Outsmarting Alzheimer's

PART ONE

Why Everyone Needs to Outsmart Alzheimer’s

Every person on this planet is at risk for developing Alzheimer’s disease. This is true regardless of our age, family history, or current state of health.

That’s the bad news. The good news is that nearly all of us are equally capable of dramatically reducing our risk and living well into our old age with vibrant health and sharp minds. In this part of the book, you’ll learn what Alzheimer’s is, how it affects our brains, and why right now is the best time to do something about it. It’s never too early, and it’s never too late to elevate your well-being and decrease your chances of devolving into dementia. You’ll also take a quiz designed to give you an idea of your personal Alzheimer’s risk score and how you might improve it.

CHAPTER 1

Your Brain on Alzheimer’s

When physician Alois Alzheimer came to examine her, Auguste Deter was sitting on the hospital bed, a helpless expression on her face. Alzheimer asked, What’s your name?

Auguste, answered the 51-year-old patient at Frankfurt Hospital.

Last name?

Auguste, she repeated.

What’s your husband’s name?

Auguste, she said, sounding confused. I think.

Your husband?

Ah, my husband.

Are you married?

To Auguste.

Later, while she was eating cauliflower and pork for lunch, Alzheimer asked, What are you eating?

Spinach, Deter answered.

What are you doing? he asked.

Potatoes.

Throughout the examination, Alzheimer took meticulous notes, jotting down the conversation word for word and commenting on Deter’s impaired comprehension and memory, disorientation, paranoia, anxiety, and auditory hallucinations. Deter, he wrote, didn’t know what year it was, could not perform basic math, and was unable to write her name. Alzheimer found himself repeating every word so Deter could comprehend his basic questions and instructions.

At the time, in 1901, doctors had no term to describe Deter’s condition. Her symptoms were much like the senility known to affect the oldest of the old. At the time, it was thought that the brain wore out over time much as joints did, leaving the elderly forgetful and confused. If that were true, though, how was it possible for a middle-aged woman to be suffering from old age? Alzheimer was fascinated. Even after leaving his post at Frankfurt Hospital, the German doctor continued to keep tabs on Deter.

In 1906 Deter died at age 55, and Alzheimer subsequently autopsied her brain. Just by holding it in his hands he could tell that it had shrunken. Her brain was roughly half the size of a normal one. Then, when he examined slices of her brain tissue under a microscope, he found the cause. Inside the neurons Alzheimer observed thick fibers that wrapped around the cell’s interior, crushing its normal contents. These structures are called neurofibrillary tangles. He also observed clumps of a smooth plaquelike material that filled the space around the cells and distorted their shape. These structures are called senile plaques.37

When he published his findings, he referred to Deter’s condition as an unusual disease of the cerebral cortex that caused memory loss and disorientation and eventually depression and hallucinations. Within the next five years, other physicians began diagnosing patients with the same disease and publishing their findings. A few years later, the disease was named after the physician who first described it, and we now know it as Alzheimer’s disease.38

The Most Common Cause of Dementia

The story of Auguste Deter is unsettling. In her case history, Alzheimer describes a condition that no one wants. Indeed, according to surveys, many of us fear an Alzheimer’s diagnosis more than we fear any other disease, including cancer, stroke, or heart disease.39

It’s the kind of disease that we wish had remained rare and obscure. We would like to read about Alzheimer’s disease and be able to say, That won’t happen to me. Yet statistics tell us otherwise. Though the early-onset form of the disease that Deter had is relatively rare, the late-onset form is not. If we’re not diagnosed with Alzheimer’s ourselves, we’ll know someone who is.

While reading about this disease may make us uncomfortable, knowledge is power. The more you understand about Alzheimer’s, the better your chances of doing everything possible to prevent it or slow its progression.

What is Alzheimer’s disease? It’s a disease that affects the brain, leading to a decline in cognition: the mental process of acquiring, understanding, and using the information we gather through our senses. Its diagnostic feature is the presence of senile plaques and neurofibrillary tangles (discussed in detail here). Though new diagnostic tests called beta-amyloid imaging allow us to peer into the brain and see these plaques, the imaging is expensive, not widely available, and is generally only offered to patients who already have persistent symptoms. For the majority of people, the disease is diagnosed based on its symptoms. It’s not until after death and during an autopsy that these hallmark features are observed. One of the many brain regions that the disease attacks is called the hippocampus, where newly learned information is first processed. As a result, the memory problems suffered by Alzheimer patients often begin with impaired learning of new information.

