Boost Your Brain (42 page)
Authors: Majid Fotuhi
Y
OU’VE READ
this far—and sprouted some new synapses as you soaked up chapter after chapter of the latest science—so you know the powerful impact of brain boosters and shrinkers that shape your brain throughout life. You know that multiple vascular risk factors can lead to strokes so small they cannot be measured on MRI or so large they cause instant, catastrophic damage. You know that multiple concussions can create silent “tears” that produce subtle changes in your brain function; that years of downing stiff drinks can quietly kill neurons and erode the brain’s highways; that sleep apnea can rob the brain of oxygen, taking a toll on grey and white matter alike. You know that all of these factors—plus a few more—can reduce your memory, clarity, and creativity long before you reach old age. And you know that any of them can combine with the presence of plaques and tangles in the brain to tip you toward dementia late in life.
In the future, we will no doubt have at our disposal ever more amazing tools to help us harness brain growers and avoid brain shrinkers. We will be better equipped than ever to measure and track brain size and health, modifying our behaviors as needed. We’ll do it all with the end goal of enhancing our brain performance now and preserving it in the future, knowing that cognitive decline in late life is anything but inevitable.
Such a mind-set seems obvious now, but that hasn’t always been the case. In fact, the way we view brain size and health, especially in late life, has changed dramatically over the years. So, before I tell you about the exciting developments on the horizon, let’s take a journey through the centuries to see just how we arrived at our current outlook on brain aging.
A Walk Through History
Long before we developed the tools to peek inside the human brain, it was recognized that old age brings with it a decline in cognition. We didn’t need imaging technologies or complex cognitive tests to figure this out. Greek philosopher and mathematician Pythagoras noted in the seventh century
BC
that the aged return to “the imbecility” of infancy. Later, Hippocrates called mental decline an inevitable consequence of aging—a fate he blamed on an “imbalance of fluids.” Aristotle, too, weighed in, noting that the elderly were gradually blunted by mental deterioration and suggesting that the heart was the center of sensation and movement (and that the brain’s job was to cool the heart).
1
It wasn’t until midway through the second century
AD
that the physician and philosopher Galen suggested the brain was the home of cognition and the center of mental disorders, including dementia. Science largely took a backseat to religion during the Middle Ages, a time when dementia and other disorders were seen as punishment for sins—payback for a lack of piety.
As the seventeenth century dawned, however, scientific heads prevailed. With religious taboos ebbing, dissection became an acceptable way to explore the mysteries of the human body. Thomas Willis, who had developed an atlas of the blood vessels in the brain, coined the term “neurology” and drafted a classification of dementia, which included in its very modern list of causes aging, head injury, and alcohol and drug abuse.
By the 1800s, scientists had documented atrophy in the brains of deceased demented people and had begun to delve deeper into its potential causes. Many felt syphilis was to blame. Others were not so sure. Researchers at the time were aided by microscopes, which had been in wide use for scientific discovery since the 1600s. But it wasn’t until 1893 that August Köhler unveiled a new technique to illuminate samples, ushering in a new era of modern light microscopy. A rush of discovery would soon follow, including the first description of gummy black clumps (plaques) in the brain of an elderly epilepsy patient in 1898 and the first identified case of dementia caused by white matter disease.
When a well-respected young German psychiatrist and neuropathologist named Aloysius “Alois” Alzheimer took on a curious case in the early 1900s, the stage for discovery was set. The patient, known to us only as “Auguste D.,” was a German woman in her early fifties who had rather suddenly begun acting strangely. She was confused and disoriented and had difficulty speaking and remembering her past. Confined to a mental institution, Auguste intrigued Dr. Alzheimer, who had an intense interest in both forensic pathology and dementia. In an elderly patient, such symptoms might be ascribed to “senile dementia”—the term of the day for late-life dementia—but in someone so young? What could it be?
Dr. Alzheimer meticulously documented Auguste’s rapid decline over the next five years. When she died, in 1906, he autopsied her brain.
