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Essay on Dementia
| Date: |
09-15-02 4:35am |
| Subject: |
Science |
| Word Count: |
3999 |
| Page Count: |
16 |
Dementia
What is Dementia ?
Dementia is an organic brain syndrome which results in global cognitive impairment. Dementia can occur
as a result of a variety of neurological diseases. Some of the more well known dementing diseases include
Alzheimer’s disease (AD), multi-infarct dementia (MID), and Huntington’s disease (HD). Throughout this
essay the emphasis will be placed on AD (also known as dementia of the Alzheimer’s type, and primary
degenerative dementia), because statistically it is the most significant dementing disease occurring in over
50% of all demented patients (see epidemiology).
The clinical picture in dementia is very similar to delirium, except for the course. Delirium is an acute
transitory disorder. By contrast Dementia is a long term progressive disorder (with the exception of the
reversible dementias). The course of AD can range anywhere from 1.5 to 15 years with an average of about
years (Katzman, Lasker & Bernstein, 1988). AD is usually divided into three stages mild, moderate,
and severe. Throughout these stages a specific sequence of cognitive deterioration is observed (Lezak,
1995). The mild stage begins with memory, attention, speed dependent activities, and abstract reasoning
dysfunction. Mild language impairments also begin to surface at this period. In the moderate stage,
language deficits such as aphasia and apraxia become prominent. Dysfluency, paraphasias, and bizarre word
combinations are common midstage speech defects. In the severe stage the patient is gradually reduced to a
vegetative state. Speech becomes non-fluent, repetitive, and largely non-communicative. In addition,
Auditory comprehension becomes exceedingly limited, with many patients displaying partial or complete
mutism. Late in the course of the disease many neuropsychological functions can no longer be measured.
Furthermore, primitive reflexes such as grasp and suck emerge as well. Death usually results from a disease
such as pneumonia which overwhelms the limited vegetative functions of the patient.
Dementia is commonly differentiated along two dimensions age and cortical level. The first dimension,
age, serves to distinguish between senile and presenile dementia. Senile dementia is used to describe patients
who become demented after the age of 65, whereas presenile dementia applies to patients who become
demented prior to that age. Late onset AD (LOAD) also known as senile dementia of the Alzheimer’s type
(SDAT) is the predominant cause of senile dementia. Early onset AD (EOAD) is the most frequent cause of
presenile dementia, but HD, Pick’s disease, and Creutzfeldt-Jakob disease though not as frequent are also
important causes in presenile dementia.
The second dimension, cortical level, differentiates between cortical and subcortical dementia. Cortical
dementia is used to describe dementia which results from brain lesions at the cortical level, whereas sub-
cortical dementia applies to dementia which results from subcortical brain lesions. AD and Pick’s disease
are amongst the best known examples of cortical dementia; whereas HD, Parkinson’s disease (PD), and
progressive supranuclear palsy (PSP) are good examples of subcortical dementia (Derix, 1994). When
dementia with both cortical and subcortical features occurs, the term mixed dementia is used. MID is a
common example of mixed dementia.
Historical Developments in Dementia
Pre-Modern Developments
The use of the term dementia dates back to Roman times. The Latin word demens did not originally
have the specific connotation that it does today. It meant ‘being out of one’s mind’ and as such was a
general term for insanity (U’Ren, 1987). It was the encylopedist Celsus who first used the word dementia in
his De re medicina, published around AD 30. A century later the Cappadocian physician Aretaeus first
described senile dementia with the word dotage: “The dotage which is the calamity of old age…dotage
commencing with old age never intermits, but accompanies the patient until death” (U’Ren, 1987, P. 1).
Curiously, dementia was mentioned in most systems of psychiatric classification throughout pre-modern
times, though the precise meaning of the word is often unclear (U’Ren, 1987).
Nineteenth Century
It can be argued that the origins of the scientific study of dementia date back to the early nineteenth
century. The initial steps were undertaken by the great French psychiatrist Pinel at the beginning of that
century. Pinel’s observations led him to conclude that dementia is caused by ‘idiotism’. He used the term
dementia in relation to the “progressive mental changes seen in some idiots” (U’Ren, 1987,3). Furthermore,
Pinel thought that dementia was a distinct abnormal entity, and thus he used the term dementia to designate
one of the five classes of mental derangement. However, by applying the term dementia to ‘idiots’ Pinel
failed to differentiate between dementia and mental subnormality. This was accomplished by Pinel’s student
Esquirol in his 1838 textbook Mental maladies-A treatise on insanity. Esquirol summed up the difference
between the demented and the mentally handicapped in the following epigram: “The dement is a man
deprived of the possesions he once enjoyed, he is a rich man who has become poor. But the defective has
been penniless and wretched all his life” (Mahendra, 1984, P. 10). Furthermore, Esquirol was also
instrumental in the popularization of the term senile dementia. Remarkably, his description of senile
dementia is very similar to our present day definition. Interestingly, in 1845 Griesinger proposed that senile
dementia was due to a disease of the cerebral arteries, a faulty view which persisted until Alzheimer’s time.
