Int J Child Health Hum Dev 2015;8(4):449-469
© Nova Science Publishers, Inc.
Dementia and people with intellectual
and developmental disabilities
Norberto Alvarez, MD
Department of Neurology, Boston Children’s Hospital
and Harvard Medical School, Boston, Massachusetts,
USA
 variable depending on the cause and the individual
Correspondence: Assistant professor Norberto Alvarez, MD,
Department of Neurology, Boston Children’s Hospital,
300 Longwood Avenue, Boston, MA 02115, United
States. E-mail: norberto.alvarez@childrens.harvard.edu
ISSN: 1939-5965
Abstract
Dementia is an acquired syndrome secondary to many
causes with a continuous progressive deterioration of
intellectual functions and personality changes, associated
with a marked decline in activities of daily living. Memory
loss, a common early sign, is followed by impairment in
other domains like language, judgment, mood changes,
psychiatric disorders, like hallucinations, psychosis, and
sleep disorders. These symptoms are also associated with
gait deterioration, swallowing disorders, loss of activities of
daily living and in some cases epileptic seizures. The
clinical presentation is variable depending on the cause and
the individual affected. This review is limited to the
presentation of dementia in persons with intellectual and
developmental disabilities (IDD) and because of the high
prevalence, special consideration will be given to the
development of Alzheimer’s Disease (AD) in persons with
Down Syndrome (DS).
Keywords: Dementia, Alzheimer's disease, disability,
intellectual disability
Introduction
Dementia is an acquired syndrome secondary to many
causes. The common feature is the continuous
progressive deterioration of intellectual functions and
personality changes, associated with a marked decline
in activities of daily living. Memory loss, a common
early sign, is followed by impairment in other
domains like language, judgment, mood changes,
psychiatric disorders, like hallucinations, psychosis,
and sleep disorders. These symptoms are also
associated with gait deterioration, swallowing
disorders, loss of activities of daily living and in some
cases epileptic seizures. The clinical presentation is
affected.
450 Norberto Alvarez

Box 1. Diagnostic criteria for the diagnosis of dementia died between January 1995 and June 2000, the
average age at death was 64 yrs (range 33-90 years).
A. Impairment in short term or long term memory In 2014 there were 314 individuals living in the
B. In association with at least one of the following: facility, average age was 63 years (range 33 to 101
Impairment in abstract thinking years) 270 of them were 65 years or older.
Impaired judgment In some groups of individuals with IDD the
Presence of other disturbances of high cortical increase in age was even more dramatic. The life span
functions such as aphasia, apraxia, agnosia of children born with Down syndrome was 9 years in
Personality changes the 1920s, increased to 30 years in the 1960s, and to
C. The clinical and cognitive changes significantly 55 years in 1993 (5, 6) In 1996 it was reported that in
interfere with work, social activities and or interactions
California the life expectancy of a 1 year old child
with others.
with Down syndrome and profound IDD was 43 years
D. Not occurring in the presence of delirium.
and increase to 55 years in those with mild to
E. Disturbances cannot be accounted for by any
moderate degree of IDD (7). At WDC, in 1999, the
nonorganic mental disorder.
average age of persons with DS at the time of death
was 61 yrs. (range 47-70 yrs.).
A prospective study done in British Columbia,
Dementia and aging Canada in 1995 (8), with a cohort of more than 3,000
individuals with cerebral palsy, found an overall
Dementia, a condition age related, is becoming more survival rate of 87% at age 30 years. Also it was
important in people with DD, as, given the marked estimated that for those in the 30-39 years bracket, the
improvement observed in the last 30 years in the possibilities of survival to the next decade was in the
quality of care they receive, the life expectancy is order of 90%. With proper resources, people with
getting longer. hemiplegia and IDD can live well after 70 years (9).
The 1923 report from the US Census Bureau on
persons with intellectual and developmental
disabilities (IDD) living in institutions showed that
around 67% were between the ages of ten and thirty
Recognition of the issue
years, 95% were under the age of 40, and only 1%
The recognition of the special needs of the elderly
above the age of sixty (1). Most of the deaths
person with IDD is relatively new. Early workers in
occurred in the first decade particularly the first two
the field presented the issue of aging in IDD in the
years of life. The mortality ratios directly correlated
1960's (10), but gerontological issues were not as
with the degree of intellectual disability and
prevalent as they are now (11) and it is only in the
approximately 50% of the deaths were due to
past 20-25 years that the special needs of older adults
infectious disorders. Epilepsy and heart conditions
with IDD were recognized. For example the first full
were also reported as frequent cause of death. Similar
session on “The aging mentally retarded” was
results were observed in a study that evaluated cause
presented at the 12th Congress on Gerontology, in
of death of individuals admitted to an institution in
Germany, in 1981 (12).
California during the period 1944-1962 (2).
This awareness led to a positive response from
The life expectancy of persons with IDD living in
governmental agencies. In USA laws, were amended
three institutions in the Commonwealth of
to ensure that the protection of the laws extended to
Massachusetts, between the years 1917-1930, was 30
all individuals with disabilities (6, 13).
years for males and 32 years for females (3, 4).
Determining the size of the population with IDD
At Wrentham Developmental Center, an
and dementia presents several methodological
institution for persons with IDD in Massachusetts,
difficulties that have been extensively discussed (5,
there were 365 individuals residing as of April 1999;
14). Despite these limitations, it is estimated that
the average age was 55 years, (range 34-91 years),
more than half a million persons with intellectual and
160 persons were over the age of 55 years, and 47 of
them were 70 years or more. Fifty-two individuals
 Dementia 451

other developmental disabilities older than 60 years, Those criteria are difficult to apply to persons
are living in the USA (6). with IDD and another set of criteria has been
established stressing the importance of the decline
rather than the impairment in performance (20). There
Diagnosis of dementia are several diagnostic instruments that can be used in
persons with IDD. The use and the validity of these
In spite of advances in neuroradiology, genetics and instruments have been extensively discussed (21).
biological markers, the diagnosis of dementia still is Some of them like The Dementia Scale for Down's
based, mainly, on clinical history and examination. Syndrome (22) was specifically designed for this
purposed. However at the present time there is not a
Box 2. Differential diagnosis of dementia single battery of tests that can determine the presence
of dementia in a person with IDD with one single
Neurodegenerative disorders administration (20). Since the diagnosis of dementia
Alzheimer Disease requires the documentation of a progressive
Frontotemporal dementias deterioration in activities of daily living, a simple
Pick Disesase battery of test that can be performed by care givers
Huntington Dissease would be an ideal solution. The Reiss Screen for
Cerebrovascular disorders Maladaptive Behavior can be used for caregivers (23).
Vascular dementia The Wrentham Developmental Center Tool is not
Multiinfarct dementia intended as a diagnostic tool but as a simple, practical
Subacute sclerotic way to document the progressive decline in activities
encephalopathy of daily living.