When these symptoms become severe enough to interfere with everyday life—for example, making it difficult to drive without getting lost—we say you have dementia. Dementia is an umbrella term that describes many different types of cognitive symptoms that can interfere with everyday tasks. Of the many different diseases that lead to dementia, Alzheimer’s is the most common, accounting for somewhere between 60 and 80 percent of all dementia cases.40

Other types of dementia include:

Vascular dementia: In this type of dementia, hardened, blocked, and leaking blood vessels stop blood from flowing to affected parts of the brain, causing brain cells to die. When physicians use MRI or CT scanners to peer inside the brains of patients with vascular dementia, they often discover that these patients have had multiple small strokes. Often these strokes were silent, meaning the individual is unaware that a small volume of brain tissue has died. Symptoms of this form of dementia vary, depending on which parts of the brain are affected, and they often overlap with symptoms of Alzheimer’s disease: confusion, trouble paying attention, difficulty with planning and decision making, restlessness, agitation, depression, and memory loss.

Dementia with Lewy bodies: Named after Frederick H. Lewy, MD, Lewy bodies are microscopic, abnormal clumps of protein that form throughout the cerebral cortex of the brain, causing nerve cells to degenerate. This form of dementia can be difficult to distinguish from Alzheimer’s disease in living individuals. It tends to lead to problems with walking and balance, hallucinations, dizziness, and other nervous system issues, and sleep disturbances.

Parkinson’s disease: Lewy bodies can also cause Parkinson’s disease. In this case, they form deep in the brain, in an area called the substantia nigra, causing tremors and problems with movement.

Frontotemporal dementia: Affecting the front and side of the brain, this type of dementia leads to changes in personality and behavior. As the disease erodes the areas of the brain responsible for inhibiting behavior, patients with frontotemporal dementia can become impulsive, and some even show a disinhibited creativity, by taking up painting for example. Inappropriate and compulsive behaviors are common, as is a flagrant lack of empathy for others.

Normal pressure hydrocephalus: Derived from the Greek words hydro (water) and cephalus (head), this condition was once referred to as water on the brain. Caused by the buildup of spinal fluid in the brain, it’s called normal pressure because spinal fluid pressure remains normal when measured during a spinal tap. This rare form of dementia can bring on intense headaches and dizziness, changes in personality and behavior, trouble walking, and thinking and reasoning problems.

An early symptom in these patients that may occur even before memory loss is urinary incontinence. Patients with normal pressure hydrocephalus are unaware of the urge to urinate. This form of dementia can sometimes be corrected with the surgical installation of a shunt that drains the excess fluid from the brain to the abdomen.

What Causes Alzheimer’s Disease?

Exactly what causes Alzheimer’s disease is a mystery that we’ve yet to solve, but it’s thought to involve at least two distinct processes:

Plaques: A dangerous protein fragment called beta-amyloid lurks in all our brains. For most of us, the brain clears away these fragments in the same way we wipe the dust off our furniture, and this regular brain dusting operates best while we sleep. But in some of us, these fragments build up over time. While diffusing through the fluid-filled spaces between cells, the fragments start to clump together into plaques, one of the villains of our story. As the beta-amyloid molecules accumulate, they damage and destroy brain cells and impair the communication between them. A type of immune cell called microglia then interpret the formation of plaques as an injury. As these immune cells rush in to repair the plaques (a process known as inflammation), they can further damage your brain cells.

Tangles: While the plaques penetrate the spaces between brain cells, another insidious process begins to cause damage inside the brain cells themselves. An otherwise normal protein called tau turns against the brain, and in partnership with other tau proteins, twists itself into a long, tangled thread that gradually strangles the neuron. The misfolded tau proteins cannot perform their usual functions. The normal function of tau is to keep cellular traffic flowing throughout the cell—all the proteins and other building blocks of the cell are busy all the time getting to work so the cell can function. However, just as a fender bender causes a major traffic jam on a highway, tau tangles can interfere with the transport of nutrients in and out of cells, causing brain cells to degenerate and die. If this damage affected only one brain cell, the effect would be inconsequential. But, the true malevolence of tau is its ability to damage tau in neighboring cells, spreading this tendency to misfold and consequently inducing these long threads widely throughout the cells of the brain.

