Research in Developmental Disabilities 30 (2009) 827838

Contents lists available at ScienceDirect

Research in Developmental
Disabilities
Review

Diagnosing Alzheimers dementia in Down syndrome:

Problems and possible solutions
Ruth E. Nieuwenhuis-Mark *
Department of Medical and Neuropsychology, University of Tilburg, Postbox 90153, 5000 LE Tilburg, The Netherlands

A R T I C L E I N F O

A B S T R A C T

Article history:
Received 17 December 2008
Accepted 22 January 2009

It is widely accepted that people with Down syndrome are more

likely than the general population to develop Alzheimers dementia
as they age. However, the diagnosis can be problematic in this
population for a number of reasons. These include: the large intraindividual variability in cognitive functioning, the different
diagnostic and methodological procedures used in the eld and
the difculty in obtaining baseline levels of cognitive functioning in
this population with which to assess cognitive and behavioral
change. Recent researchers have begun to suggest ways around
these difculties. This review explores these recent developments
and provides recommendations which may aid clinicians in their
attempts to diagnose Alzheimers dementia in the early stages in
the Down syndrome population.
2009 Elsevier Ltd. All rights reserved.

Keywords:
Down syndrome
Alzheimers dementia
Cognitive
Behavioral
Emotional functioning

Contents
1.
2.
3.

4.
5.

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Prevalence of Alzheimers dementia in Down syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Diagnosis of early Alzheimers dementia in Down syndrome . . . . . . . . . . . . . . . . . . . . . . . .
3.1.
Assessing cognitive change . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3.2.
Assessing emotional/motivational change and changes in daily functioning . . . . . .
3.3.
Assessing neurological/physiological change . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Potential difculties when trying to diagnose Alzheimers dementia in people with Down
syndrome: a summary. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Recommendations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

* Tel.: +31 13 466 2562; fax: +31 13 466 2067.

E-mail address: R.E.Mark@uvt.nl.
0891-4222/$ see front matter 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.ridd.2009.01.010

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Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Acknowledgements. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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1. Introduction
Many studies have shown that people with Down syndrome (or Trisomy 21) are more likely to
develop Alzheimers dementia, especially over the age of 35, than is the case in the general population
(e.g. Tyrrell et al., 2001; Zigman, Silverman, & Wisniewski, 1996). The main focus in this eld of
research has been on the association between genetic determinants, biological markers and decline in
specic cognitive domains.
Despite the neuropathological connection between Alzheimers dementia and Down syndrome,
the diagnosis of Alzheimers in people with Down is far from an easy task. Feldman et al. (2008)
suggested that: The diagnosis of dementia remains clinically integrative based on history, physical
examination and brief cognitive testing (p. 825). Delirium and depression (and other comorbidities)
can dramatically complicate the diagnosis as can the difculty of obtaining a level of premorbid
(cognitive, personality, emotional, etc.) functioning. Diagnosis is even more difcult in the Down
syndrome population with lack of appropriate tests and established cut-off scores available. Floor
effects on standard tests due to the impact of underlying intellectual disability (IQ scores are typically
<70, Stanton & Coetzee, 2004) are the norm rather than the exception.
Burt and Aylward (2000) (see also Aylward, Burt, Thorpe, Lai, & Dalton, 1997) proposed a model of
best practice when attempting to diagnose dementia in individuals with intellectual disabilities (IDs)
including those with Down syndrome. Their recommendations included: (a) to establish a baseline of
premorbid functioning by the age of 35 and then follow-up with annual reassessments, (b) if decline is
evident conduct a detailed diagnosis and, (c) provide appropriate care for both the client and their
carers. A person-centred approach should be used, standardized assessment tools, adequate
specialist/staff training, proper care and more research in this area was also suggested. Whether these
recommendations are implemented in practice has however been questioned in a recent article (see
Auty & Scior, 2008).
Early, accurate detection is extremely important not only for researchers but also for the clinical
care of and health policy for this population. Difculties with diagnosis are in large part due to the
intra-individual variability in performance in people with Down syndrome over cognitive tasks
(Krinsky-McHale, Devenny, Kittler, & Silverman, 2008). These uctuations in performance have been
referred to as bounce in the literature.
Another difculty is the widely accepted wisdom that the rst cognitive impairment in those
developing Alzheimers dementia is episodic memory decline. While there is no widespread
consensus, episodic memory problems, according to some researchers, may not be the rst
common sign of Alzheimers dementia in people with Down syndrome. Further, some Down
syndrome cases have been reported in the literature where the progressive nature of Alzheimers
disease has been completely or partially reversed (e.g. Burt et al., 1996; Geyde, 1995). What the
early signs of developing dementia in Down syndrome are will be discussed in more detail later in
this review.
Differing classication systems and/or methods which clinicians/researchers use is another issue
in this eld. A recent study by Strydom, Livingston, King, and Hassiotis (2007) found the DSM-IV
dementia criteria to be more inclusive than the ICD-10 criteria. While both of these classication
systems put the emphasis on memory decline, the ICD-10 also emphasizes the importance of other
cognitive, everyday and emotional/motivational functioning. Burt et al. (2005) stated that while
diagnosis based on a physicians clinical judgment is taken to be the gold standard by many
researchers their results actually suggested that clinical judgment resulted in more adults with Down
syndrome receiving a positive diagnosis than via test battery measures. Burt et al. went on to suggest
that clinicians may be predisposed to more readily diagnose people with Down syndrome with
Alzheimers dementia and that caution was necessary.

