alzheimer's disease: a conceptual history

INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, VOL. 5: 355-365 (1990)

ALZHEIMER’S DISEASE: A CONCEPTUAL HISTORY

G. E. BERRIOS Consultant and University Lecturer in Psychiutry, University of Cambridge: Director of Medical Studies and Fellow,

Robinson College, Cambridge; Honorary Librarian, Royal College of Psychiatrists; Department of Psychiatry, University of Cambridge, Addenbrooke’s Hospital (Level 4), Hills Road, Cambridge, UK

KEY woRDs-Alzheimer’s disease, dementia, history.

In the 1969 Ciba symposium on Alzheimer’s disease Professor McMenemey (1970) asked: ‘How far are we justified in departing from the criteria originally laid down by the person who first described the malady?’ (p. 6). He went on to suggest that departures in neuropathological characterization might be allowed provided that the case histories were typical, and that symptomatic (clinical) departures might be equally permissible when the neuropathology was typical. McMenemey concluded that both types of change might have taken place since the first description of Alzheimer’s disease.

This article is about mapping the events that pre- ceded, and immediately followed, the first description of this disease. To identify the boundaries of the original description is no easy matter. The writings of Alzheimer, Fischer, Fuller, Lafora, Bon- figlio, Pcrusini, Ziveri, Kraepelin, and other protagonists in this story are deceptively fresh, and this makes anachronistic reading almost inevitable. And yet the psychiatry of the late nineteenth century is a remote country: even crucial concepts such as dementia, neuron, neurofibril or plaque had not yet been fully crystallized and meant difyerent things for different people.

The mirage caused by an anachronistic reading can only be dispelled by exploring the history of the many terms and issues that played the ‘supporting cast’ to Alzheimer’s disease: these include dementia, ageing, neuronal theory, methods of visualizing brain tissue, academic psychiatry and departmental rivalries, senile psychosis, and cerebral artcriosclerosis. This might help to recon- struct the perception that alienists of the 1910s had of the new disease.

Another way of dealing with anachronistic read- ings is to ask what clinical problem the ‘creator’ was trying to solve. In this case, it would seem that

Alzheimer was interested in the early onset of the condition, its uncommon severity, its focal symptoms, and the simultaneous presence of plaques and tangles. If so, one must ask why it was these features, and not the simultaneous presence of, say, arteriosclerotic changes or of hallucinations and delusions, that bothered him.

In answering this question the historian will come to realize that the 1906 debate was not about creating homogeneous diagnoses. It was about the building blocks of neurobiology: whether neurons were independent units, or whether they were cap- able of ameboid movements (Black, 1981; Billings, 1971), or whether staining techniques were reliable, and so on.

HISTORIOGRAPHICAL ISSUES

Two metaphors control the study of historical nosology. One pictures the clinician as cataloguing species in an exotic garden; the other sees him as a sculptor carving shapes out of formless matter, ie creating ‘clinical forms’. These metaphors impose different conceptual duties. The garden approach needs to explain why the naturalist happens to be there in the first place; the creational view requires an understanding of the sculptor’s ‘inner vision’. To achieve the latter the historian must examine scientific and social factors.

To the consumers of disease, however, it matters little which allegory has been chosen: patients wear their illness in the most personal of ways; clinicians take as ‘given’ ongoing textbook definitions which they regard as a reflection of some Platonic entity. Consequently, they see themselves more as clinical cartographers than as challengers of the putative immutability of disease. This was Professor

0885-6230~90~060355-12$06.00 0 1990 by .john Wiley & Sons, Ltd.

Received 24 January 1990

356 G . E. BERRIOS

McMenemey’s point: what else it is permissible to add to the disease without upsetting its boundaries. But, is this right? Should we worry about upsetting the boundaries of any disease?

