Karl was bewildered. At the time illnesses like this were extremely uncommon in someone of Auguste’s age, and overall rare in the population because living much beyond your sixties in 1901 was a rarity in itself. At a loss, Karl took his wife to one of the most highly regarded psychiatric clinics in the world: the Asylum for the Insane and Epileptic in Frankfurt, which had a nickname indicative of the attitudes towards mental illness at the time: ‘The Castle of the Insane’.
Auguste’s illness is the first reported case of what we now know as Alzheimer’s disease, the most common cause of dementia. Dementia is an umbrella term encompassing a constellation of brain disorders–such as vascular dementia, Lewy body dementia and fronto-temporal dementia–all of which involve a gradual loss in several aspects of cognition including memory, language, attention, orientation and problem solving. It often manifests as personality changes, depression, paranoia, agitation, delusions and even hallucinations.
The sheer breadth of faculties under assault fosters much confusion when faced with an Alzheimer’s victim. This was certainly true when it came to my grandfather. His four children, including my father, never truly accepted his diagnosis. They maintained that Abbas could be a curmudgeonly and somewhat eccentric character. They only recognised the term Alzheimer’s as something abstract–a hazy miscellany of a crumbling mind. Our family certainly had little concept of a cause of dementia, let alone the existence of dementia subtypes. We know now that to say someone has dementia is like saying they have cancer without identifying which type of cancer. And so, just as melanoma is a type of cancer, Alzheimer’s is a type of dementia.
We now know that Alzheimer’s is distinguished from other dementias by its unique effect on parts of the brain that control thought and memory, as well as its characteristic pattern of structural and chemical changes that can be seen with brain imaging and post-mortem examinations–appearing as catastrophic nerve cell death, and plaques and tangles of toxic proteins scattered throughout the brain. Plaques, in pure biological terms, are sticky proteins that clump together in the spaces between nerve cells. Tangles are also clumps of sticky proteins, but they form inside nerve cells and are more threadlike in appearance. Both are thought to be a kind of molecular ‘garbage’ that distorts healthy brain function and ultimately leads to Alzheimer’s. In truth, however, we’re still not entirely sure what they are, why they form, or how they cause the disease. This urgently needs to change. According to the World Health Organization (WHO), Alzheimer’s is now estimated to account for 70 per cent of all cases of dementia.1
But it took a long time to get this far.
For centuries, mental illness was thought to be the work of spirits and gods. In the book of Deuteronomy, the ancient Hebrews interpreted disordered thoughts as a curse from God for all who disobey Him: ‘The Lord will strike you with madness and blindness and confusion of mind.’2 Dementia was so poorly understood it was regarded along similar lines: those who had it were mad or just foolish. It was a time when unfounded beliefs held sway, and people tried to treat such illnesses by ‘trepanation’, drilling holes into the skull to release evil spirits. Greek and Roman philosophers sought to bring about a change through observation and scientific rationalism.
One of the earliest accounts of what we could call dementia was by the sixth-century BC mathematician Pythagoras, who described it as an inevitable outcome of old age; a period, in his words, where ‘the scene of mortal existence closes, after a great length of life, to which, very fortunately, few of the human species survive. The system returns to the imbecility of the first epoch of infancy.’3 The word ‘imbecility’ came from the Latin imbecillus, meaning ‘weak-minded’. According to Pythagoras, human life followed the seasons–old age is winter, and so its changes, however severe or unpleasant, were natural. But others thought there was more to it.
Cicero, the Roman philosopher, was among the most vital advocates in this regard. He thought dementia affected ‘only those who are weak in spirit and will’.4 A misguided theory of course, but it was the first whisper of the notion that dementia is not an inevitable product of old age. He took things further by suggesting that exercise might even prevent such decline, which was highly progressive given what I discuss later in this book. Building on his work, the Greek physician Aelius Galenus, better known as Galen, continued to buck conventional wisdom by describing patients suffering from what he called morosis (mental slowness), elderly people whose ‘knowledge of letters and arts are totally obliterated. Indeed, they can’t even remember their own names.’5 Galen shattered the ancient, irrational views his predecessors had created, recasting dementia as a medical problem worthy of deeper investigation.