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Another difference with diagnosing dementia in the Down compared to the general population is
that clinicians may largely rely on informant reports. The reason for this is that many researchers
believe that it is very difcult to validate self reports of emotional states in individuals with
intellectual disabilities (e.g. Finlay & Lyons, 2001). Informant reports have their difculties however.
These include the fact that informants tend to assess symptoms more severely than people with Down
syndrome assess themselves and that they tend to focus on behaviors which more directly impact on
their own lives than on subtle changes in cognitive functioning in their charges (Ball et al., 2004). It is
also perhaps true to say that caregivers of those living in institutions may/may not see their charges
more regularly than those whose charges live in the community. Detecting change might be
paradoxically more difcult for those who see the individual with Down syndrome daily than for those
who see them weekly or monthly. Informant reports from parents might also be both qualitatively and
quantitatively different than those from personnel in an institution but to my knowledge this study
has never been carried out. Burt et al. (2005) did nd that changes in everyday functioning were not
affected by the number of informants used per individual over time. Bush and Beail (2004) made the
important point that caregivers themselves age and this might adversely affect their ability to report
accurately.
Studies in this eld have also had, on the whole, difculty obtaining enough representative subjects
(in both Down syndrome and matched control groups) from the oldest cohorts. As a result, survivor
bias is a problem in many studies, where healthier, more cognitively able subjects remain skewing
results and making generalizations impossible. Prevalence incidences of Alzheimers dementia in the
Down population (see below) might therefore be hugely underestimated.
A nal point, made by Burt et al. (2005) is that the scoring method used may be crucial in dementia
diagnosis in this population. They found slope scores to be more useful than difference scores in that
the former produced more consistencies between studies. The authors also suggested that following
the population over time is more useful than cross-sectional studies and emphasized that it was
change in performance that was the crucial factor. Consensus with regard to the method of scoring
used is therefore highly desirable.
While it is clearly difcult to diagnose Alzheimers dementia in the Down syndrome population it is
crucial that we attempt to do so. Early intervention helps determine optimal care and enhances
awareness in carers and family members. In the following sections of this review I will rst briey
discuss research on the prevalence of Alzheimers dementia in people with Down syndrome before
turning to research focused on diagnosis and the specic difculties encountered in this eld. I end
with recommendations which I hope will assist specialists with their diagnoses.
2. Prevalence of Alzheimers dementia in Down syndrome
While the majority of studies have suggested that everyone with Down syndrome over the age of
35 develops the neuropathological signs of Alzheimers dementia, prevalence studies indicate that not
everyone develops the accompanying clinical symptoms of this disorder. The risk of developing
Alzheimers dementia appears to be independent of living arrangement, degree of mental retardation
and gender (Prasher, Chowdhury, Rowe, & Bain, 1997) but other environmental factors in combination
with underlying genetic vulnerability may increase the risk (e.g. smoking, cholesterol, head injury,
parental age at the birth of the child, estrogen levels in females, etc., Farrer et al., 1997).
Many studies have addressed the issue of prevalence of Alzheimers dementia in Down syndrome and
the gures obtained vary from 7 to 50% (Zigman, Schupf, Sersen, & Silverman, 1995) depending on the
stringency of the criteria, the measures used and the specic populations tested. Visser et al. (1997)
followed 307 institutionalized people aged 1072 with Down syndrome and found that 18% (N = 56)
developed symptoms of Alzheimers dementia at an average age of 56 years. This prevalence rate
increased substantially the older the population which was measured (4049 years: 11%; 5059 years:
66%; 6069 years: 77%; 70 years and older: 100%). In comparison to Visser et al. (1997), Holland, Hon,
Huppert, Stevens, and Watson (1998) investigated the prevalence of dementia in a population-based
sample of older people with Down syndrome (how many were living in the community and how many in
institutions could not be discerned from their methods section). From their population of 75 adults, 24%
met the diagnostic criteria for at least one form of dementia. Younger participants (aged 3039 years)