One reason for this question is that the garden metaphor creates all manner of difficulties. For example, priority seekers may find that the ‘original’ cases of Alzheimer’s disease bear limited resemblance to those defined by current criteria, or that it is not possible to identify the precise moment when the disease was first ‘discovered’. One way out of this impasse has been to assume that the discoverer did not get it quite right, for example that he included some ‘wrong’ symptoms. Thus, some might claim that by insisting on the presence of hallucinations and delusions, or by not minding about major arteriosclerotic changes, Alz- heimer, Fuller, Bonfiglio, Lafora, and Perusini got it partially ‘wrong’.

There has of late been a shift towards the creationist view. At its basis is the assumption that there is no such a thing as the jinal description for a disease, that clinical boundaries, symptom content, and even anatomical description consti- tute temporary scripts cribbed from the ongoing medical discourse. In other words, a disease is defined not only by the power of resolution of the ongoing science, but also by periodic backroom decisions taken by her self-appointed mandarins.

Thus, the clinician trying to understand why Alz- heimer’s disease is not called, for example, Fischer’s, Fuller’s or Perusini’s disease would be wise to conceive of nosological categories as result- ing from the interaction between a descriptive (ver- bal or numerical) language and a biological process (bodily changes emitting signals in the shape of symptoms and signs). Because the language of description also reflects the beliefs of its users, disease creation is also a social phenomenon. This explains why, for example, until recently the so- called behavioural or psychiatric symptoms of Alz- heimer’s disease were ignored (Berrios, 1989). Recent interest in this issue (eg Wragg and Jeste, 1989) reflects less a change in the presentation of the disease than in observer bias,

THE ACTOR

The scenario described above tends to emphasize ideas, and this may lead to neglecting the people who entertained them; most great alienists have

been, however, good at grabbing the limelight. Not so Alzheimer, whose fame was thrust upon him by those who loved him well or had their own reasons to do so. He was born on 14 June 1864 in the small German village of Marktbreit am Main. He trained at Berlin, Wurzburg and Tubingen. In 1888 he became a county asylum officer in Frank- furt where he started his life long association with Nissl. Kraepelin called Nissl to Heidelberg in 1895 and Alzheimer joined them in 1903. In October the same year he moved to Munich, where Kraep- elin had accepted the Chair of Psychiatry at the Ludwig- Maximilians-Universitat. In 1912 Alz- heimer was appointed to the Breslau chair (now Wroclaw in Poland) and died on 19 December 191 5.

Achucarro, Lafora, Jelliffe, and the many others who worked in his laboratory saw him as a humble and hard-working man, perhaps a better researcher than a clinician (Valenciano, 1977; Lewey, 1953). Kraepelin said of him: ‘He posed a thoroughness in research which was stopped by no obstacles, by no difficulty, but above all, an almost cruel self- criticism which could not be corrupted and which controlled all his thinking, and a boundless caution in regard to all conclusions . . . ’ (Young, 1935). Alzheimer’s main contribution was on the histology of general paralysis of the insane, and in the technical field on methods for the fixation and histology of the CSF. Although not a theoretician, he was particularly interested in what he called the disintegration (Abhau) of the nervous tissue and in the hypothesis that analysis of catabolic products might provide biological markers for the functional psychoses (Alzheimer, 1906). (For further details on his life see Hoff and Hippius, 1989; Kreutzberg and Gudden, 1988; Meyer, 1959).

THE CONCEPTUAL BACKGROUND

History of the notion of dementia

At the end of the nineteenth century the term ‘dementia’ was used to name any state of psychological dilapidation associated with chronic brain disease (Guiraud, 1943; Blumer, 1907); traditionalists included within this term deficit states related to the functional psychoses, hence irreversibility was not considered as a criterion (Berrios, 1987; Marie, 1906). When dementia states occurred in the elderly they were called ‘senile dementia’, and had been

HISTORY OF ALZHEIMER’S DISEASE 357

so since the beginning of the century. In this regard, however, it must be remembered that even by 1900 the term ‘dementia’ did not necessarily evoke an association with old age, as it tends to do nowa- days. This is why Morel in the 1860s and Kraepelin 40 years later had no difficulty in using the term ‘dementia’, as in ‘dementia praecox’, to refer to states of psychological dilapidation in young people (Berrios and Hauser, 1988).

