Hans Förstl


Alzheimer_1898


Alois Alzheimer:

Neuere Arbeiten über die Dementia senilis und die auf atheromatöser Gefässerkrankung basierenden Hirnkrankheiten.

Monatsschr Psychiat Neurol 3: 101-115 (1898)

Recent Studies on Dementia Senilis and Brain Disorders Caused by Atheromatous Vascular Disease


Summary: In 1898, Alzheimer wrote an exhaustive update on psychogeriatric issues. He discussed paralytic dementia, involutional melancholia, senile dementia, presenile dementia, arteriosclerotic dementia, Binswanger disease, stroke-induced dementia, and other dementias of vascular origin. In this paper, he appeared to describe his very first case of Alzheimer disease, he anticipated the ischemic score, and outlined his opinion about numerous issues of dementia research that are of current interest. This widely neglected paper does not only represent an outline of fin de siecle psychogeriatrics, but the discussed clinical issues are refreshingly modern and its nosological hypotheses clearly prepared the groundwork for 20th century research. We chose to keep the sequence of Alzheimer's text, but to select the most important paragraphs and to briefly summarize the lengthy discussions on less interesting issues.


INVOLUTIONAL MELANCHOLIA:

( . . . ) In the new edition of his textbook, Kraepelin presents melancholia as a disorder that shows a ( . . . ) causal relationship to the onset of involution. He distinguishes it from the depressive states of periodic depressive insanity and constitutional dysthymia. This concept has never before been proposed so strongly, although earlier authors have stressed that depressive states may preferentially occur at the time of involution and onset of old age. ( . . .) From my clinical experience, I remember a large number of patients, in whom the typical melancholic disorder of involution had been preceded by a melancholic depression during the years of adulthood, e.g., after the first confinement. ( . . . ) Therefore, I think it not unlikely that, if given a certain disposition, melancholic states-perhaps triggered by exhaustion-may also occur during the prime of life, and that these individuals will then retain an increased disposition for a recurring disease during involution. It would be a rewarding and certainly not very difficult task to collect a larger body of case material in order to provide a final answer to this question, which is so relevant to Kraepelin's concept of melancholia and the periodic psychoses. ( . . . ) Undoubtedly, disorders related to constitutional periodic insanity may become manifest for the first time during the years of involution. Involutional melancholia (as defined by Kraepelin) frequently adopts a periodic character, even if not with such regular intervals. Finally, cases of melancholia are observed that-after a longer lucid interval-recur with a second attack dominated by cognitive impairment and leading to progressive senile dementia. A definitive distinction between involutional melancholias, which end with a complete recovery, and those that lead to senile dementia cannot be drawn. 

AGE-RELATED BRAIN CHANGES:
(Their Gradual Differences with Respect to Histology and Clinical Consequences)
 According to Kraepelin's concept, melancholia arises out of the weakness and decreased capacity of the brain during the incipient involution. Dementia senilis, however, develops when the brain has usually already suffered a considerable loss of weight and when histological signs of senescence can generally be shown. For a long time, we have recognized an increase of pigment in nerve cells, and the atheromatous alterations of the vessels in such patients. Weigert has proved with his "exact glial stain" that an increased glial density is a typical feature of old age. ( . . . ) Minor degrees of these changes are obviously compatible with the small decrease in cognitive capacity that generally occurs with old age. 

THE MILD AND SEVERE FORMS OF DEMENTIA


Often these changes gain a higher degree. Then they cause the mild and "quiet" forms of dementia senilis, which may perhaps represent the most frequent mental disorder. These cases are frequently found with their families or in nursing homes and rarely in mental hospitals. In other cases, worsening and finally terminal dementia is accompanied by states of depression or of maniacal excitement, persecutory ideas, and delirious states of excitement. Similar to Forel, Noetzli proposed that the quiet form of dementia senilis can affect anybody ( . . . ). The development of senile dementia with more severe features demands a stronger hereditary disposition. This opinion may sound quite convincing, but in my opinion it appears difficult to prove. All our statistics about heredity have major drawbacks. As Noetzli and Kraepelin have remarked, it is specifically difficult to obtain reliable data about heredity in the case of dementia senilis, because there is usually a lack of relatives, who can supply reliable information about the ancestors of these old people. Thus, Noetzli could not obtain any information for 24 of his 70 patients, and a definitive hereditary disposition could only be proved for 19 cases. ( . . . ) Kraepelin thinks that heredity does not play an important part. ( . . . )
 