We’re not sure which of these processes—the accumulation of beta-amyloid plaque or of tau tangles—is primarily responsible for the disease. Does one of these processes play the starring role as the villain in the Alzheimer’s saga, whereas the other serves merely as a sidekick? Are both equally involved? Does one cause the other? Or perhaps we’ve got the progression backward, and something else causes both of them.

We just don’t know for sure. As a result, for many years, heated debates erupted at neurology meetings, with some scientists (known as the BAPtists) arguing that beta-amyloid plaques were the more important of the two processes, and others (known as the TAUists) saying that it was the tau proteins that were primarily responsible for causing the disease. Each group believed strongly that they were right.

Today, we don’t see the issue as quite so black and white. My view is that science is about evidence. It’s not about belief. Though we might hypothesize that one protein or the other is primarily responsible, the proof will come from the remedies that cure the disease. With enough study, we will learn the truth.

No matter the actual cause, though, the end result is the loss of brain cells. Among the regions most intensely affected are the hippocampi (the seahorse-shaped brain structures involved in memory formation and storage), the amygdala (an almond-shaped brain structure that plays an important role in emotions), and raphe nuclei (a part of the brain stem that is involved in sleep). As more and more brain signals are lost in the hippocampi, it’s increasingly difficult to form new memories. Over time, it also becomes harder to pull older memories out of storage. The loss of neurons in the amygdala accounts for many of the emotional issues and personality changes observed in Alzheimer’s. As more and more of the raphe nuclei is affected, sleep disturbances result.

The Symptoms of Alzheimer’s Disease

Initially, Alzheimer’s disease silently snakes its damage through the brain. Plaques and tangles may spread through the hippocampi as much as 10 to 20 years before symptoms set in. It’s often not until the brain starts to shrink that memory loss and other symptoms become noticeable.

In the initial stages of the disease, many people are tempted to blame their symptoms on getting older. They experience the kind of forgetting that middle-aged and older people like to joke about: Where are my reading glasses? What is that woman’s name? Did I feed the dog yet? Why can’t I ever remember how to switch the TV over to Hulu or Netflix? What’s my password again?

Eventually those symptoms go beyond anything we might think of as normal aging. People with mild Alzheimer’s disease might repeat themselves, telling the same story more than once. Or they might continually forget appointments, become confused when attempting to follow directions, become lost or disoriented when driving or when in unfamiliar places, or struggle to balance their checkbook or budget their finances. They may abandon a task when it’s only partially finished.

At a different stage in the disease, people with Alzheimer’s might not recognize people they once knew. They can see their daughter-in-law or grandchildren and only have a vague sense, I should know who this person is. The same may happen with common objects. They don’t just lose their car keys; they don’t know what car keys look like or what they are supposed to use them for. They may pick up a Frisbee and say, Is this someone’s shoe? Or, you might ask them to turn off the light, and they may stare blankly. They don’t understand your instructions because they don’t know what a light is.

As the disease erodes the hippocampi and spreads to other parts of the brain, people with Alzheimer’s lose themselves bit by bit. When you lose your memories, you lose your ability to think about the future because thinking about the future is based upon your memories and experiences of the past. How can you know what you want to eat for dinner if you can no longer remember what foods you like and which ones you don’t? Depending on which areas of the brain are affected, Alzheimer’s disease may also bring on listlessness, depression, poor judgment, disorientation, confusion, behavior changes, and/or difficulty speaking, swallowing, and walking.

Memory enriches our thoughts. It provides the details that personalize our experience. It adds dimensions to how we ponder the future. Ask an Alzheimer patient about his or her plans for vacation, and the answer will contain little detail. Ask a child the same question, and you will be flooded with images of daring amusement park rides and sand castles and the top flavors of ice cream. From the perspective of the Alzheimer patient, this paucity of memory feels like emptiness. The saddest thing an Alzheimer patient ever said to me was in response to my inquiry about what concerned her most. This former high school language teacher said, I have nothing to think about.

The Stages of Alzheimer’s Disease

Alzheimer’s disease progresses through several stages. Technically, when you are in Stage 1 or Stage 2, we don’t say you have Alzheimer’s disease. It’s not until you’ve reached Stage 3, and you have symptoms of cognitive problems (such as forgetting) coupled with evidence of plaque formation in the brain that you would get an Alzheimer’s disease diagnosis.

