AD has become the prototypical form of dementia. From this point of view, a study of its origins should throw light on the evolution of the concept of dementia. The writings of Alzheimer, Fischer, Fuller, Lafora, Bonfiglio, Perusini, Ziveri, Kraepelin and other protagonists are deceptively fresh, and this makes anachronistic reading inevitable. However, the psychiatry of the late nineteenth century is a remote country: concepts such as dementia, neurone, neurofibril and plaque were then still in process of construction and meant different things to different people. A discussion of these issues is beyond the scope of this section (for this see Berrios, 1990b).
22.214.171.124 THE NEUROPATHOLOGY OF DEMENTIA BEFORE ALZHEIMER
Enquiries into the brain changes accompanying dementia started during the 1830s but consisted in descriptions of external appearance (Wilks, 1865). The first important microscopic study was that of Marce (1863) who described cortical atrophy, enlarged ventricles and ‘softening’. The vascular origin of softening was soon ascertained (Parrot, 1873), but the distinction between vascular and parenchymal factors had to await until the 1880s. From then on, microscopic studies concentrated on cellular death, plaques and neurofibrils.
126.96.36.199 ALZHEIMER AND HIS DISEASE
Alzheimer (1907) reported the case of a 51-year-old woman, with cognitive impairment, delusions, hallucinations, focal symptoms, and whose brain showed plaques, tangles and arteriosclerotic changes.
The existence of neurofibrils had been known for some time (DeFelipe and Jones, 1988); for example, that in senile dementia ‘the destruction of the neurofibrils appears to be more extensive than in the brain of a paralytic subject’ (Bianchi 1906, p. 846). Fuller (1907) had remarked in June 1906 (i.e. five months before Alzheimer’s report) on the presence of neurofibrillar bundles in senile dementia (p. 450). Likewise, the association of plaques with dementia was not a novelty: Beljahow (1889) had reported them in 1887, and so had Redlich and Leri few years later (Simchowicz, 1924); in Prague, Fischer (1907) gave an important paper in June 1907 pointing out that miliary necrosis could be considered as a marker of senile dementia.
Nor was the syndrome described by Alzheimer new: states of persistent cognitive impairment affecting the elderly, accompanied by delusions and hallucinations were well known (Marce, 1863; Krafft-Ebing, 1873; Crichton-Browne, 1874; Marie, 1906). As a leading neuropathologist Alzheimer was aware of this work. Did he then mean to describe a new disease?
The answer is that it is most unlikely he did, his only intention having been to point out that such a syndrome could occur in younger people (Alzheimer, 1911). This is confirmed by commentaries from those who worked for him: Perusini (1911) wrote that for Alzheimer ‘these morbid forms do not represent anything but atypical form of senile dementia’ (p. 143).
188.8.131.52 THE NAMING OF THE DISEASE
Kraepelin (1910) coined the term in the 8th edition of his Handbook: at the end of the section on ‘senile dementia’ he wrote:
the autopsy revels, according to Alzheimer’s description,
changes that represent the most serious form of senile demen-
tia … 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 degen-
erated cell bodies … The clinical interpretation of this AD is
still confused. Whilst the anatomical findings suggest that we
are dealing with a particularly serious form of senile demen-
tia, 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.
184.108.40.206 THE RECEPTION OF THE NEW DISEASE
Alzheimer (1911) showed surprise at Kraepelin’s interpretation, and always referred to his ‘disease’ as Erkrankungen (in the medical language of the 1900s a term softer than Krankheit, the term used by Kraepelin). Others also expressed doubts.
Fuller (1912), whose contribution to this field has been sadly neglected, asked ‘why a special clinical designation – Alzheimer’s disease – since, after all, they are but part of a general disorder’ (p. 26). Hakkebousch and Geier (1913), in Russia, saw it as a variety of the involution psychosis.
