History of Medicine

DR. ALOIS ALZHEIMER

     In November 1901 Mrs. August D., age fifty-one, was admitted to the Asylum for the Insane and Epileptic in Frankfurt am Main with advanced dementia. Her husband, a railway clerk, had been aware of her deterioration for about eight months.  The senior

Auguste D, Alzheimer's original case
(Wikipedia)

physician of the Asylum, Dr. Alois Alzheimer, saw this as an unusual case and examined her in detail. In time, Mrs. Auguste D's problem would make the name Alzheimer a household word.

     Alois Alzheimer was born in Marktbreit, Germany, not far from Würzburg. Son of a notary, he received his secondary education at a gymnasium, then studied medicine in Berlin, Würzburg, and

Alois Alzheimer (Wikipedia)

Tübingen. He was an enthusiastic fraternity member and while fencing sustained a large gash over his left face. Since then he only allowed photographs from his right side. He took an interest in histology, having studied under the pioneer histologist Alfred von Kölliker,  and in  neuro-psychiatry, seeking an organic basis for mental illness. He obtained a position at the above-mentioned Asylum in Frankfurt, working under Dr. Emil Sioli.

 Emil Sioli was an early advocate of “open therapy” – substituting relaxing warm baths for restraints and using activities such as crafts and gardening as therapy in a time when almost no helpful medicines were available. Alzheimer was soon joined by

Franz Nissl (Wikipedia)

Franz Nissl, already known for his development of a neuron stain. He and Alzheimer became life-long friends and colleagues. They worked together on many histologic projects (usually at night, after clinical duties), published extensively, and both became recognized authorities in neuropathology.

     In 1892 Wilhelm Erb (of Erb’s paralysis) asked Alzheimer to travel to North Africa to care for a wealthy patient. The patient died en route to Europe but his widow, Cecilie, was taken with Alzheimer and eventually proposed to him. They were married in 1894 and lived happily until her relatively sudden death of unknown cause seven years later. 

     Alzheimer moved briefly to Heidelberg and in 1903 accepted a position under the famous psychiatrist Emil Kraepelin at the Royal Psychiatric Clinic in Munich. Since Kraepelin could not find funds for him Alzheimer, now wealthy, worked for no remuneration (imagine that today!). He built a large laboratory, mainly at his own expense. His genial personality and modern lab attracted excellent scientists such as Hans Creutzfeldt, Alfonse Jakob, and Frederik Lewey (Lewey bodies). Alzheimer published on histologic findings in alcoholism, epilepsy, and mental retardation, and was promoted to “chief physician”, finally earning a modest salary.

      About one third of patients in mental hospitals at the time suffered from general paresis. Most female patients were prostitutes and among males military officers, salesmen, and firefighters predominated. Priests were rarely afflicted. Syphilis was suspected as the cause but the evidence was circumstantial. To teach at the University of Munich Alzheimer had to submit a Habilitation thesis. He had studied 320 cases at autopsy over seven years and selected 26 for the thesis. The work,

Inflammatory thickening of pia mater in paresis
(from Alzheimer, Reference 5, Hathi Trust)

published in 1904, was considered a landmark paper. The very next year the treponema of syphilis was discovered by Fritz Schaudinn and Erich Hoffmann, and the year after that Wassermann announced a diagnostic test for syphilis.

     Back at the Asylum in Frankfurt, Auguste D. was deteriorating, and died in April, 1906. Alzheimer received her brain in Munich and on examination he found plagues, fibrillary tangles, and a paucity of neurons.