At his disposal he had a newly enhanced mode of microscope and a just-created silver staining technique—two wonders that when combined offered, for the first time, a look inside the cellular structure of the brain. Peering at slices of Auguste’s brain, Dr. Alzheimer noted the presence of plaques. But he also saw something new: tangled threadlike structures within the neurons in Auguste’s brain. Some cells had just a few tangles, while others seemed to contain bundles of them. Still other neurons had disintegrated completely, replaced by masses of tangles strewn about Auguste’s brain. All told, as many as a third of the neurons in Auguste’s brain had been obliterated.
By this point, Dr. Alzheimer and the rest of the scientific community had a good feel for how the brains of the very old looked. But Auguste was different. She was, after all, not yet sixty.
Dr. Alzheimer published a brief report, calling the case “a peculiar disease of the cerebral cortex.” Over the next few years he sought out other patients who’d died after having exhibited similar symptoms. Examining their brains he found the same evidence of plaques and tangles.
It wasn’t just their ages that struck Dr. Alzheimer. The brains of these young demented patients looked distinctly different from the brains of their older counterparts. In the young, plaques and tangles mottled the brain; in the elderly, they were present but were accompanied by other signs of trouble, chiefly atherosclerosis, or hardening of the arteries, which shrunk the brain in a process then known as “senile involution.” Other scientists had already demonstrated that the brains of the demented shrink. But Dr. Alzheimer had been one of the first to describe stroke, or “the gradual strangulation of the blood supply to the brain,” as the cause of such atrophy. As he described the factors at work in the demented elderly, Dr. Alzheimer was careful to note his belief that plaques weren’t the cause of senile dementia “but only an accompanying feature of senile involution of the central nervous system,” as he wrote in 1911.
2
To Dr. Alzheimer the evidence made it clear: dementia in young patients was quite different from dementia in the elderly.
The discovery didn’t create much of a stir at the time. Alzheimer was, after all, just a fortysomething researcher with a handful of unusual cases. The disease might never have gotten his name if it weren’t for the chairman of his department, Emil Kraepelin, a renowned psychiatrist and author. Kraepelin had played a part in describing and defining the diseases we know now as schizophrenia and bipolar disorder and by 1911 was in the midst of writing the eighth edition of the diagnostic manual of the day,
Textbook of Psychiatry.
Hoping to one-up his peers at a competing university in Prague, Kraepelin decided to include Dr. Alzheimer’s cases, giving the condition its now-famous name.
What Dr. Alzheimer would have done in the years to come is anybody’s guess. He died unexpectedly in 1915 at the age of fifty-one. And while he’d gained prominence and respect for his life’s work, none of those who eulogized him thought fit to describe him at the time as the person who discovered Alzheimer’s disease.
A Pendulum Swings . . .
It would be many decades before anyone really took note of Alzheimer’s disease. The supposition by Dr. Alzheimer and others that vascular disease caused senile dementia held well into the century that followed, as did use of the term “hardening of the arteries” to describe dementia in the elderly.
In fact, vascular disease was so central to the view of late-life dementia that papaverine, a vasodilator that opens up blood vessels and was widely prescribed for dementia patients, became one of the most oft-prescribed medications in the United States.
By the middle of the century, multi-infarct dementia—dementia whose primary cause was multiple strokes—had been identified and the importance of inflammation in the development of brain pathology had been suggested. To be sure, the presence of plaques and tangles in the brains of senile dementia patients, and even in those who’d died without any symptoms of dementia, sparked some debate. But for the most part, all eyes were on vascular disease.
As health care improved, vascular problems that would have once killed people outright in their sixties and seventies were suddenly better understood and controlled (although not, it should be noted, completely), ushering more people into their eighties and nineties—and dementia. By the 1950s and 1960s, diagnosed cases of senile dementia were on the rise.
At the same time, technological advances allowed us a closer look into the workings of the brain. With the public clamoring for an answer to the vexing problem of dementia in the elderly, science took a renewed interest in the findings of Alois Alzheimer.
Homing in on the brains of those with late-life dementia, scientists documented marked shrinkage in the hippocampus and broad stretches of cerebral cortex. They found, too, that in the brains of those with late-life dementia the neurotransmitter important for memory (acetylcholine) was in short supply and that plaques in the brain were made of a protein called beta amyloid. Searching for genetic clues, they discovered the specific gene mutations in the amyloid protein that caused the formation of toxic amyloid plaques in early-onset Alzheimer’s disease. Soon after, scientists discovered the protein at the core of tangles, called
tau
.
