I'll tell you when I knew.
A little more than three years ago, or during the last autumn the problem would go unadmitted, my parents visited Washington as part of their annual eastern swing from Los Angeles. We agreed to meet at a local restaurant, and I arrived sheepishly late to find that my mother, at 71, had fallen into a conversation at the bar with a gregarious young stranger. He had evidently just arrived home from a Hawaiian vacation of much debauchery.
My mother, her well-coiffed hair the hue of a red October leaf, her head thrown back in mock pain, laughed loudly at his stories, girlishly tittering: She is, or was, one of those people who somehow look young even when old. "Please, please, please, you're too funny," I heard her saying from across the restaurant.
I'd spent a childhood in the '60s as witness to that pose. I'd wake up during the middle of the night, stumbling sleepy-eyed and pajamaed into my parents' parties, the kitchen wafting the antiseptic smell of vodka martinis being mixed like maracas in a silvery cocktail shaker, the living room redolent with perfumes. I'd hear the males telling stories in murmurous baritones and, amid it all, my boisterous mother laughing: "Oh, you're baaaaad. Oh, that's deeeelightful."
She had that skilled bonhomie of experienced hostesses; she knew how to work a room, deft at making even the socially awkward feel like Sinatra, and in the end cobbling the kind of social life without which my father, a serious-minded engineer and salesman, might have had scant after-hours contacts. She came by it all naturally, craving contact -- "a social animal," as my father said. Now, in the restaurant, her mouth opening wide and her teeth glistening, I knew that someone new was being flattered.
My father saw me at that moment.
He shouted my name several times -- much louder than necessary. I walked toward him. My mother, startled by his yells, wheeled in his direction, looking vaguely alarmed. He whispered something to her -- "Here's Michael" -- and pointed at me.
Her mouth fell into a tiny oval and she turned, staring at me with faint but perceptible confusion.
My worry began in that instant, something animal-sensed.
My father repeated, "Carol, here he is."
My mother, summoning her widest smile, cried, "Well, hello, hello, hello. Greetings and salutations."
"Here's Michael," my father repeated.
And then the map of my face must have come reasonably clear to her. I am the one who looks like her, or so the two of us were always being told. She gave me a kiss and yanked down on my neck, pulling my ear to her mouth, her whisper familiarly conspiratorial: "Dear, who is he? Tell me his name again."
She gestured not so discreetly at the young man. "Tell me his name again."
I whispered, "He's not with us, Mom. I don't know who he is."
"He's having dinner with us?"
"And who is he?" She sounded a little agitated.
"I don't know. Just a guy at the bar."
She kept hold of my neck. "Well, okay."
"It's great to see you, Mom."
She let go. "You, too, dear. The prodigal son, the prodigal son." She'd loved using the phrase since I was a small kid. "The prodigal son."
"You look terrific, Mom."
"Thanks, dear. Having these things. Nuts. And it's a thing. Delightful. And your boy. And your wife. And there it is. And there you go. And it's great."
She sounded peculiar, but I didn't think much of it -- my brain not wanting to, I suppose. She asked me about the sports jacket I had on -- "I like this. Which one of your girlfriends bought this?" -- alternately chatty and a little daffy, charming and disarming, and thus, reassuringly, quite like herself. She could fool you, and indeed had fooled many of us in the family for a while. She could squint in a manner that suggested serious contemplation. She could summon her favorite rote phrases, the ones -- like Greetings and salutations and You bet and The prodigal son and It's delightful and You better believe it -- that had been hard-wired by decades of use into millions of different neuronal pathways, the ones that, along with her Catholic prayers and favorite songs, would be among the last to go, the most resistant to aphasia and this disease slowly claiming her brain. "And it's deeeelightful," she went on. "And you better believe it. And there you go."
She pulled down on my neck again. "Tell me that man's name." She pointed up at the young reveler. "That man."
"I don't know him, Mom. I've never met him. He's just some guy. Forget him. How are you?"
"Oh, I'm getting along." She smiled brightly at the young man, and burrowed into my ear, so close I could smell hair spray. "I have to ask you something . . . Is that man having dinner with us?"
"No, he's just sitting at the bar, Mom."
"Tell me his name again."
And I knew.
We Both Knew
Sometime in the months that followed, my father broke the news of the obvious to me in a phone call, the essence of which he confirmed much later in a letter to his five children: My mother had Alzheimer's. I was 2,500 miles away, in a Virginia suburb of Washington, anesthetized by distance.
A year after the restaurant episode, in the autumn of 2000, I stood with her on a deck looking out over an ocean inlet on the New Jersey shore, where she had spent much of her youth and early married years. She knew her fate by then, though she wouldn't admit it to me, fortressed behind denial. "I don't know what's he's talking about," she whispered into my ear, the "he" a reference to my father. "He's just awful."
They had just returned from a trip to Europe, during which my mother had been disoriented for a time in Germany and Austria, beset by crying jags, demanding to go home, as if home were just minutes away, her new medications not yet including any that would address her anxieties or delusions. It was about the time when she had begun believing that my father, preparatory to abandoning her, must be having affairs with other women -- with the next-door widow back home, with a clinical nurse assisting in an assessment of her condition, even once apparently during the Jersey weekend with one of her older sisters, whom she failed to recognize, angrily demanding of my father, "Who is that woman? Why are you talking to her?"
