AGEING
AND ITS CONSEQUENCES FOR PEOPLE WITH DOWN'S SYNDROME
Tony Holland (UK)
The importance of supporting children with special needs so that
they have the opportunity to acquire the necessary educational,
living and social skills to equip them for adult life has been
recognised for some time. However, in contrast, the needs of adults,
and the importance of supporting people with intellectual disabilities
and their families at times of transition, has been relatively
neglected. Whilst the potential difficulties associated with the
transition from childhood to adult life is now receiving more
attention the fact that needs may change yet again in later adult
life is only now beginning to be considered.
In the transition from full-time education, a major concern is
that there is a very limited selection of support services for
adults, and individuals can move from a relatively structured
environment of special education to very limited support and opportunities.
In England the NHS and Community Care Act provides the framework
for decision making at times of such change and has placed a statutory
responsibility on social services to undertake a 'needs-led assessment'
at this transition, the purpose of which is to help individuals
and their families to plan for adult life. Whether this happens
still appears arbitrary and the options available vary considerably
across the country. In an ideal situation there should be a range
of imaginative services that can cater for the considerable range
of individual need and individual choice. This would include access
to full-time employment, supported employment schemes, more sheltered
work environments, adult education and so on.
Old age in particular is associated with social and biological
changes. For example, family networks alter as parents age and
for all of us there is an increasing risk of age-related health
problems. Outlined below is the evidence which suggests that ageing
and the problems of old age are particularly relevant to people
with Down's syndrome as some of these age-related problems develop
earlier in life than would normally be the case.
AGEING AND THE BRAIN
Throughout life there are changes occurring in brain structure
and function. These are particularly marked at the two extremes
of life, childhood and old age. In early childhood this is primarily
growth and the rationalisation of connections between the brain
cells (neurones). It is a combination of these brain changes in
childhood and the parallel educational and social opportunities,
which result in the increasing acquisition of educational and
other skills. The extent to which this developmental process can
be modified in children with Down's syndrome has been hotly debated
and is beyond the scope of this article.
In any research designed to address this question it is clearly
a complex task to disentangle the effects of the educational and
social environment, nutrition and the fact that there is anyhow
considerable variation in the extent and nature of developmental
delay and intellectual disabilities in children with Down's syndrome.
In any given child it is impossible to know how different he/she
might have been if a specific intervention had not taken place.
However, what has been striking is the marked improvement in life
expectancy for people with Down's syndrome that has occurred in
this century and the significantly better educational opportunities.
As with any child good physical health, sound nutrition and excellent
social and educational opportunities maximises the chance of optimum
development.
At the other end of life neuronal cell loss in the brain occurs.
Old age is associated with an increased risk of developing minor
cognitive difficulties and the development of more serious mental
health problems, such as depression and dementia, as well as physical
illnesses. In the general population relatively minor cognitive
difficulties in old age are common, however, the more serious
brain changes associated with disorders such as dementia are relatively
rare, although the risk of such disorders increases as people
live into their 70s and 80s. The most common form of dementia
which occurs in later life is called Alzheimer's disease, named
after Alois Alzheimer who, in 1906, first described the characteristic
brain changes (called plaques and neurofibrillary tangles) associated
with this disorder. In the past this was often referred to as
senile or pre-senile dementia.
In Down's syndrome it has been recognised since the early 1900's
that changes are observed in the brain from relatively early in
life and by middle age the formation of Alzheimer-like 'plaques
and tangles' has occurred. Strikingly, these 'Alzheimer-like'
brain changes are almost always found in people with Down's syndrome
who have died in middle age or later, but are not found at such
a relatively young age in people who have intellectual disabilities
for reasons other than Down's syndrome.
Presence of amyloid stained plaques and blood vessels in an
elderly individual with Down syndrome. Formalin fixed paraffin
embedded section from the frontal lobe was immunostained with
anti-amyloid protein immunoprobe. Magnification x400.
Photograph courtesy of Dr. E.B. Mukaetova-Ladinska
The appearance of these brain changes in people with Down's syndrome
is only of great significance if they lead to loss of ability
and the appearance of the clinical changes characteristic of dementia
(i.e., the development of Alzheimer's disease). It is the extent
to which these brain changes are associated with clinical changes
characteristic of Alzheimer's disease that has been the subject
of several studies in different countries. . These are considered
further below.
