The Forgetting Read online

  The middle stages bring the end of ambiguity. The subtle cues that something was not quite right—so easy to miss a few years ago—are now bright, self-reflecting signposts of decline, impossible to avoid. Conversation is now pockmarked with lost names and empty recollections. Time and dates have become fungible. Concentration wanes. The mind is now clearly ebbing.

  Inside the folds of the brain, the progression is marked by a precise trail of pathology. Now the plaques and tangles have spread well beyond their starting point in the hippocampus. It is not clear how long they germinated there to begin with—five years? twenty-five years?—but in a rather short time they have now spread throughout the limbic system and leeched into the temporal, parietal, and frontal lobes of the cerebral cortex. Throughout much of the thinking brain, gooey plaques now crowd neurons from outside the cell membranes, and knotty tangles mangle microtubule transports from inside the cells. All told, tens of millions of synapses dissolve away.

  Because the structures and substructures of the brain are so highly specialized, the precise location of the neuronal loss determines what specific abilities will become impaired, and when—like a series of circuit breakers in a large house flipping off one by one:

  In the very beginning, when the hippocampus begins to degrade, memory formation fails.

  Then, when the nearby amygdala becomes compromised, control over primitive emotions like fear, anger, and craving is disrupted; hostile eruptions and bursts of anxiety may occur all out of proportion to events, or even out of nowhere.

  From there, tangles spread outward through much of the rest of the brain, following exactly the same pathways that sensory data travel in a healthy brain. One tangled neuron leads to another tangled neuron leads to another, like a pileup of cars after an accident.

  A preponderance of neurons in the brain, 80 percent, are devoted to so-called higher-order processing—finely tuned perception, analysis, comparison, recollection, anticipation, and abstraction—with the small remainder left for perceiving stimuli and behavioral response. Of the higher-order association areas, the temporal lobes, just inside from the ear on either side of the brain, are the closest to the hippocampus and therefore the next to bear the brunt of Alzheimer’s. Temporal lobes are responsible for primary organization of sensory input, for processing language, and for ecstatic feelings of spiritual transcendence. A healthy temporal lobe stimulated by an electrical probe can spontaneously produce powerful religious images, along with specific memories of songs and vivid hallucinations of friends’ faces. Not surprisingly, auditory and visual hallucinations are not uncommon in the middle and later stages of Alzheimer’s.

  Next in line are the parietal and frontal lobes. The parietal lobes, on top of the brain, extending to the rear, handle touch, vibration, pain, and spatial awareness. They enable the control of limbs and eyes, and the recognition of objects by physical contact. Damage to the sensory portions of the parietal lobe can cause astereognosis, the inability to understand the source or meaning of touch. The patient becomes an island, floating apart from the external world.

  When tangles finally reach the frontal lobes, which help to manage the retrieval of already formed memories, identity itself begins to vanish. A lifetime of memories exists in constellations all throughout the brain, but without a reliable system of retrieval, they’ll sit dormant forever. (The temporal lobe also plays a crucial role in accessing semantic—intellectual—memories.)

  The frontal lobes are also where most of what we consider intelligent thought takes place. Here is where massive amounts of sensory data are brought together, integrated and analyzed, where the brain makes sense of unfolding events, contrasts them with previous experience, adapts future plans based on that contrast. Once the frontal lobes come under heavy fire, the will itself begins to unravel, and, as one Alzheimer’s text puts it, “the chain of mental contents is no longer guided by a logically valid executive program.” The sufferer and her family cannot continue to treat her forgetfulness as a liability that can be overcome with Post-it Notes. It now becomes the dominant force in the patient’s life, a major disability.

  The list of cognitive abilities that dwindle in the middle stages of the disease is difficult for a cognitively healthy person to fully comprehend, because the functions lost are so basic. Memories are erased not just of specific events (grocery shopping last night), but general concepts learned long ago (what groceries are). Other central competencies that wither include:

  The ability to understand simple questions, instructions, gestures The ability to follow a conversation, or even to keep track of one’s own words or thoughts

  The ability to place oneself in the right time of day, or the right time of year

  The ability, even the desire, to plan for the future

  The ability to choose one’s own clothes and draw one’s own bath

  The ability to recognize one’s friends and relatives, or even one’s spouse

  The capacity for awareness (In these years, the sufferer loses all awareness of his or her condition. Introspection vanishes. This is known as anosognosia.)

