Abstracts
Alois Alzheimer is best known for his description of a novel disease, subsequently named after him. However, his wide range of interests also included vascular brain diseases. He described Senile dementia, a highly heterogeneous condition, and was able not only to distinguish it from syphilitic brain disease, but also to discriminate two clinicopathological subtypes, that may be labeled a "arteriosclerotic subtype", comparable to the present clinicopathological continuum of "Vascular cognitive impairment", and another as a "neurodegenerative subtype", characterized by primary [cortical] ganglion cell [nerve cells] degeneration, possibly foreshadowing a peculiar presenile disease that he was to describe some years later and would carry his name. He also considered the possibility of a senile presentation of this disease subtype, which was described by Oskar Fischer a short time later. Considering the clinicopathological overlapping features of the "arteriosclerotic subtype" of Senile dementia with Arteriosclerotic atrophy of the brain, it might be possible to consider that both represent a single condition.
Alzheimer; brain vascular disease; arteriosclerosis; Senile dementia
Alois Alzheimer é conhecido principalmente por sua descrição de uma nova doença, logo designado com seu nome. Entretanto, sua ampla gama de interesses, compreendia também doenças vasculares cerebrais. Descreveu a Demência senil, uma condição muito heterogênea, e foi capaz, não somente distingui-la da doença cerebral sifilítica, como também separar dois subtipos clinicopatológicos que podem ser rotulados como um "subtipo arteriosclerótico", que pode ser relacionado ao atual continuum clinicopatológico do "Comprometimento cognitivo vascular", e um "subtipo neurodegenerativo", caracterizado por degeneração [cortical] primária de células ganglionares [células nervosas], possivelmente prenunciando uma doença peculiar pré-senil, que ele descreveu alguns anos depois e que portaria seu nome. Considerou a possibilidade de uma apresentação senil deste subtipo da doença, que seria descrita por Oskar Fischer pouco tempo depois. Levando em conta os aspectos de sobreposição clinicopatológica do "subtipo arteriosclerótico" da Demência senil com a Atrofia arteriosclerótica do cérebro, poderia ser possível considerar que ambas representariam uma só condição.
Alzheimer; doença vascular cerebral; arteriosclerose; Demência senil
INTRODUCTION
Aloysius [Alois] Alzheimer (1864-1915), was a German psychiatrist and neuropathologist, best known for his description of "neurofibrillary tangles" in brain neurons of a patient with presenile dementia.11. Alzheimer A. Uber eine eigenartige Erkrankung derHirnrinde. Allg Z Psychiat phychish-gerichtliche Medizin1907;64:146-148. A short time later this condition received the denomination of "Alzheimer's disease".22. Kraepelin E. Psychiatrie: ein Lehrbuch für Studierende und Ärzte. Vol II.
Alzheimer's interests were quite wide, including vascular brain diseases. His precursor
work greatly contributed toward introducing key knowledge of what would later be
incorporated into the field of "Vascular dementia" and related disorders. Although he
was not the only scholar to study this subject, he produced very comprehensive concepts,
including novel pathological descriptions on vascular brain diseases.33. Leipzig: Barth, 1910, pp 627-628. [Retrieved from:
http://www2.biusante.parisdescartes.fr/livanc/index.las?cote=63261x02&do=chapitre]
http://www2.biusante.parisdescartes.fr/l...
At the time, the dementia definition was somewhat loose, and comprised heterogeneous
mental conditions, including General paralysis, melancholia, mania, Senile dementia,
varied psychic disorders of the senium, vascular brain diseases, and others.22. Kraepelin E. Psychiatrie: ein Lehrbuch für Studierende und Ärzte. Vol
II.
,
44. Engelhardt and Grinberg LT. Alzheimer and vascular brain disease: the
Arteriosclerotic atrophy of the brain. Dement Neuropsychol
2015;9:81-84.
,
55. Boller F, Forbes MM. History of dementia and dementia in history: an
overview. J Neurol Sci 1998;158:125-133. Alzheimer and numerous famous scientific
contemporaries focused on extricating these many disorders according to their etiology,
and mainly on differentiating them from the prevalent syphilitic brain disorders.66. Esquirol JED. Des maladies mentales: considérées sous les rapports
médical, hygiénique et médico-légal. [Vol 2] Paris:JB Baillière, 1838. [Retrived
from: http://gallica.bnf.fr/ark:/12148/bpt6k85089d]
http://gallica.bnf.fr/ark:/12148/bpt6k85...