AGEING AND DEMENTIA
Dementia is the name given to a collection of illnesses, one of
which is Alzheimer's disease, that have a characteristic pattern
of symptoms and signs and generally occurs in later life. The
main characteristics of several of the dementias is a deterioration
in the person's memory (usually for recent events) and loss of
other abilities such as the ability to find one's way around,
to communicate through language and to undertake particular tasks,
such as getting dressed. Dementia due to Alzheimer's disease is
a steadily progressive disorder with evidence of decline over
time. It is important to stress that this is much more marked
than the memory difficulties that many of us are aware of with
increasing age! As described above the presence of Alzheimer's
disease is associated with the development of marked plaque and
tangle formation in particular areas of the brain.
BEHAVIOURAL FEATURES OF DEMENTIA
IN PEOPLE WITH DOWN'S SYNDROME
The key question with respect to the effects of ageing in people
with Down's syndrome is whether the plaque and tangle changes
in the brain are or are not associated with the development of
Alzheimer's disease. To answer such a question requires reliable
and valid methods for the diagnosis of dementia. This is more
problematic in people with Down's syndrome because of their likely
pre-existing learning disabilities, as the cognitive problems
and impairment in functioning associated with the learning disability
needs to be disentangled from the new (but superficially similar)
problems that emerge as dementia develops (see below also). To
do this we have used a modified informant-based interview schedule
that asks carers about observed changes over time together with
a formal assessment of cognitive abilities. These are called the
CAMDEX-DS informant interview and the CAMCOG neuropsychological
assessment (published by Cambridge University Press). Using such
an approach it is possible to make a reliable diagnosis of dementia
in the vast majority of situations (see paper by Ball et al, 2004).
Using this approach our own work suggests that the characteristic
clinical features of dementia do begin to appear in some people
with Down's syndrome with increasing age but not in as many as
the brain studies of Down's syndrome originally suggested would
be the case. We have examined 75 out of a total of 77 people with
Down's syndrome 30 years or older living in the Cambridge Health
District. A small percentage of this group had clinical evidence
of dementia in their 30s, approximately 10% in their 40s and 40%
in their 50s. Symptoms therefore seem to appear about 30 or 40
years earlier in life than in the general population (Holland
et al, 2000). More recent work following this cohort of people
over time suggests that changes in personality and behaviour in
mid-life that have no other explanation may in fact be very early
clinical markers of what will eventually be true dementia some
years later (Ball et al, 2006). This observation needs to be confirmed,
but if it is it will be important as effective treatments for
dementia (Alzheimer's disease) become available.
For us an important research question is to determine why some
people with Down's syndrome live into their 60s yet do not get
Alzheimer's disease, whereas others do. What might protect some
people and what might increase the risk in others? This work is
in progress.
APPARENT DECLINE IN LATER LIFE: CAUSES
TO CONSIDER
Whilst rates of Alzheimer's disease do increase with age, its
development is NOT inevitable. Outlined below and in the Table
are some of the other factors that can result in apparent decline,
particularly in later life, and which can be treated. This process
of identifying the cause of apparent change is therefore critical.
Difficulties in detecting dementia
in people with intellectual disabilities
Dementia, whatever its cause, affects a person's cognitive
abilities and his/her ability to undertake tasks or to communicate.
Whilst a decline in memory or the slow loss of specific abilities
may be readily apparent in those without a pre-existing disability,
it may be less easily noticed in people with Down's syndrome.
There are two main reasons for this:
- Firstly, unless someone has known that person for some time
and has observed the changes, the inability to do something
is all too easily put down to his/her intellectual disability.
The crucial question, in the case of an older person with Down's
syndrome, is: has he/she been able to do this in the past and
now cannot? If so, why has this change occurred?
- Secondly, loss of ability may go unnoticed if the person is
leading a life where he/she is, for example, not expected to
take part in household activities or do tasks that require good
memory. The fact that someone's memory may have deteriorated
would under these circumstances go unnoticed.
Differential diagnosis: which conditions
may mimic dementia?
Where there is good and reliable information available about
how someone has changed and how he/she is now, the diagnosis of
dementia can be made with a high degree of certainty. Those conditions
listed in the Table can be excluded either on the basis of the
history or through investigations. For example:
- Depression can mimic dementia, but has other recognisable
symptoms as well. These include a change in mood, loss of interest
and ability to concentrate, together with changes in sleep and
appetite.
- Thyroid disorders can be excluded both on the basis of clinical
features and by a blood test. The hormone thyroxine can be given
in tablet form and reverse the clinical consequences of an underactive
thyroid gland..