Stage 1: A Symptom-Free Condition

The Alzheimer disease process begins long before any symptoms are apparent with amyloid deposits in the brain. At this stage, without any cognitive symptoms we cannot say that someone has Alzheimer’s disease, although the risk of progressing to Alzheimer’s disease is very high. Although at the very earliest stage most people do not experience symptoms, some people note a subjective sense of declining memory that is difficult to pinpoint. This stage of the disease can span many years, even a decade. All the while, plaques and tangles are forming, and the brain may be shrinking, but there are no noticeable problems with memory.

Brain imaging can pick up these early amyloid plaques, which can appear as long as ten years before patients experience any cognitive decline. The imaging procedure is generally only offered to people who are enrolled in an Alzheimer’s study because these tests are expensive, involve radiation, and are not practical to administer to large numbers of people. Also, they do not show neurofibrillary tangles.

Stage 2: Mild Cognitive Impairment (MCI)

The changes people might notice at this stage are not severe enough to interfere with their independence. Though they might have trouble remembering what someone just said, have trouble judging how long various tasks might take or the sequence of steps needed to complete a complex project, they can still eat, bathe, and take care of other personal needs without assistance.

At this stage, it can be difficult to tell whether the memory lapses (such as increased difficulty retrieving names) experienced really stem from the proliferation of plaques and tangles. Because the symptoms of Alzheimer’s disease overlap with the symptoms of a few other diseases, some people who have been diagnosed with MCI will not get Alzheimer’s disease. They may be under stress, they may have an exaggerated sense of the very small amount of memory decline nearly all people incur with aging, they may have symptoms of menopause (discussed later) or have another disease that leads to symptoms of dementia (such as Parkinson’s), or their symptoms may stem from a treatable condition such as thyroid disease. Sometimes, if the underlying disease is treated, the symptoms of memory loss resolve.

Only about half of people with MCI go on to develop dementia due to Alzheimer’s. Some progress to Stage 3 quickly, while others live with MCI for 10 years or longer. We don’t currently have the ability to determine how quickly any one person’s Alzheimer’s will progress. For some people, it progresses rapidly. For others, it’s the opposite. If you are already at this stage, it’s possible that you may be able to remain in Stage 2 for a long time.41 Brain Smarts are important, both for putting off Stage 3 and also for improving your overall health, energy level, and mood. Embracing a healthy lifestyle and especially getting medical problems (such as high blood pressure) under control may slow the progression of the disease.

Stage 3: Dementia Due to Alzheimer’s

This is when enough plaques and tangles have formed to cause the brain to start to shrink. Symptoms become clearly noticeable, with the patient having repeated trouble finding the right word, forgetting new names and faces, not being able to absorb new information, losing or misplacing objects, and feeling muddled when attempting to plan and organize. As memory continues to worsen, people with Alzheimer’s disease may still recognize those close to them but not always remember their names. Sleep patterns become seriously disrupted. They have trouble controlling their bladder or bowels, and they tend to wander or become lost. In the most severe form, people with Alzheimer’s lose the ability to talk and control their movements.

Meet Your Brain

Weighing roughly three pounds, your brain consists of folded masses of white and gray matter that are composed of billions of cells called neurons, and others called glia. Unlike the round shape of most other cells in your body, each of your nerve cells is equipped with several long, spidery legs called axons and dendrites. And these legs extend toward other nerve cells, creating a complex web.

These weblike connections allow each of your nerve cells to connect with thousands of others. All told, throughout your brain, there are hundreds of trillions of connections—as many as there are leaves in the Amazon rainforest. These connections between and among brain cells are often referred to as the brain’s wiring.

So as the information from this book enters your brain, it is passed from one nerve cell to another in the form of electrical signals (or impulses). These signals travel along many spidery legs of a variety of neurons until they reach the end—the toes of this leg called a synapse. Within these toes are small packets filled with chemicals called neurotransmitters. When the electrical signal reaches these tiny packets the chemical contents get released into a gap between the end of one neuron and the beginning of the next. The neurotransmitters diffuse across the gap and stimulate a receptor on the opposite side of the synapse to renew the electrical signal. These receptors are proteins tailor-made for the neurotransmitter to fit within them and re-initiate the signal in the next neuron in the chain of neurons that make up a neuronal circuit.