However, the period that followed was almost disastrous. The Middle Ages saw a return to supernatural explanations for disease–dementia was a test of faith, a devil to be exorcised, a ‘consequence of the original sin’,6 and many sufferers were branded as witches. Even so, Christian-Judaeo beliefs also inspired a great deal of humanitarian thinking in the more enlightened. Brain diseases were looked upon with compassion and the care of the mentally ill became a religious obligation. Rational therapies, such as diets, baths and herbal medicines, came into practice: salad greens, barley water and milk, for example, were encouraged to replace red meat and wine; others endorsed a blend of aloes, black hellebore and colocynth.7
When the Enlightenment began, a string of discoveries in physics, chemistry and medicine–by Isaac Newton, Joseph Priestley, John Dalton, Luigi Galvani, Alessandro Volta and Edward Jenner–pointed towards the possibility of physical explanations for mental phenomena. The French philosopher René Descartes thought that experiences make tiny pores in the brain like needles making a pattern of holes in a linen cloth.8 David Hartley, the eighteenth-century English physician, claimed that nerve vibrations create sensations and memory, and that violent vibrations are the cause of mental illness.9 These ideas were vague and incomplete, but they were free of mysticism and the supernatural.
A tipping point arrived when the French psychiatrist Philippe Pinel became the first to separate discrete types of mental disorders from the broad-brush label of insanity; it was not good enough, he said, to call these patients ‘mad’. At the Bicêtre Hospital in Paris, Pinel called for compassion and non-violence when caring for the mentally ill. He spent hours talking to his patients and insisted that they be unshackled from their iron chains. Driven to study mental illness after the suicide of a close friend, Pinel used the term ‘dementia’ (démence, ‘out of one’s mind’) in 1797, ushering in the modern age of psychiatry.10 In 1838 his most talented student, Jean-Étienne Esquirol, fiercely denounced any remaining stigma: ‘A demented man has lost the goods he used to enjoy; he is a wealthy person turned poor. An idiot, by contrast, has always been unfortunate and poor.’11
Twenty-six years later, on 14 June 1864, Alois Alzheimer was born.
Alzheimer grew up in the small Bavarian town of Marktbreit, a place of fairy-tale houses and cobblestone streets, Roman castles and Catholic jurisprudence. His father, Eduard Alzheimer, was a lawyer who had lost his first wife to puerperal fever. After a year of grieving Eduard married her sister, Theresia, and the couple had six children together. Alois was the eldest.
In 1883, aged nineteen, he was the first in his family to apply to medical school and obtained a place at the University of Berlin, where the world’s brightest medical minds were already making history. It had been there, in 1858, that the humble-looking polymath Rudolf Virchow made great leaps in our understanding of basic biology. Virchow argued that cells, the basic structural unit of all organisms, were the roots of all disease. ‘The body,’ he wrote, ‘is a cell state in which every cell is a citizen. Disease is merely the conflict of the citizens of the state brought about by the action of external forces.’12
After five years of study surrounded by these ideas, Dr Aloysius ‘Alois’ Alzheimer was licensed to practise medicine for the German Empire. His interest was in psychiatry, so he applied fo
r an intern position at the Frankfurt Mental Asylum and was chosen for the job on the same day the application was received. When Alzheimer arrived at the asylum there was certainly no shortage of work to be done. The director, Emil Sioli, desperately needed help after the asylum’s sole medical assistant retired and the only relief doctor on duty had accepted a job offer elsewhere. The twenty-four-year-old Alzheimer was faced with 254 patients and one exhausted mentor.