It was the disease talking, my father told himself. "That's your sister," my father said. "That's Eileen."
My mother needed a long moment just to grasp that name, before next trying to make sense of my father's rebuke, clarification, assurance: "I'm with you, Carol. Aren't I always there for you?"
She stared blankly at him. She was attempting to retrieve the meaning of his words from a vanishing memory, then assess his truthfulness. This required her to remember their past together as a means of making sense of his behavior at that moment. Not even her doctors could predict how she might respond in such situations.
The uncertainty about the state of her mind lay in the murkiness of Alzheimer's: It's insidious, meaning no one could pinpoint either the extent of her brain's destruction or the disease's beginnings in her, only that her neurons might have been suffering a slow, progressive degeneration for 20 years or more. By the time of her formal diagnosis in 1999, her doctors believed, Alzheimer's had probably already ravaged her hippocampus, the part of the brain just inside the ears and instrumental in memory formation.
It had likely seeped from there to attack, in order -- from her temples inward -- her cerebral cortex's temporal, parietal and frontal lobes, the last of which are where most intelligent thought and reasoning take place, where the summoning of memories shaped and stored throughout the mass of the brain occurs. The frontal lobes held nothing less at one time than her capacity for logic and lucidity, the ability to distinguish between informed reasoning and rank suspicion.
The disease exacted its greatest toll on her brain's left side, taking away not only much of her reasoning but her capacity for language. Beyond the venting of her paranoia -- Who is that woman? -- she couldn't articulate a detailed response to a suspicion even if she framed the idea now.
Though no one fully understood how she or anyone else had been stricken by Alzheimer's, researchers already knew much of what they would find if, opening her brain, they looked at the spaces bridging the neurons: a goo. An increasing number of neurons in her frontal lobes and elsewhere no longer conveyed information to one another, their pathways blocked by sticky plaques made of an insoluble protein, with many neurons likely being choked from within by another protein that generally serves to transport life-sustaining nutrients to neurons but which, in Alzheimer's victims, mysteriously twirls and tangles, halting the nutrients' flow, the way a twisted garden hose stops the water. The effect is first to diminish the neurons' abilities, then kill these cells and reduce them in time to nothingness, so that, at the end of her life, my mother's brain will have vast wastelands amid the goo, and weigh far less than the norm. Quite literally, hers will be a little brain.
By the time she had reached New Jersey, in autumn 2000, her cerebral cortex already had proceeded a long way down the path that is equal parts destruction and reversion, slowly taking her back in neurological time to what -- if she lives that long -- ultimately will be her life's second infancy. At the end of this horrific decline, long after she has lost an ability to feed herself or even to baby-babble, even after the penultimate loss of her ability to smile reflexively like an infant, she will be left with only the capacity to lift her head. Until that passes, too.
By contrast, as oft is the case with Alzheimer's, the one part of her brain still working extraordinarily well was its most primitive component, the very part that it had in common with the brains of lizards, alligators and efficiently rapacious predators that roamed the planet millions of years before us. Known as the limbic system, it set in motion her defense mechanisms and triggered her instincts -- in the face of rational and irrational fears alike -- to flee or fight, to save herself against any perceived danger or threat to her turf.
Now she stood on the deck overlooking the inlet, and looked out, alternately giddy and despondent, toward beaches where she had once partied as a long-legged girl in a one-piece. My
father's words -- "That's your sister . . ." -- had the desired effect. Mollified, my mother accepted this information with equal parts puzzlement and embarrassment. The awfulness passed. The next day arrived.
My Aunt Eileen exuded empathy and a big sister's control, asking my mother every few minutes on the deck whether she wanted a sweater or a drink, pointing at the water, saying how nice Carol looked. The sight of the two, hips brushing as if conjoined, offered a portrait of the disease's capriciousness: Two years older, Eileen was nonetheless mentally robust, her baby sister ruined.
Eileen's presence apparently evoked something in my mother's brain that transported her back to kinder places and frolics -- Coney Island, summer beaches, trips into New York City, and the day my mother cut classes as a Catholic schoolgirl with her fearless friends, evaded the nuns, stealthily boarded a bus and rode out of Jersey into Manhattan, where, squealing, jumping in plaid skirts, they swooned for Frank Sinatra at the Paramount Theater. New Jersey was where she'd been a cheerleader, and necked with young Jack Leahy, and had her first saltwater taffy, and swum in the Atlantic.
Eileen reminded her of how their mother would wait up whenever they had a date, rapping on a window with her wedding ring if they lingered too long outside.
"You bet," my mother groaned, laughing, rolling her eyes.
If you hadn't known the truth, she might have fooled you all weekend. She smiled and pointed at sea gulls. She addressed me by name and even chastised me, maternally, for not getting a haircut. But, eventually, to be on the deck with her was to feel pieces of her floating off.