Simchowicz (1911) considered ‘Alzheimer’s disease’ as only a severe form of senile dementia. Ziehen (1911) does not mention the disease in his major review of senile dementia. In a meeting of the New York Neurological Society, Ramsay Hunt (Lambert, 1916) 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 agreed suggesting that, as far as he was concerned, the underlying pathological mechanisms were the same (Lambert, 1916). Lugaro (1916) 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” ( fretta battezzate) as “Alzheimer’s disease” ‘ (p. 378). He went on to say that this state is 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 [in general] and believed that they might have discovered a new disease’ (p. 221). These views, from men who lived in Alzheimer’s and Kraepelin’s time, must be taken seriously (for a detail discussion of these issues see Berrios, 1990a).
Of late there has been an attempt to rewrite the history of AD. After having been lost for years, the case notes of Auguste D., the first patient with AD, were found in the late 1990s (Maurer and Maurer, 1998). As mentioned above the original report by Alzheimer (1907) clearly stated that Auguste suffered from severe confusion, delusions, hallucinations, focal symptoms, and on post mortem her brain showed plaques, tangles and, most importantly, arteriosclerotic changes. As if to confirm the ontology of AD, Graeber et al. (1998) reported that in tissue sections belonging to this case they confirmed the presence of neurofibrillar tangles and amyloid plaques. Most interestingly, and given that vascular changes are currently not supposed to be a diagnostic criterion, these authors have put Alzheimer right by stating that Auguste’s brain showed no arteriosclerotic lesions. Furthermore, they report that the apolipoprotein E (ApoE) genotype of Auguste was ϵ3/ϵ3, ‘indicating that mutational screening of the tissue is feasible’.
On the basis of these findings, can one say that back in 1910 Kraepelin was, after all, right in claiming that Alzheimer had ‘discovered’ a new disease? The answer has to be that one must judge his decision in terms of what Kraepelin knew at the time and of the academic pressure he was under. He knew what Alzheimer’s report stated in 1907, what the latter might have verbally added, and upon Kraepelin’s perusal of Auguste’s case notes, which were requested by him from Frankfurt (indeed this is the reason why they were lost for such a long time). In clinical terms, Auguste was not a ‘typical’ case. At 51 she had delusions, hallucinations and Alzheimer’s reported arteriosclerotic changes. None of these features is mentioned in Kraepelin’s original claim. The question is, why?
It is also interesting that the so-called ‘second case’ of Alzheimer’s (Graeber et al., 1997), Johann F., reported in 1911, is now considered to have suffered a ‘plaques-only’ form of AD. The same authors suggest that knowledge of this case may have encouraged Kraepelin to report the discovery by Alzheimer of a new disease. Unfortunately, there is no evidence that Kraepelin knew of this case when he was writing the relevant section of the 8th edition of his Lehrbuch. More to the point is that he knew of Perusini’s review (1909) as he himself had asked the young Italian assistant to collect four cases. In addition to Auguste D. (which includes more information than that provided by Alzheimer in 1907), Perusini reviewed the cases of Mr. R.M., a 45-year-old basket maker who had epileptic seizures, of Mrs. B.A. a 65-year-old who had marked clinical features of myxoedema, and Schl. L, a 63-year-old who had suffered from syphilis since 1870, was Romberg positive, had a pupillary syndrome and heard voices. Since these are likely to have been the cases on which Kraepelin based his decision to construct the new disease, it would be interesting if the neuropathology and neurogenetics of the other three cases (Auguste’s has already been done) were to be investigated.
Alistair Burns MPhil, MD, FRCP, FRCPsych
Professor of Old Age Psychiatry,
John O’Brien MA, DM, FRCPsych
Professor of Old Age Psychiatry,
Institute for Ageing and Health,
University of Newcastle upon Tyne,
Newcastle upon Tyne, UK
David Ames BA, MD, FRCPsych, FRANZCP
Professor of Psychiatry of Old Age,
University of Melbourne, St George’s Hospital, Melbourne,
German Berrios BA (OXFORD), MD, DM H.C. HEIDELBERG, FRCPsych, FBPSS
University of Cambridge Department of Psychiatry,
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