Brain gains?

Last summer I interviewed a renowned (and award-winning) neuroscientist who specializes in Alzheimer's disease (AD) research. I found her predictions and ongoing lab results to be both fascinating and hopeful. This feature story was originally commissioned by a leading health content provider but was never published. Its medical board ruled her views might be too hopeful—it chose to err on the side of caution, rather than post a piece that suggests a cure for AD may be on the horizon. I certainly understand this official position; the cutting-edge work presented here is not yet mainstream. Still, I'd like to share my conversation with one of the most respected voices in the field of AD research, so I'll post it here.--LPK

​​Many people think of Alzheimer’s disease (AD) as a kind of genetic bullet. One that’s impossible to dodge for an unlucky subset of people who develop this debilitating, degenerative, and (at least for now) always-fatal condition.
 
The surprising news?
 
The latest research from a leading neuroscientist and her team suggests only 1% of all AD patients, those with a specific genetic inheritance, are predetermined to develop it.
 
“There is time to intervene” for the remaining “99% who do not have a single mutation issue. It’s a constellation of factors,” says Roberta Diaz Brinton, director at the Center for Innovation in Brain Science at the University of Arizona, and a key founder of the Alliance of Women Alzheimer’s Researchers (AWARE), who was also named “Scientist of the Year” in 2015 by the Alzheimer Drug Discovery Foundation. “This is not an overnight disease.”

She refers to the 20-year window of time—called the prodromal phase—between ages 52 and 72, when initial signs and symptoms of AD—memory loss, cognitive disability, physical decline, and dementia—generally first surface. (Early onset AD, which comprises just 5% off all patients, shows a different, accelerated trajectory, with symptoms appearing before the age of 65.) 

Rather than an unavoidable bullet, then, late onset AD can be thought of as a perfect storm of risk factors that may, or may not, result in its emergence. Scientists are in the process of understanding the hows and whys. And they’re making real progress. 
 
Brinton says a growing body of evidence suggests that genetic inheritance, while clearly influential, is not always destiny. That’s because lifestyle choices—diet, weight, activity levels, mental acuity, amount of sleep—and scientific intervention may help delay or even prevent the disease, which currently affects roughly 5 million Americans and their extended, caretaking families. 
 
These lifestyle choices may be significant in AD’s development due to their connection to how the brain fuels itself—through lipids, or fats—especially among aging women.
 
Brinton and her team are also working on therapeutics to treat—with the aim of curing—AD. “The message is this,” says Brinton. “We are at a tipping point. Many thousands of scientists whose ideas were thought to be too innovative twenty years ago? That innovation space is now open. It’s very exciting. … the idea the brain could regenerate itself was [once] considered outlandish. Now the idea is that it’s possible. That’s our opportunity. There is going to be, in the very near future, prevention, delay and a cure for Alzheimer’s.”
 
Here’s what Brinton has to say about the latest findings in Alzheimer’s research:
 
Researchers are just beginning to understand why two-thirds of all Alzheimer’s patients are women—and it’s not just because they live on average of 4.5 years longer than men.
Menopause may play a key role—that’s because the brain is fueled by lipids it takes from the liver. Declining estrogen levels in women, a common side effect during and after menopause, which on average occurs at age 51, interfere with lipids metabolizing and/or reaching the brain, Brinton says. All post-menopausal women then mimic what happens among people who are starving: deprived of lipids, their brains burn what are called ketone bodies instead, feeding off the body to protect precious brain matter. This “backup generator” process works for many, but not all, aging women. When the brain cannot find enough ketone bodies—available fats—to utilize as fuel, research shows it can turn on its own white brain matter for energy, which may then result in late onset AD.
 
Being overweight is a risk factor for developing Alzheimer’s—but only until age 65.
After age 65, your brain may actually benefit from a few extra pounds. “Not obesity, not to the point of developing metabolic syndrome,” Brinton warns, but instead a little extra padding as you age may protect the brain. Why? Because, again, the brain is fueled by lipids.

​“This is true of both women and men,” the scientist adds. So if you’re of retirement age, perhaps it’s time to stop denying yourself a little dessert or that (small) second helping. Your pants will feel tighter, but your brain might thank you.

Brinton strongly believes “a constellation of factors”
join to spur on the condition in some, but not all, 
people. This means there are lifestyle choices 
you can make right now that may delay
or even prevent Alzheimer's at its earliest stages.

​The jury is still out, however, on the correlation between pregnancy and the disease.
“Some studies show pregnancy in women may help prevent Alzheimer’s; some studies indicate it actually may increase risk. The short answer, then, is we still don’t know,” Brinton says.
 
The inherited AOPe4 gene indicates an increased risk for AD.
About 20% of the population, evenly distributed between men and women, is born with the AOPe4 gene, which increases the risk for developing AD by about 50%, Brinton reports. “Interestingly, this gene is a transporter of lipids between cells, and those lipids are critical to cellular and brain function,” she says.

Women with this gene, inherited from one parent, are shown to be twice as likely to develop AD, while men only show the same increased risk when both parents pass on AOPe4. However, not all women with the gene from one or both parents get AD. Which suggests other factors—including lifestyle choices—play a role in both the development of the disease and keeping it at bay.
 
Brain regeneration has been shown to occur in normal, aging female mice.
Brinton and her team are “very excited” by extensive, decades-long studies in aging female mice that were injected with allopregnanolone—a molecule found in abundance in both pregnant women and their third-trimester developing fetuses, and thus deemed safe in similar quantities by the FDA—that then showed brain regeneration in the animals. Now the questions are: Will the same thing happen in human brains? What about aging people with initial signs of AD?

​“We’re halfway through an early-stage study where we’re treating people with early Alzheimer’s for three months with this molecule,” Brinton says. The results are not yet in. “And we’re now developing our clinical trial plan to treat humans [with AD] for 12–18 months with allopregnanolone.” Brinton believes the longer study will begin sometime next year. Watch this space.
 
Brinton strongly believes “a constellation of factors” join to spur on the condition in some, but not all, people. This means there are lifestyle choices you can make, right now, that may delay or even prevent AD at its earliest stages.
“Your body and brain are messengers,” this top researcher says. “Pay attention to what they’re telling you. They tell you what works for you, when the body has energy, and when it functions well. The opposite is also true. We each need to be our own internal scientists and collect data on ourselves,” she adds.

​“Sleep deprivation doesn’t work for anyone, particularly as we age. Same with alcohol abuse. We are literally what we eat … There is no magic pill. Late onset Alzheimer’s is the culmination of multiple factors over the course of twenty years.” In other words, take great care of yourself, especially into middle age and beyond, if you want to decrease your risk of developing late onset AD.