By the cnd of the nineteenth century this state of dilapidation was considered to result from a primary disorder in cognitive function, and defined almost entirely in terms of memory decline (Berrios, 1990; Toulouse and Mignard, 1914; D’Allones, 1912; Jaspers, 1910). Again, some traditionalists still adhered to the older view that the psychosocial incompetence of dementia was not necessarily related to memory impairment. Cour- bon (1912) felt able to write: ‘In dementia this faculty [memory] is in fact much less impaired than i t seems’ (p. 300). He believed that the central problem of dementia was one of chronic confusion which impeded the adequate use of all cognitive faculties. This explains why there was little difficulty in accepting that temporary or permanent remissions might occur in the course of a dement- ing disease; this although efforts had been made since the 1820s to tie up the concept of dementia with irreversible brain changes (on this see first- class paper by Kowalewski, 1886).

The view that dementia was both a clinical and a neuropathological category was put on a firm footing by Bayle in 1822 (Berrios, 1985). However, no clear idea existed as to what type of lesions were involved or whether they affected the same area of the brarn. From the 1860s (particularly since the work of Marce, 1863) efforts began to be made to identify a separate brain pathology for senile dementia in subjects who had not previously suf- fered from mental illness. Research in this age group became important for it avoided the problem of having to decide whether the brain lesions were related to primary states of mania or melancholia. By the early 1900s efforts had also been made to: (a) measirre the symptoms and severity of dementia (Jaspers, 1910; Puillet and Morel, 1913; Berrios, 1990); (b) ascertain the differential importance of the senile and vascular aetiology of dementia (McGafin, 1910; Treadway, 1913); and (c) study the comparative prevalence of senile dementia in relation to other psychiatric disorders affecting the elderly (Pickett, 1904; Southard, 1910; Bolton, 1903). These enquiries were influenced by ongoing

theories on ageing of brain tissue (Marinesco, 1900).

Histological techniques

Up to the middle of the nineteenth century putative brain changes associated with psychiatric disease were described in the language of gross anatomy (Parchappe, 1841; Wilks, 1865). They involved changes in colour, consistency, weight, volume, relative proportion of solids to fluids, etc. These observations, as indeed all the early microscopic descriptions, were hampered by inadequate brain preservation and fixation and staining techniques. The relevance of staining artifacts, for example, cannot be exaggerated. At the very end of the century the Cambridge anatomist Hardy wrote: ‘It is, I think, one of the most remarkable facts in the history of biological science that the urgency and priority of this question should have appealed to so few minds. It is notorious that the various fixing reagents are coagulants of organic colloids, and that they produce precipitates which have a certain figure or structure. It can also be shown that the figure varies, other things being equal, according to the reagent used’ (Hughes, 1959).

But the ‘seeing’ also depended upon theory (Fou- cault, 1963), for the issue was not only agreeing on shapes and colours, but also on what they meant, on what structures these features were assumed to represent, on what Maulitz (1987) has aptly called the ‘code of the body’. After the 1880s, however, staining techniques improved in quality, and animal studies (like those carried out by Ram6n y Cajal (DeFelipe and Jones, 1988)) allowed a closer analysis of resolution power (for details see Conn, 1933).

Alzheimer himself contributed to the development of staining methods. However, his descriptions of pathological changes, like everyone else’s in his time, were hampered by the fact that there was not yet full agreement on what the ‘units of change’ (eg neurons, glia, etc.) really looked like. For example, Nicolas Achucarro, the talented Spa- nish pathologist (who died very young), showed in Alzheimer’s own laboratory that glial cells could give rise to formations which mimicked neurofibrillary tangles (Moya, 1968).