Though magnificent from the outside, the inside of the asylum was anything but. Like most things German at the time, it aimed to set the standard for ingenuity and so imposed the modern ‘non-restraint’ principle of treating patients, designed by the English psychiatrist John Conolly for a more humane treatment of the mentally ill. Straitjackets were forbidden. But as Alzheimer found out, this approach was not without its downsides: non-restraint also meant no forced feeding, bathing or cleaning. And with so many patients and so few staff, conditions soon spiralled out of control. As Alzheimer mused:
Everywhere cursing, spitting patients sat around in the corners, repulsive in their manner, peculiar in their dress, and completely inaccessible to the doctor. The most unclean habits were quite common. Some patients appeared with pockets filled with all sorts of waste, others had masses of paper and writing materials hidden all over the place and in big packets under their arms. When one had to finally follow the rules of hygiene and do something to get rid of the filth, one could not proceed without resistance and loud cries.13
Alzheimer immediately began to make changes. He introduced long baths where particularly uncontrollable patients could wind down; large consultation rooms where the doctors could talk and develop a dialogue with the patients; and special rooms designated solely for the microscopic examination of brain tissue. In this setting Alzheimer dived head first into research. Inspired by his years at Berlin University, he spent hours at the microscope, analysing hundreds of patient samples. The hunt for the biological origin of brain disease had begun.
But Alzheimer needed the right tools, and that’s exactly what his like-minded peer, Franz Nissl, provided. A twenty-nine-year-old physician from Munich, Nissl had been working on a technique he had discovered as a medical student half a decade earlier. Using a variety of chemical dyes with exotic names such as cresyl violet and toluidine blue, Nissl stained thin slices of brain tissue to see if they would show structures in the brain never before seen. The images he produced were striking. The detail of individual nerve cells–their size, shape, position and internal components–were suddenly visible to the human eye in bright colour. The ‘Nissl stain’ became a sensation, and scientists around the world used it to reveal a host of different brain structures. Alzheimer himself described it as ‘quite superb’.
With his transformation of the asylum, championing of the microscope, and a number of great thinkers by his side, Alzheimer’s career flourished. He gave lectures around the country where he talked about bizarre patient cases and showed beautiful images of his latest microscopic examinations using the Nissl stain. His peers called him ‘the psychiatrist with a microscope’.
In 1894 an extremely wealthy woman called Cecilie Geisenheimer, the widow of a diamond dealer, was bold enough to ask Alzheimer to marry her. Alzheimer had met her in Algeria, where he was sent to treat her husband, Otto Geisenheimer. Otto and Cecilie had been travelling around North Africa on a scientific expedition when he fell ill with general paresis (a neuropsychiatric disorder caused by late-stage syphilis). The situation was grave, and so Alzheimer, whose reputation now preceded him, was asked to accompany the couple back to Germany. They made it as far as the south of France before Otto died in a hospital in St Raphael. In the years that followed Alzheimer watched over Otto’s widow and the couple became close. Cecilie was a ‘highly educated woman with great heartfelt kindness’, one of their granddaughters later remarked.14 The couple were married on 14 February 1895, and had three children together. Alzheimer’s happiness, both professionally and personally, had reached its peak.
Six years later, aged forty-one, Cecilie died of suspected kidney disease. Alzheimer was devastated. Life had been going so well for him but now he was left with three young children to raise alone. His unmarried sister, Elisabeth, took on the role.
Nine months passed. On 26 November 1901 the grief-stricken Alzheimer was working diligently at the asylum. He’d been burying himself in work, seeing more patients and working later into the night than ever before. Little did he know that the patient who would make his name echo through history was now sitting in front of him eating cauliflower and pork for lunch.
The newly admitted Auguste Deter intrigued Alzheimer. One minute she would appear calm and lucid, the next frightened and confused, roaming the ward and grappling other patients’ faces. Alzheimer interviewed her extensively, asking her to identify a series of objects: a pencil, a book, a bunch of keys. These small confusions are often the things that stick in the mind of those who first notice the onset of Alzheimer’s in a loved one: car keys are found in the fridge, clothing in the kitchen cabinet, objects like kettles and mail can disappear and then turn up somewhere completely unexpected. When asked to write down her name, Auguste began with ‘Mrs’ but would then forget the rest–something Alzheimer had never seen before. He first called it ‘amnestic writing disorder’.