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who received a diagnosis of dementia using The Cambridge Examination for Mental Disorders of the
Elderly (CAMDEX, Roth, Huppert, Mountjoy, & Tym, 1999) criteria tended to be diagnosed with the
frontal lobe variant, while those in the 5059 age group tended to receive a diagnosis of Alzheimers.
Overall, 7% met the DSM-IV or ICD-10 criteria for Alzheimers dementia, compared to 13.3% using the
CAMDEX criteria. CAMDEX diagnosed Alzheimers dementia was more common among people with
mild or moderate learning disability, while frontal lobe dementia was more common in those with
severe learning disability.
Tyrrell et al. (2001) found a prevalence rate of 13.3% for Alzheimers dementia among a
community-based population of 285 people with Down syndrome. Advanced age, Daily Living Skills
Questionnaire (DLSQ; NIA, 1989) score and epilepsy were the most predictive variables for
Alzheimers dementia in their study (R2 = .80). Coppus et al. (2006) found a prevalence rate of 16.8% in
an even larger population of 506 people with Down syndrome aged 45 years and up. The prevalence
rate doubled with each 5-year interval: up to the age of 49 it was 8.9%, from 50 to 54 it was 17.7%, and
from 55 to 59 it was 32.1%. After 60 years there was a slight decrease to 25.6% and this dip was
explained by the authors to be due to increased mortality among the older subjects with Alzheimers
in comparison to those without. They also found that a history of depression was strongly associated
with Alzheimers dementia.
In summary, the average prevalence rate of Alzheimers dementia in Down syndrome is around
15% with increases typical with increasing age and depending hugely on the choice of diagnostic
instruments and criteria employed. The consensus seems to be that while the overall prevalence rate
may be similar or just slightly higher than that found in the general population, the average age of
onset is considerably younger in the Down population (Burt et al., 1998). Fromage and Anglade (2002)
referred to this early aging as precocious aging.
3. Diagnosis of early Alzheimers dementia in Down syndrome
Matthews (1974) was one of the rst researchers who attempted to design a neuropsychological
test battery for use with people with mental retardation using selected subtests from the HalsteadReitan. Schapiro (1988) suggested that cognitive decline in Down syndrome occurred in two stages
which could be separated by 20 years or less. He said that decline due to poorer processing skills came
rst while in the second stage overlearned behaviors are lost and this in turn leads to wide-ranging
decline in social, occupational and adaptive skills. Since Matthews, more researchers have tried to
home in on how to diagnose early Alzheimers dementia in the Down syndrome population and have
used a number of neuropsychological tests in an attempt to do so. The question is: are the instruments
used to assess Alzheimers dementia in the general population suitable to use with people who have
Down syndrome? More specically, do they not have problems with verbal and non-verbal tests due
to their already low IQs thereby increasing the likelihood of oor effects?
As Prasher, Farooq, and Holder (2004) indicated, most diagnostic tests are based on the premise
that respondents have an IQ of at least 100, and many people with Down syndrome fall of course well
below this cut-off. These tests also require good verbal skills, compliance, dexterity, adequate
attention, etc. all of which are often missing in this population. There may also be a gender difference
in the Down population with females having better cognitive abilities, more developed speech and
less challenging behavior than men (e.g. Maatta, Trevo-Maatta, Taanila, Kaski, & Iivanainen, 2006).
Depression too might out itself differently in the Down syndrome population with less
verbalization and more behavioral signs like crying, depressed appearance, withdrawal, insomnia, etc.
(see Maatta et al., 2006 for a list). Depression has also been found to be the main mental health
problem in this population (e.g. Maatta et al., 2006) and it can have a very strong inuence on how
people perform on (neuro) psychological tests and in turn complicate the possible diagnosis of
dementia. For example, Burt, Loveland, and Lewis (1992) found signicant positive correlations
between poorer memory, lower level of adaptive functioning and lower mental age with depression,
while neurological changes have also been associated with depression in this population (see Maatta
et al., 2006).
A large variety of physical illnesses and sensory impairments (especially hearing, e.g. see Das &
Mishra, 1995) are especially common in the Down population and should be considered when

