Alzheimer's Disease: Everything You Need to Know

First Chapter

Chapter One

The First Case of Alzheimer's Disease

On a cold and colorless November afternoon in 1901, a distraught husband brought his wife to the mental asylum in Frankfurt am Main for treatment. She was examined by a young German neurologist, and even at that first encounter he was perplexed by her, unable to understand or diagnose her strange symptoms and behavior. In all his medical training and experience he had never seen a case quite like this. The woman was obviously suffering from a severe alteration in her mental function, similar to what he had often seen in the very old and senile. She had the same memory loss, the same difficulty with speech, the confusion and the general feebleness of reasoning. Yet she wasn't senile. She wasn't even very old. Her problem couldn't be diagnosed as "senile dementia" -- she was only 51!

Across the desk from him in the chilly examining room sat the woman, a housewife from Munich whose first name was Auguste. She appeared much older than her age. Her hair was disheveled, her clothes unkempt, and in her eyes was a wild, animal-like fear he had seen before in the mentally infirm and the truly insane. Her husband looked worn, almost haggard, but there was good reason for this. He had just finished describing his wife's unusual behavior over the last several months, and the story was heartbreaking.

She had been perfectly healthy for most of her life, had never been in the hospital, had rarely been sick. She'd worked as a laborer in a factory till they were married and children came. Now she was a Frau at home. She had been not only healthy but also happy, of even temper and trusting disposition --until she began to change.

He hadn't noticed it at the time but, looking back, he saw that the first hint of a problem had been her jealousy. They had enjoyed a good marriage -- she had always been devoted to him. But for some reason he could not understand, she had begun to grow distrustful of him, had accused him of being unfaithful to her and angrily confronted him on several occasions. These outbursts were violent and irrational. The poor man had pleaded his innocence in front of his frightened children and professed his love, but his wife would not be satisfied. The jealousy was bad enough, but soon she began to suspect him of tricking her, and became even more agitated. He realized after a while that her memory was the problem. She would forget where she had left things -- inconsequential things, such as her daughter's mittens -- then fly into a rage when she couldn't locate them and accuse him of stealing and hiding them from her. These confrontations occurred frequently, with much shouting and furious agitation directed at him, for he was the object of her wrath. Such explosive fits of temper were completely out of character for his wife. Sometimes he would find things hidden in bizarre places. One time he found her hairbrush in the oven, and another time he found his pipe tucked away in the clothes for the laundry. Several times she got lost when out walking in the neighborhood. Once she went to the butcher shop half a block away, where she had shopped for years, and got quite frightened when she couldn't find her way home. He had to accompany her to be sure she was safe whenever she left to do errands.

The situation worsened. She became confused and disoriented within the confines of their small apartment -- she couldn't remember where the bathroom was and she forgot the names of simple household objects such as the bed or the icebox. She could no longer cook. Not only could she not remember recipes, she couldn't remember what to do with pots and kitchen knives. She couldn't even set the table. And she had difficulty with the simplest tasks, such as dressing herself. It wasn't that she was physically incapable. Her hands and legs were still strong, and she thrashed about when she was angry -- her poor husband had to hold her to stop her from beating him, so he could attest to her strength. But she had lost the will to do these simple tasks, or perhaps the under-standing of the purpose behind them.

Then one night the screaming started.

Her sleep had been getting slowly worse over the months. As nighttime approached, she'd become more confused and agitated. When she finally did fall asleep (usually quite late) she often awakened later and left the bed. Her husband would follow in the dark to be sure she was safe, and watch her wander around the small apartment. Sometimes she would just stand still in the hall, or sit in a chair with a bewildered look on her face. The night she woke up screaming, she would not be soothed. The sound was unnatural, hideous. She was certain that she was about to be murdered and kept yelling, "No! No! Stop! Please!" The neighbors banged on the door to offer assistance and the husband had to assure them that his wife was simply having a bad dream.

The days that followed were agonizing. She'd pace the apartment for hours on end, sometimes dragging small pieces of furniture or bedclothes with her. Then suddenly she would pause in her wandering, cock her head as if listening and shout an answer to some voice only she heard.

The couple's life was in ruins. At last the husband had brought his wife to the hospital for examination.

The portly neurologist reviewed his notes and considered the case. Although Auguste's mind was clearly gone, she had no infirmity in her body. The diagnosis wasn't insanity, nor was it any of the other mental diseases he had seen so often before. This wasn't the general paralysis of the insane seen in syphilis, or the dementia of schizophrenia. Nevertheless, it was clear that the pitiable woman in front of him had a rapidly progressive mental disease, and that she could no longer be looked after safely at home. He signed the admission papers, and she was led away into the asylum.