Amyloid angiopathy The ICD-10 requires at least 6 months of
Subarachnoid hemorrhage symptoms before the diagnosis is accepted, however,
Infectious disorders unless the dementia is advanced it is very difficult to
Post-meningitis
establish the diagnosis in persons with IDD in such a
Post-encephalitis
short period of time. From my experience, an average
Neurosyphilis
period of 1 to 1 and ½ years was needed to be certain
Toxic disorders
Alcohol of the diagnosis. Exceptionally a person with IDD
Heavy metals: ie:lead, mercury will provide reliable information; most of the time the
Carbon monoxide information is provided by caretakers. Since the
Metabolic disorders perception and the observations might vary from
Hypoglicemia observer to observer, it is common to find conflicting
Hypoxic ischemic events information that hampers the accurate diagnosis
Nutritional deficiencies: ie: vitamins mostly in the early stages.
B1;B12 Some laboratory tests of memory functions can
Hormonal deficiencies document early memory impairment even in persons
Hypothyroidism with severe and profound IDD (24). In practice
Pseudodementias memory losses should be suspected when individuals
Multiple medications fail to remember familiar names or get lost in familiar
Depression environments.
Modified from Morris JC. The nosology of dementia. In the particular case of persons with IDD, and
Neurol Clin 2000;18(4):733-88. especially in those with a severe to profound degree
of MR, the early recognizable signs of dementia are in
Guidelines for the diagnosis of dementia have the behavioral sphere (apathy, irritability, emotional
been published by different associations (15-18). instability, psychiatric disorders) (25).
Following these guidelines the accuracy of the There are many combinations of signs and
diagnosis in individuals without IDD is around 90% symptoms, but in general, parallel to the progressive
(19).
452 Norberto Alvarez

deterioration in mental function, there is a progressive Table 1. Diagnostic Test around Here
deterioration in motor function. This results in gait
difficulties, speech disorders, and eating disorders. In In all cases Optional
some cases abnormal movement disorders such as Blood studies
Complete blood count Lipid profile
tremors or parkinsonian symptoms are part of the
Liver function tests Paraneoplastic
clinical picture. Generalized tonic clonic and antibodies
myoclonic seizures may be seen as the AD advances, Electrolytes Apolipoprotein E
particularly in persons with DS. genotype
The documentation of progressive decline in Thyroid function tests Drug screening
areas such as reasoning, thinking, planning and Serum B12 and folates Tests for syphilis and
organization, is as difficult to document as the HIV
Imaging studies
memory changes and, again, is mostly through direct
MRI of the head PET
observations by caretakers that these changes can be
(preferred)
suspected. Inability to select appropriate clothing, or CT scan of the head Magnetic resonance
to prepared food, or set the table might be the early angiography
indication of dementia. There are few studies Duplex scanning of
evaluating the decline in cognitive abilities in carotid or vertebral
individuals with IDD in the absence of demonstrable arteries
brain disease. Other studies
Electroencephalogram Spinal tap
A longitudinal study showed that between the
Electrocardiogram Genetic studies for
ages of 20 and 40 years there was a small but Alzheimer’s and
increased score in cognitive abilities in persons with Huntington’s diseases
mild to moderate degree of IDD, and no change for Chest x-ray
those with severe and profound degree of IDD. Psychometric testing
However people living in institutions showed a
decline in functions (26).
Longitudinal studies in males with Fragile X Diagnostic tests
showed a steady decline in IQ with age, even in
young individuals (27). Others found that the decline Blood studies are indicated to rule out medical
was more important in in those with initial higher IQ conditions that may mimic dementia. The indications
(27); others found that the continued rate of learning are described in the text.
was slower (28). The field of IDD has benefited from new
A recent longitudinal study (29) in which babies neuroimaging techniques which are particularly useful
born with DS where followed from the age of 6 weeks in the diagnosis of structural lesions of the brain, in
up to the age of 45 years, found that the mean IQ, in documenting the evolution of degenerative diseases of
verbal and nonverbal tasks, changed little between the the brain (CT scan, MRI) as well as in some aspects
ages of 21 to 45 years. In this study tests for dementia of the functioning and metabolism of the brain
given to persons over the age of 30 years showed (positron emission tomography (PET) or magnetic
some decline in performance from 40 to 45 years. resonance spectroscopy (MRS). Presently CT or MRI
In general, and with few exceptions, in the are almost routinely indicated in the evaluation of
absence of another valid explanation, the presence of individuals with IDD. These techniques have been
progressive loss of functions should be considered an used for a long time in the evaluation of dementia in
indication of dementia. persons with DS (30) and other conditions.
White matter signals in MRI images that increase
in frequency with age have been described in the
periventricular and deep white matter. The clinicaland
pathological correlation of these images is not clear,
since they have been found in patients with AD,
 Dementia
psychosis, depression, and multinfarct dementia but
since they are also present in healthy elderly
individuals the correlation, specifically with dementia,
should be done with caution (31). In addition they
have been described, among others, in individuals
with neurofibromatosis 1, probable associated with
lower IQ and learning disabilities (28); in persons
with phenylketonuria (32); in children with cerebral
palsy, in this case associated with reduction level of
cognitive development (33) and visual impairment
(34).
CT studies of the brain comparing young
individuals (19-34 years) with Down syndrome and a
comparable group control of healthy individuals
without mental retardation found no significant
differences between the two (35). Quantitative studies
with CT and MRI suggested that young adults with
DS have no ventricular dilatation, no indications for
atrophy, and no consistent malformation that could
explain the IDD. Small brain size was consistently
reported however this may be an expression of having
small stature and a small cranial vault (35).
A study comparing brain anatomy, measured by
volumetric MRI , involving 19 adults with DS and
AD and 39 adults with DS without AD found that
individuals with DS and AD had smaller volumes
bilaterally in the hippocampus and caudate and also in
the right amygdala and putamen. In addition there was
a larger volume of the left peripheral CSF when
compared with those individuals with DS and no AD.
Significant reduction in medial temporal and striatal
volume reductions may be a reliable marker of AD in
persons with DS (36). However age-related reduced
volume in frontal, temporal and parietal lobes as well
as increase volume of peripheral cerebrospinal fluid
have also been described in individuals with DS
without clinical indications of dementia (37).
Cerebral atrophy and ventricular enlargement,
suggesting brain atrophy, was consistently reported in
individuals with DS when cognitive deficiencies were
present (35). In advanced cases the atrophy is seen as
a generalized event; however, regional differences
with more involvement of the temporal horns (38)
were reported.
In summary CT/MRI studies in individuals with
AD, consistently demonstrated significant progressive
changes even in the early stages of the disease,
however the presence of a certain degree of atrophy is
453
not enough to establish the diagnosis of dementia, and
clinical correlation is needed in every case. Serial CTs
and or MRIs can differentiate older persons with DS
who have dementia from those who do not. In
addition CT/MRI are very useful to rule out other
causes of neurological deterioration.
