Untangling the Mysteries of the Brain

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Photo of brain neurofibrillary tangles (the white blobs) by Gabriel Luna of the Kosik Lab at UC Santa Barbara.

A new study published mid-February in the Proceedings of the National Academy of Sciences found that adrenaline boosts the body’s processes for getting rid of garbage proteins from our cells. And that, in turn, has positive implications in the body’s fight against diseases of aging such as Alzheimer’s.

Well, of course, it’s a bit more complicated than that. Nevertheless, that was the one insight from a paper on the impact of exercise and fasting on our cells that piqued my interest. The paper was from researchers at the Blavatnik Institute at Harvard Medical School.

It caught my eye because I’ve just returned from an incredible, adrenaline-inducing week in Costa Rica, where I ziplined through vast rain-forested canyons, rappelled down waterfalls, and walked up and down the country’s steep forested hills. I also ate relatively little, drank very little alcohol, swam in the ocean and got a lot of sun … and I feel healthier than I have in months.

I mention all of this because these are all factors (a physically active life, healthy eating habits, and exposure to the sun) that help to stave off — or at least postpone — diseases related to aging, such as Alzheimer’s. An active social life, getting enough sleep, and maintaining low blood pressure are other important ones. You can read about this, and more, for my article “Untangling Mysteries of the Brain,” for Senior Living Executive this month.

It’s a must read for anyone who cares about the health of their brains.

The National Institutes of Health (NIH) describes Alzheimer’s Disease as “an irreversible, progressive brain disorder that slowly destroys memory and thinking skills and, eventually, the ability to carry out the simplest tasks. In most people with the disease — those with the late-onset type — symptoms first appear in their mid-60s.”

Alzheimer’s is just one of several other kinds of dementia that afflict elderly people worldwide. More than 50 million people suffer from some form of it worldwide, according to the Global Council on Brain Health, and that number is expected to balloon to 152 million by 2050. That’s larger than the population of Russia.

As the Alzheimer’s Association reminds us, there is no one test for Alzheimer’s. You can get a PET scan, but it’s often not covered by insurance and it can costs thousands of dollars. And by the time symptoms manifest, it’s too late to do anything significant to prevent the disease from progressing. Alzheimer’s can start developing in your brain 20 years before the first outward signs of it show up.

For my article, I spoke with Dr. Cyrus Raji, an assistant professor of radiology at the Washington University School of Medicine in St. Louis, who has been doing some fascinating work examining both healthy and diseased brains with magnetic resonance imaging (MRI.)

He argues that “brain aging” isn’t actually a natural phenomenon. Rather, he told me that “brain aging is an artifact of the pathologies that accumulate throughout life. The reason that’s an important concept is because if you can minimize the contributions of brain aging, of all these different co-morbid diseases, then you don’t necessarily have to see an aging brain.”

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Hendrikje van Andel-Schipper, from Wikimedia Commons.

As evidence, he pointed to centenarian Hendrikje van Andel-Schipper (pictured above,) a Dutch woman who died at the age of 115. She donated her body to science, and when they autopsied her brain, the researchers found that it was completely free of any diseases related to old age. Andel-Schipper had led a relatively healthy life: She never owned a car, walked and biked everywhere, drank rarely, and ate fish everyday. Her genetic makeup also helped.

“Heart disease, diabetes, high blood pressure — these are all factors that reduce the integrity of the brain,” Raji told me. “They lead to brain atrophy, they lead to white matter damage, they lead to reduced cerebral blood flow over time. And yet, that’s not Alzheimer’s. By definition. However, they’re more common with aging: People with high blood pressure are more likely to be older. People with diabetes are more likely to be older. So it is these conditions that contribute to what we call ‘the aging brain.’

But if these contributions were minimized, then you could be 80 and have a brain that looks as good as a 45-year-old. Conversely, you could be a 50-year-old with horrible blood pressure, horrible heart disease, and have the brain of an 80-year-old.”

Raji’s thinks we can use MRIs to better predict our chances of developing Alzheimer’s. We could organize the data that’s already out there and use artificial intelligence algorithms to establish what’s normal and what’s not in our brains at various ages. That information could be used to quantify our individual risks of developing the disease.

“What I hope to see in the future is a process whereby individuals who are not yet demented or losing their memory can have their baseline risk quantified, say at age 50,” Raji said in a phone interview. “If they had the brain scan information, and the risk quantification, and the genetics, it’d be more like trying to predict somebody’s risk of getting Alzheimer’s 15–20 years beforehand, as opposed to the probability of them already having the disease, and nothing can be done about it. And so that to me would be the logical hope — so that you don’t have to wait to get demented to find out that you’re demented. You can have more of a lead time of a decade or so in advance. That would be my hope for the ultimate outcome of this work.”