This encounter between the German neurologist and the Frau produced the first detailed description of a dementia, or loss of thinking power, that had not been recognized before, one that afflicted the middle-aged and those in their prime. We know the woman only as "Auguste D." Her personality is lost to history; her particulars, aside from the details of her illness, are forgotten. The name of the doctor, however, has become a household word. He was Dr. Alois Alzheimer.

Dr. Alzheimer

Alois Alzheimer was born in 1864 in the village of Markbreit, just outside of Wurzburg in southern Germany. Following secondary school, the young Alzheimer studied medicine at the universities of Wurzburg and Berlin. He graduated in 1887, after writing his final-year thesis on the functioning of the wax-producing glands of the ear. Alzheimer spent his first six months as a physician accompanying a mentally ill woman on her travels. This kind of posting was common for young physicians, and the experience gave him an interest in psychiatry and brain disorders. At the time physicians hotly debated whether the causes of mental illness were medical -- that is, related to some disease of the brain or nervous tissue causing malfunction -- or psychological, rooted in emotional trauma, as the influential Viennese psychiatrist Dr. Sigmund Freud claimed. Later Alzheimer obtained a job as medical officer at the mental asylum in Frankfurt am Main. By the time he met Auguste D., Alzheimer was 37 and had already established himself as a leading neurologist. He had published studies on epilepsy, brain tumors, syphilis, hardening of the arteries of the brain and other topics, and was known for his meticulous correlation of the clinical course of his patients -- their complaints and his findings in hospital -- with the changes that he observed after their deaths when he examined their brains under the microscope at autopsy.

Auguste's Fate

For the next four years Auguste lived in the insane asylum in Frankfurt where Dr. Alzheimer was the admitting neurologist. They were years of anguish for both her and her family. The poor woman didn't know where she was or who she was, and after several months she failed to recognize even her husband or daughter. At first she wandered the halls of the hospital constantly, dragging sheets and bits of bedding, calling out for help. She said that she couldn't understand why she was there, that she felt confused and totally lost. She couldn't remember where her room was, nor was she able to recognize Dr. Alzheimer on his rounds. Sometimes she considered his coming an "official visit," and would apologize for not having completed her work; other times she would just scream in fear and misery. On several occasions Auguste sent the doctor away with a string of curses, telling everyone in attendance that he was making sexual advances toward her. She had a curious way of talking and would mix up words, often not using the precise word needed but rather words of similar or related meaning -- she would say "milk jug," for example, instead of "cup." Many nights she screamed for hours, a horrible, inhuman wail that echoed up and down the dark stone corridors of the asylum.

Auguste worsened year by year. Eventually she became bedridden, forced by contractures to lie on her side like an infant, her legs drawn up and her arms curled across her chest. She had large, fetid bedsores and was incontinent, and she was completely unaware of her surroundings. Four and a half years after her disease had first shown itself as jealousy toward her husband, Auguste D. died at the age of 55, undiagnosed and alone, a frail shell of the woman she had once been.

The Signs in Auguste's Brain

For four years, as he watched her decline in the asylum, Dr. Alzheimer was puzzled by the strange mental disease of Auguste D. But it was only several days after she died -- after her brain was removed from her skull and stained so that various cell types could be identified -- that the neurologist was able to investigate the disease that had so ravaged his patient.

He began by studying her brain as a unit. After weighing it, he held it gently in his hands and turned it round and round, inspecting its minute details. It was certainly smaller than it should have been, perhaps by a third, and lighter than expected, and it appeared shriveled. Normally, the outer layer of the human brain is so massive and well developed that it must fold back on itself to fit inside the skull. The resulting accordion-like pleats of this outer layer of brain are known as the cerebral cortex (cortex from the Latin for "tree bark"; the human cortex looks like wet bark). Alzheimer noticed immediately that these pleats were much thinner than usual in Auguste D., with wide areas between them -- as if the very tissue of the brain had wasted away.

Next, Alzheimer looked through his microscope at thinly sliced pieces of brain tissue. As a result of advances in staining techniques and German optics technology, he had become one of the leading European specialists in diseases of the brain, particularly the microscopic changes evident in the various disorders that cause neurological signs. What he saw in the brain of Auguste D. were the characteristics of a new dementia.