Much of today’s basic knowledge about dementia was accumulated throughout the second half of the
nineteenth century, and the first decade of the twentieth century. In 1872 Huntington presented a paper
called “On chorea”, in which he discussed a typical case of what is now known as Huntington’s disease.
Twenty years later in 1892 two significant events took place. First Pick (1892), in a paper called “On the
relation between aphasia and senile brain atrophy” described the case of August H. a 71 year old patient with
senile dementia. Although the case is not typical of our present day conception of the disease, Pick was
given credit for discovering a new disease. The other more significant event which occurred in 1892 was
Blocq and Mariensco’s description of scattered silver staining plaques in the cortex of senile patients. These
plaques were subsequently named senile plaques (SP) by Simchowitz in 1911.
The year 1894 saw Alzheimer’s first major contribution, a differentiation between senile and vascular
(arteriosclerotic) dementia. Alzheimer described the specific changes observed in arteriosclerotic atrophy of
the brain, which resemble what we might call vascular dementia. In 1898 another milestone occurred when
Binswanger introduced the term presenile dementia. Thus by the twentieth century significant changes were
taking place in our understanding of dementia. The nineteenth century view that there is only one mental
disease, insanity, and that dementia is its terminal stage was dispelled by Kraepelin in the 6th edition of his
textbook Psychiatrie, published in 1899 (U’Ren, 1987). Kraepelin separated dementia praecox (a concept
he proposed in 1898 in relation to schizophrenia) from the other dementias (paralytica and organic), and
included senile dementia under another category called involution psychosis (U’Ren, 1987).
Twentieth Century
In 1907 Alzheimer published his landmark case “A unique illness involving the cerebral cortex” in which
he described a fifty-five year old demented woman. The case was very unusual for two reasons, its clinical
course and the discovery of a striking microscopic lesion in the woman’s brain (Beach, 1987). Alzheimer
speculated that a chemical change had occurred in the neurofibrils. Thus Alzheimer had described for the
first time neurofibrillary tangles (NFT), which together with SP are considered to be the neuropathological
hallmarks of AD. Alzheimer concluded that he had discovered a unique entity separate from senile dementia
as it was known at that time. However, it was not until 1910 when Kraepelin discussed the condition in the
8th edition of his textbook Psychiatrie that AD gained official recognition.
The second decade of the twentieth century witnessed the end of the golden period in dementia research
(this only lasted until the 1960’s when a renaissance occurred). U’Ren (1987) cites two reasons as the
principal causes. First the rise of Freud’s Psychodynamic theory caused American psychiatry to turn in the
direction of psychological explanations. Second Kraepelin’s descriptions and classifications seemed to leave
little room for therapeutic efforts or optimism.
Notwithstanding, several key contributions have been made in the ‘Dark Ages’ of dementia research. In
1920 Creutzfeldt and in 1921 Jakob described cases of dementia with pyramidal and extrapyramidal signs.
Although it is now thought that only Jakob’s case was typical of the disease the Creutzfeldt-Jakob disease
(CJD) was given to the world. In 1936 an important change emerged with regards to the diagnosis of AD.
Before 1936 it was common practice to provide a diagnosis based on both clinical and pathological
characteristics. However, when it became clear that many non-demented people had some SP and NFT,
Jervis and Stoltz advised that only clinical criteria would suffice for the diagnosis of AD (Mahendra, 1984).
In 1948 Jervis published his landmark paper called “Early senile dementia in Mongoloid idiocy”. Jervis
described three individuals with Down’s syndrome (DS), aged 37, 42, and 47, each of whom displayed
intellectual deterioration in the last few years of life (Beach, 1987). At autopsy, all three were found to have
SP and two also displayed NFT. This was the first demonstration of NFT in DS and the first full clinical and
pathological correlation supporting an Alzheimer-like syndrome in DS (Beach, 1987). Later it was
discovered that EOAD and DS share a common genetic pathology on chromosome 21 (see risk factors).