- Age-related visual and hearing impairments may result in changes
in behaviour and apparent loss of skills, thereby mimicking
dementia. It may be possible to correct such sensory loss.
If there is doubt a computerised brain scan (CT or MRI scan) may
help by showing evidence or not of brain changes which would normally
be expected with Alzheimer's disease. Sometimes the reasons for
change in later life cannot be established with certainty and it
is necessary to follow-up over time. Detailed psychological tests
of memory and other abilities can be particularly helpful in this
situation. The most valuable information is invariably that given
by those who have known the person over his/her lifetime or at least
over many years. There is no substitute for this.
Common causes of decline in later life
in people with Down's Syndrome
| Cause |
Characteristic features |
| Stress following life event |
Deterioration follows stress e.g., after bereavement |
| Depression |
Evidence of depressed mood, disturbed sleep
and appetite, loss of interest, poor concentration |
| Underactive thyroid gland |
Dry skin and brittle hair, intolerance of cold,
weight increase, lethargy, abnormal blood test |
| Hearing or visual impairment |
Hearing or visual impairment Evidence of sensory
impairments on testing |
| Alzheimer's disease |
Progressive cognitive and functional decline
not due to the above |
GENETIC MECHANISMS :
Given that Down's syndrome is due to inheriting three, rather
than two copies of chromosome 21 (trisomy 21), there has been
much research interest in the genetic material (genes) on chromosome
21 which might account for these age-related brain changes. This
genetic research has resulted in the discovery that the gene,
which produces the 'amyloid precursor protein' (APP), is located
on chromosome 21 and therefore occurs in triplicate in people
with Down's syndrome. In the general population, abnormalities
(mutations) in that particular gene that occur in families are
associated with a rare form of early onset Alzheimer's disease.
Neurofibrillary changes (tangles, neuritic plaques and dystrophic
neurites) in an elderly Down syndrome individuals. Formalin fixed
paraffin embedded section from the frontal lobe was immunostained
with anti-tau protein immunoprobe. Magnification x400.
Photograph courtesy of Dr. E.B. Mukaetova-Ladinska
Much work is focused on the role of APP and the protein amyloid
as it is this protein that is found in the brain plaques of Alzheimer's
disease. The scientists engaged in brain research on Alzheimer's
disease cannot agree whether abnormalities of how amyloid is dealt
with in the brain, abnormalities of another protein called 'tau'
(found in a changed form in the tangles) or a combination of mechanisms,
are the fundamental abnormalities which lead to Alzheimer's disease
in later life. There are also other age-related changes, which
may increase the vulnerability to such problems as dementia. These
include changes in the levels of a particular steroid which may
have a protective effect on the brain. As can be seen, in this
field there are competing hypotheses that need to be further investigated.
In the case of Down's syndrome the working hypothesis is that
excessive amyloid production is likely to be a key factor, but
this is far from being proven. Before the location of the APP
gene was shown to be on chromosome 21, another gene on this chromosome
and its product was the focus of attention. This was the gene
coding for superoxide dismutase (SOD). Increased activity of SOD
was found in post-mortem studies of people with Down's syndrome.
It has been argued that this results in an increased potential
for damage to cell membranes in the body due to the effects of
SOD activity and increased oxidation. It is for this reason that
attention has focused on the use of 'anti-oxidants' (vitamins
C and E), on the theoretical basis that they might prevent such
damage occurring. There are of course many other genes on chromosome
21, and their products may be equally important, but whether this
is the case or not is not known.
TREATMENT
Treatments proposed in the hope that they might arrest or reverse
the course of Alzheimer's disease are numerous but as yet no specific
treatment has been found that stops brain cells dying. One key
area of therapy has to focus on maintaining the levels of a key
brain transmitter (acetylcholine). It is the brain cells that
produce and use this transmitter which seem to be particularly
affected in Alzheimer's disease. The earlier attempts to maintain
levels of this transmitter resulted in medications that were unpleasant
to take, caused serious side effects and were of doubtful efficacy.
More recent medications, which have a similar effect on brain
chemistry but appear less unpleasant, have been developed. In
trials that been undertaken in the general population, temporary
improvements have been reported.
