Secret Life of the Grown-Up Brain (15 page)

“Individuals may diverge in their rates of aging as they transit through middle age, approaching the state of ‘old age’ at different rates,” said Bruce Yankner, the Harvard neuroscientist who examined the brains in the freezer. Though the brain samples were obtained from cadavers or those undergoing brain surgery, and those conditions could have had some impact, overall the brains were considered normal and indicative of what would be found in healthy, living adults.

“At middle age,” Yankner said, “brains become particularly variable.”

The study by Yankner and his colleagues, published in 2004 in the scientific journal
Nature,
was the first to take a systematic look at how a brain ages on its most basic level, its genes, using these gene chips or microarrays.

Yankner’s studies, more than any others, have taken advantage of this new technology to try to figure out what is happening at a genetic level as the brain ages. His team has now looked at twenty thousand protein-linked genes in the brain and they’ve found the very same thing twice.

The changes in genes that are affected by aging (about 4 percent of the total) generally begin in our late thirties, much earlier than expected. In particular, Yankner found age-related changes in about twenty genes that are crucial for learning and memory and brain-cell flexibility.

But there’s good news here, too. Yankner found that around the same time—late thirties to early forties—another group of nurse genes steps in to help out. These are the genes that protect and repair neurons from damage, and they begin to work overtime, perhaps delaying the net impact of the damage. This, too, could be part of the reason why cognitive decline often doesn’t show up until later in life—and why some retain their intellectual prowess longer than others. Perhaps some people simply have more nurse genes—or for some reason have been able to retain better-functioning nurse genes—than others. And these microscopic differences begin to show up in middle age.

“There seems to be a similar profile for the young before age 40 and a similar profile after age 73. But the most variable group was between ages 40 and 70. Right around middle age you can see the transition in age-related genes. They were just not aging at the same rate. Some resembled the young and some were more like the old. It was very striking.

“The research is still in early stages, but these changes in genes for synaptic function, learning, and memory could help explain the subtle declines in middle age in abilities such as short-term recall,” Yankner told me when I spoke with him recently.

But, he added, more optimistically, other genes are stepping up to the plate. “These are the ones that protect the cell from damage, help build new connections. So at the same time that there is this decline, there is this compensatory activity kicking in, too. I would guess that with most at middle age, there’s probably a balance between the two.”

Of course which side wins that balance game is obviously crucial. Yankner likes to talk of one ninety-three-year-old woman who was in nearly perfect cognitive shape when she died and donated her brain to Yankner’s lab. And perhaps not surprisingly, when the researchers took a look at her brain, they found she had the genetic brain patterns of a middle-aged person.

“We know that she was cognitively intact and her brain was, too,” Yankner told me.

How can some get so lucky? Is it something they ate or read or did? And how can some, on the other end of the spectrum, get so unlucky, brain-wise? Are the lucky ones better from the get-go, or, as Yankner suspects, do they have—or develop—better repair mechanisms and adaptive strategies in their brains? And do these mechanisms mean that they remain able to call on more of their brains—two brains—to help them out?

It’s possible that all this is simply following some set genetic program. Perhaps along the way, Yankner speculates, evolution produced choices. It may have proven over time that it was more important to keep our heart muscles going strong and let our brains, in particular short-term memory, slip a bit. After all, it might be more important to get our hearts pumping to get away from an angry tiger than to recall exactly what we ate for breakfast.

Still, he, along with most, believes it’s likely that in the end we will find that changes in the aging brain arise not just from genes alone but from a combination of our DNA and the soup it lives in—our environment and the way we live our lives. And that means we can make a real difference—and what we do for ourselves during middle age may be particularly crucial.

“There are a lot of redundant systems built into human cells to repair damage. There is a good system to keep the brain intact,” said Yankner, who at age fifty is right at the brain crossroads himself.

“What’s more surprising is that this system breaks down at all. That is the great mystery of aging.”

8 Extra Brainpower

A Reservoir to Tap When Needed

So if our middle-aged brains are—on balance—so masterful and marvelous, what can we do to keep them that way?

For an answer to that, there’s no better place to start than with a now-dead nun.

Her name—or the name she’s been given in the scientific literature—is Sister Bernadette, and she’s given us provocative clues to what may be the brain’s most powerful ploy. Sister Bernadette was a part of what’s been famously called the Nun Study. Since 1986, University of Kentucky scientist David Snowdon and his colleagues have studied 678 Catholic nuns in an extraordinary experiment to look at how the brain ages and why.

As part of the study, the nuns, members of the convent of the School Sisters of Notre Dame, have had periodic mental tests—how many animals they can name in a minute, how many coins they can count correctly, how many words they can remember after seeing them on flashcards. Through the years, they’ve also provided personal information—who their parents were, what illnesses they suffered, how many years of schooling they had—details that have been meticulously cataloged and stored in convent archives.

And perhaps most important, the nuns all agreed that after they died they would donate their brains, which are placed in plastic tubs and shipped to a laboratory where they are stored and analyzed.

Nuns are a particularly good study sample because you can usually eliminate a slew of activities—heavy smoking and drinking, for instance—that aren’t particularly good for a brain and skew results. And the Nun Study has had a score of fascinating findings, including suggestions that dementia may be linked to small strokes or insufficient folic acid in the diet. And, in an especially striking result, the nuns who used the most elaborate sentences—packed with more complex and optimistic ideas when writing autobiographies in their twenties—had a lower risk of dementia decades later.

Still, in the midst of such revelations, the story of Sister Bernadette stands out. Among the nuns, she was a class star. Early in her life, she had earned a master’s degree and taught elementary school for twenty-one years and high school for another seven. At ages eighty-one, eighty-three, and eighty-four, she aced any cognitive test thrown at her. Then, about ten years ago, after she died of a massive heart attack at age eighty-five, Sister Bernadette’s brain was sent to be analyzed, initially without its identity being known.

