Hans Förstl


Seltene Demenzen


Common dementia coming of age:


(draft)

It is a fairly recent development that humans expect their organs to function at a high level until their sudden death at a very old age. Many classical Greek and Roman authors had known the syndrome of dementia and felt that cognitive impairment – sometimes severe – was the natural and not at all uncommon effect of ageing (“senectus ipsa morbus est”).

Renaissance scientists began to develop sophisticated concepts about the origin of dementing disturbances and its clinical consequences. Philip Barrough (1583) wrote in his chapter “Of Memory Lost: … the losse of memorie chaunceth sometime alone, and sometimes reason is hurte with it. It is caused in the lethargie and other soporiferous diseases. … If reason be lost together with the memorie, then the affect is called fatuitas or stultitia, foolishnes or dotishnes, …” Pathophysiologically Barrough held a “cold distemper” responsible for the failing of memory. Richard Cosin (1592) defined dementia as “a passion of the minde, … when a mans perceivance and understanding of all things is taken away, and may be englished distracted of wit, or being beside himselfe.”

It has been a long and it is an ongoing process to define dementia as a disease and to distinguish the common from the less common forms, and not always has cognitive impairment been considered as the essential element of these age-associated changes of performance (Berrios, 1990). Kahlbaum (1863) characterized presbyophrenia, a subtype of paraphrenia with amnesia, confabulations, hyperactivity, but preserved interpersonal skills (Berrios, 1986). Interestingly presbyophrenia, which had been considered as a common form of age-associated disturbance, became associated with the presence of fibrillary plaques, with “sphaerotrichia multiplex cerebri” (Redlich 1898; Fischer 1907; 1910a; 1910b), at the same time when Kraepelin made an early attempt to extend Alzheimer’s findings from a single patient with presenile dementia to senile dementia (Alzheimer 1906, 1907; Kraepelin, 1909). 

Research on the organic causes of age-associated disease had already moved from macropathology to histology, but the attempt to compare clinical and microscopic findings did not always contribute to a better understanding of the mind-brain relationship. Thomas Willis (1672) had first observed a correlation between brain atrophy and cognitive impairment. Plaque pathology, “miliary sclerosis”, had already been described since the 1890s (Beljahov, 1889; Blocq and Marinesco, 1892; Redlich, 1898; Leri, 1906). Alzheimer had written several reviews (e.g. 1898) on age-associated neurodegenerative brain changes, before he employed Bielschowsky’s (1903) new staining method and described neurofibrillary tangles in his classical patient with presenile dementia (1906; 1907). Samuel Fuller (1907), while working in Alzheimer’s laboratory, observed the same tangles together with plaques in several patients with senile dementia, but Alzheimer found it much easier to attribute the clinical deficits in younger patients the observed brain changes than to establish such a correlation in elderly individuals, who almost always showed plaques and tangles (1911). The essential neuropathological ingredients of “involutional psychosis” remained unclear (Soukhanoff, 1913). Some scientists felt that there was evidence enough to assume an association between neurodegenerative changes and dementia (e.g. Simchowicz, 1911), while others stubbornly claimed, that the existence of non-demented elderly individuals with abundant neurodegenerative pathology discredited this assumption (Gellerstedt, 1933). More modern scientific reasoning was necessary to establish the relevance of such a correlation even if it exceptions were observed (Blessed et al., 1968; Roth et al., 1966). Therefore it took a some time until similarities between presenile and senile dementia were mentioned again (e.g. Albert, 1964) and a larger scientific community accepted the concept of senile dementia due to neurodegenerative brain changes and that this was probably the most common form of dementia, “Alzheimer’s disease”.