"Bird," she said, pointing at another gull.
"Bird," I said.
"It's a pretty bird," she said. "Flying."
"Don't be sad," she said.
"The boy is handsome, Michael. Delightful."
"And you are going home? I'm glad you're home."
"Well, not California. I live in Virginia now."
"Oh. Tell me what you do."
I attempted this. I spoke very slowly, looking at her green-gray eyes, which squinted fiercely, eyelashes beating hard, as if a terrible gale were blowing into them. She craned her neck and looked at me from down there wherever she was, slack-jawed and vaguely panicked, as if she could faintly make out my muffled voice -- the way an underwater swimmer in a pool hears conversation above the surface -- but couldn't grasp what I was saying or even turn my sounds into words.
Her eyelashes stopped beating, and the green in her eyes seemed to recede, like light at the other end of a tunnel. I guess we both knew. We just looked at the water. I felt like I should say something that mattered before it was too late for anything I said to matter, but I didn't. I just pointed at a gull and said, "Bird." She looked up at me. "Hug me, pray for me," she said, and her hug was long and insistent and finally not a hug at all but a tug of sorts, as if she wanted to bring me down into the tomb to be with her.
A National Imperative
For America, already beset by about 5 million Alzheimer's patients -- and nearly 500,000 new ones a year -- the most alarming spike in the figures will hit as soon as the next decade, as the graying of the '50s and '60s children means there will be more elderly Americans and dementia patients -- both in real numbers and as a share of the population -- than at any other time in the country's history. The numbers of Alzheimer's victims will soon after explode, exceeding 14 million Americans before mid-century, according to Alzheimer's Association projections. The costs of Alzheimer's -- everything from savings lost to business productivity slashed -- are forecast to rise more than threefold to $375 billion a year, threatening to put a chokehold on Medicare and Medicaid.
Medically speaking, the damage to boomers already has begun. Alzheimer's, contrary to popular belief, is a young person's disease at its origins, invisibly eroding neurons for at least 10 years before serious symptoms appear, despite the better medical care, diets and lifestyles that have led to more enduring bodies.
The new longevity, once a goal in itself, as American a concept as Manifest Destiny, complicates the dilemma, the incidence of Alzheimer's roughly doubling every five years after the age of 60. At that point, only 1 percent of all Americans have yet exhibited symptoms. At 70, the numbers are about 4 percent; at 75, about 8 percent. Thereafter, the risk curve turns harrowingly steeper, growing about 40 percentage points in the next 10 years. Fully 47 percent of 85-year-olds are afflicted.
Such a forecast creates a national imperative, argues Harvard Medical School neurology and psychiatry professor Marilyn Albert, who also serves as the chairwoman of the Medical and Scientific Advisory Council for the Alzheimer's Association. Pointing to studies that suggest only about a quarter of proposed clinical trials for Alzheimer's experimental drugs and preventive approaches receive funding, Albert argues that federal research funding ought to be swiftly increased to $1 billion from its current annual level of about $595 million.
Albert echoes another consensus opinion within the Alzheimer's research community: Given the rapidly impending explosion of Alzheimer's as boomers age, the window for developing a better class of drugs to delay or arrest Alzheimer's worst symptoms is small. Maybe 10 years.
The disease strikes with what can seem to be freakish randomness, afflicting some and sparing others like my wife's 91-year-old aunt, Bea Dean, who remains preternaturally alert to the doings of neighbors and naughty politicians. Bea's brain looks nothing like my mother's, which likely began to deteriorate no later than the late 1980s, at a time when her mental health seemed no different from that of my Aunt Eileen. My mother and Eileen had a significantly higher risk for Alzheimer's than the general population: Their mother, a sister and a brother all had suffered from strokes and vascular dementia, which is caused by a disruption in the brain's blood flow. Researchers increasingly believe that a history of strokes and vascular dementia places family members at greater risk for Alzheimer's.
Researchers posited possibilities for the two sisters' contrasting fates: It could be that my mother, and not her sister, inherited copies of a gene known as APOE epsilon 4 from both their mother and father. While not a guarantee of Alzheimer's, APOE-4 places those who have one copy at greater risk for the disease, and those with two copies at greater risk still.
Yet if, as most Alzheimer's experts believe, the disease typically stems from a mix of genetic and environmental factors, then my mother's risks may have been compounded, studies suggest, by her paucity of formal schooling and lack of intellectual rigor after high school. (Education grows neuronal pathways, leaving the intellectually active with a greater reserve of cerebral troops against Alzheimer's armies, and the less-educated with often scant forces more likely to be overwhelmed. A study of older Catholic priests, brothers and nuns -- published last year in the Journal of the American Medical Association -- suggested that even a modest increase in cognitive activity at midlife can substantially reduce the risk of Alzheimer's.)
Other research indicates her lack of exercise at various points in her adult life (her slender figure, once a genetic blessing that had made aerobics an unnecessary chore, may have become a curse) and a high-fat, cholesterol-inviting diet were possibly factors as well (we happily ate like the Brady Bunch, gluttons for outsize meatloafs and juicy T-bones just waiting to unleash free radicals). In my childhood, she regularly sent me off with a grocery list that included one of her favorite gossip magazines and "12 center-cut pork chops." It was a combo that spoke volumes about her appetites and perhaps her concomitant risks.