PET and SPECT studies
Positron emission tomography (PET) and single
positron emission tomography (SPECT) use isotopes
to measure general and regional glucose metabolism
of the brain.
There is some inconsistency in the results, but in
general there is a reduction of cerebral blood flow in
normal aging individuals. With this technique there
were no differences between healthy persons with DS
and individuals without mental retardation (35), but
significant reduction in the parietal-temporal
association neocortex were observed in individuals
with DS and dementia.
Unfortunately there are of errors in the
interpretation of PET scans with a tendency to over
diagnosed dementia (39). Studies with [133] xenon
inhalation technique, which evaluated the cortical
cerebral blood flow, showed no abnormalities in
young healthy persons with DS (35).
EEG
EEGs are indicated for the diagnosis of epilepsy and
help to decide if antiepileptic medication is indicated
but are not useful for the diagnosis of dementia.
Biological markers
Biological markers that can be related to
neuropathological changes of AD present in the brain
of individuals many years before the first clinical
symptoms of AD are observed, have been developed.
A recent consensus (18) reviewed the status of
potential biological markers (see also table 2 AD
spectrum). At the present time there is no effective
treatment for AD, but if a treatment becomes
available then an early and accurate diagnostic test
454 Norberto Alvarez
might help to treat and even arrest the disease. In this
context, biological markers for early diagnosis, “pre-
clinical AD,” might be very important.
Differential diagnosis of dementia
The accurate diagnosis of dementia as a syndrome as
well as the particular cause of the dementia is very
important. There are disorders that mimic dementia,
also there are treatable forms of dementia, and, even
when there is no treatment to reverse the dementia, as
is the case of AD, there are several medications that
might help to ameliorate the severity of the
symptoms. The information obtained through the
medical history, might lead to certain etiologies. For
example: dementias of rapid progression are more
commonly the result of toxic or metabolic
disturbances.
Vascular dementias are characterized by a step-
wise but continuous deterioration. In these conditions
acute events such as strokes or transient ischemic
attacks are important clinical features. New
neurological signs, such as paralysis of one side of the
body or loss of vision, are seen after the acute events.
The presence of a progressive Parkinson
syndrome, in the absence of the use of psychotropic
medications, might suggest Lewy bodies disease,
Parkinson’s dementia syndrome, or progressive
supranuclear palsy.
The frontotemporal dementias , that affect the
frontal and temporal areas of the brain, are
characterized by episodes of disinhibition, poor social
judgment, and other behavior and psychiatric
disorders.
Systemic diseases such as cancer or connective
tissue disorders might also be associated with
dementing illness. Some clinical conditions such as
sensory deficits, hypothyroidism, psychiatric
disorders, depression, polypharmacy, sleep disorders
and sleep apnea among others may mimic dementia.
Progressive hearing loss and/or visual impairments,
frequent in elderly individuals with IDD (40), for
example, may result in deterioration in activities of
daily living or in behavior. In a ten year prospective
longitudinal study of 70 elderly individuals (mean age
70 yrs., range 60-92) living in an institution in the
Netherlands, Evenhuis (41) found an incidence of
hearing loss of 50% at the time of the first evaluation
in 1983 (33% for ages 60 to 70; 70% for those over
71), that increased to 75% at the time of the second
evaluation in 1993, with a marked increase in the
prevalence of moderate and severe hearing
impairment. Interestingly 50% of the individuals that
passed the initial screening presented with hearing
loss at follow-up (41,42). In a similar population of
elderly individuals (43) an assessment of visual
deficiencies showed that 27% had moderate to severe
impairment. Others found similar results (44). These
studies highlight the importance to rule out
progressive sensory losses in persons with DD and
deficits in performance
Polypharmacy is probably one of the most
common causes of pseudodementia in the elderly and
should be considered in any person who is on a
number of medications. Endocrine disorders,
particularly hypothyroidism, as well as depressive
disorders, might be unrecognized in persons with
IDD.
Causes of dementia
Dementia is an age related disorder, the prevalence in
the general population is approximately 1% among
individuals in their 60's and increase to 40% among
individuals 85 years old (45). The most common
forms of dementia are presented in table 2.
The causes that result in dementia in individuals
with and without IDD are very similar, but there is a
very high incidence of early-age onset of AD in
persons with DS. Some studies, but not all, found a
higher incidence of dementia in persons with IDD but
no DS.
A recent longitudinal study by Strydom (46)
evaluated the incidence of dementia in 222 adults
older than 60 years (mean age 68.8, SD 7.5; range 60-
94) with developmental disabilities but excluding
individuals with DS. The average follow up was of
2.9 years (SD+0.42; range 25-45 months). Fifteen
percent developed dementia while being in the study.
In this study the incidence of dementia was five times
higher than in individuals without IDD. The incidence
peak at age 70-74. Other studies in non-DS IDD are
also in agreement regarding higher incidence of
dementia in person with IDD (47,48).
 Dementia 455

However in other reports, when persons with DS
are excluded, age at onset, type of dementia, duration
and symptoms of dementia observed in
institutionalized and non-institutionalized individuals
over the age of 60 years, with mild to profound IDD,
are comparable to those of the general population (11,
49). Also, when persons with DS were excluded (50),
autopsy findings in individuals with IDD confirmed
that the incidence of AD is the same as in individuals
without IDD. These differences might be related to
diagnostic criteria used, level of disability and
mortality from other causes (48,51-53).
Regarding the etiology Strydom et al (48) found
that Alzheimer’s disease, with a prevalence rate of
12% (7.1–18.5%) among those with at least 65 years
of age, was, as in the general population, the most
common form of dementia. Different from the general
population vascular dementia, was less common than
Lewy body and fronto-temporal dementias. This
reduced risk of vascular dementia may be related to
the fact that some factors leading to vascular dementia
like alcohol consumption, drugs or smocking are less
frequent in people with IDD (54).
Alzheimer’s disease
AD is the most common form of dementia, and it has
particular importance in persons with IDD because of
the high incidence of a dementia syndrome with many
of the characteristics of AD in individuals with DS.

Table 2. Alzheimer disease spectrum

Category Subcategory Cognitive/Functional Signs Biomarkers

Preclinial Stage 1-3 Asymptomatic or subtle decline Stage 1 Abeta injury
Stage 2-3+ neuronal injury
MCI due to AD Intermediate likelihood Impairment in episodic memory and Abeta or neuronal injury
possible in other domains
High likelihood Mild impairment Abeta + neuronal injury
Atypical presentation
Unlikely due to AD Negative biomarkers
AD dementia Probable amnestic Impairment in learning and recall and Abeta + neuronal injury
one other cognitive domain
Probable non-amnestic Language, visuospatial or executive Biomarkers increase certainty
dysfunction Abeta + neuronal injury
Possible Meets clinical criteria for atypical or Abeta + neuronal injury
mixed etiology
Unlikely due to AD Meets clinical criteria Biomarkers negative for Abeta
and neuronal injury
Modified from Carrillo MC, Dean RA, Nicolas F, Miller DS, Berman R, Khachaturian Z, et al. Revisiting the framework of
the National Institute on Aging Alzheimer’s Association diagnostic criteria. Alzheimers Dement 2013;9:594-601.