The first thing Alzheimer noted was that many of the expected brain cells were not visible -- they were simply not there. He could see the empty sites where they had once been, but the neurons (the basic cells of the brain responsible for all neurological thinking and activity) had disappeared.

Brain Cells Choked by Strange Tangled Fibers

Many of the remaining neurons were definitely not normal--in their cell bodies they had strange, threadlike, spindle-shaped objects that were very prominent and absorbed the stain well, becoming dark under the microscope. Some cells had only one or two of these unusual filaments, but in other cells the fibers were matted side by side in bundles so thick that they appeared to be choking the neurons. In the worst cases, the neurons had all but disappeared, leaving only a tangled mass of coarse, ropelike structures. Alzheimer called these filaments "fibrils" -- meaning small fibers -- and the presence of groups of these fibers in layers throughout the cerebral cortex is a diagnostic microscopic sign of Alzheimer's disease.

These "neurofibrillary tangles" (as Alzheimer labeled them) appeared in many cells in Auguste's brain -- he estimated between one-quarter and one-third of the brain had the dark, threadlike rods that filled up and overpowered the normal cells. No wonder the poor woman couldn't reason properly! Alzheimer postulated that since the fibrils had stained differently from normal brain tissue, and since they had survived the destruction of the cell, they must have undergone some sort of chemical transformation. He wrote: "It seems that the transformation of these fibrils goes hand in hand with the storage of an as yet not closely examined disease-producing product of metabolism in the neuron." Time has shown the careful German neurologist to be right. Understanding the cause of the twisted fibers he observed is crucial to understanding the disease process.

Plaquelike Scars in the Brain

There were other unusual microscopic findings. Dispersed over the entire surface of the brain, the barklike cortex, were large numbers of thick, viscous-looking blobs that Alzheimer called "plaques." Through the microscope it looked as if someone had splattered globs of paint across the cortex. These plaques were so prominent that they could be recognized even on a cut section of the brain that had not been stained, as a large number of dense, irregularly edged black spots -- very foreign-looking, like microscopic craters in a biological battlefield. The unusual plaques had been identified before, in the brains of the very old -- Alzheimer recognized them as the so-called senile plaques. These three pathological changes in the brain -- the loss of brain cells, the mats of destructive fibers he called "neurofibrillary tangles" and the senile plaques -- were Alzheimer's chief findings after he examined Auguste's brain. A century later, they remain the basis for the microscopic diagnosis of the disease.

Several months after the autopsy on Auguste was concluded, Alzheimer presented the case to a group of psychiatrists at a meeting in southern Germany in 1906 -- with the first published description of this new dementia. He stressed the clinical deterioration in one so young, the shrunken brain and the presence of so many senile plaques along with the strange tangles of fibrils. He concluded that "It is evident that we are dealing with a peculiar little-known disease process." How prophetic his conclusion was!

Alzheimer's Later Years

At the time he presented the strange case of Auguste D., Dr. Alzheimer was at Heidelberg University, where he taught neurology and histology, the newly founded science of examining diseased tissue microscopically. He was a revered teacher and students came from all around the world to his laboratory. He smoked constantly and used to set down his lit cigar beside a student's instrument in order to demonstrate the significant points of the microscopic examination. So enthusiastic and absorbed was he that by the end of the day half-smoked cigars sat beside every microscope. Others began to refer to the case not as that of Auguste D., but as the disease Dr. Alzheimer had observed. (The habit of naming a disease after the physician who first described it was well established at the time -- Parkinson's disease and Huntington's chorea are well-known examples.) Soon other neurologists began to recognize similar cases, and confirmed Alzheimer's microscopic findings as being diagnostic.

In 1912, Alzheimer accepted a position as full professor at University Hospital in the German town of Breslau. As he was traveling by train to his new appointment, he fell ill with acute streptococcal tonsillitis -- "strep throat." Before the age of antibiotics, tonsillitis was a serious infection, and he spent several weeks in hospital. He was left with heart damage from rheumatic fever, a complication of his tonsillitis, and spent the next three years in the hospital with increasing weakness and heart disease. He died in 1915 of endocarditis, a form of heart valve infection, and kidney failure. He was 51 years old -- the same age as Auguste D. when she first came to him with the strange disease that now bears his name.

How Common Is Alzheimer's Disease?

"The disease of the century" is what the scientist Lewis Thomas called Alzheimer's, and there is good evidence to support his claim. Fear of "losing one's mind" is the greatest single worry of our aging population; this dread of loss of mental faculties, and thus of personal control, is greater than the fear of cancer, heart disease, arthritis or other painful conditions, or indeed any other aspect of aging. Unfortunately, for many seniors this fear becomes a terrifying reality.