,
77. Alzheimer A. Neuere Arbeiten über die Dementia senilis und die auf
atheromatöser Gefässerkrankung basierenden Hirnkrankheiten. Monatsschr Psychiat
Neurol 1898;3:101-115. This body of work resulted in advances to a
field in which knowledge had remained stagnated since Antiquity.44. Engelhardt and Grinberg LT. Alzheimer and vascular brain disease: the
Arteriosclerotic atrophy of the brain. Dement Neuropsychol
2015;9:81-84.
,
88. Román GC. A historical review of the concept of vascular dementia:
lessons from the past for the future. Alzheimer Dis Assoc Disord 1999; 13(Suppl
3):S4-S8.
,
99. Berchtold NC, Cotman CW. Evolution in the conceptualization of
dementia and Alzheimer's disease: Greco-Roman period to the 1960s. Neurobiol Aging
1998;19:173-189.
The objective of the present paper was to discuss Alzheimer's studies on Senile dementia, a condition to be later subdivided into several independent diseases.
SENILE DEMENTIA
Alzheimer previously mentioned the term Senile dementia (Dementia
senilis, senile Demenz) in the main text and discussion of
his 1894 paper.1010. Berrios GE. A Conceptual History in the Nineteenth Century. In:
Principles and Practice of Geriatric Psychiatry. 3rd ed. Abou-Saleh MT,Katona CLE,
Kumar A eds. Chichester: John Wiley& Sons, 2011, pp 3-6. He further commented, in 1898,
about the lack of systematic clinicopathological studies on Senile dementia, yet an
abundance of studies on Paralytic dementia (Paralysis).66. Esquirol JED. Des maladies mentales: considérées sous les rapports
médical, hygiénique et médico-légal. [Vol 2] Paris:JB Baillière, 1838. [Retrived
from: http://gallica.bnf.fr/ark:/12148/bpt6k85089d]
http://gallica.bnf.fr/ark:/12148/bpt6k85...
Additionally, he highlighted that most studies on Senile dementia had
included conditions that more closely resembled mental disorders of the senium or senile
mental impairment (Greisenblödsinn) such as melancholia, mania,
depression, among others, which might equally be related to arteriosclerosis, as cited
by Kraepelin. Such disorders of the senium could eventually show regressive changes,
with feebleness and reduced brain performance, finally evolving to Senile dementia.22. Kraepelin E. Psychiatrie: ein Lehrbuch für Studierende und Ärzte. Vol
II.
,
66. Esquirol JED. Des maladies mentales: considérées sous les rapports
médical, hygiénique et médico-légal. [Vol 2] Paris:JB Baillière, 1838. [Retrived
from: http://gallica.bnf.fr/ark:/12148/bpt6k85089d]
http://gallica.bnf.fr/ark:/12148/bpt6k85...
Thus, regarding this conceptual heterogeneity,
Alzheimer stated that "Senile dementia may develop in the form of extraordinary colorful
and richly varied pictures, making it difficult to classify the disease based solely on
clinical symptoms, similarly to the challenges in Paralysis".66. Esquirol JED. Des maladies mentales: considérées sous les rapports
médical, hygiénique et médico-légal. [Vol 2] Paris:JB Baillière, 1838. [Retrived
from: http://gallica.bnf.fr/ark:/12148/bpt6k85089d]
http://gallica.bnf.fr/ark:/12148/bpt6k85...
Alzheimer discussed the possible underlying pathology of Senile dementia and the
correlation with clinical manifestations He cited Weigert's work that demonstrated an
elevated number of glia in the upper cortical layers [astrogliosis], and that their
processes constituted a dense fiber meshwork in the cerebral grey and white matter. He
further suggested a correlation between astrogliosis severity and cognitive decline,
highlighting that older brains with milder glial changes may manifest less severe
regression of mental performance.66. Esquirol JED. Des maladies mentales: considérées sous les rapports
médical, hygiénique et médico-légal. [Vol 2] Paris:JB Baillière, 1838. [Retrived
from: http://gallica.bnf.fr/ark:/12148/bpt6k85089d]
http://gallica.bnf.fr/ark:/12148/bpt6k85...