Over the next few months Auguste became increasingly disorientated, forgetful and mentally unhinged. Hauntingly, she would often look Alzheimer in the eyes and repeat the words: ‘I have, so to speak, lost myself.’
Alzheimer was fascinated. Auguste’s condition fitted previous descriptions of dementia, of a confused state that still had no better explanation than normal ageing. But surely, at fifty-one she was still too young for that. He examined her every day, looking for subtle clues in behaviour that could shed light on the underlying disturbance. But Auguste’s condition deteriorated to the point where Alzheimer could no longer gain any meaningful insight. In May 1902 his final entry in her medical record reads: ‘Auguste D. remains hostile, screams, and lashes out as soon as one tries to examine her. She also screams spontaneously and then often for hours, so that she has to be held in bed. As far as food is concerned, she no longer keeps to prescribed meal-times. A boil has formed on her back.’15
Having done all he could with such an impenetrable disorder, Alzheimer moved on. There was little he could glean while Auguste was still alive. And he had been offered a position in the clinic of world-renowned psychiatrist Emil Kraepelin, in Munich. After fifteen years, Alois left the Frankfurt Castle of the Insane.
It was a wise decision. Though only six years Alzheimer’s senior, Kraepelin had gained international fame with the publication of various psychiatry textbooks in which he declared his conviction that all mental disorders are biological in origin–a conclusion Alzheimer had already been moving towards.
This idea, however, met resistance. The theories of Sigmund Freud had already taken hold of both the public and scientific imagination in Germany, and in doing so gave rise to a scientific factionalism that would ultimately cost Alzheimer his audience in November 1906. Sigmund Freud’s imaginative and beautifully crafted ideas on how the mind works and why it becomes disturbed were highly alluring. Childhood repression, the Oedipus complex, the id, ego and superego were just some of the ingenious concepts Freud espoused to explain the source of psychiatric diseases–which, he claimed, could be completely remedied using the subtle art of psychoanalysis. And in a time where so little hope of a cure for mental illnesses existed, it was no surprise that the Austrian physician’s new outlook enraptured so many.
Back in Frankfurt, Sioli kept a close eye on Alzheimer’s most important patient. But Auguste’s castaway mind had now come to the end of its journey. On 6 June 1906 Alzheimer was informed of her death. He requested that Auguste’s brain be sent to him for a post-mortem at his new laboratory in Munich.
The first thing Alzheimer noticed from the small, soft, slightly off-white ball of tissue–now sitting on his
laboratory bench–was just how small it was. There was a large loss of brain tissue throughout the cerebral cortex–the top layer of the brain–and this seemed to be the result of a catastrophic extinction of nerve cells. Bordering these biological ruins were also what looked like scars made up of other cell types. When Alzheimer peered down the microscope, the most perplexing omen of all appeared.
Peppered throughout the brain were dark particles of an unknown substance. They appeared to have nestled themselves in the spaces between nerve cells. Some were much larger than the surrounding cells, others smaller. And unlike the shrivelled form of dying brain cells, these particles possessed a rugged, patchy texture that clearly marked them as separate entities. What these particles–or plaques, as they later came to be known–consisted of, and where they came from, was a mystery. Alzheimer called them aufbaum productif (‘build-up products’).
What they did reveal, or at least highly suggest in his opinion, was genuine biological evidence for a brain disorder that had so far been considered purely psychological. More determined than ever, Alzheimer continued to examine the samples, in which he uncovered another intriguing peculiarity. Swarming within the debris of dead nerve cells was a second dark substance. This one was less lumpy and more threadlike in appearance. It took on the shape of variegated tangles of material that stretched out within the carcass of the deceased cell. But whether this was the same enemy in a different uniform, or a different species of adversary altogether, was not clear.
In Pursuit of Memory Page 2