When Spielmeyer (191 1) published his classic work more than 100 techniques had become avail- able, out of which about 15 were dedicated to the visualization of neurofibrils. These included the

358 G. E . BERRIOS

techniques based on gold developed by Apathy, on molybdenum by Bethe, on pyridine-molybdenum by Donaggio, on silver by Bieslchowsky and Ramon y Cajal and on toluidine by Bethe and Lugaro (Spielmeyer, 191 1; Bertrand, 1930).

The debate on the concept of neuron

Between 1880 and the Great War two views vied for supremacy: the neuronal theory considered neurons as independent units, never touching or touching only sporadically, and had Ramon y Cajal as its champion; reticularism, on the other hand, held that brain cells formed a syncitium, a network of cells, and its leading proponent was Golgi (Ramon y Cajal, 1952; Clarke and Jacyna, 1987). Waldeyer is recognized as having coined the term ‘neurone’ in 1891, although Hughes (1959) has reported that the term ‘neuron’ had already been used by B.G. Wilder in 1884.

The first round of the debate was won by the neuronists, but early in the twentieth century Held, Bethe and Apathy revived a version of the reticularist view. The latter two men were, interestingly enough, also important to the discovery of neurofibrils (Fuller, 1907). These structures, significant in the later definition of some forms of senile dementia, played an important role in the reticularism debate. Alzheimer’s position on neuronal theory is unclear although Nissl, his lifelong friend, was a reticularist (Fuller, 1907; Ramon y Cajal, 1981).

The neuropathology of dementia bejore Alzheimer Enquiries into the putative brain changes ac-

companying dementia had started earlier during the nineteenth century. As mentioned above, these consisted in descriptions of the appearance of the brain in subjects who had died in a dementia state (Wilks, 1865). The variety of changes, and their non-specificity, impeded any meaningful conclu- sion. In 1822 Bayle had described more or less recognizable changes affecting the arachnoid in subjects thought to be suffering from a disease which caused both motor and psychiatric symptoms (including dementia). This encouraged the view that all manner of psychiatric symptoms might also be related to brain pathology (Parchappe, 1841).

Efforts were made after the 1850s to separate from the group of the dementias the subcategory of the so-called ‘vesanic dementias’, which included

the terminal states of the functional psychoses. With Marce (1863), cortical atrophy, enlarged ven- tricles, and tissue ‘softening’ became the macro- scopic hallmark of ‘senile dementia’. The vascular nature of the ‘softening’ was soon ascertained (Par- rot, 1873), but the distinction between vascular and parenchymal factors had to wait until the early twentieth century. After the 1880s microscopic descriptions started in earnest and three changes were singled out as important: cellular death and disintegration, plaques and neurofibrils. As early as 1887 Beljahow reported that the ‘cells seemed to be broken down into formless clumps’ (p. 262). Plaques were described in 1982 by Blocq and Mari- nesco (a great Rumanian histologist) in the brain of an epileptic patient. Redlich redescribed them in two elderly epileptics in 1898, and called them ‘miliar sclerosis’. This was confirmed by Leri in 1906 (Simchowicz, 1924).

THE HISTORY OF ALZHEIMER’S DISEASE

The historical vignettes and warnings expressed above should help in exploring the history of this clinical state. The conventional account goes as fol- lows. Alzheiiner reported on 4 November 1906 at the Tubingen meeting of the South West German Psychiatrists the case of a 5 I-year-old woman from Frankfurt who had presented with progressive cognitive impairment, focal symptoms relating to higher cortical functions, hallucinations, delusions, and marked psychosocial incompetence. On postmortem she exhibited brain atrophy, arteriosclerotic changes, senile plaques and neurofibrillary tangles. The case was published in 1907 under the title of ‘Uber eigenartige Erkrankungen der Hirn- rinde’. By this act, it is felt, Alzheimer discovered a new disease which in 1910 was rightly baptized by Kraepelin.