Abbreviations: AD, Alzheimer’s disease; Abeta, amyloid-β; neuronal injury: tau protein, positive fluorodeoxyglucose
(FDG), positive structural magnetic resonance imaging (sMRI); MCI, mild cognitive impairment.

Recently the diagnostic criteria as well as the
definition of AD has been updated (18), and AD is
defined as a condition in which there is a cognitive
impairment that interferes with work of daily
activities and represents a decline from a previous
level, that cannot be explained by other disorders,
including psychiatric. The clinical diagnosis required
a failure in two of the following domains: memory,
executive function, visuospatial performance,
language, and personality/behavior. In addition
biological markers were incorporated in the revised
criteria when needed to increase the accuracy of the
diagnosis (18). Biological marker may help to rule out
AD but they are not enough to diagnose AD.
The definitive diagnosis of AD is done only by
the presence of specific neuropathological changes in
the brain. However since in many instances the
autopsy might show other lesions, in some individuals
the diagnosis of AD might be a probabilistic one.
456 Norberto Alvarez
Causes of Alzheimer’s disease
AD is a syndrome due to many causes that in most
instances are unknown. Age is one the most consistent
risk factors. The prevalence of AD in the general
population increase exponentially with age, from 1%
in the 60 to 64 years old to 4% in the 70 to 74 years
old, 16% in the range 80 to 84 years and over the age
of 85 is around 35 to 40 % (55). The incidence
follows a similar pattern (56).
Genetic mutations in chromosomes 21, 14 (PS1),
the most common, or 1 (PS2), inherited in an
autosomal dominant mode are related, in few
instances (less than 5%) to the familial early-onset of
AD. Clinical differences among family members
carrying the same mutation, suggests that
environmental factors play an important role in the
expression of the gene. The common link to all these
mutations is the increased production of, a toxic
fragment (Aß42) derived from the amyloid precursor
protein (APP). The gene for the APP is in
chromosome 21. The higher risk for AD in persons
with Down syndrome might be related to the extra
copy of chromosome 21, the extra production of APP
and subsequent increase of the toxic fragment Aß42
(57). The overexpression of the APP gene seems to be
a critical factor in the association between DS and
AD. Interestingly enough a 78-year-old women with
partial Trisomy 21 and only two copies of the APP
gene did not developed clinical dementia and did not
had important pathology of AD (58).
Approximately half of the individuals with family
history of AD in first-degree relatives when followed
into the 90s developed the disease suggesting that
family history is a strong predictor, however some
studies question this statement (59).
The presence of certain genes made individuals
vulnerable to AD. The best known is Apolipoprotein
E (ApoE) gene present in the chromosome 19th and
encoded by three alleles (e2, e3, and e4). The ApoE ε
-4 allele is 3 to 4 times more often found in
individuals with late onset AD and it is also
associated with increased deposition of beta amyloid
in persons with DS (60). A study involving 252
individuals with DS found that those that have the
Apo E ε -4 allele had a higher risk of AD, had the
onset of the disease at a younger age and a more rapid
progression to death when compared with the ApoE ε
-3. Also persons with DS and ApoE ε -4 died earlier
even in those persons with DS and no AD (61) while
the Apo E ε 2, the least common, was associated with
decreased risk of dementia in persons with DS (62).
However because of its low specificity and sensitivity
it is not possible to depend upon this factor for the
prediction of AD (63), besides most of the individuals
that inherited e4 do not develop AD. However it may
play a diagnostic role in individuals with a dementing
disorder (63) but cannot be used alone as a diagnostic
tool.
Neural thread protein (AD7C-NTP), associated
with the NFTs of AD, is increased in brain,
cerebrospinal fluid (CSF), and urine of individuals
with AD (64). This factor was found to be increased
in the brain of persons with AD and DS.
Pittsburgh compound B (PIB) positron emission
tomography (PIB/PET) imaging, and CSF Aß42 are
biomarker of cerebral amyloidosis in vivowhile
18fluorodeoxyglucose PET imaging (FDG-PET), CSF
tau and hippocampal volume are biomarkers of
neurodegeneration. Amyloid biomarkers may be
abnormal 20 years before clinical symptoms are
observed, while indications of neuronal injury are
seen much closer to the time of the first symptoms.
These biomarkers can be used to predict AD and also
help to diagnose individuals with other forms of
dementia but AD (65).
A PiB/PET study performed in seven individuals
with DS older than 20 years of age, with an
intelligence quotient of ≥40, with documented
evidence of trisomy 21 and no indications of
cognitive decline in the year preceding the study,
showed that the five younger subjects had no
evidence of specific PiB retention in neocortex. One
individual showed PiB retention similar to
presymptomatic PS-1 mutation carriers. Also the only
individual older than 40 showed a PiB pattern
suggestive of AD and the follow up showed that this
individual developed clinical symptoms of AD. This
study suggests that PiB can be a good marker for the
prediction of future dementia in some individuals
(66), however there is also evidence that negative PiB
studies do not exclude the presence of beta amyloid.
The capture of PiB is higher in compact/cored plaques
than in diffuse neocortical plaques (67) which are
primarily found in the brains individuals with DS
younger than 30 years (68).
 Dementia
In a study involving 9 people with DS (4 women
and 5 men) aged between 25 and 64 years, in the six
participants with clinical diagnosis of AD significant
PiB binding was found in all 6 participants with DS
older than 45 years, and no PiB binding was found in
the 3 females participant younger than 36 years (69).
Females are at slightly higher risk than men in the
general population. In persons with DD, Lai et al (62)
found higher incidence of AD in woman with DS
when compared with men. Reduced estrogen level has
been considered a potential factor in women without
DD (70). Early menopause, frequently seen in women
with DS, is also considered a factor in early AD in
women with DS (71, 72).
Small head circumference, small brain, low
intelligence, history of head trauma has also been
related to higher incidence of AD. One potential
explanation is the assumed reduced brain reserve in
persons with DD the result of having smaller brains,
less neurons, less synaptic connections. Following
this hypothesis people with less brain reserve would
develop dementia more often and also earlier in life
(73, 74). Low albumin serum concentration in persons
with DS, may be a risk factor for AD (75).
Protective factors
The ApoE-2 genotype, as compared to the ApoE-4, is
correlated with decreased risk and delayed onset of
the disease. High level of education as well as mental
and physical activity have been suggested as
protective factors (59).
Decrease risk of AD was reported among persons
who have been on nonsteroidal anti-inflammatory
drugs for more than two years (76). Anti-
inflammatory protective effect has also been claimed
for statin-type anticholesterolemic drugs (77), and
dietary fish oil (78).
