new terrain, a person’s independence could no longer be taken for granted.
In the summer of 1984, at the age of eighty-five, E. B. White, the tender essayist and author of Charlotte’s Web, became waylaid by some form of dementia. It came on very swiftly. In August, he began to complain of some mild disorientation. “We didn’t pay much attention,” recalls his stepson, Roger Angell, “because he was a world-class hypochondriac.” But just a few weeks later. White was severely confused much of the time. By the following May, he was bedridden with full-on dementia, running in and out of vivid hallucinations and telling visitors, “So many dreams—it’s hard to pick out the right one.” He died just a few months after that, in October 1985.
An obituary in the New York Times reported White as having Alzheimer’s disease, but that appeared to miss the mark. In fact, he was never even informally diagnosed with the disease, and his symptoms strongly suggested another illness. The rapid onset of the confusion and the abrupt shift from one stage to the next were classic signs of multi-infarct dementia, the second-most common cause (15 percent) of senile dementia after Alzheimer’s (60 percent). Multi-infarct dementia is caused by a series of tiny strokes. Its victims can have much in common with those of Alzheimer’s, but the experience is not as much of an enigma. Its cause is known, somewhat treatable, and, to a certain extent, preventable (diet, exercise, and medication can have an enormous impact on risk of strokes). Its jerky, stepwise approach is easier to follow and understand as symptoms worsen.
Alzheimer’s disease is not abrupt. It sets in so gradually that its beginning is imperceptible. Creeping diseases blur the boundaries in such a way that they can undermine our basic assumptions of illness. Alzheimer’s drifts from one stage to the next in a slow-motion haze. The disease is so gradual in its progression that it has come to be formally defined by that insidiousness. This is one of the disease’s primary clinical features, one key way that Alzheimer’s can be distinguished from other types of dementia: those caused by strokes, brain tumor, underactive thyroid, and vitamin deficiency or imbalance in electrolytes, glucose, or calcium (all treatable and potentially reversible conditions).
It is also nearly impossible to officially diagnose. A definitive determination requires evidence of both plaques and tangles—which cannot be obtained without drilling into the patient’s skull, snipping a tiny piece of brain tissue, and examining it under a microscope. Brain biopsies are today considered far too invasive for a patient who does not face imminent danger. Thus—Kafka would have enjoyed this—as a general rule, Alzheimer’s sufferers must die before they can be definitively diagnosed. Until autopsy, the formal diagnosis can only be “probable Alzheimer’s.”
These days, a decent neuropsychologist can maneuver within this paradox—can make a diagnosis of probable Alzheimer’s with a confidence of about 90 percent—through a battery of tests. The process almost always begins with this simple quiz:
What is today’s date?
What day of the week is it?
What is the season?
What country are we in?
What city?
What neighborhood?
What building are we in?
What floor are we on?
I’m going to name three objects and I want you to repeat them back to me: street, banana, hammer.
I’d like you to count backwards from one hundred by seven. [Stop after five answers.]
Can you repeat back to me the three objects I mentioned a moment ago?
[Points at any object in the room.] What do we call this?
[Points at another object.] What do we call this?
Repeat after me: “No ifs, ands, or buts.”
Take this piece of paper in your right hand, fold it in half, and put it on the floor.
[Without speaking, doctor shows the patient a piece of paper with “CLOSE YOUR EYES” printed on it.]
Please write a sentence for me. It can say anything at all, but make it a complete sentence.
Here is a diagram of two intersecting pentagons. Please copy this drawing onto a plain piece of paper.
This neurological obstacle course is called the Mini Mental State Examination (MMSE). Introduced in 1975, it has been a part of the standard diagnostic repertoire ever since. The MMSE is crude but generally very effective in detecting problems with time and place orientation, object registration, abstract thinking, recall, verbal and written cognition, and constructional praxis. A person with normal functioning will score very close to the perfect thirty points (I scored twenty-nine, getting the date wrong). A person with early-to-moderate dementia will generally fall below twenty-four.
The very earliest symptoms in Alzheimer’s are short-term memory loss—the profound forgetting of incidents or conversations from just a few hours or the day before; fleeting spatial disorientation; trouble with words and arithmetic; and some impairment of judgment. Later on, in the middle stages of the disease, more severe memory problems are just a part of a full suite of cognitive losses. Following that, the late stages feature further cognitive loss and a series of progressive physical disabilities, ending in death.
One brilliantly simple exam, the Clock Test, can help foretell all of this and can enable a doctor to pinpoint incipient dementia in nine out of ten cases. In the Clock Test, the doctor instructs the patient to draw a clock on a piece of paper and then draw hands to a certain time. Neurologists have discovered that patients in the early stages of dementia tend to make many more errors of omission and misplacing of numbers on the clock than cognitively healthy people. They’re not entirely sure why this is, but the accuracy of the test speaks for itself.
A battery of other performance tests can help highlight and clarify neurological deficiencies. The Buschke Selective Reminding Test measures the subject’s short-term verbal memory. The Wisconsin Card Sorting Test gauges the ability to deduce sorting patterns. In the Trail Making Test, psychomotor skills are measured by timing a subject’s attempt to draw a line connecting consecutively numbered circles. Porteus Mazes measure planning and abstract-puzzle-solving ability.
If the patient performs poorly in a consistent fashion, the next step will likely involve elaborate instruments. Conveniently for physicians, Alzheimer’s disease always begins in the same place: a curved, two-inch-long, peapod-like structure in the brain’s temporal lobes called the hippocampus (the temporal lobes are located on either side of the head, inward from the ear). Doctors can get a good look at the hippocampus with a magnetic resonance imaging (MRI) scanner, which bombards the body with radio waves and measures the reflections off tissue. A simple volume measurement of the hippocampus will often show, even in the very early stages of Alzheimer’s, a pronounced decrease in volume, particularly in contrast with other brain structures. By itself, the MRI cannot diagnose Alzheimer’s. But it can add one more helpful piece to the diagnostic puzzle.
Other advanced measurements might also help: A positron emission tomography (PET) scan may detect a decrease in oxygen flow or glucose metabolism in the same area. A single photon emission computed tomography (SPECT) scan may catch decreases in blood flow. A moderate to severe amount of slowing in the alpha rhythm in an electroencephalogram (EEG) is often characteristic of dementia. But such measurements are generally not required for a tentative diagnosis. In the face of convincing results from memory and performance tests, and in the absence of any contravening evidence—disturbance in consciousness, extremely rapid onset of symptoms, preponderance of tremors or other muscular symptoms, difficulties with eye movements or reports of temporary blindness, seizures, depression, psychosis, head trauma, a history of alcoholism or drug abuse, any indication of diabetes, syphilis, or AIDS—a diagnosis of probable Alzheimer’s is rendered.
Alzheimer’s disease. The diagnosis is a side-impact collision of overwhelming force. It seems unreal and unjust. After coming up for air, the sufferer might ask, silently or out loud, “What have I done to deserve this?” The answer is, simply, nothing. “I remember walking out of the clinic and into