This version invites comment. The first concerns the ambiguity of the adjective eigenurtig, which has been variously translated into English as ‘peculiar’ and ‘characteristic’. Agreement on which ofthe two Alzheimer actually meant should throw some light on his reasons for reporting the case in the first place. Interestingly enough he went on to use the term again in his paper of 191 1, when he reported a second case, not quite analogous to the first: on this occasion he entitled the paper ‘Uber eigenartige Krankheitsfalle des spateren Alters’ (Alz- heimer, 191 1) .


Analysis of the context and of the semantics of eigenurtig during the period in question shows that Alzheimer is likely to have meant ‘peculiar, odd, or queer’. So, those who have translated it as mean- ing ‘characteristic’ might be making him say something he did not mean. A finding is ‘characteristic’ when it can mark out a group, species, or disease; it is ‘odd or peculiar’ when it marks out one case, which may not be repeated again. In fact, in 191 1 (after Kraepelin had named the putative new disease after him), Alzheimer still insisted on the fact that he did not think that it was a new disease, and that he was more interested in ascertaining how it related to similar cases in the elderly. For this reason it i \ also a pity that a recent book, The Eurlj~ Story ($ illzht4mer’s Diseuse, has not included the 191 1 paper (Bick et ul., 1987).

By 1910 about eight cases had been published, although at least two of them had been reported twice (for example Alzheimer’s original case appears, with some features changed, as Perusini’s third) (Perusini, 1909). To summarize what has been said so far:

I . Alzheimer was not particularly keen to see his ‘peculiar’ form of dementia described as a new disease; he in fact believed that it was simply an atypical form of senile psychosis. Perusini (191 1) also thought this was the case.

2. There were surprisingly few cases described after the original one and before Kraepelin decided to baptize it as a separate disease. All except one were reported by men working in Alz- heimer’s laboratory. Furthermore, there was some double-reporting, which is surprising in view of the fact that these workers had in all probability large numbers of dementia cases at their disposal; in addition, none of the cases was pure either clinically or pathologically.

3. There was little reason (on purely scientific grounds) to elevate this ‘peculiar’ form of dementia into a disease, particularly since during this period clinical and histopathological variations upon current ‘diseases’ were often reported.

Alzheim~r und his diseuse

Alzheimer described a form of dementia occur- ring in subjects younger than 65 with delusions and hallucinations, with some focal symptoms, and whose brains showed plaques and tangles but also arteriosclerotic changes. What was new in it? Was

it his observation on plaques, tangles, age of onset, ‘focal’ symptoms, or combinations thereof?

The existence of neurofibrils had been known for years (DeFelipe and Jones, 1988; Barret, 191 1; Fuller, 1907) but surprisingly there had not been much work on their value as markers of disease. Even so, it was known already that in senile dementia ‘the destruction of the neuro-fibrillae appears to be more extensive than in the brain of a paralytic subject’ (Bianchi, 1906, p. 846). Frag- nit0 (1904) had also described damage and disap- pearance of neurofibrils in the cortical cells of senile dementia patients. More to the point, in June 1906, that is j i v e months bejore Alzheimer’s report, Salo- mon Fuller (1907) had specifically remarked on the presence of neurofibrillar bundles in senile dementia (p. 450). So, in terms of published mater- ial, Alzheimer’s report cannot be considered as having priority as has been claimed (Amaducci et ul., 1986, p. 1497).