However, these
changes often reached higher degrees of severity and caused the milder or "silent form"
of Senile dementia (stille Form der Dementia senilis), possibly the
most frequent mental disorder, found commonly among patients living with their families
or in asylums, and rarely in institutions, as also observed by Windscheid.1111. Alzheimer A. Die arteriosklerotische Atrophie des Gehirns. Neurol
Centralblatt 1894;13:765-767.
12. Alzheimer A. Die Seelenstörungen auf arteriosklerotischer Grundlage.
Allg Z Psychiat 1902;59:695-710.
-
1313. Alzheimer A. Die Seelenstörungen auf arteriosklerotischer Grundlage.
Monatsschrift für Psychiat Neurol 1902;12:152-153. [Presented at the Yearly Meeting
of the Society of the German Paychiatrist, in Munich, directed by Dr. J Raecke]
[Retrieved from: https://www.karger.com/Article/Pdf/220780]
https://www.karger.com/Article/Pdf/22078...
Other cases, however, exhibited a progressive
course, finally reaching a marked degree of dementia, with serious manifestations of
senile mental impairment (Alterblödsinn).66. Esquirol JED. Des maladies mentales: considérées sous les rapports
médical, hygiénique et médico-légal. [Vol 2] Paris:JB Baillière, 1838. [Retrived
from: http://gallica.bnf.fr/ark:/12148/bpt6k85089d]
http://gallica.bnf.fr/ark:/12148/bpt6k85...
In the same paper, Alzheimer cited Noetzli, who following Forel's opinion, expressed
that the silent form of Senile dementia might affect everyone, possibly more so those
predisposed to atheromatous disease, whereas individuals with more advanced
manifestations accompanying age related-mental impairment required a psychic hereditary
load, in agreement with some authors that held the opinion that a 2nd item
must be added to elucidate the process.1414. Windscheid F. Die Beziehungen der Arteriosklerose zur Erkrankungn
des Gehirns. Münchn Med Wochenschrift 1902;49(9):345-347. [Conference held at the
Medical Association of Leipzig, in 1901][Retrievedd from: This
view, despite its tempting appeal, seemed barely demonstrable to Alzheimer.66. Esquirol JED. Des maladies mentales: considérées sous les rapports
médical, hygiénique et médico-légal. [Vol 2] Paris:JB Baillière, 1838. [Retrived
from: http://gallica.bnf.fr/ark:/12148/bpt6k85089d]
http://gallica.bnf.fr/ark:/12148/bpt6k85...
Later, Noetzli himself referred to atheromatous
degeneration as the fundamental cause of Senile dementia, contradicting his former
belief and in agreement with Alzheimer's previous opinion.66. Esquirol JED. Des maladies mentales: considérées sous les rapports
médical, hygiénique et médico-légal. [Vol 2] Paris:JB Baillière, 1838. [Retrived
from: http://gallica.bnf.fr/ark:/12148/bpt6k85089d]
http://gallica.bnf.fr/ark:/12148/bpt6k85...
Thus, at the time, most researchers agreed that atheromatous
degeneration of the brain vessels was the underlying mechanism of Senile dementia.
Alzheimer, however, reconsidered this position after examining a case classified as
presenile dementia featuring severe atrophy of [cortical] ganglion cells [nerve cells,
neurons], but with negligible atheromatous vessel changes. The case, at least for this
form, contradicted Noetzli's latest views, and prompted Alzheimer to consider the
possibility that a hereditary load might lead to precocious atrophy of the nerve cells
independently of vessel disease. These results encouraged him to propose that
degenerative changes of the nerve cells might also appear, independently of a vascular
disease, in cases of typical Senile dementia. Therefore, an influence of psychic
hereditary load on the cause of Senile dementia would make more sense. However, he
concluded that a single case could not be considered final proof, and further
investigation was needed to support this assumption.66. Esquirol JED. Des maladies mentales: considérées sous les rapports
médical, hygiénique et médico-légal. [Vol 2] Paris:JB Baillière, 1838. [Retrived
from: http://gallica.bnf.fr/ark:/12148/bpt6k85089d]
http://gallica.bnf.fr/ark:/12148/bpt6k85...
,
1111. Alzheimer A. Die arteriosklerotische Atrophie des Gehirns. Neurol
Centralblatt 1894;13:765-767.