Based on my research, I think that there’s a good chance of this happening. But it might not happen in the United States first, but in China.

AI is already being used in other areas of medicine to detect diseases. The New York Times published one of the latest stories on this in early February. But it points out that the subjects in the study mentioned were 600,000 patients in Chinese pediatric hospitals. The story mentioned that the Chinese were able to do the study because of the relative lack of regulations and the ease of data transfer between systems. I heard about some of these issues first hand from someone working at a massive Chinese conglomerate at a dinner last month organized by Silicon Foundry in San Francisco. So I do think more of the future of research and medical discoveries might look like the collaborations described in the NYTimes story. Or the Chinese may do it entirely by themselves.

Of course, our genes affect our chances of developing Alzheimer’s. Theresa Braymer, a 59-year-old retired Naval officer, told me that four years ago, she discovered through a 23andMe test that she has a set of genes that significantly increases her chances of developing the disease at a relatively early age. Like several other people who’ve made similar discoveries, she’s adopted several measures to lower her risk and postpone its progression — though there have been no large-scale studies to prove that the measures she’s taking are effective.

But that’s the whole point of getting a diagnosis as early as possible — to be able to prepare physically and financially. The paradox is that the medical community does not recommend screening the general population for dementia. They are still figuring out what kind of physiological test is reliable enough to use on people for diagnostic purposes. There are more details in my article.

The adrenaline part of the Harvard Medical School study was the element that was new to me. The other parts of the study seemed to confirm a lot of the research that I read beyond Raji’s work. The short version is that the Harvard researchers found that intense exercise, fasting, and “an array of hormones can activate cells’ built-in protein disposal systems and enhance their ability to purge defective, toxic, or unneeded proteins.”

(The caveat here is that these findings came from research on just four humans and some mice.)

There’s still a lot of disagreement within the medical community about the causes of dementia in the elderly, and what can be done to prevent or address it. There are lots of reasons for this. But there seems to be an emerging consensus on the important role of diet and exercise.

“Right now, today, there isn’t any prevention for Alzheimer’s,” said Beth Kallymer, the Alzheimer’s Association’s vice president of care and support in an interview with me. “There are things people can do to alter their risk for other kinds of dementia — things like vascular dementia, and taking care of your heart, and you blood pressure, and your diabetes. Taking care of all those things keeps your brain healthier.”

Nevertheless, the association is embarking on an ambitious two-year $35 million clinical trial that it’s calling the U.S. Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk (U.S. POINTER.) It’s going to look at the impact of regular exercise, nutrition, and other factors on brain health. The study will involve 2,500 volunteers aged between 60 and 79.

If you, or someone you know might want to participate in this study, you can find out more about it here.

For her part, Braymer told me that she follows a version of the Bredesen Protocol. That’s Dr. Dale Bredesen of UCLA and The Buck Institute, who wrote the New York Times bestseller The End of Alzheimer’s. The book argues that his recommended regime of lifestyle changes can reverse cognitive decline.

Dr. Bredesen’s claims are controversial because they haven’t been subjected to vigorous vetting. But as he notes, we’re complex organisms, and Alzheimer’s is a maddening disease to tackle because our brains are affected by several factors in our lifestyles — not just one. And the myriad causes of each person’s mental decline are different. He says that there are more than three dozen factors that when taken together can contribute to the development of the disease. There’s more about his work in my article, and the Alzheimer Association’s take on it.

One of the big takeaways from this reporting experience is the importance of being personally vigilant about the state of your mind, as well as your parents’ minds. One of the disturbing discoveries I made is that primary care physicians may think a patient has dementia, but they often don’t share the diagnosis. There may be many reasons for this — the economics of needing to see dozens of patients a day by the physicians and not having enough time to spend with the elderly patient and their families, as well as the lack of treatment options.

“Sometimes we just call it getting older, so it contributes to a lack of a clear diagnosis,” said Nicole Fowler, a research scientist at The Regenstrief Institute at the Indiana University School of Medicine. Fowler and her colleagues conducted a study of dementia diagnosis rate changes with the implementation of annual wellness visits for those using Medicare benefits between 2011 and 2014. They found that there were no significant changes. They explain more about their findings here.

Of course, I’m not saying that you need to go zip lining and so forth to maintain a healthy lifestyle. But author Dan Buettner did find some commonalities among healthy, long-lived people who live in so-called Blue Zones around the world. One of the communities is in Costa Rica.###

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