Was perhaps Alzheimer describing a new clinical syndrome‘? States of persistent cognitive impairment affecting the elderly, often accompanied by delusions and hallucinations, were well known (Marc&, 1863; Krafft-Ebing, 1873; Crichton Browne, 1874; Marie, 1906). Cases of subjects younger than 65 had even been reported. So it cannot be said that there was originality in the clinical observation itself. Indeed, Alzheimer’s original description was wider than current operational definitions (eg DSM-111-R). Nor was the description of plaques in association with dementia a novelty in 1906. Beljahow had reported them in 1887, and Redlich and Leri did so a few years later (Simchowicz, 1924). In Prague, Fischer gave an important paper in June 1907 pointing out that miliary necrosis could be considered as a marker of senile dementia (Fischer, 1907). He also suggested that subjects thus affected showed clinical features similar to those of ‘presbyophrenia’. This term, originally used by Kahlbaum to refer to a subtype of paraphrenia in the elderly, was rescued by Wernicke to name a condition similar to Kor- sakofYs polyneuritic psychosis (Berrios, 1986). Fischer used the term ‘presbyophrenia’ to refer to a subtype of senile dementia characterized by ‘con- fabulations, more serious memory disorder . . . rapid development of the disease and specially by frequent hallucinations’ (p. 18). For Fischer plaques were the final product of the destruction of neurofibrils. He concluded ‘in senile dementia there occur very peculiar claviform proliferations in the neurofibril. . . ’ (p. 18). Indeed, some were later to confuse

360 G . E. BERRIOS

Alzheimer’s disease and presbyophrenia (eg Stod- dart, 1913).

So if patients had already been described who exhibited senile dementia, pathological neurofibrils and increased plaque count, where was the novelty in Alzheimer’s description? It is likely that all he meant to emphasize in his short report was the fact that a dementia of the senile type could also occur in a younger person. This is confirmed by what he said in his paper of 191 1 and by the commentar- ies of those who worked with him. For example, Perusini (191 1) wrote that for Alzheimer ‘these morbid forms do not represent anything but atypical forms of senile dementia’ (p. 143).

ALZHEIMER’S DISEASE UP TO THE FIRST WORLD WAR

The cases

Table 1 summarizes the first 15 cases after Ah- heimer’s 1907 publication. But the curious thing is that when Kraepelin baptized the disease (it is likely that he completed writing that section of the Handbook in 1909) only five cases had been reported. It is also of some interest to note that Perusini’s (1909) first case (he reported four in his 1909 paper) is in fact Alzheimer’s first case in which some features have been changed (for example the postmortem results no longer showed arteriosclerotic changes!). Likewise, Perusini’s fourth case (in the same paper) was Bonfiglio’s (1908).

It is an important historical question to ask why these cases needed to be re-reported. The answer is that probably there was great pressure in the laboratory to accumulate evidence in favour of the new ‘disease’.

The naming of the disease

In view of the multiple descriptions of the disease, one is left with the problem of why Alz- heimer’s disease, and not Fuller’s or Fischer’s? Kraepelin (1910) baptized it thus in the eighth edition of his Handbook. The section on presenile dementia he mostly occupies discussing the rela- tionship between depression and chronic stupor and dementia. Alzheimer’s findings he mentions only at end of the section on ‘senile dementia’: ‘the autopsy reveals, according to Alzheimer’s description, changes that represent the most serious form of senile dementia , . . the drusen were very numer-

ous 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 . . . ’. Then he concludes: ‘The clinical interpretation of this Alzheimer’s disease is still confused. Whilst 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. In such cases we should at least assume a “senium praecox” if not perhaps a more or less age-independent unique disease process’,

For Kraepelin this was the stark conceptual choice: he went on to make other distinctions but the general tenor of his views was to be that a new disease had been found. Indeed, followers inter- preted him in the same way: ‘Kraepelin has clearly demonstrated that these morbid forms described by Alzheimer cannot be considered forms of senile dementia’ (Perusini, 1911, p. 142). As far as it is known, Kraepelin never ‘demonstrated’ the inde- pendence of the disease in the sense of offering further scientific evidence; what he did was to throw his considerable academic power behind one of two interpretations of Alzheimer’s data that he himself had formulated.

What is more curious (and cannot be explained away as academic coyness) is the surprise shown by Alzheimer (191 1) at Kraepelin’s interpretation. Alzheimer referred to it as Erkrankungen (which in the medical language of the 1900s was softer than Krankheit), while Kraepelin had called it Alz- heimersche Krankheit (p. 356).