Estrogen replacement was first suggested as a
protective factors in postmenopausal women (79)
however a more recent prospective study lean in the
direction that estrogen replacement slightly increased
risk for dementia (80, 81).
Similar contradiction was found with the
antioxidants selegiline and tocopherol, with some
studies showing benefits (82) not seen in others (83).
457
In persons without DD the metabolic
syndrome (an association of obesity, dyslipidemia and
irregularities in glucose metabolism, probable related
to insulin resistance) has been found to be a risk
factor for AD (84). In persons with DS and total
cholesterol higher than 200 mg/dl, those who were not
on statins developed AD more often than those on
statins (85) however the study of Prasher et al (86)
could not confirm that results. The preventative value
of statins in the non DD population is not clear at the
present time.
Neuropathology
The histopathologic hallmarks of AD are the amyloid
beta (Abeta ) plaques and the neurofibrillary tangles
(NFTs) (87). Other findings, although not diagnostic
are granulovacuolar degeneration, dystrophic neurites,
amyloid angiopathy and decreased numbers of
neurons and synapses.
Plaques consist of extracellular deposits of
amyloid-beta, a 40 or 42 amino acid residue in length,
byproduct of the metabolism of the amyloid precursor
protein (APP), which under certain circumstances,
can be neurotoxic and proinflammatory. The plaques
also contained apolipoprotein E, alpha-1-
antichymotrypsin, and proteoglycans. Many of these
plaques may show evidence of inflammation as well
as abnormal residues of neuronal processes the
dystrophic neurites. There is general agreement that
the Abeta peptides played a role in the pathogenesis
of AD (87).
The intracellular NFTs are composed of
aggregated of abnormal phosphorilated Tau, a normal
intracellular protein. The NFT remains as
extracellular when the neuron died. There is certain
order in the development of the NFTs in the brain
with early presence in the entorhinal cortex in
preclinical stages, and progressing to other areas of
the cortex. The multiplication and the progression of
the NFTs are associated with the clinical progression
of the disease. The NFTs are not unique of AD and
can be seen in other forms of dementia such as
Parkinson dementia complex of Guam or Pick
disease, among others (45, 87).
Of interest to understand the relationship between
AD and DS is that the gene for APP is in chromosome
458 Norberto Alvarez
21, given the persons with DS a triple dose of APP
gene.
Theories that explain Alzheimer's
disease
One theory considers AD as a cascade of molecular
dysfunctions depending of several dynamic processes
(45). APP contains the neurotoxic A?42 fragment,
which is set free when the APP is catabolized. All the
recognized mutations and some risk factors (age, head
trauma) for AD are associated with increased
production of Aß42. This accumulation results in
selective and progressive neuronal death, followed by
the collapse of related neurons not able to survive due
to the lack of neurotrophic factors. The clinical
picture follows this neuronal death; however a certain
degree of neuronal plasticity provides a limited
balance that keeps the individual functioning at a
normal level, even though the disease process is
active. There is a certain degree of asymmetry in this
neuronal death which explains the protean picture
presented, for example individuals with more frontal
and temporal lobe damage might have more agitation
and psychiatric disorders, while individuals with more
damage in the left hemisphere might have more
language disorders.
A complimentary hypothesis suggests that there
are different thresholds for the presentation of clinical
symptoms depending upon the cognitive reserve of
the individual.
Following these two interrelated hypotheses
persons with Down syndrome, for example, develop
symptoms earlier in life because there is an increased
production of Aß42 in individuals with limited
cognitive reserve.
Oxidative stress, the damage cause by the
accumulation of free radicals in the brain, may be a
\risk factors in persons with DS, the gene encoding
the enzyme Cu/Zn superoxide dismutase (SOD-1) is
in chromosome 21. The overexpression of this
enzyme could lead to accumulation of free radicals
and brain damage (88,89).
Neuroinflammatory changes, documented in the
brains of fetuses, neonates, and children with DS,
suggests the possibility that chromosome 21 genes are
associated with overexpression of pro-inflammatory
cytokines, that may contribute to APP overexpression
and favor the appearance of A? plaques in children
with DS (90,91). Following these observations the use
of non-steroidal anti-inflammatories could be useful
in the early stages of the disease (91).
Therapeutic interventions
Box 3 lists the most common medications indicated
for the treatment of AD. None of them modify the
underling pathology of AD. There are a few studies
evaluating these treatments in individuals with DD,
most of them in persons with DS.
Box 3. Medications that can be useful in the treatment
of Alzheimer’s disease
Donepezil (Aricept)
Rivastigmine (Exelon)
Galantamine (Remynil)
Antioxidants
Alphatochoferol (Vit E)
Selegiline
Estrogen replacement therapy
Nonsteroid antiinflamatory drugs
Cox2 inhibitors
A study involving 3 individuals with DS showed
that donepezil treatment resulted in urinary
incontinency in two (92). Improvement in cognitive
functions with donepezil was reported in another
study involving four individuals with DS (93).
Donepezil was evaluated in a 24-week double
blind placebo control, parallel-group trial in 30
persons with DS and mild to moderate degree of AD
(94). The average age in the placebo group was 55
years (range 45-62 years) and it was 53 years (range
40-69 years) in the treatment group. The tolerance
was good; however, there was a non-significant
reduction in deterioration as measured by the
Dementia Sale for Mentally Retarded Persons, Severe
Impairment Battery and the Adaptive Behavioral
Scale.
In an open crossover study 14 individuals with
DS older than 40 years and diagnosed with possible or
probable dementia received 5 mg of donepezil during
the first month of treatment and 10 mgs for the next 5
months. There was an improvement in cognition and
 Dementia
social activities in the first three months of the
donepezil phase of the study but there was no
difference with the control group at the end of the
study (95).
Twenty-one female individuals with DS, ages 32
to 58 years (mean 45.6) and severe cognitive
impairment were assigned to a low dose of donepezil
(3 mg daily) or a placebo for 24 weeks. In this study
(96) donepezil treatment was beneficial for DS
patients at ages of 30 to 50 years when many of these
individuals develop AD-like progressive cognitive
dysfunction. Most of the patients had IQs below 20,
suggesting that donepezil treatment could be
beneficial even for severely impaired patients. Also
the improvement in daily activity in donepezil group
was seen in the early part of the treatment phase and
was never reduced throughout the trial.
In a retrospective study Prasher et al (97)
reviewed the medical records of 17 patients with DS
and AD that received rivastigmine, started at 1.5 mg
twice daily and gradually increased up to 12 mg a day
over 8-weeks. Repeat assessments took place at 6, 12
and 24 weeks. The findings for the patients treated
with rivastigmine were compared to findings in 13
persons with DS and AD treated with placebo
previously. The individuals treated with rivastigmine
had less of a decline, over 24 weeks, in global
functioning and adaptive behavior compared to the
untreated group, however it was not statistically
significant.