It is pertinent to summarize Jean Noetzli's and Alfred Campbell's data on brain weight,
and Campbell pathological analysis for a better understanding of brain pathology of
insane patients. Noetzli, Forel's adherent, in his inaugural dissertation Ueber
Dementia Senilis (On Senile dementia),1414. Windscheid F. Die Beziehungen der Arteriosklerose zur Erkrankungn
des Gehirns. Münchn Med Wochenschrift 1902;49(9):345-347. [Conference held at the
Medical Association of Leipzig, in 1901][Retrievedd from: described a clinicopathological analysis of 70 cases mostly dissected by
Forel himself. He provided data on the brain weight of 40 selected cases of "senile
psychosis without focal symptoms", which displayed a significant loss of brain weight
[brain atrophy] in both genders, compared to controls.66. Esquirol JED. Des maladies mentales: considérées sous les rapports
médical, hygiénique et médico-légal. [Vol 2] Paris:JB Baillière, 1838. [Retrived
from: http://gallica.bnf.fr/ark:/12148/bpt6k85089d]
http://gallica.bnf.fr/ark:/12148/bpt6k85...
,
1414. Windscheid F. Die Beziehungen der Arteriosklerose zur Erkrankungn
des Gehirns. Münchn Med Wochenschrift 1902;49(9):345-347. [Conference held at the
Medical Association of Leipzig, in 1901][Retrievedd from: Along the same lines, Campbell detected brain
atrophy among males and females, in a comprehensive study of the nervous system of 50
patients that he called "aged insane".1515.
http://www.bium.univ-paris5.fr/histmed/medica/cote?epo0561]
http://www.bium.univ-paris5.fr/histmed/m...
Campbell
also provided detailed gross and microscopic description of the material. Alzheimer
apparently considered "aged insane" and Senile dementia equivalent, transcribing part of
Campbell's text in his 1898 paper66. Esquirol JED. Des maladies mentales: considérées sous les rapports
médical, hygiénique et médico-légal. [Vol 2] Paris:JB Baillière, 1838. [Retrived
from: http://gallica.bnf.fr/ark:/12148/bpt6k85089d]
http://gallica.bnf.fr/ark:/12148/bpt6k85...
(Box 1).
Alzheimer also acknowledged that: "Besides the typical Senile dementia, where diffuse
changes in cerebral cortex are found, it was still possible to distinguish among the
senile psychosis, various disease forms (subforms), well-characterized clinically and
histologically, having arteriosclerotic degeneration of brain vessels in common as the
underlying cause, and equally observed in the aged. Many of these subforms, depending on
the base disease, can resemble the clinical picture of Senile dementia". He affirmed
that some of these conditions are to be considered as mere subforms of
Arteriosklerotische Hirnatrophie (Arteriosclerotic atrophy of the
brain).66. Esquirol JED. Des maladies mentales: considérées sous les rapports
médical, hygiénique et médico-légal. [Vol 2] Paris:JB Baillière, 1838. [Retrived
from: http://gallica.bnf.fr/ark:/12148/bpt6k85089d]
http://gallica.bnf.fr/ark:/12148/bpt6k85...
,
1616. Meyer A. Ueber Dementia Senilis by Jean Noetzli. Psychological
Review 1896; 3(2):224-226. [Retrieved from:
https://ia600302.us.archive.org/29/items/psychologicalre02assogoog/psychologicalre02assogoog.pdf]
https://ia600302.us.archive.org/29/items...
The subforms he mentioned will be addressed
later.
Concluding, Alzheimer stated that: "Regarding Senile dementia, it is necessary to see
with reservation whether arteriosclerosis of the brain vessels should be considered as
the only underlying cause of senile degeneration of the brain, or whether primary
atrophic processes of ganglion cells should also be taken into consideration. In the
remaining disease forms, atheromatous vessel degeneration is clearly a central factor in
the degenerative process."66. Esquirol JED. Des maladies mentales: considérées sous les rapports
médical, hygiénique et médico-légal. [Vol 2] Paris:JB Baillière, 1838. [Retrived
from: http://gallica.bnf.fr/ark:/12148/bpt6k85089d]
http://gallica.bnf.fr/ark:/12148/bpt6k85...
,
1111. Alzheimer A. Die arteriosklerotische Atrophie des Gehirns. Neurol
Centralblatt 1894;13:765-767.