From the start doubts were expressed as to whether early onset dementias (even if showing severer clinical features) warranted the creation of a new disease. Fuller (1912), whose contribution to this field has been neglected, asked ‘why a special clinical designation - Alzheimer’s disease - since after all they are but part of a general disorder’ (p. 26). HakkCbousch and Geier (1912) in Russia saw it as a variety of the involution psychosis. Sim- chowicz (191 1) in his monumental monograph on the histology of senile dementia considered Alz- heimer’s disease as only a severe form. Ziehen (191 1) in his major review of senile dementia does not even mention Alzheimer’s case of 1906.

In a meeting of the New York Neurological Society in 1916, Ramsay Hunt tackled the presenter of a case of ‘Alzheimer’s disease’ with the request that ‘he would like to understand clearly whether

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912

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(190

7)

2. B

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908)

3.

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hi (1

909)

Pe

rusi

ni (1

909)

4.

Per

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i (19

09)

5. P

erus

ini (

1909

) Pe

rusi

ni (1

909)

6.

Bar

rett

(191

0)

7. A

lzhe

imer

(191

1)

8. F

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9.

Bie

lsch

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1 1)

10. L

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362 G . E. BERRIOS

the reporteur made any distinction between the so- called Alzheimer’s disease and senile dementia other than . . . in degree and point of age’. Lambert had to agree that he did not and suggested that as far as he was concerned the underlying pathological mechanisms were the same (Lambert, 1916).

Lugaro (1916), in his great paper on ‘La psichiatria tedesca . . . ’, wrote: ‘For a while it was believed that a certain agglutinative disorder of the neurofibril could be considered as the main “marker” (contrassegno) of a presenile form [of senile dementia], which was “hurriedly baptized” Vretta battezzate) as “Alzheimer’s disease”’ (p. 378). He went on to say that this state was only a variety of senile dementia. Simchowicz (1924), who had worked with Alzheimer, wrote: ‘Alzheimer and Perusini did not know at the time that the plaques were typical of senile dementia and believed that they might have discovered a new disease’ (p. 221). Finally, in his monumental work on Pick’s disease, van Mansvelt (1 954) summarized the issue well: ‘In the early part of this century the state of things was such that the histopathological work of Alz- heimer and others had called the attention to the possibility of arriving at a more exact differentia- tion . . . within the large group of the senile dementias.. . . We see therefore that the so-called Alzheimer’s disease and the lobar atrophy of Pick should not be contrasted with each other as two separate diseases’ (pp. 9-10).

The views described above belong to men who lived in Alzheimer’s and Kraepelin’s time and in many cases knew them well, so they must be taken seriously. Since Alzheimer shared their view, it would be unwise to rule them out as envious rivals. It would be equally vacuous to justify Kraepelin’s action on the basis of what is currently known of the disease. The issue is whether in terms of what they then knew it was reasonable to conclude that a new disease had been discovered. The historian would find it difficult to say that it was. So reasons other than scientific must be sought for the hurried baptism of the disease.

The his tor ical hypotheses

Two historical hypotheses have been put forward to account for the haste with which Kraepelin created the new eponym, thereby giving rise to a long-lasting separation between presenile and senile forms of the disease. One states that he did so for scientijic reasons, that is, he genuinely believed that Alzheimer had discovered a new dis-

ease (Beach, 1987). The other view suggests that he did so because: (a) he wanted to resolve in his favour the existing rivalry between his department and Pick’s in Prague (which included the great pathologist Fischer) (Amaducci et al., 1986); or (b) he needed to show (vis-d-vis Freud) that there were mental disorders organically based (Torack, 1979); or (c) he needed to justify the creation of an expens- ive pathological laboratory in Munich (Thomas and Isaac, 1987).