PRESENILE DEMENTIA

Dementia praesenilis represents a subgroup within senile dementia. ( . . . ) It affects preferentially those individuals whose cognitive development has remained relatively modest from their youth and whose judgement becomes progressively impaired from the end of their 40s. They become lame, dull, indifferent; their memory shows appreciable gaps, they appear physically more limp, and language and movement become trembling. Due to their exaggerated excitability and uncritical mood, they commit foolish deeds, which often lead to their admission. Their pupils react slowly without becoming paralytic. Their language becomes trembling and nasal, although they do not stumble or hesitate. ( . . . ) Presenile dementia differs from normal senile dementia by the pre-existing cognitive impairment and by the earlier on set ( . . . ). It differs from paralysis in its slow course and a lack of the physical signs that characterize paralysis.

THE NEUROPATHOLOGY OF PRESENILE DEMENTIA

Turning to the anatomical basis of dementia senilis, it is widely accepted that atheromatous degeneration of the brain vessels is essential for the development of senile brain atrophy. Some authors appear to believe that a second additional factor is necessary to explain the process. Noetzli believes that dementia senilis shows parallels with arteriosclerotic kidney atrophy. He probably wants to express the view that arteriosclerosis of cerebral blood vessels must be considered the primary cause of senile dementia. Earlier, I also believed this understanding to be correct. Then, however, I investigated a case that had to be diagnosed as presenile dementia, and that showed severe atrophic alterations of the nerve cells, but quite unremarkable atheromatous vascular changes. This case seems ( . . . ) to argue against Noetzli's hypothesis and it raises the suspicion that ( . . . ) inherited weakness of the central nervous system may lead to early atrophy of the nerve cells. If this were true, it would be apparent that degenerative changes of the nerve cells-independent of vascular disorders-could also develop in a typical case of dementia senilis. This single case cannot serve as a final proof, but further investigation may support the supposition.

ARTERIOSCLEROTIC BRAIN ATROPHY:

(An Early Account of the Ischemic Score)

Initially, we must make mention of arteriosclerotic brain degeneration, which was simultaneously and similarly described by Binswanger and myself. Arteriosclerotic brain atrophy almost without exception occurs at the beginning of the 50s. The clinical differential diagnosis from paralysis often poses difficulties. This disorder produces a stepwise deterioration with shorter or longer ( . . . ) intervals and leads ultimately to severe dementia. The nature of the dementia is normally in striking contrast to paralytic dementia. Extensive parts of the original personality are preserved, so that the patients may long retain a surprisingly deep insight, degree of judgement, and orderly behavior that is only severely disturbed during sudden acute exacerbations. The mood is mostly gloomy and desperate. A grave awareness of disease is often retained until the late stages. Binswanger is presumably right to consider that these striking differences from paralysis are due to the different underlying pathology. The diffuse process of paralysis primarily and diffusely destroys nervous tissue, whereas arteriosclerotic dementia causes focal damage, leaving extensive regions of the brain to function normally. The accompanying neurological signs are of great diagnostic importance: ( . . . ) the language becomes slow, sluggish, and clumsy without showing the disturbances typical of paralysis. Orofacial and hypoglossal pareses and pareses  of the trunk and extremities are observed; hemipareses are common. Ataxic and aphasic phenomena are observed after the exacerbations. Arteriosclerotic kidney atrophy, myocardial hypertrophy ( . . . ), or degeneration occur regularly. The postmortem findings are remarkably different from paralysis. They show a widespread vascular atheromatosis, with alterations in the kidney, liver, and brain. The brain shows a remarkable weight loss. ( . . . ) The ventricles are always dilated. ( . . . ) 

BINSWANGER'S DISEASE:

(The Definition as a Pure White Matter Disease Leading to Disconnection Syndromes)