Far more meaningful, in the eyes of a dissident body of researchers, may have been my mother's lack of estrogen replacement following a total hysterectomy in her early forties, limiting the natural ability of many neurons to repair themselves and withstand the normal onslaught of aging. It left her with famished neurons, argue these scientists, placing the brain at far greater risk for developing Alzheimer's than if her neurons had been estrogen-nourished. So many hypotheses raised provocative and wistful questions, such as whether her future might have been different had she listened to one of my siblings, who urged her to seek estrogen therapy. But no answer could save her any longer, and she seemed to know it. She wanted only a refuge that might transport her to a more serene place in her mind, given that real places like Austria and Germany no longer worked. There might be no more trips at all, my father said then. "They just upset her. I'm looking for some different drugs. It's her delusions that concern me. They're getting worse."
'Having a Little Difficulty'
For a few months through the autumn and winter after my mother's New Jersey trip, her decline appeared minimal to me, as if she had landed on a neurological plateau. There, she seemed to discover her refuge, talking dreamily about a long-ago trip to the movies with her big sisters as if this had happened just that day, and how she'd love to see two charming boys from her childhood named Ozzie and Cozzie.
She sounded surprisingly lucid at moments, the effect of a drug called Aricept that her doctors had prescribed about a year earlier. While not addressing her delusions, Aricept at least slowed the destruction of her brain's neurotransmitters, sustaining the ability of some cells to communicate with one another, and thus give her a better chance to reason and speak.
But the Aricept had limits. About eight months or so after the New Jersey trip, in the summer of 2001, I spoke briefly to my father, who, as he typically did, turned the phone over to my mother. "You need to put it to your ear," I heard him saying. "To your ear."
"I had a nice do-day," she said, coming on. "Carif."
"Hi, Mom, it's Michael."
"Hi, dear. Having the thing. It's sunny. Who is this?"
Then came the sound of a receiver crashing from the other end.
"You have to pick up the phone," my father said to her. "Put it to your ear."
"Who is this?" she demanded.
"Of course it is."
"Oh, I'm sure Dad's around. How are you, Mom? You said sunny. Is it sunny?"
"Well, just a little thing. Drinking it. And who's this?"
The receiver crashed. Then nothing for a couple of minutes. Then howls. I could hear my mother: "Jaaaaaaaaaaacccccck. Jaaaaaaaaaacccck, where are you? Jaaaaaaaaaaccccck. Jaaaaaaaaaaaacccccck."
The next voice was my father's. Having momentarily stepped outside, he had hurried back in. "Having a little difficulty here. We'll talk later."
'Is It Already Happening to Me?'
Because genetics count for much in who gets Alzheimer's, I have accepted that my four siblings and I are walking risks. Our chances of inheriting the disease -- like those of Ronald Reagan, who had an afflicted mother, and like Ronald Reagan's biological children now -- are about four times greater than other Americans'.
That places the possibility for me, and tens of millions of other at-risk Americans, at somewhere between 25 and 30 percent. Those are worse odds than what you'd get, say, with a loaded handgun in a first round of Russian roulette -- though not nearly as bad as that 47 percent chance for all Americans in that 85-plus group.
After hearing enough of the numbers, many children of Alzheimer's patients start stressing. "I try to remember when my
father first had problems and wonder if I'm showing any signs," says 50-year-old Los Angeles educational counselor Barbara Bickel. Her father, Bernie Bellinson, and my mother attend the same Alzheimer's support group in the San Fernando Valley, and Bickel already wonders whether she can glimpse her future. "I look at something like a stapler sometimes and I can't find the word for it. And, see, it wasn't even a stapler, I can't remember what it was. I think, Is it already happening to me?"
Indeed, much like the disease itself, that fear sneaks up on you. A few weeks ago, I half-heard a breathless television anchorman discussing domestic unhappiness in the life of the actor Tom Cruise, who had split from his actress-wife, Nicole Kidman. While my brain semiconsciously processed this banal factoid, it occurred to me that Cruise had been married before, to a brunette, whom I could picture from her movies, right down to her long legs and glistening smile. Only now I couldn't summon her name.
For the next half-hour, I hardly moved, trying to imagine shiny white molars and lush brown hair. The brunette couldn't be retrieved: Had some patch of my neurons perished? Was it beginning?
My life is different now, my obsessions and tests of myself unsparing. Because I felt a compulsion to commit it to memory, I can tell you that an obscure New York congressman named William Miller was Barry Goldwater's 1964 vice presidential candidate. A professional tennis player named Canas won a lesser tournament last year by beating four guys ranked in the top 10. Every now and then my brain insists that I flawlessly recite this quartet -- Federer, Kafelnikov, Haas, Safin -- or else. Or else I will be made to fret, lie awake in my bed, wonder if it is already taking hold. Federer, Kafelnikov, Haas, Safin . . .
