In 1901, a 51-year-old woman, Auguste D, was admitted to the state asylum in Frankfurt. She was suffering from cognitive and language deficits, auditory hallucinations, delusions, paranoia and aggressive behaviour, and was studied by Alois Alzheimer (1864–1915), a doctor at the hospital.
Alzheimer moved to the Munich medical school in 1903 to work with Emil Kraepelin – one of the foremost German psychiatrists of that era – and when Auguste D died in April 1906, her brain was sent to him for examination. In November of that year, Alzheimer presented Auguste's case at a psychiatry meeting, and he published his talk in 1907.
In 1910, Kraepelin coined the term 'Alzheimer's disease' – a term still used to refer to the most common cause of senile dementia. But had Alzheimer actually discovered a new disease, and was Kraepelin justified in calling it such?
Alois Alzheimer (1864–1915)
The concept of dementia
During the eighteenth century, the term 'dementia' had a clinical and a legal usage, referring to states of psychosocial incompetence regardless of age, reversibility or pathological antecedents. This broad view was gradually narrowed down, culminating at the end of the nineteenth century with what I have called the 'cognitive paradigm' – the view that dementia is an irreversible disorder (mainly in the elderly) of intellectual functions (particularly memory).
This paradigm is still in place today, although it was partially modified during the 1980s when it was accepted that non-cognitive features – such as hallucinations, delusions and behavioural deficits – were part of the disease. Before the adoption of the cognitive paradigm, such symptoms actually formed part of the definition of senile dementia.
In his original presentation, Alzheimer discussed Auguste D's cognitive and non-cognitive deficits, and reported that, on post mortem, he had found plaques, tangles and arteriosclerotic changes in her brain. Two important issues emerge here: were these markers new, and why, in his announcement, did Kraepelin omit to mention Auguste D's arteriosclerotic changes, hallucinations, delusions and other psychiatric symptoms?
The markers of the new disease
All the markers that Alzheimer reported were well known at the time, and it is clear from his writings that he never meant to say that they were new. For example, it was the prevalent view before 1906 that in senile dementia "the destruction of the neurofibrillae appears to be more extensive than in the brain of a paralytic subject". Indeed, five months before Alzheimer's report, the American worker Fuller – whose contribution to this field has been neglected – had drawn attention to the presence of "neurofibrillar bundles in senile dementia".
Nor was the association between plaques and dementia a novelty, as it had been reported in 1887 by Beljahow, and confirmed by Redlich and Leri a few years later. Oskar Fischer, the neglected researcher from Prague, had also pointed out, in June 1907, that 'miliary necrosis' should be considered as a marker of senile dementia.
At the end of the section on 'senile dementia' in the eighth edition (1910) of his Handbook of Psychiatry, Kraepelin wrote:
"...the autopsy reveals, according to Alzheimer's description, changes that represent the most serious form of senile dementia... the Drusen were numerous and almost one-third of the cortical cells had died off. In their place instead we found peculiar deeply stained fibrillary bundles that were closely packed to one another, and seemed to be remnants of degenerated cell bodies... The clinical interpretation of this Alzheimer's disease is still confused. While the anatomical findings suggest that we are dealing with a particularly serious form of senile dementia, the fact that this disease sometimes starts already around the age of 40 does not allow this supposition [i.e. it should be considered as a new disease]. In such cases we should at least assume a 'senium praecox' if not perhaps a more or less age-independent unique disease process."
Neither the biological markers nor the symptom constellation reported by Alzheimer were new, and he was fully aware of it. In fact, states of persistent cognitive impairment affecting the elderly, and accompanied by delusions and hallucinations were well known at the time. So, did Alzheimer actually mean to describe a new disease? The likely answer is that he did not. His surprise at Kraepelin's claim must have been tempered, however, by his knowledge that the continuation of research grants depended upon the Munich department performing well and 'discovering' new diseases every year.
A conservative interpretation of the primary data suggests that Alzheimer's only intention was to point out that senile dementia could occur in younger people (in this case, in a woman of 51). In this regard, Perusini (a man who worked with him) wrote that, for Alzheimer "these morbid forms do not represent anything but atypical form of senile dementia".
The reception of Alzheimer's disease
Others also expressed surprise at Kraepelin's announcement. In Russia, Hakkeboutsch and Geier referred to Alzheimer's disease as a variety of the involution psychosis and Simchowicz considered it as only a severe form of senile dementia. Ziehen does not mention Alzheimer's disease in his major review of the senile dementias. Lastly, Lugaro wrote: "For a while it was believed that a certain agglutinative disorder of the neurofibril was considered as the main marker of the pre-senile form [of senile dementia], and that this was hurriedly baptised as Alzheimer's disease." He went on to state that he believed that the latter was only a variety of senile dementia.
The same view was taken in the USA. Fuller asked: "Why a special clinical designation – Alzheimer's disease – since, after all, they are but part of a general disorder?"
At a meeting of the New York Neurological Society, Ramsay Hunt asked Lambert, the presenter of a case of 'Alzheimer's disease' that "he would like to understand clearly whether he made any distinction between the so-called Alzheimer's disease and senile dementia, other than...in degree and point of age". Lambert stated that, as far as he was concerned, the underlying pathological mechanisms were the same.
There is little point in the claim that, by dint of painstaking research, Alzheimer 'discovered' a new disease (as a botanist might have discovered a new species of orchid), or that, by dint of great scientific insight, Kraepelin realised that he was onto something important.
Closer to the facts is the following account: at the time of the 'discovery', both the clinical picture of senile dementia and its various biological markers were already well known, and Alzheimer had no intention whatsoever of describing a 'new disease'. He presented the case of Auguste D as one of senile dementia occurring in a youngish woman. Likewise, had his academic department not been under great pressure to perform, Kraepelin might not have been so keen on 'hurriedly baptising' this solitary case as a 'new disease'. As it happened he did and, to enhance its novelty, he went so far as deleting some of the crucial clinical features of the case.
Yet it would be equally counterproductive to demonise Kraepelin for this action. This was not the first or last time that an exaggerated or distorted claim was made by a scientist in order to keep a funding body happy. Most of these claims die out. For complex sociological reasons, Kraepelin's story stuck.
It can be argued, therefore, that the concept and boundaries of Alzheimer's disease were constructed by a scientist who wanted to keep his grants going. Because his database of original cases was minimal (two cases: Auguste D with some data missing, and a second mysterious case which can be identified as Auguste D with name and other features changed) it could have been predicted that his new concept would be unstable. This explains, for example, why at the very end of this century, clinicians are witnessing the fragmentation of the old 'unitary concept' of Alzheimer's disease into an increasing number of genetic subtypes and clinical phenotypes.
Dr German E Berrios is in the Department of Psychiatry, University of Cambridge.
1 Berrios GE. Non-cognitive symptoms and the diagnosis of dementia. Historical and clinical aspects. British Journal of Psychiatry 1989 154: 11–16.
2 Berrios GE. Alzheimer's disease: a conceptual history. International Journal of Geriatric Psychiatry 1990 5: 355–365.
3 Berrios GE and Freeman H (1991) Alzheimer and the Dementias. London, Royal Society of Medicine.
4 Maurer K ,Yolk S, Gerbaldo H. Auguste D and Alzheimer's disease. Lancet 1997 349: 1546–1549.