Now, let’s say you just read the above paragraph, and your eyes glazed over. Perhaps you’ve rarely seen words like synapse and neurotransmitter. In that case, your eyes glazed over for a good neurological reason—you don’t yet have the cell-to-cell connections needed for the previous paragraph to sound familiar. But the more often you encounter a piece of information, the stronger the connections and the faster that information can get to its destination.

This is not unlike our transportation system. The first human traveler to go from point A to point B has to forge a rough dirt path. It’s hard work that can require some bushwhacking, and the result often isn’t terribly easy for other humans to follow. As more and more people walk the same path, however, the path becomes smoother and wider. As the path becomes more traveled, someone might lay down macadam or asphalt or replace a downed tree with a bridge, making it still easier to travel.

The same process takes place in your brain. The stronger the connections between neurons, the easier it is to absorb, retain, and recall new information. So even if words like axon and neurotransmitter might feel foreign to you right now, with repeated exposure, they can eventually roll in and out of your memory and on and off your tongue as easily as other words like dog and belt buckle.

How the Brain Works

Many of the first clues about what happens inside the brain we owe to a few unlucky humans whose brains suffered undue trauma. One of them was Phineas Gage, the foreman for a railroad construction gang in the mid-1800s. He was using a three-and-a-half-foot tamping iron to pack blasting powder into a rock when he accidentally triggered an explosion. The blast launched the tamping iron into his left cheek, through the left frontal cortex of his brain, and out the top of his head. The iron landed several yards behind him.42

Amazingly, Gage survived the accident and was even discharged from the hospital within 10 weeks, but he was forever changed. His physician noted that the once capable and efficient foreman was now impatient, irreverent, fitful, obstinate, and grossly profane. His friends remarked that he was no longer Gage, and the railroad refused to employ him. Gage eventually joined the circus as a sideshow act.

The tale of his life is a sad one, but it’s nonetheless one that has greatly advanced our understanding of the brain. Thanks to Phineas Gage, we now know that the frontal cortex is where much of our personalities is housed, and damage to this area of the brain can cause our personalities to change dramatically.43

We learned about the importance of another area of the brain, called the hippocampus, from a similarly unlucky person named Henry G. Molaison (known only as H.M. until his death in 2008).

In 1953, at age 27, Molaison suffered from frequent and severe epileptic seizures that did not respond to anticonvulsant medications. His disease had disabled him, preventing him from working and forcing him to live with his parents. Out of desperation, he agreed to undergo an experimental treatment, during which portions of his medial temporal lobes—including most of his hippocampi—were removed.

Shortly after the surgery, Molaison’s physician noticed that something was wrong. Though Molaison’s seizures had abated, the young patient failed to recognize the staff who attended to him day after day. Molaison could carry on a conversation, but then, just minutes later, could not remember the conversation had occurred or even the person he’d spoken to.

For the rest of his life, Molaison kindly allowed neuroscientists such as Brenda Milner and later Suzanne Corkin to interview him over and over again. Though she met with him repeatedly over a 30-year span of time, every time I walked into the room, it was like we’d never met, Milner told The New York Times.44

In one of those interviews, about four years after Molaison’s surgery, Corkin asked, I understand that you have a little bit of trouble remembering things?

Molaison replied, Yes, I do.

How long have you had trouble remembering things?

That I don’t know myself. I can’t tell you, because I don’t remember.

Well do you think it’s days, or weeks? Months, or years?

Well, see, I can’t put it exactly on a day, week, or month, or year basis.45

His memory had been frozen in time. He did not remember what he’d eaten for breakfast or lunch on any given day. Nor did he remember anything that had taken place after his surgery. On the other hand, he could remember most of what had taken place in his life before the operation.

Molaison eventually would go on to donate his brain to science, allowing us to learn just how important the hippocampi are in making long-term memories out of short-term ones.46

The Brain’s Filing Clerk

There are two hippocampi in the brain, one in each hemisphere. Named after the mythological seahorselike creature they resemble, these structures are among the brain’s star players when it comes to memory. Information must pass through either hippocampus before it can be stored. In this way, the hippocampi serve as filing clerks that separate useless memories from useful ones and put like memories