There are tests, and I have considered taking them. Their mere availability reflects the distance traveled since the German scientist Alois Alzheimer, peering through his microscope during an autopsy of a "senile" woman in 1906, saw a brain's tangles and the plaques now known as beta amyloid. Now someone can draw my blood and I can learn, if nothing else, whether I am carrying the APOE-4 gene. (According to a New England Journal of Medicine article, an estimated 30 percent of Americans have the gene, and one study found that 97 percent of persons with both the gene and mild cognitive impairment -- an elusive term defined by many researchers as a subtle but abnormal decline in acuity -- developed Alzheimer's.)
Or for a couple of thousand dollars or so I can subject myself to Positron Emission Tomography, a PET scan, which, in measuring the brain's metabolic activity, could forecast in a fortysomething like me whether I am a candidate for some degree of cognitive impairment and perhaps Alzheimer's disease down the road. But what would I do with such information, when there is not yet a vaccine to undo the implicated amyloid plaques or the tangles that choke off neurons, assuming either of these is the actual cause of Alzheimer's, and not merely an effect?
There are already medications that could forestall the worst symptoms, and the patient who uses them long before any symptoms appear has a better chance of delaying his decline. But would their benefit, asks prominent Los Angeles-based Alzheimer's researcher David Sultzer, be worth "the crazy-making consequences" of receiving genetic test results that "you might regard as devastating"? And what if such an exam, asks Sultzer, showed you did not have APOE-4? Some researchers believe that about one-third of people with Alzheimer's do not have APOE-4. "So," Sultzer adds, "being
told you don't have it would guarantee you nothing."
Typically, the talk in the Alzheimer's research community is cheery, weirdly so. For political reasons, in a climate where they must discreetly compete for federal research dollars with AIDS (whose funding is about four times higher), cancers (eightfold greater) and heart disease (about twice the level), prominent Alzheimer's advocates try exuding at once urgency and excitement.
The greatest hope arrived at the start of the new millennium, as the Irish-based Elan Pharmaceuticals developed a vaccine that halted amyloid production in the brains of mice genetically engineered with an Alzheimer's-like condition. Spurred by research leader Dale Schenk, Elan then reported to the world that the mental deterioration of the mice not only ceased, but that, in cognitive terms, the new vaccine had turned back the clock: The mice actually had regained mental skills, making up for much of what the disease had stolen. It was the most extraordinary Alzheimer's research news in a decade, maybe ever.
Early in 2002, the Alzheimer's community collectively held its breath. To believe in the possibility of Schenk's success, one needed to believe for starters in the amyloid cascade hypothesis, which asserts that once enough beta amyloid gathers between neurons, a threshold is exceeded and damage ensues. The destruction, goes the argument, includes the production of tangles within neurons -- the twisting and wreckage of the tau protein, which is responsible for transporting nutrients within individual brain cells. In this view, the amyloid triggers everything. The tangles are nothing more than a damaging effect, according to the hypothesis.
But there is a second, opposing group of researchers who believe that tau malfunctions without the involvement of beta amyloid, triggering Alzheimer's on its own.
By the '90s, the stakes of the debate between the amyloid faction and the tau contingent transcended science. Someone here had a chance to become wildly famous -- to achieve the kind of immortality reserved for a Jonas Salk or the bearer of a seminal concept like Alois Alzheimer. In research science, unlike on Wall Street, fame precedes wealth. That knowledge only escalated tensions, particularly among tau researchers who believed they had been vilified and unfairly deprived of a just share of federal research funds.
With the two sects openly deriding each other, their feud turned especially noxious in the '90s, as amyloid leaders declared there did not exist enough evidence even to warrant funding a part of tau research that hypothesized genetic links to Alzheimer's. The rivals found themselves hung with nicknames indicative of their zeal: The beta amyloid people (wags saw the seeds of an acronym in those three words: BAP) were dubbed the "Baptists," the tangle acolytes the "Tauists." The more ecumenical voices in the Alzheimer's community began worrying. Zaven Khachaturian, a former director of the Alzheimer's Research Office at the National Institute on Aging, and a legendary figure in the field, feared that the animosities might poison the chances for theory exchange and an equitable distribution of research funds. "I thought," remembers Khachaturian, "that this competition might be . . . impeding research."
A truce seemed out of the question. In Allen Roses, the Tauists had their own star, a brilliant geneticist who, in 1992, while director of an Alzheimer's research project at Duke University, had become a Galileo of sorts -- equal parts hero and heretic -- when he discovered the APOE gene and then declared that APOE-4 presented a substantially increased risk of Alzheimer's, immediately diminishing the luster of the amyloid theory by presenting a major discovery by the competing faction. It became obvious that amyloid theorists did not have all the answers.
But, long after the acceptance of his genetic discovery, little had changed, insisted Roses, who argued the "biased" amyloid-dominated Alzheimer's establishment still controlled most funding decisions.
Other researchers went beyond Roses, arguing that the relentless focus on the Baptists and Tauists, like the fervor surrounding the American two-party political system, constrained new ideas. A third research sect, slowly stirring interest after two decades of work, believed that neither amyloid nor tau tangles directly caused Alzheimer's, arguing instead that mysterious inflammatory responses in the brain were the real culprit.