Focal Cortical Atrophies - Frontotemporal Dementia

If the frontotemporal degenerations are considered as forms of dementia, they are definitely a little less common than plaque and tangle dementia. Gall and Spurzheim’s “organology” had prepared the ground for Broca’s (1861) and Hughlings Jackson’s (1863) work on the specific relationship between different brain areas and distinct cognitive functions. Cotard’s (1868) study on partial brain atrophies went almost unnoticed, but there has been a number of other publications on  focal brain atrophy, which Arnold Pick quoted in his first paper on the topic (1892). Over more than a decade (1892, 1901, 1904, 1906) Pick had collected six patients with intriguing associations between focally accentuated cortical brain changes and neuropsychological deficits. Unfortunately Chiari, Pick’s collaborator in neuropathology, did not report histological details, - a task, which was later carried out by Alois Alzheimer (1911). Alzheimer found intraneuronal argentophilic inclusion bodies (Pick bodies) and achromatic neuronal ballooning (Pick cells).

In 1913 Mingazzini discussed a number of potential earlier reports on focal cortical atrophies by Alzheimer, Ascher, Bischoff, Dejerine and Serieux,  Franceschi, Liepmann, Marie and Leri, Mills, Rosenfeld, Shaw, Stransky and of course Pick. Rosenfeld (1909) had described posterior cerebral atrophy. Tissot et al.  (1975) distinguished three clinico-pathological subgroups of  “Pick’s disease” according to the presence of Pick bodies, Pick cells, and their distribution. Wechsler (1977) observed a 67-year old patient with aphasia and marked dilatation of the left Sylvian fissure. Mesulam (1982) found more and called the syndrome “slowly progressive aphasia”.  After a large number of publications on “Pick’s” until world war II, the interest had receded in most parts of the world, but was still kept alive in Scandinavia (e.g. Sjögren, 1952). Gustafson (1987) defined the clinical and Brun (1987) the neuropathological criteria for “frontal lobe degeneration of non-Alzheimer type”. With the contemporary momentum of neuropsychology, functional neuroimaging and genetics, the frontotemporal degenerations have gained importance as a modern research subject.


Subcortical dementias

Von Stockert (1932) coined the term subcortical dementia for a patient with postencephalitic cognitive impairment (no sign of Parkinsonism). Stertz (1921) had observed that extrapyramidal disorders did not only affect motor, but also cognitive functions. Naville (1922) described bradyphrenia as a consequence of encephalitis lethargica. Forgetfulness, slowing, apathy, affective changes are now considered the clinical hallmarks of this pathologically heterogeneous group of diseases of subcortical dementias.
Since Albert’s work (1974), progressive supranuclear paresis (PSP) became the prototype of subcortical dementia. Bradyphrenia and bradykinesia, rigidity particularly of the head and trunk, paralysis of downward gaze were described as the classical signs of PSP (Richardson et al., 1963).

McHugh (1973) used the term “subcortical dementia” to describe the cognitive disturbances in Huntington’s chorea. Huntington (1872) had not been the first to describe familial cases of choreoathetosis and cognitive deterioration (Elliotson, 1832; Dunglison, 1842; Wood, 1855; Lyon, 1863), but Huber (1887) suggested the eponym “Huntington’sche Krankheit”.
There are numerous other uncommon dementing diseases, which can be integrated into the loose concept of subcortical dementia, for example:
-    Wilson’s disease (1912) with familial liver cirrhosis and progressive lenticular degeneration with emotional changes, apathy and slowing
-    extrapyramidal and cognitive disturbances in five of twelve siblings due to atropy of the globus pallidus and substantia nigra named after Hallervorden and Spatz (1922)
-    Thalamic dementias without (Stern, 1939), or with atrophy of the red nucleus and chorea (Grünthal, 1942)
-    spinocerebellar degenerations (Greenfield, 1954),
-    Guam-Parkinson-dementia complex (Hirano et al., 1961)
-    subcortical gliosis without cortical involvement (Neumann and Cohn, 1967),