Research in dementia began to revive in the early sixties. New causes of the dementia syndrome were
recognized including progressive supranuclear palsy and normal pressure hydrocephalus. Prior to the 1960’s
dementia was still viewed as a “chronic, irreversible and untreatable condition” (Mahendra, 1984, P. 14).
Accordingly, in the 1960’s several writers in Europe called for a revision of the concept and emphasized that
irreversibility should not be viewed as an essential feature of dementia. Another important change that took
place in the 1960’s concerned epidemiology. Before the sixties arteriosclerosis was thought to be the
predominant cause of dementia, whereas AD was thought to be rare. However, arteriosclerosis was
decisively challenged as the prime cause of dementia by several reports between 1960 and 1970. These
reports demonstrated that arteriosclerosis was greatly overestimated as a cause of dementia, and that the
majority of patients who were dying with dementia in fact showed the characteristic plaques and tangles of
AD (U’Ren, 1987). Furthermore, Katzman (1976) [as cited by U’Ren] argued that because of the similarity
in the clinical picture and the identical nature of the histopatholgy, distinctions between AD and senile
dementia were arbitrary and no longer useful. Thus when it was understood that AD and senile dementia are
similar, it was clear that AD is a common illness.
In the 1970’s two important contributions were made. First, Butler in his 1975 book Why survive ?
Being old in America criticized the widespread notion that senility was a normal part of aging. Butler
argued that, senility, was either the result of brain disease or depression, and that it was potentially treatable.
The extension of this view was that senility was abnormal, and that its usual causes were diseases and not
just aging (U’Ren, 1987). Second, three different labs (Brown et al. , 1976; Davies & Maloney, 1976; and
Perry et al. , 1977) [as cited in U’Ren, 1987], reported low levels of choline acetyltansferase, the marker
enzyme for acetylcholine (ACh), in the brains of patients who died from AD. ACh deficiency has since been
the target of most therapeutic efforts in AD (see treatment).
Throughout the 1980’s and 1990’s two trends emerged. First, with regards to diagnosis, criteria have
been made stricter. Classification systems like the Diagnostic and Statistical Manual have evolved towards a
more precise and comprehensive definition of dementia. Moreover, neuroimaging techniques are
increasingly becoming more standard in assessment, allowing in some cases for a more accurate diagnosis.
Second, the past fifteen years have witnessed a substantial growth in genetically based research. For
instance one of the genes involved in AD, the amyloid precursor protein (APP), has been localized to a
specific segment of chromosome 21 (see risk factors).
Epidemiology
Dementia is known as the quiet epidemic, but it affects a significant proportion of our population. In
1989 the Canadian consensus conference on the assessment of dementia reported that Canada had about
250,000 cases of dementia (which at the time comprised about 1% of the population), with 25,000 new
cases occurring annually (Clarfield, 1989). Jorm et al. (1988) [as cited by Clarfield, 1989] project that by
the year 2025 Canada will experience a growth in the prevalence of dementia, more rapid than the rise in the
elderly population aged over 65. The majority of dementia cases are attributable to AD, Vascular
dementias, or a combination of these (see Table 1). In the past there were hopes that up to 40% of the
dementias had reversible causes. However, recent reports (Clarfield, 1988; Barry and Moskowitz, 1988)
suggest that the true incidence of reversible dementias is at the most only 11% and is probably far lower with
drugs, metabolic causes, and depression accounting for about two thirds of the cases (Clarfield, 1989).
Overall, there are no significant gender differences in prevalence and incidence rates for dementia as a
whole (Graves & Kukull, 1994). However, for AD, an increased prevalence rate is observed in females.
Jorm et al. (1987) [as cited by Graves & Kukull, 1994] estimate a female to male AD prevalence ratio of
Ethnically there seem to be important differences in both prevalence rates and in the dementing
diseases. With respect to prevalence, Heyman et al. (1991) [as cited by Graves & Kukull, 1994] found that
out of a random sample of 4116 people 16% of African Americans had dementia compared to only 3.1% of
Caucasians. The same study also found that MID and mixed dementia were more likely to occur in African
Americans than in Caucasians (26% of all dementia cases in African Americans were of the MID and mixed
type compared to only 14% in Caucasians). No clear explanation is given for these findings besides the
mention that “Blacks were more likely than whites to have a history of risk factors associated with MID”
(Graves & Kukull, 1994, P. 30). Interestingly, in both Europe and North America most studies point to AD
as the most common dementing illness; whereas in Asia (especially Japan) MID predominates. The
observed high rate of stroke in Japan is consistent with a high MID rate (Graves & Kukull, 1994). Possibly
the higher level of stress in Japan leads to more strokes and therefore a higher prevalence of MID.