A prospective randomized double-blind trial,
involving adults (>40 y) diagnosed with DS with and
without dementia, that were allocated to receive
memantine or placebo for 52 weeks, showed that the
two groups declined in cognition and function at the
same rate. There was a minimally non statistically
significant difference in favor of placebo. Also both
groups showed side effects, with a mild increase
although non-significant in favor of the placebo group
(98).
In a 2-year randomized, double-blind, placebo-
controlled trial 53 individuals with Down syndrome
and dementia received daily oral antioxidant
supplementation (900 IU of alpha-tocopherol, 200 mg
of ascorbic acid and 600 mg of alpha-lipoic acid),
antioxidant supplementation was safe however
ineffective as a treatment in individuals with Down
syndrome and Alzheimer type dementia (99).
459
Acylcarnitine was suggested as treatment for AD
in persons without DS. A double blind study (100)
involving 40 individuals with DS who received 10 to
30 mg/kg/Day of acyl-L-carnitine failed to show any
enhancement of central nervous system functions.
In summary, presently the benefit that these
treatments produce in people with AD is still modest,
and when present are mostly seen in the early stages
of the disease. The studies performed on persons with
DS and AD are not very supportive of the use of these
medications in this population.
Special relationship
Down syndrome was first identified as a special form
of DD in 1866, descriptions of early aging were
already published in 1876 (101), other publications
documented not only the premature aging and the
deterioration but also the presence of the
neuropathological changes described by Alois
Alzheimer in 1906 (85, 102). The recognition that DS
is associated with Trisomy 21 helped in the
understanding of genetic basis of this association.
Studies of prevalence of AD in persons with DS
confirmed that AD is common in older adults with DS
(103) the main difference with the AD in DS being
the early onset of the dementia when compared with
individuals without DS (104). The prevalence is age
related and with a sharp increase between the ages of
40 until the age 60 (105-107). For example, an study
performed in the Netherlands, including 506
participants with DS aged 45 years and older (108),
found a 9% prevalence in people younger than 49
years, from them forward the prevalence practically
duplicates every 5 years period (17% between the
ages of 50 and 54, 32.1% between 55 and 59),
paradoxically in this study the prevalence decrease to
25 % after the age of 60 probable related to mortality.
A study including people with DS living in
institution found dementia in 100% of persons with
DS who were 65 years or more (107) leading to the
impression that AD is always present in persons with
DS. However this is not necessarily the case in all
instances since some people with DS may survived
without indications of dementia into the 70s (85).
460 Norberto Alvarez

Interestingly in persons with DS accelerated
aging is seen in many other systems (109) and is not
limited to CNS alone.
The natural evolution
Box 4 presents the clinical evolution of a person with
DS that developed Alzheimer-like dementia and in
whom the autopsy showed clear changes of AD. He is
one of 11 individuals, with DS, living in a facility for
persons with DD, whom I closely followed from the
beginning of the symptoms until the moment of death.
Even though the clinical condition in the advanced
stages is very similar, the course of the progression of
the symptoms varied among individuals.

Box 4. Clinical evolution of AD in a person with DS

BORN 1930 ADMITTED 1939 DIED 1991

BASELINE
Pleasant, congenial. No behavior problems. Follows simple commands and understands simple orders. Walks
independently. Independent in activities of daily living. Eats regular diet, does housework, showers very well.
Good leisure skills. Has an active social program, goes to dances, outdoors trips. Sings with the radio.
Safety issues: understands he has to leave the building when the fire alarm goes off. Vineland Adaptive Behavior
Scale: 1975 (40 years old) 4.9 yr;
1979 (44 years old) 4.9 yr

FIRST SYMPTOMS
1981 (51 yrs) Disorientation, confusion. Behavior changes: refuses to accept that the program is over and return
to his residence. He is found wandering around the grounds of the institution, crying, yelling and in a state of
confusion.
1982 (52 yrs) Increased forgetfulness. Emotional problems: periods of agitation. Verbal outburst, throwing
objects.
1983 (53 yrs) ADL: needs constant prompting. Still showering and changes clothes daily. Leisure skills: no
changes. Behavior: three incidents of major aggression and agitation. Vineland Adaptive Behavior Scale: 3 years
1984 (54 yrs) Leisure skills: poor participation due to frequent sleeping.ADL: increased assistance, still
Independent. Choking episode
1985 (55 yrs) Steady rate of regression. Increase in disorientation, confusion, wandering, and forgetfulness.
Increase in sleeping. Behaviors: undressing in dining room and at work ADL: regression, needs much help, but
still independent. Frequently found wandering outside his residence unable to find the way. On occasions he did
not know how to find his bedroom. Vineland Adaptive Behavior Scale: 2.1 yrs.
1986 (56 yrs) Difficulties in gait. ADL: much regression, can still eat and drink but with constantreminders.
Transfer to a safer more restrictive place. Photomyoclonic response. Myoclonic seizures.
1987 (57 yrs) Assaultive. Gait: marked deterioration, but still able to walk. Occasionally needs awheelchair. Feeds
himself using adaptive equipment. Schedule toilet training but still a few accidents. First generalized tonic clonic
seizure
1988 (58 yrs) Lethargic. Frequent inappropriate behavior. No longer able to feed himself. Increased toileting
accidents. Can no longer tolerate bus rides to community. Enjoys music, expresses pleasure by smiling and
laughing.
1989 (59 yrs) Aspiration pneumonia. Very poor social interaction. ADL: totally dependent. Gait: requires
wheelchair Incontinence of urine.
1990 (60 yrs.) Sleeps almost continuously. Minimal social interactions. Occasionally conveys pleasure and
displeasure by laughing or crying. Frequent pneumonias. No longer able to swallow. ND tube in place. PEG tube
placement. In diapers.
1991 (61 yrs) Sleeping almost continuously. Minimal responses to environmental stimulation.
 Dementia
A close description of the main characteristics of
this group is illustrative of the clinical evolution as
well as the challenges presented by individuals with
AD.
These individuals were all in good health with no
medical problems that could explain the progressive
disorder. They all had Trisomy 21 documented by
chromosomal studies. The diagnosis of AD was
confirmed in 10 of them by autopsy showing the
typical pathology of AD. They all had a high degree
of independence in activities of daily living. The
highest IQ ever reported in psychometric evaluations
done before they developed clinical symptoms was
less than 20 in 7 individuals, and 24, 40, 68 and 72 in
each one of the other 4 individuals.
The mean age at the time of the first symptom
was 50 yrs. (range 36-62 years); however the
diagnosis of the disease was confirmed by the age of
52 yrs. (range 37-62 years), that is, there was a gap of
approximately two years between the earlier
indication of the disease and the time of the diagnosis.
This is not unusual and is related to several factors
one of the most important it is the recognition of
subtle symptoms in individuals with severe to
profound degree of mental retardation. Also persons
with AD might have initial declines followed by
recovery of functions (110). In addition, the diagnosis
of AD requires documentation of obvious and
persistent failures in performance in more than one
area. In general, early in the disease, the use of data
collected in only one evaluation is not enough to
diagnose AD (110,111). So, long periods of
observation are a good practice before accepting the
diagnosis of AD (112). Besides time is needed to
differentiate from age-related decline in skills that
might not be related to AD (58).