Today the variants of Parkinson’s disease are clearly considered the most important forms of subcortical dementia. James Parkinson (1817) reported six patients with “shaking palsy”, three of whom he had studied in detail. Their “senses and intellect” were allegedly “uninjured”. Charcot (1881; 1883) contributed many more details to characterize Parkinson’s disease clinically, particularly in patients older than those originally observed by James Parkinson. He introduced the term “la maladie de Parkinson”. Gowers (1893) still attributed Parkinsonism to anxiety and “emotional shock”. Lewy (1913) first saw the “Lewy bodies” of shaking palsy in the magnocellular neurons of the basal nucleus, earlier delineated by Meynert, and much earlier - nee “substantia innominata” – by Reil (1809). Hassler (1938; 1965) made significant contributions to the understanding of the relationship between neuropathology of pigmented nuclei in the brainstem and the neuropsychiatry of Parkinsonism and ageing. Von Buttlar-Brentano (1955) correlated clinical and neuropathological changes of the basal nucleus of Meynert in patients with Parkinson’s disease. Deutsch (1971) suspected a correlation between cholinergic and memory function, a position supported by Drachman and Leavitt (1974). Perry et al (1977) demonstrated cholinergic deficits in senile dementia, and Barfus et al. (1982) elaborated the cholinergic hypothesis of geriatric memory dysfunction. According to current evidence demented patients with Parkinson’s disease gain even greater benefit from cholinesterase-inhibition than the patients with common Alzheimer’s disease (Emre et al., 2004).


Vascular Dementias

They are uncommon, because  –
-    There is not one vascular dementia, there are many pathophysiologically and clinically distinct forms, which need to be considered separately; this is one reason which makes these individual forms uncommon;
-    Purely vascular forms of dementia may occasionally be observed in younger, but hardly ever in elderly patients. Mixed neurodegenerative plus vascular components are the most common forms of dementia in old age.

The concept of vascular dementia is old and outdated. Conrad Victor Schneider (1672) delivered one of the earliest and most extensive treatises on vascular dementia, covering most of the older historical views on vascular dementia on 1200 smallprint pages. Dechambre (1838) first used the term cerebral “lacunes” in a paper on the curability of cerebral softening. Pierre Maire (1901) defined the “etat lacunaire”.  Durand-Fardel wrote extensively on cerebral softening (“ramollissement”) in his textbook of geriatric medicine and elsewhere (1843; 1854). “Apoplectic dementia” was a concept introduced by Ball und Chambard (1881). Charcot (1881; 1883) contributed a large number of significant observations on clinico-anatomical correlations in elderly patients with cerebrovascular disease. Jackson (1875) lectured on the softening of the brain. Walton (1912) doubted whether atherosclerosis was important for senile dementia. Critchley (1929) suggested the concept of arteriosclerotic Parkinsonism.

Binswanger (1894) described his eponymous disease during his elaborations on the differential diagnosis of progressive paralysis. Alzheimer (1902) suggested “Binswanger’s disease” and wrote extensively about vascular brain changes in dementia (1895; 1898; 1902). Julius Mayer-Gross (1944) had carried Alzheimer’s expertise on vascular brain changes and their clinical symptoms into the English speaking world and published the symptom list typical of multiple cerebral infarcts, a list which later became the substance of Hachinski’s (1974) “ischemic score”.


Infectious & inflammatory forms of dementia

No other group of dementias has had a comparable impact on cognitive neurosciences, in no other group has a shift of paradigms led to such obvious diagnostic and therapeutically important consequences. Originally Binswanger (1894) and Alzheimer (1904) had set out to differentiate progressive paralysis.

Infectious diseases were the most likely cause of “phrenitis”, a confusional state with hallucinations eventually leading to a dementia syndrome as mentioned in the Corpus hippocraticum and by Celsus (25 BC – 50 AC). Armstrong (1824) wrote about the cognitive effects of typhus, Bayle (1822) and Calmeil (1826) about the acute and chronic stages of paralysis. Marce (1863) attempted a clinical and pathological differentiation of general paralysis and senile dementia. Esmarch and Jessen (1857), and Fournier (1875) investigated the relationship between syphilis and mental disease. Baillarger (1889) suspected that general paralysis of the insane was a heterogeneous group of disturbances including “pseudo-general paralysis”, and some other reversible forms. Binswanger (1894) still believed that general paralysis was undoubtedly the consequence of a functional exhaustion of the brain, particularly of the neocortex. In 1901 Max Nonne published the first edition of his extensive textbook on syphilis of the nervous system.