The incidence of Alzheimer's -- and other dementias -- is directly related to age. Though some verified cases have been diagnosed in people still in their twenties, these are exceedingly rare, as is the diagnosis before the age of 50. From studies done around the world we know that dementia occurs in approximately 8 percent of all people over 65, though the incidence varies from country to country and study to study. It occurs in approximately 25 percent of those over 80, and up to 40 percent of those over 90. This means that almost one in ten of the population we consider "seniors" has dementia of some kind. It also means that of those who survive to age 90 or greater, about one in three will be demented.

These days our population is aging and our life expectancy is increasing. Five hundred years ago it was unusual to be aged; people died younger. Over the past several centuries, improvements in nutrition, public health measures to prevent disease and illness and advances in medicine have protected us from premature death, so that a larger and larger percentage of our population lives decades longer. Because we are living longer, degenerative brain diseases such as Alzheimer's now pose a major health problem to our society. With further improvements in medical care, we expect that a larger percentage of our population will be able to live comfortably into their eighties and nineties -- and this means that the incidence of Alzheimer's disease will rise dramatically over the next few decades. Half the children born in Canada this year are expected to live 81 years or more, and approximately one in four will develop a severe dementia such as Alzheimer's. Alzheimer's disease has become the fourth-leading cause of death in the United States, and one family in three has a member with a dementia problem. By enabling our citizens to grow older, we have changed the pattern of disease and death in our society.

Alzheimer's in Canada

To understand the scope of these changes, consider the figures for the aged population in Canada. In 1900, 5 percent of Canadians were over 65. The figure rose to 10 percent in 1991. It was predicted to reach 12 percent by the year 2000, and it is projected that by 2031 fully 21 percent of Canadians will be over 65. This means that over only a century and a third the percentage of Canadians over 65 will have more than quadrupled -- an incredible increase.

Alzheimer's disease is reported to be by far the commonest type of dementia. A 1994 study estimated that by 2002 more than 300,000 Canadians would suffer from Alzheimer's. There are 10,000 new cases diagnosed each year -- 27 cases a day. Twice as many females as males are diagnosed as having dementia in Canada and, as elsewhere in the world, the prevalence of dementia of any kind is very much age related. In Canada only 2.4 percent of those aged 65 to 74 are demented, but this figure rises to 34.5 percent in those 85 or older. As the Canadian population ages, the incidence of dementia is predicted to increase dramatically. According to the same study, by the year 2030 three-quarters of a million cases of dementia are expected in Canada -- an increase of 300 percent over present figures; the population will have increased by only 40 percent.

The cost of caring for dementia is incredibly high -- higher than the cost of caring for stroke and cancer combined. In Canada this cost was estimated in 1991 at $3.9 billion -- 6 percent of the nation's total health costs for that year. The 1994 study estimated that by the year 2030 the cost would rise to $12 billion a year. (A new study is expected in the near future.)

Alzheimer's in the U.S.A.

The situation is similar in the United States. It is estimated that in 2000 Alzheimer's disease affected four million Americans and that it kills 100,000 each year, and these figures will become even more alarming as the nation ages. In 1900 there were three million seniors (over age 65) in America, and in 1980 there were 25 million -- an eightfold increase. It's estimated that there were about 31 million people over the age of 65 in the year 2000. The figures are even more startling for the "very old," those over 75. In 1900 there were only 900,000 "very old" in the U.S., but by 1980 there were 10 million. (There are presently over 50,000 seniors in the U.S. who are over 100 years old.) According to estimates, in the year 2000 there were more than 13 million persons over age 75 living in the U.S., and approximately one in four of them was demented.

The cost of caring for those with Alzheimer's disease in the United States in 1992 was estimated at $100 billion a year -- a figure that is almost unimaginable.

Alzheimer's As a Global Problem

By the year 2020 there will likely be a billion people on this planet who are over age 60, and it seems clear that as the population ages, the incidence of Alzheimer's disease (and other dementias) will rise proportionately. Each of the individuals with Alzheimer's will survive an average of nine years, and most will require ongoing care either at home or in the hospital for the duration of their illness. They will have a progressive decline in mental function to the point where they are no longer able to look after themselves and are completely dependent on others for their safety, personal hygiene, nutrition and medical care. This will place an incredible burden on the health care systems of our countries, as well as be an over-whelming practical and emotional responsibility for our citizens and families.