From Chapter 2
GLITCHES, GAPS AND GAFFES:
The Memory-Hungry Crowd Speaks Candidly About Screwing Up
Occasionally, I encounter someone who, despite the chronological onset of middle age, proudly claims to possess a memory like a steel trap. As the embarrassed owner of the cognitive equivalent of a kitchen sieve, I listen with interest. “Eureka, I’ve found one,” I say to myself, and the hairs on my arms stand on end. I want to believe that such people exist.

Within a few minutes, I am almost always disappointed. One woman, a senior executive managing a workforce of four hundred, all of whom she claimed to know by name, had bent my ear at lunch, assuring me that her memory was unscathed. In fact, she confided, it was better than ever. I mentioned that I’d just had a conversation with Brian, a close friend of her husband’s. “Brian?” she asked, surprised. “How do you know him?” To remind her that I’d sat next to him at a dinner party at her house seemed too cruel. In another disappointment, the father of one of my son’s friends, a crackerjack trader on the stock exchange, promised me that his memory was still tops. It had to be, he explained. All day long, he kept track of puts and calls in his head. Could I imagine the disaster that would ensue if he forgot? I’d barely made note of that when he phoned back. He’d just realized that he couldn’t drive the kids over to our house, as we’d planned. That morning, he’d taken his car to the shop.

From Chapter 5
INTO THE DOUGHNUT HOLE:
What a Brain Scan Can (and Can Not) Tell You About What’s Going On Upstairs

Ten days later, I learned that my tests were fine, at least so far. I could move forward, into Stage Two. Andrea Kaplan, Small’s research associate, scheduled me for a PET scan, an fMRI and a stretch of neuropsych testing. Normally, these evaluations were conducted over two or three sequential visits. I’d complete them in six hours so I could catch the evening plane back to Oakland. Kaplan warned me not to be late: Five research studies shared the PET scanner, and securing time on it required negotiation skills worthy of the United Nations.

As soon as I walked through the door, a graduate student escorted me to the PET scanner in the basement. Repeatedly, the attendant behind the counter in the waiting area answered the phone “pet department,” making me think of dog bones and squeaky toys. Briefly, that diverted me from dwelling on what was to come.

I wasn’t worried about the scan itself—not the ninety minutes of immobilization, or the needles in my arms, or the radioactive isotopes that were about to enter my body. What disquieted me was the realization that I’d set something in motion that I was now powerless to stop. If regions of my scan, instead of coming up in healthy vivid colors displayed more muted tones that signified abnormal glucose metabolism, my future prospects would be irrevocably changed.

I was startled out of my own thoughts when the imaging technician announced that he had patients stacked up in the hallways as if it was Christmas Eve at LAX. It was time to get started. He eased me into the scanner bed, encouraging me to slide my head up toward the doughnut hole. He slipped a foam bolster beneath my knees, but the bed itself was a rock-hard half-pipe, barely wide enough to contain me. He carefully positioned my head. Then, with a flourish, he pulled some hardware-store masking tape off a fat roll and wrapped it around my cranium, securing my head to the cradle. “This is our high-tech method,” he joked. “We tried everything else, but nothing works so well.” He set the laser line, positioning my brain in the crosshairs. When he pushed a button, sending the half-pipe into the doughnut hole, I entered a beige, featureless world. “Perfect,” he said. “Don’t move or the next hour will be wasted.”

The machine made a purring, gurgling noise that was actually soothing. I’d have slept except that I knew what came next—the part with the needles. A nurse prepped one arm to receive FDG, the radioactive isotope that would enter my bloodstream and rapidly cross the blood-brain barrier. The PET scan measured the rate that glucose was taken up by brain cells, which would indicate how effectively the cells were functioning and communicating. The other arm, the one I’d shortly wish I could use to scratch my nose, was catheterized so that I could provide three test tubes of blood, one every fifteen minutes. The samples would be spun in the on-site lab, to make sure that the isotope, which had a short half-life, was leaving my bloodstream on schedule.

When the technician returned to release me from bondage, he ripped the masking tape off my head and hustled me off the table. He apologized, explaining that they needed this scanner right that second. The other one had malfunctioned, after they’d already injected a patient with the radioactive isotope. I grabbed my shoes and greeted my graduate student, who guided me to the cafeteria. She waited patiently while I bought myself a turkey sandwich on whole wheat with extra pickles, and rushed me back up to the eighth floor for my neuropsychological testing.

From Chapter 9
YEARNING FOR ESTROGEN: Rejecting Hormone Therapy Could Leave Your Neurons in the Lurch

Estrogen’s role in the brain is only beginning to get the attention it deserves. Neuroimaging has allowed scientists far more insight into cerebral metabolism. Sufficient levels of the hormone are essential for neurons to properly utilize the neurotransmitter acetylcholine, critical for optimal function of the hippocampus and frontal lobes. Estrogen also increases the rate of neurogenesis and helps neurons build new synaptic and dendritic connections, limiting the damage wrought by an over-abundance of midlife cortisol. The hormone has shown a remarkable ability to fight off the ravages of beta-amyloid, the protein that builds the nerve-cell-destroying plaques that accompany the development of Alzheimer’s disease. Estrogen also helps protect brain cells against the destructive effects of oxidation, while stimulating glucose metabolism and blood flow in the brain. Recent evidence suggests that it may also slow the shrinkage of gray matter, the darker colored tissue in the brain that is composed mostly of the bodies of nerve cells that are critical for information processing.