These individuals had sensory deficiencies that
interfered with the interpretation of some of the
presenting symptoms. Ten of the eleven individuals
had visual disturbances before the beginning of the
symptoms. Two were legally blind; one was blind in
the right eye due to a congenital lesion and had very
compromised vision on the left eye due to an advance
cataract; one had poor vision due to bilateral cataract
and become blind 4 years after the diagnosis of AD
was made; one had poor vision due to earlier retinal
detachment. The other 5 had cataracts, two of them
with keratoconus, a disease of the cornea that
461
produces a progressive impairment of vision. Marked
hearing loss was demonstrated in two patients and
moderate in another two. Sensory deficiencies were
reported in other series (58).
Intermittent periods of confusion and
disorientation were, often, the earlier signs of the
disease. In many most instances the patients were sent
for consultation 2 to 3 months after the first
behavioral incidents were observed, however in some
the gap was almost 2 years. Behavioral issues as early
signs of AD have been described in persons with DD
(113) as well as in persons without DD (114). There
was continues deterioration in the mental status and
an average of 4.4 yrs. (range 2.5 yrs.-6.11 yrs.) after
the diagnosis was made these individuals were totally
unaware of their surroundings.
Simultaneously with the behavior changes, gait
impairment, speech or communication disorders,
decreased participation in leisure activities were also
commonly seen. A combination of these symptoms
was a common reason for the referral.
Using as a point of reference the time when the
diagnosis of AD was made, evidence of deterioration
in activities of daily living were observed around 5
months (0-1.8 years) after the diagnosis was made; in
leisure activities the average was 10 months (0-2.9
yrs.); early problems in ambulation were evident at
approximately 1.10 yrs. (0-3.7yrs), and deterioration
in the communication sphere was 1.4 years (0-4yrs).
There was a significant decline in all these functions
in a relative short period of time and in approximately
4.5 years (1.5-7.4) after the diagnosis was made, all
these functions were severely impaired or totally lost
and these individuals were totally dependent on
others. Death occurred at the age of 60.11yrs (46.7-
69.8). The length of the disorder from the time of the
first symptom was 9.10 yrs. (range 6.9-11.1 years),
and from the time of the diagnosis was 8.2 yrs. (range
5-12.4 years).
As the disease progresses other medical issues
emerge. A common medical problem, in all of them,
was the development of epileptic seizures either
generalized tonic clonic seizures or more commonly
myoclonic seizures. Epilepsy in persons with DS has
a bimodal distribution, with infantile spasms like
syndrome in early life and then generalized tonic
seizures associated with AD late in the third to fourth
decade (115,116). Generalized tonic clonic seizures
462 Norberto Alvarez
were infrequent, most often lasting for a few minutes
and never life threatening: status epilepticus was
exceptional. However myoclonic seizures were a
serious problem. Usually the first episodes, early in
the disease, when the patients were mobile and still
independent, were, in many instances, not recognized
as such. Increased frequency of injuries and falls in
individuals who had never had accidents, were an
indirect indication of the early myoclonic seizures.
The myoclonic seizures had the characteristics of
being very sensitive to external stimulation. For
example, noises in the environment could induce the
seizures. A common occurrence was at the time in
which the patient was changed or fed; touching, or
moving the patient was enough to induce clusters of
myoclonic seizures. In the advance stages these
seizures were almost a constant event. Myoclonic
seizures were resistant to treatment. On the positive
side they are not life threatening and in general, it is
not beneficial to be very aggressive in the control of
these seizures. Myoclonic seizures are also described
in individuals with AD non-DS (117).
Eating disorders, becomes a problem in all of
these individuals. Choking, vomiting, coughing and
aspiration pneumonia become a serious problem. In
four cases nasogastric tubes were used an average of
6.9 years (range 4.9-8.2 years), and in three,
gastrostomy tubes were placed an average of 7.4 years
(range 5.10-9.2 years) after the diagnosis was made to
facilitate feeding.
Decubitus ulcers were observed in the advanced
stage of the disorder. In general they were difficult to
treat, and in some cases the ulcer lasted for several
weeks before it was fully healed.
Injuries, the result of poor balance, unsteady gait,
poor visuo-spatial perception and/or seizures, were
frequently seen. For example, a person standing in
front of a chair, looked at the chair and attempted to
sit on it, misjudged its position and fell to the floor; or
while walking suddenly stiffened up and fell
backward hitting her head on the floor.
These individuals were all independent and
moved freely throughout the campus of the institution
before having AD, however many safety issues were
presented mostly due to the continuous wandering and
getting lost even in familiar environments and they
were transferred from their free environment to a
more protective environment an average of 2.1yrs (5
months to 6.7 years) after the diagnosis was made.
Hypothyroidism was diagnosed in 4 patients
before diagnosis and in three more during the follow
up. High incidence of autoimmune thyroiditis with
hypothyroidism is common in persons with DS (112)
and in a few instances the treatment of
hypothyroidism can reverse the clinical dementia
(118). However in this particular group of patients, I
could not demonstrate any positive effect on the
dementing process associated with euthyroidism due
to medication. It is possible than in many instances
the abnormal blood results are not associated with
clinical symptoms (119).
Depression was diagnosed in 8 persons after the
symptoms of AD were obvious. There was some
improvement in mood with antidepressants, but in
some individuals they might increase the severity of
the myoclonus. Other studies also showed that
dementia and depression are associated in individuals
with Down syndrome, however this association is not
present in individuals with mental retardation due to
other etiologies (120). Depression should always be
considered in the differential diagnosis of AD, since
there are descriptions of pseudo dementias resulting
from depression (110). However in these individuals
the diagnosis of depression was considered another
symptom of the dementing disorder.
As the disease progresses ethical issues, to be
addressed with the participation of the legal
guardians, are frequent. The most relevant are the use
of tubes to feed the patients, resorting to hospice care
when the disease is considered in the terminal stages
or deciding whether CPR should be indicated.
Electroencephalograms (EEG) obtained before
the beginning of the disease were normal. As the
disease progresses the EEG activity deteriorates
showing generalized slowing and epileptiform
activity.
CT scan showed diffuse brain atrophy with
decreased brain matter, and enlargement of the
ventricles, changes that are not diagnostic of AD, but
when present, there is a high correlation with AD,
mostly if temporal lobe atrophy is present.
Progressive regional enlargement of the temporal and
occipital horns are linearly related to the duration of
the dementia, and this focal enlargement is not seen in
 Dementia
non-demented people with Down syndrome nor in
normal individuals (121).
Other dementias
Vascular dementias are the second more frequent
cause of the dementia syndrome in USA. Diseases of
the small arteries of the brain produce small infarcts,
that, when frequent, lead to multi-infarct dementia.
