normal part of being human”- it certainly helps us to chill instead of panic and mistake them with concerning dementia and AD symptoms. She also highlighted that sleep, diet, exercise, stress, and learning new things to build more neuro networks as a reserve are the ways to better memory and brain health, as supported by numerous scientific studies.

The breakthrough discoveries in recent years from the Nedergaard group at the University of Rochester Medical Center were especially fascinating. A nice summary can be found in this 2018 Harvard blog on science news. By conducting novel imaging experiments, researchers showed how cerebrospinal fluid flows through the brain and takes away brain waste including amyloid beta, where microglia act as the janitor cells in the brain (intriguing, isn’t it). And by the imaging study on mice, demonstrated that the flow of cerebrospinal fluid increases significantly when mice enter sleep, which correlated with faster clearance of amyloid beta. In addition, they found the same beneficial effect from exercise to clear brain debris.

The transformative benefit of exercise for brain health was also shown by Dr. Wendy Suzuki in her 2018 TED talk. The benefits include improving memory, attention, and long tern mood-boosting, as exercise changes the brain’s anatomy, physiology, and function, therefore protecting against neurodegeneration and cognitive decline associated with aging.

Interestingly, more recent studies such as those from UCSF and MIT discovered that microglia, when damaged, can interfere with neurons’ ability to communicate with each other, contributing to AD rather than protecting against it.

There were descriptions of certain symptoms and behavior in TCM documents that could be related to dementia and AD. Can ancient wisdom also teach us something about brain health and prevention?

According to TCM, the body is a whole with strong interrelations among multiple organs, body and mind, different emotions, and nature and us. These are reflected in its Yin-Yang theory, Five Elements, Four Examinations, Meridian system, etc. So brain health is not just a brain matter. It is strongly linked to functions of other organ systems i.e. Kidney, Heart, Liver and Spleen (beyond modern anatomy definition), thus a holistic issue. Modern medicine also has started a deep dive into the risk factors of AD in connection with other vascular conditions including stroke, heart disease, high blood pressure, and diabetes.

While it is important to maintain an active mind, letting the brain constantly race is not wise. This may sound counterintuitive, but that’s what is expected through the lens of Yin and Yang. Too much can be as bad as too little, according to the Chinese idiom 过犹不及. Give the brain mini-breaks and quiet time so it can be refreshed from time to time. When it comes to exercise, it is not just vigorous workouts in the gym, but also those low-intensity stretches with rhythmic breathing i.e. Yoga, Tai Chi and Ba Duan Jin.

As for food and diet, TCM puts a strong focus on variety and portion to fuel our body and mind — “五谷 (grain)为养，五果 (fruit) 为助，五畜 (meat) 为益，五菜 (vegetable) 为充” were the guidelines documented in medical classic Huang Di Nei Jing more than two thousand years ago, consistent with the framework of modern nutrition. “五谷之精液和合而为膏者,内渗入于骨空,补益脑髓”, highlighting that essential nutrients flow into the brain to nourish it. It’s the material foundation. Black sesame, black beans, walnut, dates, and Goji berry are among the many brain-healthy foods documented in TCM. While the brain represents just 2% of a person’s total body weight, it accounts for 20% of the body’s energy use, as science tells us. That’s why eating well is so important.

Actually, not just what we eat, but more importantly, the ability of digestion to convert food into nutrients and the ability to transport them to the right place for absorption, where the Spleen system and circulation play key roles according to TCM.

Also on emotion. In the Five Element theory of TCM, emotions are closely intertwined with the physical health of key organs. 喜怒忧思悲恐惊 (joy, anger, worry, sadness, fear, and fright) are the types of emotions associated with the Heart, Liver, Spleen, Lung, and Kidney. While each emotion has its place in life, negative ones could adversely impact the organ function and circulation of Qi and blood if they go overboard. Constant great fear correlated with Kidney is especially harmful. Besides, excessive emotion drains energy. It’s a good idea to keep our emotions in check.

I can’t help but wonder: could repetitive pessimistic emotions and negative thinking generate more brain waste exceeding the norm to be cleared away? Could that also contaminate the environment surrounding brain nerves? And degrade the microstructure integrity of microglia and their cleansing ability to clear harmful brain debris? While also worsened by poor diet, nutrition, and circulation? When positive drug results from lab testing on mice can’t be replicated in humans, perhaps because human thinking/emotion can’t be counted in a lab experiment, at least one of the aspects?

According to National Institute on Aging, the number of people with AD doubles about every 5 years beyond age 65, and about one-third of all people age 85 and older may have AD. It could be someone we know, a friend, a close family member, or even ourselves. A rather gloomy picture. By then, maybe we have a lot of time to binge-watch Netflix but can’t digest what is going on, because of losing memory and cognitive function. Perhaps the above is the least unfortunate scenario based on some sad AD stories I stumbled upon. Not the future to look forward to.

Hopefully, there will be a miracle drug someday, an arduous goal though. While scientists and medical experts are continuing to probe the extremely complex pathophysiology of AD, we average people can dive into the basics to empower ourselves for better self-care and prevention to mitigate the risk. Bear in mind even older adults can still grow new brain cells as shown in a study. After all, many people live into their 90s and beyond without developing dementia.

Sleep, exercise, food, digestion, circulation, stress, emotion, and learning new things. All of these can influence brain health based on scientific studies and ancient wisdom. It takes years for amyloid plaque to form and be detected by imaging. Don’t wait. Let the journey begin.

Thank you for reading. I write about culture, work-life learning, and the ancient wisdom of Traditional Chinese Medicine for better living. Click here if you would like to be notified when I publish.