At first glance, the brain seemed fine. It weighed 1,020 grams, about normal. But, as Dr. Snowdon writes in his moving and personal book,
Aging with Grace,
about his relationship with the nuns he both studied and grew to love, a microscopic look at Sister Bernadette’s brain soon revealed something far different. There was, Dr. Snowdon writes, “little doubt that Alzheimer’s disease had spread far and wide. Tangles cluttered her hippocampus and her neocortex all the way up to the frontal lobe. Her neocortex had an abundance of plaques as well.” In fact, on one scale used to determine the degree of Alzheimer’s, Sister Bernadette rated the most severe, Level 6.

How could it be? How could a woman who was, up until the moment of death, a cognitive champ also have extensive plaques and tangles, the hallmark of Alzheimer’s disease? Expressing his own surprise at the time, Dr. Snowdon said, “Despite an abundance of plaques and tangles in her neocortex, the function of that brain region seemed to be incredibly preserved. It was as if her neocortex was resistant to destruction for some reason. Sister Bernadette appears to have been what we, and others, have come to call an ‘escapee.’ ”

An escapee?

Is that possible? Was there something in Sister Bernadette’s background—her richly endowed sentences, perhaps—that, although her brain had all the physical signs of dementia, had somehow protected her?

On one level it would be easy to dismiss the case of Sister Bernadette as interesting but odd. It would be easy if she were a fluke.

But she is not.

Take the case of the retired professor from London. The professor—he’s called the Chess Player in scientific studies—loved to play chess and was uncommonly good at it. As he played, he could easily think seven moves ahead. But at a certain point, he noticed a change. Although his wife and family thought he was fine, he was worried. He found he could think only
four
moves ahead. Convinced there was something terribly wrong, he went to the clinic of Nick Fox, a neurologist at University College London’s Institute of Neurology. No problems were found. The professor cruised through a battery of tests intended to detect early signs of dementia. A brain scan was normal. The professor, then seventy-three, continued to play chess, read history books, cook elaborate meals, do the family’s finances, and even learned how to use a computer. He also continued to have brain scans, which detected few significant changes.

Then a few years later, the professor died of causes unrelated to his brain. And much to the surprise of Fox and the professor’s family, an autopsy showed that the Chess Player’s brain, too, was riddled with the plaques and tangles of Alzheimer’s. The professor had what appeared to be an advanced case of dementia. Yet for years the only outward sign of it was that he could think four chess moves ahead instead of seven.

How could that be? How could a brain so ravaged by disease still be functioning at such a high level? Had something shielded the brain of the chess-playing professor? Was he, like Sister Bernadette, an escapee?

For many years, scientists have puzzled over why some people seem to withstand brain injury better than others or why two people can have strokes of the same severity and yet one suffers severe impairment and the other recovers.

The differences have been particularly perplexing to neuroscientists because most believed that healthy brains, aside from a few IQ points here and there, were pretty much the same. After about age three, according to long-held scientific thinking, a window of opportunity began to close. Sure, we could polish our French, but the basic structure of the brain was thought to be largely set. And in many ways, that view made sense. Unlike other cells in the body, brain cells don’t divide, so the same neurons stick with us for as long we stick around. With age, some brain cells die off, but it was thought that they were not replaced, leaving our brains to accumulate all the junk and insults thrown their way. Indeed, major changes were considered not only impossible but, if they did take place, mostly bad.

But that view has changed now, too. Even the most conservative of neuroscientists agree that brains can be tinkered with, perhaps even vastly improved, on their most basic synaptic level throughout our lives.

And the very fabric of our daily lives—how we spend our work-days and even our vacations—may influence how we respond to disease, brain injury, or even the more nuanced shifts that come with age.

This is the fundamental idea behind what’s now called “cognitive reserve,” that some brains have—or can develop—a reservoir of strength that, when the going gets rough, offers protection, perhaps much like the brains of Sister Bernadette or the Chess Player. It’s not that those with cognitive reserve are smarter in the conventional sense. Rather, they seem to have an emergency stash of brainpower—perhaps stronger, more resilient, or more efficient brain connections or repair systems that can be called up when necessary. Certain brains may develop a sort of mental padding that allows them to tolerate more damage.

“When we did the autopsy [on the Chess Player] it was amazing that with such a relatively mild level of apparent dysfunction, he had such widespread changes [in his brain],” said Fox when I spoke with him about his own study of the Chess Player.

But if it exists, what exactly is this reserve? Can you see it? Touch it? Can you, if you want to, get more of it?

The story of cognitive reserve is still being written. It is also one of the most encouraging stories ever to be told about the brain—certainly the best news yet for the middle-aged brain. And it’s a story that began not that long ago.

In the early 1980s, Robert Katzman was living in Rye, New York, working as the chairman of neurology at Albert Einstein College of Medicine in New York. In his job, he saw hundreds of patients suffering from dementia, but there was little he could do. At that time—as now—very little was known about Alzheimer’s disease.

So Katzman decided to dig deeper. Scientists knew that those who died with Alzheimer’s usually had plaques and tangles of fibers in their brains, but the relationship was murky. Did more tangles equal more disease? Hoping to clarify at least this aspect, Katzman began a study of a group of elderly people living in a Manhattan nursing home. His initial aim was simply to replicate an earlier finding suggesting that the level of plaques and tangles determined the severity of the dementia.

And, in fact, Dr. Katzman found exactly that. In his 1988 study of 137 nursing home residents whose brains he dissected after their deaths, he saw a clear relationship between the number of tangles and mental decline.