“It’s overwhelmingly clear in the literature,” said Stanford neuroscientist Robert Sapolsky, “that estrogen is critical in terms of keeping neurons from becoming dysfunctional and dying.” The difference in tests of verbal fluency, (where women are called up to name, for instance, as many zoo animals as they can think up), between post-menopausal women who take estrogen and those who do not, is one-half to one standard deviation. That’s not a huge gap, but for many women, it’s significant enough to be noticeable.

From Chapter 10
THE VULNERABLE BRAIN:
The Repercussions of Concussions You Never Knew You Had

Over the next two days, for more than seven hours, Canick put me through my cognitive paces. Numbers, letters, words, figures—they kept coming, and there was no time to rest. He wanted to wear me out so that I’d be unable to compensate for my deficits. He was succeeding: As each half hour passed, my performance diminished. “Keep going,” he said, when my energy and attention flagged. “Go to the end.” He worked my brain like a trainer probing for weakness.

After lunch, he had a stack of papers in his lap, and some preliminary results. When we first spoke on the phone, he acknowledged, he’d believed that my problems arose from a perimenopausal condition. He’d now changed his mind.

“Then what is it?” I asked. “Panic? Anxiety?”

“Not at all,” he said. “From what I have seen so far, the panic and anxiety show up only when your brain shuts down. You are suddenly, inexplicably, cut off from all you know, which is surely disturbing.”

He went over my scores on the tests he’d given me that morning. He’d shown me a flip book with dozens of black-and-white head shots. Then, after a few minutes, he showed me a similar book with the same pictures plus some additional ones I hadn’t seen before. My job was to tell him which faces were familiar. I had no idea: I’d have done just as well if I were blindfolded. Nothing about their faces seemed familiar. No wonder I was unable to identify celebrities the rest of America knew on sight. My performance on a test where I was asked to connect the dots through an ascending lineup of letters and numbers was no better: I lost the sequence and had to backtrack to recover it. Nor was I able to reverse a short string of numbers and repeat it back to him.

Each test told him something about the function of a specific part of my brain. In my case, the frontal lobes and the right temporal lobe were reluctant to get up and go to work. I processed information far more slowly that he’d expect, which suggested that synaptic connections were impeded.

“For now,” he said, “it’s only a hypothesis, but your symptoms and your test results show the distinct neurobehavioral fingerprint of brain damage, the kind that emerges from a series of mild traumatic brain injuries.”

“I don’t think so,” I said, certain that he was mistaken. “I’ve never even been knocked unconscious.”

From Chapter 11
COSMETIC NEUROLOGY:
The Potential for Pharmaceutical Cognitive Enhancement is Vast and Possibly Irresistible

The morning after I picked up my prescription, I went to my office and shook a two-tone blue capsule into my hand. I observed it warily. I had warned my husband that I’d be playing Jean-Paul Sartre that morning (he took stimulants every day, in order to write), and that he should check in with me in a couple of hours to make sure that I was not jumping out of my skin. I got myself a glass of water and gulped down the pill. The bright young psychopharmacologist had assured me that at such a meager dose—only 10 milligrams, about the same quantity that a pediatrician would prescribe for a ten-year-old child with ADHD—I wouldn’t feel a thing. Within fifteen minutes, I knew for a fact that he was mistaken.

I’ve viewed enough dizzying charts illustrating nerve-cell transmission to have a pretty good idea of the party that was going on in my brain. Because the drug blocks the reuptake of dopamine and norepinephrine and also stimulates the release of dopamine, there are more of these two neurotransmitters than usual kicking around in the gaps between synapses. The receptors on the surfaces of the neurons embrace this bounty, snapping up molecules, opening ion channels, and notifying DNA to issue orders for the manufacture of various proteins, which relay signals to cells farther down the line. The result: an increase in my level of attention and ability to resist distraction, which I appeared to have taken to extremes. Every item in my visual field—the arm of my chair, my tea mug, the big silver power button on my laptop—was suddenly as riveting as if it were the Hope diamond. I felt wildly attentive.

From Chapter 13
I’LL SLEEP WHEN I’M DEAD:
Sacrifice Your Slumber and You’ll Perform As Well as If You’ve Had a Few Stiff Drinks

Conventional wisdom dictates that you need less sleep as you age. It isn’t true: Unless you get eight hours, or very close to it, your brain feels the pinch. Sleep deprivation affects sustained attention, spatial learning, processing speed and accuracy, working memory and reaction time—in short, it hammers every one of your cognitive abilities.

“One complete night of sleep deprivation is as impairing in simulated driving tests as a legally intoxicating level of blood alcohol,” reported Mark Mahowald, a professor of neurology at the University of Minnesota. Nor do you need to stay up all night to act as if you’ve tied one on: Have yourself two or three late nights and early mornings (maybe right before your deadline for a big presentation) and you’ll be as savvy as a guy with three Scotch and sodas under his belt.