One of the inflammation group's leaders, Joe Rogers, looked for respect for years from the amyloid wing, in part because this was where power and status still resided. A year and a half ago, he sought to contact Dale Schenk, who for the moment had become the most talked-about Alzheimer's researcher in the world -- ready to move beyond mice and test his famous vaccine, AN-1792, on 375 human subjects gathered at Elan Pharmaceuticals trial sites throughout Europe and the United States. Like several prominent researchers, Rogers worried that the Elan vaccine -- which involved the introduction of beta amyloid into patients' bloodstreams, in the belief that their bodies, mimicking the effects of Jonas Salk's polio vaccine, would send out antibodies to destroy all unwanted invaders -- would provoke a dangerous inflammatory response. He said he warned Elan officials and offered his assistance in preparing an anti-inflammatory medication that perhaps could be simultaneously administered with the vaccine. "Elan wasn't responsive," he said wanly, months later, from his office in Sun City, Ariz. "They didn't think that any inflammatory reaction would be adverse."
But in most of the Alzheimer's community, the excitement about the impending trials far outweighed the concern. The hopefulness reached all the way to the Los Angeles suburb of Northridge, where Carol Leahy, her cognition steadily declining, sat not knowing that she might be leaving on a long trip at any moment. In front of his computer, Jack Leahy had logged on to the Internet's many Alzheimer's sites, and gathered information about the Elan clinical trial, seeking next to learn how he could enroll my mother.
But by then, the Elan trial had been halted. At least 5 percent of his subjects, acknowledged Dale Schenk, had encountered brain inflammation and become seriously ill. The talk of the magic vaccine was dead for now.
In Arizona, still wishing that he could assist in addressing Elan's inflammation problem, Joe Rogers said pointedly, "I'm surprised that somebody from Elan hasn't come back to me."
In Bethesda, Zaven Khachaturian, while not talking directly about the failed clinical trial, expressed an old frustration. "We need to minimize our tribal warfare," he said. "One of the biggest barriers is us . . . The stakes, the egos, the financial conflicts and the relationships with drug companies -- they're all standing in the way of what we're trying to solve. There's real suffering out there."
My mother takes tests, more or less against her will. By early 2002 in Los Angeles, she had sat for batteries of cognitive exams at Kaiser Permanente Hospital, the UCLA Alzheimer's Disease Research Center, and the West Los Angeles Veterans Affairs hospital.
She performed adequately on the tests during 1999, able to draw a clock whose hands correctly read 11:10, and later successfully sketch two intersecting pentagons from a picture of the configuration. But in February 2000, her performance began sharply declining. Futilely trying to draw the intersecting pentagons (imagine two houses connecting at a corner) left her shaken. The task of writing a sentence became her vehicle for agonizing self-confession. She wrote next to the pentagons that day: "At this time I feel like a dummy."
Just six months later, in August 2000, she ceased to know the month or the year. She didn't even try to draw the clock. There is just an empty circle on the page, time having run out on her, the neurons overrun. Over the next year, her deterioration had a frightening momentum, until the day arrived in December 2001 when she lost a slice of her identity. Having failed with the pentagons, she tried to write her name. The letters to "Carol" would not come. Stymied, she tried a second and a third time; it was hopeless. "C A Me," she wrote on her test paper.
C is me.
Lost for Good
Two months later, I found myself standing next to her, on my parents' front lawn in Northridge. Gesturing down the street, toward what once had been a barren field, I began reminiscing about a day when, at 12, with the help of friends, I'd broken into somebody's garage, removed a glider the size of a small airplane, and triumphantly rolled it down our street. The police came to our house. I'd never been able to strike the memory of her words: "Michael, I will never forget this day as long as I live."
She looked up now, slack-mouthed, searching my face the way you would a newcomer's. "Michael was hard," she said finally.
And, as she asked where I lived in the neighborhood, I realized that we had arrived at a new place, one in which "Michael" was lost for good, back there somewhere with Ozzie and Cozzie. If she no longer knew me as her son, at least we could do things together. I'd evolved into a safe, familiar face, maybe a jocular fellow or a relative of sorts, the one without a name. Along with my father, we went to dinner one night at a local Mexican restaurant, the last time we ever went out together.
The difficulties of that evening had nothing to do with my mother removing a straw from her beverage and sticking it in the salsa, in an attempt to drink. It wasn't her paranoia, or even the understanding that, once home, she might have another sodden collapse, insisting between sobs on seeing her mother and father, each of whom had been dead for at least 40 years. It was just the sheer weight of anxiety, of not knowing what was coming.
My father mentioned casually her participation in the UCLA Alzheimer's program, and she flared. "I'm not in any program," she snapped, putting her straw back in the salsa. "What are you doing, the talking?"
My father seemed to understand what she meant. "I don't hide anything from you, Carol. I just said you're in a program."
My father tried to comfort her. "It helps, dear, that you're in good shape."