Table 1. Etiology of Progressive Dementia and Approximate Incidence
Senile dementia of the Alzheimer type (AD) 50%
Multi-infarct dementia 10-15%
Mixed SDAT and MID 10-15%
Alcoholic-nutritional dementia 5-10%
Normal pressure hydrocephalus 5%
Miscellaneous: Huntington’s disease, neoplasms, chronic
subdural hematomas, Parkinson’s disease,
Cruetzfeldt-Jakob disease, AIDS, Unknown causes 5-20%
____________________________________________________________
Note: Reproduced from Adelman, 1987, Encyclopedia of Neuroscience
(Vol. I), Boston: Birkhauser
Life Expectancy and Mortality Estimates
The following summary is based on Katzman’s et al. (1988) review of the Wang (1978) and Barclay et al.
studies. The Wang study examined senile dementia (mean age of onset 71.3 years) and presenile
dementia (mean age of onset 53.8 years) survival rates during the 1960’s. Senile dementia patients survived
on the average 6.0 years, close to half the expected survival rate of similarly aged non demented people
which is 11.1 years. Presenile demented patients survived a slightly longer average of 6.9 years against an
expected survival rate of 22.3 years. The Barclay et al. (1985) study examined survival rates in AD and
MID patients in the 1980’s. The mean survival rates for these diseases were 8.1 and 6.7 years respectively.
Interestingly, the survival rate of demented woman on the whole is significantly higher than that of men.
Katzman et al. (1988) suggest that the lower survival rate of demented men is due to a higher incidence of
MID in men.
Risk Factors
Age
Age is the biggest risk factor for developing dementia. According to a model proposed by Jorm et al.
[as cited by Graves & Kukull, 1994] a doubling of the prevalence rate occurs every 5.1 years. For
the elderly population aged 65 and above the prevalence of dementia is estimated at about 10% (Clarfield,
1989). Whereas in the very elderly it can reach up to 40% (Evans et al. , 1989) [as cited in Clarfield, 1989].
Genetics
Genetic factors are important in some dementing diseases. In HD an autosomal dominant gene on
chromosome 4 is directly responsible for the disease. The genetic evidence in AD is less conclusive. On the
one hand, studies such as Breitner et al. (1988) [as cited by Graves & Kukull, 1994] have reported a
cumulative risk of AD among relatives of patients approaching 50%, thus implying an autosomal dominant
mode of transmission. On the other hand, however, genetically transmitted diseases should be concordant in
monozygotic twins, but this does not appear to be the case in AD. For instance both Creasey et al. (1989)
and Kumar et al. (1989) [as cited by Graves & Kukull, 1994] have reported three pairs of monozygotic
twins who were discordant for AD. Whereas Nee et al. (1987) [as cited by Graves & Kukull , 1994] only
found a 41% concordance rate for AD in 17 monozygotic twins.
Farrer et al. (1990) [as cited by Lezak, 1995] suggest that AD appears as an autosomal dominant in
families in which the average age of onset among kindreds is under 58. Supporting evidence for this comes
from studies which have linked EOAD with DS. It has been shown that individuals who are afflicted with
DS and who survive to age 40 almost invariably develop Alzheimer like dementia. During the intermediate
and terminal stages of DS the individual suffers from recent memory loss, apraxia, temporal disorientation,
and mutism, all of which are also common in AD (Graves & Kukull, 1994). Thus it is not surprising that
four studies have found an increased risk for AD with late maternal age. According to Rocca et al. (1991)
[as cited in Graves & Kukull, 1994] the increased risk of AD to patients born to mothers over 40 is
consistent with the DS risk curve.
Both EOAD and DS have been localized to chromosome 21. However, chromosome 21 does not appear
to be a very good genetic marker for EOAD. Recent studies have shown that a defect in chromosome 14 is
more likely to be associated with EOAD, but the specific gene(s) have not yet been isolated (Marco, 1995).
Evidence for genetic predisposition to LOAD has only emerged over the last two years. It is now known
that a gene which codes for a lipoprotein called ApolipoproteinE (APOE) in chromosome 19 is involved.
APOE is linked to the type 4 allele (e4). It has now been proven that an increase risk for dementia is
dependent on a strong chemical binding between the main ingredient of SP, the Beta amyloid protein, and
the APOE-e4 (Marco, 1995). Table 2 summarizes the genetic findings that have been made thus far.
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