The clinical picture is characterized by a progression
of motor and cognitive deficiencies, plus other
progressive neurological symptoms such as gait and
speech disorders, Parkinson syndrome, focal
weakness, and exaggerated deep tendon reflexes. The
progression of the symptoms is characterized by
periods of clinical stabilization followed by periods of
deterioration. High blood pressure and diabetes are
recognized as risk factors for this type of dementia.
Recent series showed a decrease in the incidence of
vascular dementia, associated with better control of
hypertension. However autopsies showing indications
of both vascular disease and AD make the
differentiation of these two entities very difficult in
some instances.
Huntington disease
This is an autosomal dominant disorder; the clinical
symptoms start in midlife, and are characterized by a
progressive combination of movement disorder plus
cognitive impairment. Some patients might have a
family history. Motor incoordination, mild clumsiness
followed by a choreo-athetoid syndrome is the
predominant motor disorder. Simultaneously with,
and in some cases before the motor disorders, the
patients present with cognitive deficiencies and
psychiatric disorders (122). There is no indication that
this disorder is more frequent in persons with DD.
Dementia with Lewy bodies
This form of dementia accounts for 17 to 30 % of all
the degenerative dementias. The clinical picture is
characterized by a progressive dementia with
Parkinsonism and prominent psychiatric disorders
463
mostly visual and auditory hallucinations, and
delusions. The rate of decline is faster than in
individuals with AD. These individuals have a special
sensitivity to neuroleptic drugs and small doses can
produce severe rigid-akinetic disorders. The essential
pathological finding is the presence of a particular
structure, Lewy bodies, scattered through the brain.
This type of dementia does not seem to be more
frequent in persons with prior IDD, however the
Lewy bodies have been described in persons with
Down syndrome.
Reversible or treatable dementias
(pseudodementia)
Clinical deterioration resembling dementia may occur
in different conditions that may improve with specific
treatments. They may coexist with non-reversible
causes of dementia; the treatment of the reversible
cause can improve the clinical picture.
The most common cause of reversible conditions
is related to the use of drugs, including prescription
drugs. Among the psychiatric disorders depression is
the most commonly observed mimicking dementia.
There are several publications of individuals with
Down syndrome in whom symptoms of aggression,
acting out, irritability and disturbances of vegetative
functions suggesting dementia, improved with
treatment of the depression (123).
A potential treatable form of dementia is the
normal pressure hydrocephalus, which is
characterized by gait difficulties, a mild degree of
dementia, and incontinence of urine. In these
individuals a ventricular shunt might reverse the
symptoms.
In older persons poor eating habits or perhaps,
absorption problems, might lead to B12 deficiency, a
rare but treatable form of dementia. Hypothyroidism
may present with lethargy, intellectual deterioration,
decline in overall functioning or clinical symptoms of
depression, might easily be confounded with AD,
especially in persons with Down syndrome who
frequently present clinical and biochemical signs of
hypothyroidism preceding or in association with AD
(119, 121, 124).
464 Norberto Alvarez
Management of dementia
Dementia presents challenges in several areas and a
multi-disciplinary team is needed for the proper
management of these patients. The individual
presented in Box 4 is a good example of the variety of
problems presented.
Usually the caregivers are not prepared for the
challenges associated with the management of a
person with dementia (125). Given the complexity of
the problems the caregivers should have the benefit of
a team to provide the caregivers with education,
support, and the means to reduce the caregiver’s
burden. The ultimate goal should be to keep a high
quality of life for both the caregivers and the person
with dementia.
It is important to recognize early signs of
caregiver stress. This stress happens in caregivers
who are in community settings as well as those who
work in institutions (126). Caregivers are at high risk
of developing symptoms of depression, anxiety, sleep
disturbances, and emotional disorders (127). General
information regarding the disease, the expected
progression of the symptoms, as well as the ultimate
prognosis should be provided in simple terms. An
important component in the management should
include information regarding local resources
especially community-based services oriented to
individuals with AD. For example respite programs,
adult care centers, and local associations that will
help. For this purpose the local Alzheimer’s
Association, Visiting Nurse Association, local health
centers, and Association for Retarded Citizens may be
of help.
Since the disease presents different problems as it
progresses, providing information and support to
caregivers is an ongoing process that last as long as
the disease last.
Many of the symptoms of AD might improve
with changes in the home environment or in the way
help is provided. Establishing some routines with
specific cues might help to overcome common
problems in orientation to place and time. For
example walking into the dining room would be the
cue that it is time for lunch. Some individuals develop
fears to water coming down on their heads; for them
showering might turn into a serious aversive
procedure. Changing to bathing with a sponge might
be a simple solution. A similar problem can be
presented at eating time, if the patient has swallowing
disorders, choking could be a common and
uncomfortable complication, in these situations food
might also become an aversive stimulus and the
patient might refuse to eat. Training the caregivers in
the proper techniques might be a solution.
Nighttime restlessness, with increased agitation,
confusion and impulsiveness, can be seen in the late
afternoon. Simple environmental changes such as soft
light in the bedroom without producing shadows
might be the solution.
Some areas to be discussed with the caregivers
include long term financial planning, since in most
instances caregivers share the economic burden of the
disease.
Advances in medical technology and the
possibility of prolonging a dying process present
many ethical issues. The guiding principles regarding
the right of the individual to accept or refuse
treatment as well as avoiding unnecessary pain and
suffering should be explained to the caregivers. Issues
like selecting a person to make medical decisions for
the patient, advance directives specifying the
individual’s preference, especially in issues related to
death and dying should be addressed as soon as
possible. When the dementia is advance patients have
very little understanding. One concept that has gained
acceptance as a humane and sensitive response to the
needs of these individuals at this stage is the idea of
hospice care (128). The implementation requires a
partnership between the patient, the legal guardians,
the family and the caregivers. Issues such as feeding
tubes, do not resuscitate orders, transfers to hospitals,
should be discussed at this point. For example feeding
tubes indicated to facilitate feeding and to decrease
complications such as aspirations, are usually not
recommended in the hospice programs since there is
no evidence that they improve quality of life in
advance dementia. With education of the care givers
and, considering that the nutritional needs at this stage
are reduced, oral feedings might be the best
recommendation even in those individuals in the
advance stages of AD (129, 130). In relation to do not
resuscitate orders may help in making the decision, to
know that, in persons with dementia, when
resuscitation is performed in a hospital setting, the
survival rate at time of discharge is around 3% (131).
 Dementia
The use of medications for the treatment of AD [11]
was already discussed above. These medications do
not change the natural evolution of the disease, have
[12]
not been extensively used in persons with DD there is
no reason to suspect that they will be more effective
in persons with DD than in those without DD.
Antiepileptic medications are prescribed, usually, for [13]
the management of seizure disorders.
Psychotropic medications might be indicated in
cases of hallucinations, aggression or severe psychotic
disorders, however side effects may overcome the [14]
benefits (132). In this area there is not that much
research in persons with DD.
[15]
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