Unfortunately, hypotheses concerning motiva- tions (Kraepelin’s) are notoriously difficult to test as they require evidence in the form of private inti- mations-provided that the person involved has ‘insight’ into his real motives. To deal with the ‘non- scientific’ reasons first, it can be said that no evidence seems to exist to support (a) above: as far as it is known, nowhere did Kraepelin state that he coined the eponym ‘Alzheimer’s disease’ for ‘strategic’ reasons. Amaducci et u1. (1986) suggest, without must evidence, that ‘competition between universities was probably one of the underlying determinants’ (p. 1499). With regard to (b) Torack (1979) has speculated about the theoretical rivalry between Kraepelin and Freud. However, the great theoretical abyss that separated these two great men might have protected them from it. In fact, and apart from some sniping, their worlds rarely touched (Decker, 1977). More to the point, the discovery of a disease such as Alzheimer’s would have made little difference to Freud’s views as, in prin- ciple, he accepted an organic basis for dementia. Finally, Thomas and Isaac (1987) seem to suggest that (c) was of some relevance. However, it is unclear whether Kraepelin was at the time under any pressure to justify the existence of the laboratory; after all, little public money was involved in its running for ‘Alzheimer was forced to cover the laboratory costs himself (Kreutzberg and Gudden, 1988).

So we are left with the ‘scientific hypothesis’. Beach has claimed (1987) that Kraepelin had some ‘objective reasons for supporting this entity’ (p. 338), which, he suggests, might have been its severity and rarity (p. 338). In the end, Beach continues, Kraepelin suspended judgement and never resolved the matter. Of course, with the start of the First World War he had other worries on his mind. It is more likely, however, that his silence reflected the fact that the definitive evidence he hoped for never materialized.

Finally, it must be said that Kraepelin was too good a clinician to believe himself in arguments


such as those which he had put forward in favour of the ‘independent’ view. The surprise shown by Alzheimer himself and by those who worked with him and the view expressed by Lugaro and others also indicate that he had little justification for creating a new disease. But this nonetheless he did.

CONCLUSIONS

This article has dealt with a very specific period in the history of psychiatric nosology: the creation of Alzheimer’s disease. It can be concluded that:

1. In 1906 Alzheimer described one clinical case which for reasons which still remain obscure was soon to be considered by Kraepelin as illustrat- ing a new disease. Its features included early onset of severe memory and cognitive impairment, focal symptoms by which were meant aphasia, apraxia, etc; delusions, hallucinations, and marked psychosocial incompetence. Neur- onal loss, high plaque count, neurofibrillary tangles and arteriosclerotic changes were present on postmortem.

2. It is historically difficult to claim that Alzheimer was saying something new with regard to either the clinical picture or the presence of plaques or tangles. He was saying something new, however, with regard to the combination of all these features, and the age of his subject.

3 . Alzheimer did not mean to suggest that this combination constituted a new disease, nor did many during this period think he did.

4. Kraepelin for reasons of his own, which historical work has so far not fathomed, decided to present it as a new disease. As with all hurried creations, it was left with unclear boundaries. The unwillingness of its discoverer, and the inability of its sponsor, to carry out the required clinicopathological research left the disease adrift. Those who followed did their best, but the marked differences between the cases they managed to report show their confusion (as shown in Table 1).

5. Alzheimer’s disease is a good illustration of the creationist view in nosology.

6. Not even the early cases fit in well with the original description. The most common interpretation by those living and writing during Alzheimer’s period was that the ‘new’ disease simply named cases with early onset, marked

severity and focal symptoms. As the cognitive paradigm consolidated, a clear move towards narrowing down the syndrome by, for example, dismissing the presence of delusions and hallucinations can be detected. Likewise, arterioscler- osis was quietly dropped, and became an exclusion criterion.

7. It is likely that current research into the molecu- lar biology of tangles might yet provide reasons for separating the presenile form of the disease. Unfortunately, this has no retrospective value, and cannot help the historian to explain why Kraepelin did separate it. Evidence on this will come only from further historical research.

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