Following Baillarger, general paralysis had been diagnosed in a large proportion of psychiatric patients before the discovery of Treponema pallidum (Schaudinn & Hoffmann, 1905) and the availability of a laboratory test (Wassermann, 1906). Noguchi and Moore (1913) identified treponema pallidum in the brains of patients with general paralysis. With improved diagnostic techniques (serology, histology, etc.), new competing conceptual issues (senile dementia, Alzheimer’s disease, Pick’s disease, etc.), and new diseases (encephalitis lethargica), the once so common general paralysis became an uncommon form of dementia.

-    Encephalitis lethargica was an epidemic, probably of viral origin, prevalent until 1926 (Economo, 1918, 1929). Bebb (1922) investigated the memory deterioration in encephalitis lethargica.
-    Creutzfeldt (1920) and Jakob (1921) observed peculiar disseminated brain changes in patients with rapid clinical deterioration of cognitive and motor symptoms.
-    Gajdusek and Zigas (1957) described the clinical symptoms of Kuru in Papua New Guinea. In 1959 Hadlow suggested a relationship of kuru and scrapie, a slow viral disease in sheep. Gibbs et al. (1968) succeeded in transmitting the infectious agent to chimpanzees.


Other uncommon forms of “organic” dementia

There is a vast number of metabolic, toxic and other diseases, which may eventually lead to a dementia syndrome, for example:
-    Metabolic & endocrinological. Vitamin deficiencies, Addison’s, Cushing’s, Wilson’s disease, anoxic brain lesions, etc.  George III is one historic figure in whom psychogenic, bipolar, and also metabolic causes were suspected (MacAlpine & Hunter, 1969). Manfred Bleuler (1954) described an endocrinological mental syndrome affecting social behaviour, sleep, sexuality, movement, temperature sensation, hunger and thirst.
-    Drug & alcohol-induced dementia. Ulysses’ comrades fell prey to a legendary intoxication, probably with an anticholinergic cocktail mixed by Circe (Homer). Aretaeus (50 – 130) found that the anticholinergic hyoscin causing “phrenitis”, a confusional state. Sutton (1813) observed “delirium tremens” with visual hallucinations, which could be relieved with opium. Wernicke (1881) and Korsakow (1887) observed the acute and chronic stages of thiamine deficiency due to chronic alcoholism or other causes: confusional states leading to an amnestic syndrome caused by a “polioencephalitis haemorrhagica superior”, i.e. bleeds into the Corpora mamillaria of the limbic system. In 1915 Moll reported a series of 30 cases of Korsakow’s amnestic syndrome. Eugen Bleuler’s (1916) “diffuse mental syndrome” largely corresponds to Korsakow’s psychosis.
-    Traumatic dementia. Bleuler’s (1916) “local brain syndrome” (“hirnlokales Psychosyndrom”) with a loss of drive and mood changes corresponds to the sequelae of traumatic brain lesions. “Dementia pugilistica” represents the extreme variant of traumatic organic personality change (von Baeyer, 1947).


Uncommon psychiatric dementia syndromes

-    Dementia praecox. Kraepelin (1919) had sent Alzheimer on a mission to discover the morphological hallmarks of “dementia praecox”, later called schizophrenia. Alzheimer died before this mission was accomplished, but he left an unfinished draft of his opus magnum (which is now sadly left neglected in the office of an obscure neuroscientist).
-    Dementia syndrome of depression.  Mairet (1883) published a volume on melancholic dementia leading to stupor and severe physical complications. Dumas (1894) wrote a complete thesis about mental fatigue as cause of melancholic dementia. Gaupp (1903) examined and reviewed the brain changes and somatic diseases leading to melancholic dementia.
-    Dissociative dementia. Sigbert Ganser (1898) observed patients, who – during stressful conditions – exhibited impaired cognitive performance with typical “near-miss” answers (“Ganser syndrome”). Nitsche and Wilmanns (1912) described a “prison psychosis” with similar symptoms.


Summary

There is one common form of dementia, “Alzheimer plus” other neurodegenerative, vascular, inflammatory, traumatic, … brain changes, found in more than 90% of all demented patients. The other forms of dementia are uncommon (MRC-CFAS, 2001). 


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