"And you're in bad shape."
He changed the subject before the fury came. When she became angry or terribly disoriented, she sometimes told him he needed to go home; that her husband would be arriving soon, and that he better be gone.
I am your husband, he would say, smiling.
She would yell: Go. Go home.
My father sat at home every night now.
Having spent a career on the technical periphery of the film business, in its sound recording industry, he had retired with visions of easy days and frequent globe-trotting with my mother. Now, a year shy of 80, he had new rituals. After his chronically restless mate fell off to sleep, he returned to the other end of the house and did their dishes and laundry. At some point, logging on to his computer, he tried to lose himself in games, the former bridge aficionado playing solitaire, rubbing his eyes. "This is my break, I guess, the only one of the day," he explained. "I kind of need it for my sanity. But I think about what's ahead, too -- what I'll need to do for Carol."
He prepared in big ways and small. Death, his own, absorbed him. What would happen if -- the foreboding likelihood, he thought -- he died before she did? He'd carefully prepared a will and accompanying letter of instructions: how and where to bury him, what care facility my mother, now 74, would be placed into, how to pay for it by cashing his investments and selling the house.
During a late night this past October, his mind segued from death to the prosaic, the matter of the next day, and her meals. He decided upon the breakfast he would assemble for her: cereal, three kinds of fruit, Danish rolls, juice -- all of this to go along with her pills, of course, pills that she didn't so much as know how to put her in her mouth any longer, he said in disbelief.
He fingered the pills. See? he muttered. This little brown one is for her delusions, this bigger one for restlessness, and this new one for cognition and alertness is called memantine, purchased from a company in Germany and paid for -- at roughly $600 a month -- out of his own pocket, since the Food and Drug Administration hadn't approved it and his insurance company therefore wouldn't pay for it. "I've increased her dosage to a pill and half in the morning," he said, "and a pill and a half at night, and then I'll . . ."
He tried to lose himself in details. He talked expansively about her doses and diet, but any reference to his own agonies came grudgingly -- his reticence about nearly anything personal having shrouded much of his life for me. It spoke to Alzheimer's power that the disease gradually wore away his stoicism. "I've gotta try anything; she's my love," he blurted that night, a statement so direct in its intimacy that it bent him over, his legs needing to find a chair.
Because he cared so deeply, he felt the guilt that afflicts so many caregivers. "I just don't think I'm doing very good for her," he said. "I got so frustrated yesterday afternoon. I lost it."
My mother had followed him from room to room after lunch. He had wanted just a few minutes to relax, maybe to read the paper, close his eyes. "Just give me a little space, please," he pleaded. She didn't understand, scared of being alone, lost, abandoned. She followed him like a puppy.
"Please go into the other room," he snapped. "Please. You stay in here, I'll go in there."
This had been another wrenching day. He had had difficulty getting her to sleep, and worried that perhaps he had given her a couple of her pills too late. But she had fallen off; all must be well. It was nearly 10:30 now, and he thought he might watch some news on the television when he heard a rustling in the hall.
There she was. At the foot of the den. "Oh, oh," she kept saying, like a stranger in pajamas who, in some somnambulant state, had stumbled into the wrong house. She looked around, completely disoriented, until my father's face seemed to snap her out of it. "Jaaaaaccck, what are you doing?" She had her bearings now. "Jack, what are you doing?"
"Carol," he groaned, but not loudly, trying to mute his exasperation, slowly rising. "Why are you up?"
"What are you doing, Jack?"
"I'm doing the laundry, what do you think I'm doing? Why are you looking at me like that? I'm not going anywhere, Carol. Come on. Let's go back to bed now. Come on. Give me a hug and let's go back to bed."
He gave her a hug, which seemed only to confuse her.
"Come on, sweetheart, let's go to bed," he said gently, and kissed her on the cheek. "Let's go. I'll help you. C'mon, sweetheart."
She took a wobbly step back, not going anywhere yet. "I'm fis'." She sounded less angry than lost. "And this. And that my thing. And I. Oh." She glanced furtively at me, clucking her tongue, and walked closer to my father, whispering, "That man."
My father winced. "That's your son Michael."
He led her away. I stayed at the other end of the hall, as a stranger does.
"I think I might have waited too long to give her her pills tonight," he said when he returned. "Darn it, she's gonna be up again in the middle of the night. I know it. I'm just getting so little sleep."
At times my father turned for advice to David Sultzer, part of a joint UCLA-West L.A. VA clinical trial providing a series of antipsychotic drugs to Alzheimer's patients. For his part, the doctor marveled at how many caregivers maintained dignity amid the indignities. "It's quite heroic what your father is doing," he said. "I'm sure his loyalty helps to sustain your mother."
But at a cost. Now he sat at his old office desk, cradling his head, the portrait of despair. An upper-middle-class man, he dreaded thinking about how much he would continue to pay for drugs and my mother's day-care program at roughly $10,000 a year. He worried about his own health. "I don't know how much longer I can do this," he said, the first time he gave voice to the possibility that one day he might need another living arrangement for her. Then he shook his head, as if exorcising the idea. "I just couldn't do that."
