Kraepelin,Alzheimer and Munich

The city of Munich takes its name from Muenchen, meaning ‘monks’. It had been a monastery and, from the 12th century on, was settled as a city. In modern times it has had an infamous history, being the capital of the Nazi movement, but there is much more to Munich than that connection. From a psychiatric perspective, my recent sabbatical took me to the Department of Psychiatry of the city's Ludwig-Maxmilians University. It is an example of Jugenstil architecture and was designed by renowned architect Max Littmann, who also designed the Prinzregenten theatre. Both buildings survived the allied bombings in World War II.

First morning was a tour of the department, conducted by Professor Kapfhamer, second in charge. A grand entrance hall with a high ceiling provides access to various levels and the wards. In the hall were portraits of past directors of the department. Among them was Emile Kraepelin, who established the concept of dementia paraeox, later consolidated by Bleuler under the rubric of schizophrenias. ¹ The hospital wards are separated by large, open courtyards that to this day have tall trees planted by Kraepelin himself. Some of these he brought from his travels in the east. The courtyards provide venues for relaxation and sporting activities.

Readers would be interested to learn that Alois Alzheimer also worked at the university. A remark in Kraepelin's memoirs reads: ‘It was only after Alzheimer had failed in his ambition to become director of an institution that he came to me and I succeeded in persuading him to join our group. Before he could be appointed to a university post in Heidelberg, I was offered the chair in Munich and he moved there with me in 1903’. Kraepelin's ideal, a natural system of nosology with prognostic implications, encouraged Alzheimer to devote himself to theoretical questions and the task of bringing together histopathological and psychopathological findings and models.

Alzheimer's classic paper on a strange and severe illness of cerebral cortex originates from a case report of a 51-year-old woman from Frankfurt, whose symptoms included disorientation, aphasia, delusions and unpredictable behaviour, and who died in April 1906 after 41/2 years of her illness. ² Pathological examination revealed diffuse atrophy of the entire brain and characteristic changes in its internal structure, in particular the cortical cell clusters. The findings were presented at a Congress in Tübingen in 1906. In 1911 Alzheimer seemed surprised when he stated that Kraepelin in the eighth edition of his psychiatric textbook had already given a short summary of presenile dementia with diffuse atrophy of the brain and called it ‘Alzheimer's disease’. Among many publications and archives of the time, it was fascinating to find Alzheimer's vocal opposition to the proposal for induced abortion in mentally ill women. ³ He rejected any overly simplistic social Darwinism, which postulated that the process of degeneration is intensified in the offspring of mentally ill patients.

Kraepelin emphasized commitment to duty and teaching, but with a sense of humour. The following extract from the Kraepelin memoirs illustrate this.

In 1892, I tried to clarify whether the use of alcohol was practical for mental health reasons. To my surprise, I found that there was really no reasonable motive for drinking unless one wanted to improve one's mood. This discovery impressed me. Until now, I had considered the use — even the necessity — of alcohol to be undisputable. Therefore, I thought that one had to put up with the dangers of alcohol, which were only too well known in my career. At this time, I met Forel again, as I had been requested by the government of the Canton Freiburg in Switzerland to give my opinions on the establishment of a psychiatric clinic in Freiburg. On this occasion, there was much talk about the problems of alcohol. I slowly became convinced that I should use my own personal abstinence to fight against the usual drinking customs and the serious problem of alcoholism in our country. Therefore, I did not drink one drop of spirits for some months and during a journey to Madeira in 1894, I turned down the wines, which were offered to me persistently. I stopped drinking wine and beer on social occasions. At first, I was considered to be a crone. A campaign was launched against me with good and bad jokes, people picked quarrels with me or tried to give me good advice. The worst problem was that I was constantly involved in endless discussions on alcohol. My strange views were gradually accepted and an increasing number of people assured me that I was quite right and that they hardly drank either, only now and again on social occasions. I caused a sensation. I am quite sure that my entire scientific work did not make my name as famous as the plain fact that I did not drink alcohol.