There have now been small trials of the treatment of Alzheimer's
disease in people with Down's syndrome using such 'anti-dementia
medications' (Prasher et al, 2003; 2004). There are, however,
a number of potential different treatment approaches that may
well develop in the future. For example, if amyloid were the main
culprit, then when drugs that influence this are developed they
would be potentially useful. Vitamin E has been considered because
of its potential protective effect. There is no solid evidence
to support this. If medications appear safe, have minimum side
effects, and if there is good reason to believe that they can
temporarily, at least, arrest the decline, then in my opinion
this needs to be tested out in a careful and thoughtful manner.
There has been much debate within the Down's Syndrome Association
and internationally about whether the consequences of having Down's
syndrome or the potential for Alzheimer's disease can be modified
through dietary supplements or by other means. This is a very
complex issue and it has not been resolved. The issues are the
same as with assessing the value of specific dietary or other
interventions in childhood. Trials, which are conducted in a carefully
controlled manner, are essential if these questions are to be
answered. If any treatment is to be used there is always a careful
balance between the likelihood of improvement, on the one hand,
and the risk of side effects, on the other. If trials have shown
that the balance is towards the former then treatment can be justified.
SUPPORTING THE INDIVIDUAL
Identifying the cause of apparent decline in later life is crucial.
If it is due, for example, to depression or an underactive thyroid
gland, this can usually be reversed with the appropriate treatment.
Similarly, people can be helped to get over the effects of life
stresses or of life events, such as bereavement. Carefully preparing
and supporting people with Down's syndrome for adult life may
help to minimise the psychological impact of family bereavements
and other life events which they will inevitably face. Knowing
about the health risks associated with later life helps to ensure
that they are detected and, where possible, treated.
The recognition that someone with Down's syndrome has Alzheimer's
disease clearly is distressing but the positive aspect is that
it helps to explain why that particular person has changed and
has been behaving in the way that he/she has. The recognition
that Alzheimer's disease is present should be the starting point
for developing a package of support that will be able to meet
the person's changing needs. The Down's Syndrome Association has
information which will be helpful in that regard. Once it is recognised
that a person's memory is not as good or their ability to make
sense and use language has deteriorated, then carers can compensate
for this in the way they interact with the person. Good and informed
support can help to maintain the quality of life of the person
affected (see material by Karen Dodd published by the British
Institute of Learning Disabilities (BILD)).
THE FUTURE
The changing age structure of western society and the resulting
increase in the proportion of older people has meant that there
has been an explosion of research into those illnesses specifically
associated with later life. This includes Alzheimer's disease.
There is therefore a real hope that effective treatments will
be developed. What is critical is that the needs of people with
Down's syndrome are not forgotten. We now know more about how
Alzheimer's disease presents in those with Down's syndrome and
also its course over time. We need to tackle the question of treatment
trials. People with Down's syndrome have the right to expect that
their health problems will be taken seriously, and that treatments
will be developed within the same high ethical and scientifically
valid framework as should always be the case. At present informed
support that includes, for example, changing the environment in
ways that helps to reduce the effects of the progressive loss
of skills is crucial. Much can be done to maintain the quality
of life providing that progression is monitored and support modified
with the person's changing needs.
REFERENCES
Ball, S.L., Holland, A.J., Huppert, F.A., Treppner, P., Watson,
P., Hon, J. (2004) The modified CAMDEX informant interview is
a valid and reliable tool for use in the diagnosis of dementia
in adults with Down's syndrome. Journal of Intellectual Disability
Research, 48(6):611-620
Holland, A.J., Hon, J., Huppert, F.A., Stevens, F. and Watson,
P. (1998) A population-based study of the prevalence and presentation
of dementia in adults with Down Syndrome. British Journal of Psychiatry,
172: 493-498
Ball, S. L., Holland, A. J., Huppert, F. A., Treppner, P., Watson,
P. & Hon, J. (2006) Personality and behaviour changes mark
the early stages of Alzheimer's disease in adults with Down's
syndrome: findings from a prospective population-based study.
International Journal of Geriatric Psychiatry; 21: 661-673
Prasher, V. P., Adams, C., Holder, R. & the Down's Syndrome
Research Group. (2003) Long term safety and efficacy of donepezil
in the treatment of dementia in Alzheimer's disease in adults
with Down syndrome: open label study. International Journal of
Geriatric Psychiatry, 18, 549-541.
Prasher, V. P. (2004) Review of donepezil, rivastigmine, galantamine
and memantine for the treatment of dementia in Alzheimer's disease
in adults with Down syndrome: implications for the intellectual
disability population. Int J Geriatr Psychiatry, 19, 509-515.
This article was revised by the author in 2006.
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