But in the last two years he has experienced more chaos and craziness, more pain and misery, than in his previous 77. He loves her enough to accept that she cannot love him back; knows that this part of their lives is over. And not once but several times she has struck him, until he has gently restrained and soothed her.
The limbic system remains well-preserved to the end.
'I Got My Eye on You'
My neurons never had found the identity of Tom Cruise's first wife. I'd resigned myself to a panic attack or two, and an ongoing obsession about the nameless brunette, until a prominent UCLA neurologist named Gary Small, an advocate for Alzheimer's PET imaging, told me that stress could actually kill neurons in a region around my hippocampus, in turn compounding my risk for Alzheimer's.
So I'd tried to forget all about her when one night, reclining in my old bedroom, she came to me: Mimi Rogers. She had been nothing less than the unfathomable riddle, and now I reacted as if I'd saved myself. I felt bathed in relief, only later that same week to puzzle abruptly over a new name -- my brain soon again subjecting itself to a new wave of tests.
During that same October week, my father attended an alumni session of the Memory Club, a support group made up largely of Alzheimer's spouses. More than 40 percent of spouse caregivers, according to Alzheimer's Association studies, suffer from clinical depression, and a full quarter are on medication. "This is all the counseling I need," my father said gruffly. The stories at the club were bleak on this day, particularly from women caregivers, who in some cases had gone from worry for their husbands to fear of them. One Alzheimer's husband, since committed to a long-term facility, had become "physical" with his wife. Rubbing at teary eyes, two women bitterly complained about a lack of government funding for Alzheimer's day care, home care, drugs and long-term hospital stays. "The caregivers need help; I'm going through something that's almost a depression," said one woman. Heads nodded.
Another woman, Harriet Bellinson, whose husband, Bernie, was diagnosed in the late '90s, groaned that Bernie, deep into his delusions, woke up on Sunday and demanded to be driven to work. "I don't argue with him," she said, "but it's getting harder . . ."
Looking on was Alan Holtzman, whose wife, Bobbi, a former actress and theater director, suffers from vascular dementia. "That sounds right, not to push it," he said. "I just know certain questions aggravate Bobbi. I don't use the W-words -- Why? What is this? Where is it? Who are you talking about?"
The next day, during a day-care session of dementia patients in the same building, Bobbi Holtzman sat next to my mother, the two of them singing parts of "California Here We Come," my mother yelling above the music, "That's deeeee-lightful."
Across the room, Bernie Bellinson tapped on shoulders, reminding people of a meeting he wanted them to attend. Bald and bespectacled, carrying a folder, he had the bearing of the pool company manager he once was, now clutching my shoulder. "You're just the guy I wanted to talk to," he said. "Meet me back at the plant later and we'll talk about the thing."
"Sure. The thing."
"I got my eye on you."
Bernie exuded an authoritative air. He thought nothing ought to change in his life, despite having lost his driver's license. One day, he had wandered away from home and his frantic daughter found him at a bus stop. Distraught, she yelled that he could never, never, never do that again.
She didn't know how her father might react. You didn't want to push him too hard. But Bernie soothed her: "I know I have Alzheimer's, and I know I won't always be able to do this much longer. I'll know when I've gotta stop."
My mother, singing along to Bing Crosby, happily approached Bernie from behind. "Greetings and salutations," she said, swinging her hips, eyes closed, back at a party for all anyone knew, with the music playing softly and the silver cocktail shaker shimmying, and more guests in need of charming.
My mother always had the capacity for surprise. One of my favorite memories involves a balmy Los Angeles spring day when she stopped me, at a restless 14, from climbing on the back of an older friend's motorcycle and rocketing a long way down the 405 freeway, to buy treasured tickets to a UCLA basketball game. No, she said, taking one look at that bike. No way. Then the girl inside her who had sneaked off to see Sinatra must have realized the obvious: that I had come by my wanderlust honestly. She half-relented: While no great fan of freeway drives, she offered to chauffeur us if I took my schoolbooks. Her memory flawless when it came to my missteps, she interrogated me most of the way: Are you getting your homework done? How can you do your English with the radio on? Why would you do your math on the back of an old basketball program? I'm never gonna forget this.
Maybe it's only because I want to believe it, but I always had the impression she loved that ride, the escape of it, the coming off Sunset Boulevard and snaking down to the campus. Someday soon, though not behind the wheel, she will go on that same drive one more time, the disease having stilled her body. She'll return to UCLA to be marveled over in a quiet room by men and women who will touch and slice the two-pound oily organ that once held in its lobes the thoughts of the girl waving her cheerleader's pompoms, and those of the woman who balanced the family checkbook, and dressed her toddlers for preschool, and fixed them a couple of thousand spiced ham sandwiches, and wrote artful absence excuses after boys developed sore throats on World Series days, and gave them keys to cars, and danced with their father, and readied the house for guests -- an organ that held endless cries of Greetings and salutations.
Michael Leahy is a Magazine staff writer. He will be fielding questions and comments about this article at 1 p.m. Monday on www.washingtonpost.com/liveonline.