On the third floor of the university was the laboratory in which Alzheimer spent many years — without payment from the university because he had inherited a fortune — and that now serves as a museum. The original microscopes are still here. There is also record that Creutzfeldt and Jakob were among the proteges who assisted Kraepelin and Alzheimer in the department.

While Kraepelin set the platform for devotion to clinical excellence, it is Alzheimer's name that is arguably more synonymous with scholarship in this department. Alzheimer commented critically on the way clinical information was obtained in psychiatry, stating ‘what we urgently need in the field of mental disorder is an improvement in the way symptoms are recorded. Today, to their detriment in my opinion, case notes are often more a summary or judgement than a description of original complaints and symptoms by the patient.’

Alzheimer had a profound influence on modern psychiatry in the way he supported Kraepelin's nosological concepts against those of Hoche. Alzheimer maintained that the unsatisfactory distinctions between various psychiatric conditions could be resolved through progress towards psychiatry that was orientated towards the ideals of natural science and was not, as Hoche claimed, simply an inevitable consequence of an uncritical ‘hunt for phantoms’ (i.e. natural categories of disease). Like many psychiatrists before him, Alzheimer regarded the history of the investigation of general paralysis as a paradigm for the success of the research method to which he adhered. He appeared to have felt more at home in the difficult terrain of nosology than Kraepelin, who was frequently plagued by doubt. In an essay of 1910, Alzheimer describes clearly the distinction between ‘organic’ (or ‘exogenous’) psychoses and ‘functional’ (or ‘endogenous psychosis’). He classifies dementia praecox as belonging to the first group ‘on account of histological findings and … its tendency to result in a state of idiocy or dementia’; into the second group he puts ‘manic-depressive psychosis, paranoia, hysteria litigious paranoia and degenerative psychosis in the narrow sense’. ⁴ Alzheimer later moderated his stance on the dichotomy to take Bleuler's position into account from the latter's compelling monograph on the schizophrenias. However, the undertones of Alzheimer's disappointment are evident when he called the available data on histopathology, ‘rather insufficient’ (i.e. not convincing enough to support Bleuler's hypotheses).

Alzheimer left Munich in 1912 to take up the professorial Chair of Psychiatry at the University of Breslau. On the train journey to Breslau he contracted purulent tonsillitis and subsequently developed subacute bacterial endocarditis. Kraepelin recalls his last meeting with Alzheimer thus.

I saw him in Breslau in 1913 at the meeting of German psychiatrists … he was in low spirits and despondent, he had gloomy misgivings about the future. In his efforts to carry out his duties as well as possible, Alzheimer neglected to take care of himself, as the ever more difficult conditions of wartime forced him to take on one new responsibility after another.

He died on 19 December 1915 at the age of 51. Uraemia is the cause of his death given by most sources. ⁴

Alzheimer had intended to produce empirical evidence in favour of Kraepelin's nosology, especially for the dichotomy between dementia praecox and manic depressive illness by means of histopathology. However, he did not succeed in that endeavour and it is fair to say that any significant histopathological findings in dementia praecox still elude us. Alzheimer favoured a ‘medical’, in modern terms a ‘biological’, approach to psychiatric research and emphasized that research should be firmly related to clinical questions.

Almost 100 years after Kraepelin and Alzheimer, the same third floor of the university now houses a large and highly sophisticated laboratory. The staff are dedicated to research in molecular pharmacogenetics and psychoneuroendocrinology. Drug effects on genes of the signal transduction pathways, association studies concerning treatment response and incidence of side-effects with genetic variants of candidate genes, functional genetics and ‘proteomics’ (i.e. the identification of new genes and proteins that are involved in the pathophysiology of psychiatric disorders) are now being studied. Several hundred patients and their family pedigrees provide a large pool of data. Previous director Hans Hippius and the current director Hans-Jürgen Möller have been major forces in the world of biological psychiatry and psychopharmacology.