COMMENTARIES
Based on his own observations, in addition to work by Weigert, Noetzli and Campbell ,
Alzheimer was a pioneer in conceptualizing Senile dementia as a disorder featuring
diffuse changes of the cerebral cortex and subcortical structures, and distinct from
syphilitic disease, one of his objectives.66. Esquirol JED. Des maladies mentales: considérées sous les rapports
médical, hygiénique et médico-légal. [Vol 2] Paris:JB Baillière, 1838. [Retrived
from: http://gallica.bnf.fr/ark:/12148/bpt6k85089d]
http://gallica.bnf.fr/ark:/12148/bpt6k85...
,
1515.
http://www.bium.univ-paris5.fr/histmed/medica/cote?epo0561]
http://www.bium.univ-paris5.fr/histmed/m...
Alzheimer extricated from the group of "senile psychosis", many of them at the time
included under the umbrella-label of Senile dementia, two subtypes of disorders,66. Esquirol JED. Des maladies mentales: considérées sous les rapports
médical, hygiénique et médico-légal. [Vol 2] Paris:JB Baillière, 1838. [Retrived
from: http://gallica.bnf.fr/ark:/12148/bpt6k85089d]
http://gallica.bnf.fr/ark:/12148/bpt6k85...
,
1111. Alzheimer A. Die arteriosklerotische Atrophie des Gehirns. Neurol
Centralblatt 1894;13:765-767. which can be denoted as an "arteriosclerotic
subtype" (Box 2) and a "neurodegenerative subtype"
(Box 3).
Additionally, Alzheimer, as did Weigert, Noetzli, and Windscheid, provided insights on
the relationship between neuropathological and clinical severity. Milder pathology was
associated with lesser cognitive decline. However, he added, the disease could worsen
leading to the mild or "silent form" of Senile dementia and even progress to a severe
dementia state, accompanied eventually by several kinds of behavioral disturbances.66. Esquirol JED. Des maladies mentales: considérées sous les rapports
médical, hygiénique et médico-légal. [Vol 2] Paris:JB Baillière, 1838. [Retrived
from: http://gallica.bnf.fr/ark:/12148/bpt6k85089d]
http://gallica.bnf.fr/ark:/12148/bpt6k85...
The "arteriosclerotic subtype" of Senile dementia (Box
2) and the several grades of clinicopathological presentations he described,
also quoting other colleagues, might be considered comparable to the current dimensional
concept of the "Vascular cognitive impairment" continuum.1818. Alzheimer A. Beitrag zur pathologischen Anatomie der
Seelenstoerungen des Greisenalters. Neurologisches Centralblatt
1899;18:95-96. It is opportune to reiterate that this was verified and suggested in
relation to Arteriosclerotic atrophy of the brain in a previous paper.33. Leipzig: Barth, 1910, pp 627-628. [Retrieved from:
http://www2.biusante.parisdescartes.fr/livanc/index.las?cote=63261x02&do=chapitre]
http://www2.biusante.parisdescartes.fr/l...
An analyzes of Senile dementia based on
Alzheimer's 1898 paper was performed by Förstl and Howard, where they commented on the
clinical progression of Senile dementia etiopathogenesis according to Noetzli and
Alzheimer, and on Arteriosclerotic brain atrophy.1919. Derouesné C. La maladie d'Alzheimer: regards sur le présent à la
lumière du passé. Une approche historique. Psychol NeuroPsychiatr Vieil
2008;6:115-128. In 1999, Román commented on Senile dementia, focusing on the main points
of Alzheimer's study, and made remarks on Arteriosclerotic brain atrophy and also on
some subforms.77. Alzheimer A. Neuere Arbeiten über die Dementia senilis und die auf
atheromatöser Gefässerkrankung basierenden Hirnkrankheiten. Monatsschr Psychiat
Neurol 1898;3:101-115.
The "neurodegenerative subtype" of Senile dementia (Box
3) was based upon severe primary atrophy of [cortical] ganglion cells [nerve
cells, neurons], with insignificant atheromatous vascular changes, found in the material
of a presenile dementia case.66. Esquirol JED. Des maladies mentales: considérées sous les rapports
médical, hygiénique et médico-légal. [Vol 2] Paris:JB Baillière, 1838. [Retrived
from: http://gallica.bnf.fr/ark:/12148/bpt6k85089d]
http://gallica.bnf.fr/ark:/12148/bpt6k85...