     Dr. Alzheimer presented the case of Auguste D. at a lecture in November, 1906, during a meeting of the Southwest German Psychiatrists. Much of the meeting was taken up with criticisms of Freud’s theory of the sexual basis for hysteria. Alzheimer’s paper, despite numerous illustrations, provoked no discussion. It was published the following year (1907) without illustrations in a German journal of psychiatry and “psycho-forensic” medicine. Alzheimer asked a coworker, Dr. Gaetano Perusini, to watch for similar cases at the Clinic, and after three more turned up the four were published in a serial work on the histology and histopathology of the cerebral cortex edited by

Plaque and fibrils seen by Alzheimer
(from Reference 6, Hathi Trust)

 Alzheimer and Franz Nissl. Three years later Emil Kraepelin, in the eighth edition of his popular psychiatry textbook, formally named the disorder “Alzheimer’s disease”. 

     Before long other reports drifted in, and eventually the gap between “pre-senile” dementia and the dementia of old age (“senile dementia”) narrowed. Today the disease is referred to as dementia of the Alzheimer type or Alzheimer’s dementia. The advancing age of the population plus a few cases in celebrities such as Rita Hayworth and Ronald Reagan have assured the disorder a prominent place in the public eye.

     In 1912, at the age of 48, Alzheimer was appointed full professor of psychiatry in Breslau, a prestigious post. Unfortunately his health began to fail shortly after and he died in 1915 of kidney failure.

     Was Alzheimer really the first to characterize the pathology

Oskar Fischer (Wikipedia)

of early dementia? In the journal Brain, 2009, Michel Goedert writes about Oskar Fischer, a Czech investigator at the now defunct German University in Prague, who made almost simultaneous observations. In 1907 – the same year as Alzheimer’s first publication on dementia, he reported on 16 cases of senile dementia (called “presbyophrenia” by him), 12 of whom had neuritic plaques and neurofibrils. Later papers of 1910 and 1912 enlarged the findings. The plaques were, in fact, often called “Fischer’s

Plaque and fibrils by Fischer
(from Reference 7, Hathi Trust)

plaques”, and "presbyophrenic dementia" and "Alzheimer’s disease" were terms used interchangeably for several years.  While Fischer felt that the plaques and fibrils were important in causing dementia, Alzheimer, mentioning Fischer, was less convinced of the causative role of plaques.

     Fischer, being Jewish, was eventually let go from the German University and perished in a concentration camp. After the war communism ruled in Czechoslovakia and the German University was never reopened. It is not surprising that Fischer’s name was forgotten until Dr. Goedert rescued him from archives in Prague.

    

SOURCES

1. Maurer, K and Maurer U, Alzheimer: The Life of a Physician and the Career of a Disease (Eng trans) 2003; Colombia Univ Press, NY.

2. Maurer K, et al, “Auguste D and Alzheimer’s Disease” 1997; Lancet 349:1546-9.

3. Goedert, M and Ghetti, B, “Alois Alzheimer: His Life and Times”. 2007; Brain Pathology 17: 57-62.

4. Goedert, M. “Oskar Fischer and the Study of Dementia” 2009; Brain 132: 1102-11.

5. Alzheimer, A. “Histologische Studien zur Differentialdiagnose der progressiven Paralyse” (Histologic studies in the differential

diagnosis of general paresis). 1904; Histologische und

Histopathologische Arbeiten. F Nissl, ed. 1: 1-297.

6. Alzheimer, A, “Über eigenartige Krankheitsfälle des späteren Alters”1911; Zeitschr für die gesamte Neurologie u Psychiatrie 4: 356-85.

7. Fischer, O. “Miliare Nekrosen mit drusigen Wucherungen der

Neurofibrillen, eine regelmässige Veränderung der Hirnrinde bei

seniler Demenz” (Miliary necroses with plaque-like growths in the

neurofibrils, a regular alteration of the cerebral cortex in senile

dementia) Monatsschrift Psychiatrie und Neurologie 1907; 22:36-    

72.

8. Perusini, G, “Über klinisch und histologisch eigenärtige psychische Erkrankungen des späteren Lebensalters”. 1909; in Histologische und Histopathologische Arbeiten. F Nissl, A Alzheiner, eds. 3: 297-351.