What followed was a sea change in the perception of dementia. These were, after all, the same amyloid plaques and tau tangles found in patients with early-onset Alzheimer’s disease. Since demented patients late in life also had plaques and tangles, they should all fall under the broad umbrella of Alzheimer’s, unless there was some obvious other cause. Or so the thinking went.
The unwavering focus on Alzheimer’s pathology—those plaques and tangles in the brain—from the 1980s on seemed to swing the pendulum of scientific thought away from a focus on vascular disease and its role in late-life dementia.
At the time, from 1988 to 1992, I was a graduate student at Johns Hopkins University working with Dr. Solomon Snyder, one of the most prominent neuroscientists of our time. Next door was one of the pioneers in Alzheimer’s research, Dr. Donald Price, who was then director of the Johns Hopkins Alzheimer’s Disease Research Center.
I vividly recall the excitement in the hallways as Dr. Price’s army of graduate students and lab technicians zeroed in on the genetics and physiology of amyloid plaques. In the early 2000s, the thrill of the race to cure Alzheimer’s disease ratcheted up yet again as interest focused on the “amyloid cascade hypothesis,” which suggested that amyloid was the chief cause of Alzheimer’s disease. The idea had been proposed a decade earlier, but suddenly it was hot.
3
Under this theory, the damage seen in Alzheimer’s disease—shriveled synapses, dead neurons, shrinkage in the hippocampus, loss of overall brain volume, and disappearance of key neurotransmitters like acetylcholine—all had amyloid plaques at their root. Even neurofibrillary tangles were believed to be downstream damage caused by amyloid plaques, secondary to the inflammation that occurred as the body attempted to defend itself from excess amyloid.
Not everyone was sold on the idea. Still, the hypothesis generated immense enthusiasm in the medical community. If Alzheimer’s disease was caused by amyloid plaques then curing it might simply be a matter of developing a drug to prevent amyloid plaques from forming or to clear the brain of amyloid plaques once they formed. Right? A decade later—and after several failed trials—we know it’s not nearly so simple. Amyloid plaques, as Dr. Alzheimer said in 1911, are only part of the picture.
. . . And Swings Back
As you read this book, the pendulum is swinging once again toward a consensus that vascular disease is one of the chief culprits in late-life dementia. One reason for the shift is that we now have overwhelming evidence of the link between vascular disease and shrinkage in the brain with aging. The second reason is that we’ve accumulated evidence that the older we get, the weaker the link is between Alzheimer’s pathology and symptoms of dementia. In fact, by the time we’re in our eighties and nineties, the presence of plaques and tangles isn’t strongly tied to the development of dementia.
4
In one study published in the
New England Journal of Medicine,
for example, researchers in the United Kingdom examined 456 donated brains from people aged sixty-nine to a hundred and three and found that the older the people were when they died, the weaker the relationship between amyloid plaques and dementia was.
5
It’s the opposite of what you’d expect to see if amyloid plaques alone were at the heart of Alzheimer’s disease: as they aged, demented study subjects had
lower
levels of amyloid plaques in their brains than those who weren’t demented.
The third reason for the shift away from an emphasis on plaques and tangles as the sole cause of dementia in the elderly is the discovery that older people may accumulate a significant load of Parkinson’s-type pathology (called Lewy body lesions) in their brains in addition to plaques, tangles, and vascular damage. Dr. Lon White, the principal researcher of the long-running Honolulu-Asia Aging Study, has intensely explored the link between clinical dementia and pathological findings in brain autopsies. In an interview with
Neurology Today,
White noted that the majority of the elderly patients he studied have a combination of vascular lesions, Lewy body lesions, and Alzheimer’s lesions.
6
In fact, only 22 percent of brain autopsies showed plaques and tangles as the sole cause of dementia. It’s an important reminder, Dr. White said, that “there is an enormous overlap” in the causes of late-life dementia. David Knopman, a Mayo Clinic professor of neurology, took it one step further, telling
Neurology Today
that “our idea of thinking about Alzheimer’s disease as a single clinicopathological entity simply doesn’t work.” Alzheimer’s disease, in other words, is not just a simple accumulation of plaques and tangles. There are other culprits at work.