A second form (of vascular dementia) is the encephalitis subcorticalis chronica progressiva, which was also described by Binswanger. 1t is clearly related to dementia senilis. Occasionally, this disorder occurs in the late 40s, but more frequently from the early 50s and until old age. Again, it may be assumed that atheromatous vascular disease is the cause of this disorder. The postmortems yield remarkable white matter atrophy, which may either be confined to one or more areas or may simultaneously but to various degrees occur in multiple hemispheric regions. In the most extreme cases, the hemispheric white matter seems to have vanished almost completely. The posterior brain areas are preferentially affected. Binswanger states that slow decay of the intellectual powers is characteristic of the clinical course. It first becomes apparent as a slowly progressive difficulty and ultimately as a loss of the associative connections between certain cortical sensory and motor areas. Thus, hemiamblyopia or hemianopsia, hemipareses with a loss of the sensation of pressure, position, and touch can be observed. It is accompanied by a gradually progressive decay of the intellectual capacities. The course is very protracted up to 10 or more years. In the final stages, the patients resemble decerebrate laboratory animals.

DEMENTIA APOPLECTICA:

(Cognitive Impairment Following Hemorrhage)

Furthermore, dementia apoplectica should be mentioned in this context. It is clinical experience that a slowly progressive dementia, which is extraordinarily similar to senile dementia, may frequently develop after apoplexy. This may also occur in younger individuals and even if neither cortex nor hemispheric white matter are involved. According to my observations, the anatomical basis of this dementia is alteration in the cortex, not restricted to the hemisphere that is affected by the bleed. These changes are remarkably similar to changes in dementia senilis. Beyer recently described the mental state in dementia apoplectica. He reported that it was characterized by apathy, labile mood, blunting of response, disorientation, confabulation, and weakened memory for the recent past together with a good memory for more remote things. Speech was often sluggish and slow without monotony. Quite frequently, tremor was present and unilateral facial nerve and pupillary abnormalities and normal or exaggerated reflexes. 

PERIVASCULAR GLIOSIS

 In other cases, the arteriosclerotic process appears to be restricted to single areas in the cortex. I have described this form as perivascular gliosis of the brain cortex, because of the remarkable glial proliferation, which mainly characterizes the histological change. This is only a specific localization of arteriosclerotic vascular disease. It is often combined with diffuse senile cortical atrophy ( . . . ). The individual lesions show a wedge-shaped form, the broad base touching the surface and the sharp edge of the wedge lying in the fourth or fifth cortical layer. The site of an old infarct gives itself away through a small hollow on the surface of the gyrus. In the middle of the small lesion, a severely degenerated vessel can always be found. The nerve cells in this area perished as the glial cells increased. The fresh !esions consist of densely aligned arachnoid cells, and the older ones are arranged like a den se wickerwork of sturdy glial fibers with corpora amylacea between them. At times, the older lesions are softened. ( . . . ) Perivascular sclerosis of the cerebral cortex does not seem to be a rare disease as I have already seen eight cases. These persons were 50 to 70 years old. Depending on the site of the disease, the clinical features resemble dementia senilis (perivascular gliosis in the frontal cortex) or a slowly developing focal brain disorder as cortical pareses, aphasic symptoms, cortical deafness, or cortical blindness may occur. ( . . . ). 


(ALZHEIMER'S OUTLOOK: The Neuropsychology of the Dementias )
In our discussion of dementia senilis, we had to admit to so me doubt as to whether or not the arteriosclerosis of the brain vessels may be considered the only cause of senile brain degeneration, or whether perhaps primary atrophic alterations of the nerve cells had to be taken into account. In other forms of disease, atheromatous vascular degeneration obviously represents the core of the degenerative process. Whereas in arteriosclerotic kidney atrophy, the clinical effect may be the same whether the whole kidney is diffusely involved to a mild degree or whether numerous more severe lesions are present ( . . . ). In the central nervous system ( . . . ) where every single part has a different function and no element is equivalent to the next ( . . . ), very different clinical features will arise. This depends on whether the degeneration occurs here or there, diffusely, or with numerous smaller or single larger lesions. In recent years, we have not made an unremarkable progress in the recognition of the various disorders caused by atheromatous vascular degeneration. Most of these diseases deserve further clinical and anatomical research; however, it is to be hoped that we will soon be able to differentiate the mental disturbances of old age into an even larger number of clinically and histologically clearly distinct forms. 

(translated by Hans Förstl and Robert Howard; a commented version was published in “Alzheimer’s Disease and Associated Disorders” 1991)