  Perhaps the only practical way to understand such a catastrophic loss is to imagine oneself as a very young child who has not yet developed these abilities in the first place. “All actions of the bodie and minde are weakened and growne feeble,” a physician of King Henry IV of France said of old age in 1599. “The senses are dull, the memorie lost, and the judgment failing so that they become as they were in the infancie.” That same century, Erasmus suggested even more fully:

  Old men are more eagerly delighted with children, and they, again, with old men.… For what difference between them, but that the one has more wrinkles and years upon his head than the other? Otherwise, the brightness of their hair, toothless mouth, weakness of body, love of mild, broken speech, chatting, toying, forgetfulness, inadvertency, and briefly, all other their actions agree In everything. And by how much the nearer they approach to this old age, by so much they grow backward into the likeness of children, until like them they pass from life to death, without any weariness of the one, or sense of the other.

  Five hundred years later, caregivers use the same comparisons. “Not long after my [recently diagnosed] mother came to live with us, our daughter also came with her fourteen-month-old son,” Daisy from Raceland, Kentucky, told fellow caregivers via the Alzheimer List. “I find that what works with him also works with Mom, and they give the same angelic smile when pleased. On the downside, there is also the same tantrum at times and stamp of the foot. What I do to safety-proof the house for the baby also works as Nana-proofing, for the most part. The same behavior-addressing works as well. Often when he is cranky, it is due to some other influence—just like her. I have learned to read between the lines at both ends of the age spectrum. Sadly enough, he is learning to potty train at the time when my mom is losing that ability.”

  In 1980, New York University neurologist Barry Reisberg realized that the Alzheimer’s-childhood analogy is not just anecdotal—that it could be measured scientifically. Reisberg was a pioneer in defining stages and substages of Alzheimer’s, trying to gain a much more precise understanding of the disease’s trajectory. The more he drilled down on the exact order of abilities lost, the more he was impressed by the comparison to child development. He began to notice that there were precise inverse relationships between stages of Alzheimer’s disease and phases of child development in the areas of cognition, coordination, language, feeding, and behavior.

  He documented these observations in comparison charts. Placed side by side, the sequences of abilities gained and lost nearly perfectly mirror one another.

  CHILD DEVELOPMENT

  Age

  Acquired Ability

  1–3 months

  Can hold up head

  2–4 months

  Can smile

  6–10 months

  Can sit up without assistance

  1 year

  Can walk without assistance

/>   1 year

  Can speak one word

  15 months

  Can speak 5–6 words

  2–3 years

  Can control bowels

  3–4.5 years

  Can control urine

  4 years

  Can use toilet without assistance

  4–5 years

  Can adjust bath water temperature

  4–5 years

  Can put on clothes without assistance

  5–7 years

  Can select proper clothing for occasion or season

  8–12 years

  Can handle simple finances

  12+ years

  Can hold a job, prepare meals, etc.

  ALZHEIMER’S DISEASE

  Stage

  Lost Ability

  1

  No difficulty at all

  2

  Some memory trouble begins to affect job/home

  3

  Much difficulty maintaining job performance

  4

  Can no longer hold a job, prepare meals, handle

  personal finances, etc.

  5

  Can no longer select proper clothing for occasion or

  season

  6a

  Can no longer put on clothes properly

  6b

  Can no longer adjust bath water temperature

  6c

  Can no longer use toilet without assistance

  6d

  Urinary incontinence

  6e

  Fecal incontinence

  7a

  Speech now limited to six or so words per day

  7b

  Speech now limited to one word per day

  7c

  Can no longer walk without assistance

  7d

  Can no longer sit up without assistance

  7e

  Can no longer smile

  7f

  Can no longer hold up head

  In neurological exams, there were similarly precise inverse relationships in EEG activity, brain glucose metabolism, and neurologic reflexes. The only possible conclusion Reisberg could draw was that, like the winding and unwinding of a giant ball of string, Alzheimer’s unravels the brain almost exactly in the reverse order as it develops from birth. Clearly, the phenomenon warranted more formal study, and a name. Reisberg called it “retrogenesis”—back to birth.

  Retrogenesis is not a perfect reversal, of course—not literally the unwiring of the brain, neuron by neuron, according to some bizarre genetic instruction booklet. But the deconstruction is remarkably similar to the construction. What researchers realized in delving further into this comparison was that Alzheimer’s degeneration followed the opposite pattern of brain myelinization—the insulation of nerve axons with a white myelin sheath in order to boost the strength of their signals.

  Imagine a house thoroughly wired for electricity and phone use, but without any wire insulation—all the unprotected copper wires wrapped up together and touching one another. Infants are born with billions of neurons but almost no myelin insulation protecting these neurons, rendering them virtually useless. As neurons in various regions of the brain become insulated during child development, generating the femous “white matter” of the brain, these regions are brought online, made effective.

  We know much about child brain development, thanks to J. L. Conel, a Boston neuropathologist who in 1939 began painstakingly dissecting the brains of deceased children. Over nearly thirty years, he examined the cerebral cortex from brains aged one month, three months, six months, fifteen months, two years, four years, and six years.