The average adult now sleeps 6.9 hours on weeknights and an hour more on weekends, about 20 percent less than he slept in 1900. There are loads more reasons to stay up. There’s the siren song of the Internet, of course, but gyms are also open around the clock, as are 1,300 Wal-Marts, 237 Home Depots, and nearly all FedEx Kinkos facilities. At the Apple store in Manhattan, you can get your computer fixed or buy a new iPod twenty-four hours a day. The lure dangles before us—if we just ignore our circadian rhythms, we’ll get more done and have time for fun. In a study conducted by the National Sleep Foundation, two-thirds of the subjects reported that sleepiness interfered with their concentration, and estimated that the quality of their work, when sleepy, declined by 30 percent.

From Chapter 16
THE LAST PLACE YOU LOOK:
Thyroid Low? Blood Pressure High? A Host of Common Midlife Disorders Pack a Cognitive Wallop

I figured I knew what was wrong with me. Both my mother and my sister had developed thyroid conditions at various times of their lives. I thought I might have one as well. I got the name of a local endocrinologist and made an appointment. This doctor, whose practice was geared toward the treatment of diabetes, didn’t take much time with any of her patients. In fact, she booked one every ten minutes.

I sat waiting in an exam room for a long time, shivering in a blue paper sarong. When the doctor finally appeared, she stepped back and took a long look at me. Then she made a comment I don’t think I’ll ever forget. “Well, I agree that you look more like someone in her mid fifties than a woman of forty-two,” she said. What was she saying? Tears sprang into my eyes. “You’re sort of weepy,” she observed. “Maybe you could use some antidepressants.” She ordered a blood panel, including a full complement of thyroid and reproductive hormone tests. She wrote out a prescription for Prozac, and told me to return in a couple of weeks.

When I did, she said she had good news—my tests were fine. My TSH level, thyroid stimulating hormone, was within normal range, a perfect 3.8. She was sure the Prozac would do me good. What she didn’t know was that I’d thrown it in the trash because I hated the “who gives a damn” way it made me feel. I listened to what she told me, and for the next six years, I never again considered my thyroid. Instead, I overturned every rock, looking for the source of my cognitive troubles.

Hypothyroidism has been called “the great imitator” for the vast number of medical conditions it can mimic. Thyroid imbalances may elicit fatigue, depression, coldness, constipation, poor skin, headaches, PMS, dysmenorrhea, fluid retention, weight gain or weight loss, anxiety or panic attacks, decreased memory and concentration, muscle and joint pain and low sex drive, among other symptoms. In women, who have ten times the risk of hypothyroidism that men do, the condition commonly surfaces at times when there are changes in the levels of reproductive hormones—particularly during pregnancy or menopause. The culprit is a tiny, butterfly-shaped gland at the base of the neck. When you’re hypothyroid, it means that the gland isn’t producing sufficient hormones to do its work—and it has an extensive job description.

In simplest terms, the thyroid is the gas pedal for every organ and cell. The thyroid hormone helps regulate virtually every cell in the body, including those in the brain. One of its most important functions is to control metabolism at the cellular level, affecting the rate at which cells use oxygen and burn energy. When you become hypothyroid, many bodily functions—including brain function—slow down. Your thyroid level affects how you use carbohydrates and protein, and how you store fat. It determines vitamin utilization, mitochondrial function, digestion, muscle and nerve activity, blood flow and oxygen utilization, hormone secretion and reproductive health.

Scientists speculate that the brain uses thyroid-stimulating hormone in the hippocampus to store and encode memory; when there is not enough TSH, or the body fails to metabolize it properly, the cognitive problems begin. One possible explanation for thyroid-related cognitive impairment is that as hypothyroidism slows the metabolism, it decreases blood flow to the hippocampus and the frontal lobes. Thyroid hormones affect the rate of cell growth in the brain, as well as the rate at which synaptic impulses travel.

Hypothyroidism results when thyroid-stimulating hormone (TSH) is either inadequately produced by the thyroid gland, or is underutilized by the blood cells. It affects an estimated thirteen million people in the United States—or maybe, many more. Among endocrinologists, who typically treat thyroid problems, there’s considerable scuffling over what TSH level is normal, and what level suggests thyroid dysfunction in need of treatment. Testing labs consider TSH levels to be normal when they are between 0.4 milliunits and 4.5 milliunits—but 95 percent of Americans have TSH levels lower than 2.5, which suggests that 4.5 is far too high—and my 3.8 might be teetering on the edge. Some doctors, among them, Georgetown University professor Leonard Wartoffsky, find mounting evidence that any TSH over 2.5 is abnormal, and requires treatment. Lowering the TSH range would increase the percentage of the population diagnosed with hypothyroidism from 5 percent to 20 percent, an enormous leap. Many doctors think there’s no need to futz around with TSH levels—that to do so will benefit no one except Abbott Laboratories, the company that manufactures Synthroid (levoxothyrine), the drug most doctors prescribe when they treat hypothyroidism.