,
2020. Hachinski V. Vascular dementia: a radical redefinition. Dementia
1994; 5:130-132. He extended this possibility to senile cases,
an issue confirmed later by Oscar Fischer's studies.2222. Engelhardt E, Gomes MM. Alzheimer's 100th anniversary of death and
his contribution to a better understanding of Senile dementia. Arq Neuropsiquiatr
2015;73:159-162. Román,77. Alzheimer A. Neuere Arbeiten über die Dementia senilis und die auf
atheromatöser Gefässerkrankung basierenden Hirnkrankheiten. Monatsschr Psychiat
Neurol 1898;3:101-115. as well as Derouesné,1717. Campbell AW. The morbid changes in the cerebro-spinal nervous system
of the aged insane. J Ment Sci 1894;40: 638-649. [Retrieved
from:http://www.evolve360.co.uk/Data/10/RainhillDaysFinalText.pdf]
http://www.evolve360.co.uk/Data/10/Rainh...
also commented on this possibility.
CONCLUSION
Alzheimer was able to distinguish Senile dementia from syphilitic brain disease. Additionally, he discriminated two clinicopathological subtypes, an "arteriosclerotic subtype", possibly related to "Vascular cognitive impairment", and a "neurodegenerative subtype", characterized by primary [cortical] nerve cell degeneration, in a presenile dementia case, possibly foreshadowing a disease he described years later that would carry his name, "Alzheimer' disease". He extended the latter possibility to also encompass senile cases, confirmed later by Fischer's studies.
Acknowledgements.
The authors are grateful to Mrs. Melanie Scholz, librarian, Institute for History of Medicine, Charite, Berlin, Germany, for kindly supplying the digitalized versions of Alzheimer's publications on vascular diseases of the brain.
REFERENCES
-
1Alzheimer A. Uber eine eigenartige Erkrankung derHirnrinde. Allg Z Psychiat phychish-gerichtliche Medizin1907;64:146-148.
-
2Kraepelin E. Psychiatrie: ein Lehrbuch für Studierende und Ärzte. Vol II.
-
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» http://www2.biusante.parisdescartes.fr/livanc/index.las?cote=63261x02&do=chapitre -
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-
5Boller F, Forbes MM. History of dementia and dementia in history: an overview. J Neurol Sci 1998;158:125-133.
-
6Esquirol JED. Des maladies mentales: considérées sous les rapports médical, hygiénique et médico-légal. [Vol 2] Paris:JB Baillière, 1838. [Retrived from: http://gallica.bnf.fr/ark:/12148/bpt6k85089d]
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-
9Berchtold NC, Cotman CW. Evolution in the conceptualization of dementia and Alzheimer's disease: Greco-Roman period to the 1960s. Neurobiol Aging 1998;19:173-189.
-
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-
11Alzheimer A. Die arteriosklerotische Atrophie des Gehirns. Neurol Centralblatt 1894;13:765-767.
-
12Alzheimer A. Die Seelenstörungen auf arteriosklerotischer Grundlage. Allg Z Psychiat 1902;59:695-710.
-
13Alzheimer A. Die Seelenstörungen auf arteriosklerotischer Grundlage. Monatsschrift für Psychiat Neurol 1902;12:152-153. [Presented at the Yearly Meeting of the Society of the German Paychiatrist, in Munich, directed by Dr. J Raecke] [Retrieved from: https://www.karger.com/Article/Pdf/220780]
» https://www.karger.com/Article/Pdf/220780 -
14Windscheid F. Die Beziehungen der Arteriosklerose zur Erkrankungn des Gehirns. Münchn Med Wochenschrift 1902;49(9):345-347. [Conference held at the Medical Association of Leipzig, in 1901][Retrievedd from:
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» http://www.bium.univ-paris5.fr/histmed/medica/cote?epo0561 -
16Meyer A. Ueber Dementia Senilis by Jean Noetzli. Psychological Review 1896; 3(2):224-226. [Retrieved from: https://ia600302.us.archive.org/29/items/psychologicalre02assogoog/psychologicalre02assogoog.pdf]
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» http://www.evolve360.co.uk/Data/10/RainhillDaysFinalText.pdf -
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-
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Support. Lea T. Grinberg is supported by NIH grant R01AG 040311 and institutional grants by NIH grants P50AG023501, P01AG019724.
Publication Dates
-
Publication in this collection
Apr-Jun 2015
History
-
Received
20 Jan 2015 -
Accepted
27 Mar 2015