  What he discovered comported with every parent’s experience of their growing child: The first neurons to gain myelin insulation are in the primary motor area, enabling gross movements of the hands, arms, upper trunk, and legs. Next come the primary sensory area neurons in the parietal lobe, bringing gross touch sensations online. After that comes some development of the occipital lobe for visual acuity, followed by the temporal lobe for auditory processing. Gradually, the association areas are then formed, allowing the brain to make more and more sense of the perceptions being registered. Symbolic processing areas then begin to develop slowly, enabling language. Eventually the frontal cortex matures, enabling concentration, abstract thought, and the ability to plan.

  One of the very last structures in the brain to be covered in protective myelin is the hippocampus, making it one of the last places to work effectively. This is why children generally don’t have any permanent memories prior to age three (although the amygdala can store some very early emotional memories).

  The reverse myelinization process of Alzheimer’s begins with the most recent and least-myelinated brain region—the hippocampus. From there it moves to the next least-myelinated, and so on. In this one respect, at least, the disease process makes sense. It has its own logic.

  For better or worse, the strange notion of reverse childhood turns out to be the best map we have to understand the terrain of Alzheimer’s. Think of a teenager you know today and try to imagine her rapid development suddenly halting and beginning to reverse course at roughly the same developmental pace. Over the next twelve years or so, she loses everything she has gained, slowly and steadily.

  First, she begins to lose her sense of humor and fashion sense. Now, watch her ambitions become less and less pronounced; then begin to peel away what she has learned from school and parents and peers and television over the last couple of years. Her sense of the world and her place in it fades away. Week by week she becomes not more but less articulate, less independent. She loses her Dairy Queen job because she has forgotten what “ice cream” and “cone” mean, and cannot add very well. As time ticks forward but seems to be going backward, she is now having a hard time picking out her own clothes; most of what she is saying you can no longer understand, and vice versa.

  Further imagine your backwards teenager traversing her way back to infancy, to her very first day of birth, her first breath, and you have a surprisingly good grasp of the unraveling of mind, soul, and body that Alzheimer’s inflicts on a person. Every skill, feeling, and fact that the patient has learned slowly, satisfyingly, is being steadily erased as if by some sort of cosmic punishment.

  The child analogy understandably rankles many caregivers. They are deeply offended at the suggestion that their mother or father or husband or wife is now to be regarded as a mere child. It feels like the ultimate insult one could inflict on someone. Not yet fully formed, children are regarded as incomplete persons. We love them, of course, and recognize them as human beings, but we do not fully trust them. We assume a certain responsibility and even moral superiority over them. To assume this same posture toward a parent or grandparent who has stood for a lifetime in a position of moral authority is a sad and sour thing. It is tragic and demoralizing to suddenly strip our esteemed elders of their authority and reposition them as untrustworthy and intellectually inferior.

  But the comparison is a valid, and even necessary, one to make. Here is an instance where scientists fighting disease and caregivers trying to make peace with a human tragedy can come to some common ground: the science of retrogenesis can help caregivers forge a new understanding and appreciation of what their loved ones are going through. Caregivers like Daisy from Raceland find the prism of second childhood helps ease both their chores and psychological strain. By viewing their loved ones as reverting back to childhood abilities and mentalities, caregivers can establish a more humane formula for their care. Whether or not it feels demeaning, retrogenesis can be instructive.

  As reverse childhood came to seem more and more medically relevant, Alzheimer’s researchers in the 1990s began dredging up everything known about developmental biology and psychology to test it for the possible application to their field. Colleagues of Reisberg, for instance, decided to test on severely demented patients a specially modified version of the Ordinal Scales of Psychological Development (OSPD), a test originally designed for in
fants and toddlers and based on Jean Piaget’s theories of development.

  This kind of ultra-basic testing had never been done before on Alzheimer’s victims. The testers stripped down the OSPD so that it required no vocal abilities at all. They designed it to measure five rudimentary skills:

  1. Visual pursuit and object permanence. Can the patient keep track of an object moving through an arc of 180 degrees?

  2. Means-ends. Can the patient reach out for an object, causing an event to occur?

  3. Causality. Does the patient react to a spectacle with an expression of understanding, such as a smile or frown?

  4. Spatial relations. Can the patient adjust her vision between two objects?

  5. Schemes. Can the patient visually inspect an object in her hands?

  The experiment worked beautifully. Using criteria initially crafted to measure infant development, the researchers found what they called “residual cognitive capacities” in advanced-stage Alzheimer’s patients who had previously been considered untestable.

  The implications of this discovery are enormous for the development of caregiving strategies for middle and late-stage Alzheimer’s patients. With new layers of understanding what patients are capable of and what they are no longer capable of at any specific stage of the disease, caregivers can be much more prepared. They can train themselves, in effect, to be competent reverse parents—not a skill that comes naturally.