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attempting to assess cognitive and behavioral change. Knowing what the individual has (always or
recently) suffered from is a good place to start when forming an idea of baseline functioning and it
cannot be more strongly emphasized knowing this premorbid or baseline level of functioning is
crucial when attempting any assessment.
As I have already hinted, early presentation of symptoms of Alzheimers dementia may be different
in Down syndrome. In the general population episodic memory and orientation problems are
generally the rst signs of developing Alzheimers dementia. In Down syndrome prefrontal lobe
symptoms may be more common (but see for example Stanton & Coetzee, 2004 who retain the
emphasis on episodic memory). These include signs and symptoms of: indifference, uncooperativeness, apathy, depression and socially decient communication or impaired adaptive functioning in
general (Ball et al., 2006; Lott & Head, 2001; Zigman et al., 1996). Only in the later stages of the disease
do the memory problems typical of Alzheimers dementia manifest themselves in people with Down
syndrome according to Zigman et al. (1996) among others. The idea that executive functioning might
be problematic in the early stages of Alzheimers disease in Down syndrome is not a completely new
one. Das and Mishra (1995) recommended that sensitive measures for detecting early Alzheimers
dementia in Down syndrome were those that involved planning, articulation and attention all
aspects of the umbrella term that is executive functioning.
As an explanation for this frontal signs rst hypothesis, Azizeh et al. (2000) suggested that the
sequence of brain regions affected by Alzheimers dementia may differ with earlier amyloid deposition
in the frontal lobes in the Down population while in the general population the hippocampus (and
thus episodic memory) would atrophy rst. Holland et al. (1998) extended Mortimers (1988) reserve
capacity model by implying that early compromise was to be found in the frontal lobes in Down
syndrome. Also relevant to this discussion is that the frontal lobes have been found to be
underdeveloped in Down syndrome (Crome & Stern, 1972) and this could suggest that only a small
amount of neuropathology may tip the threshold into impairments, especially on frontal tasks in these
people.
Deb, Hare, and Prior (2007) also found the earlier appearance of frontal lobe dysfunction (data
based on carers interviews) in adults with Down syndrome suffering from Alzheimers dementia,
while, like in the general population, forgetfulness, impaired recent memory and confusion were also
common. Ball, Holland, Treppner, Watson, and Huppert (2008) found further support for a specic
impairment in executive functioning using 6 executive functioning tasks in Down syndrome with
early Alzheimers dementia while Krinsky-McHale et al. (2008) found decits in selective attention. In
contrast, Devenny, Krinsky-McHale, Sersen, and Silverman (2000) found memory decits, reduced
Block Design performance and problems with new learning and visuospatial organization in a Down
population who had cognitive declines but who had not (yet) been diagnosed with Alzheimers
dementia. Therefore, while not all researchers nd frontal dysfunction in early Alzheimers dementia
in Down syndrome many clearly do.
It is important however to emphasize that it is not only cognitive decline which is important in the
diagnosis of Alzheimer dementia but that behavioral and emotional symptoms must also be taken into
account. We will now address all three domains with the emphasis on diagnosing Alzheimers
dementia in the Down population.
3.1. Assessing cognitive change
In order to assess cognitive functioning in the Down syndrome population a wide variety of tests
have been used including: the CAMDEX-R and the Cambridge Cognitive Examination (CAMCOG-R)
(Roth et al., 1999). Due to the fact that the original CAMCOG was designed for testing an (general)
elderly population, Hon, Huppert, Holland, and Watson (1999) adapted it for use in a populationbased sample of 74 adults with Down syndrome aged 3065. These modications resulted in more of
the Down syndrome population sampled scoring above oor. Hon et al. (1999) concluded that their
modied CAMCOG is a potentially useful instrument for the detection of cognitive change in people
with Down syndrome who are mildly to moderately mentally disabled and in the early stages of
Alzheimers dementia but that the more severely mentally disabled scored at oor on all the subtests.
These authors also stated that the CAMCOG should not be used on its own for diagnosis of Alzheimers

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dementia in this population because cognitive decits could only be linked with increasing age in their
study.
Recently, a new modied version of the CAMDEX-R has been created for use with people with
Down syndrome and other intellectual disabilities the Cambridge Examination for Mental Disorders
of Older People with Downs Syndrome and Others with Intellectual Disabilities (CAMDEX-DS, Ball
et al., 2004). Ball et al. (2006) went on to assess this instrument in a longitudinal study of 55 people
with Down syndrome. They found declines in executive functioning (as measured via: verbal uency,
attention span, clock drawing and abstract thinking), and personality and behavioral changes which
preceded declines in memory and orientation. Thus, the CAMDEX and CAMCOG (modied for use in a
Down population) can be useful in the diagnosis of Alzheimers dementia. They should not however be
used alone or out of context when attempting to make a diagnosis of dementia.
Cognitive screens have also been used to aid diagnosis in the Down syndrome population. Deb and
Braganza (1999) used the Dementia Scale for Downs Syndrome (DSDS; Geyde, 1995), the Dementia
Questionnaire for Persons with Mental Retardation (DMR; Evenhuis, 1992), and the Mini-Mental State
Examination (MMSE; Folstein, Folstein, & McHugh, 1975) for the diagnosis of Alzheimers dementia in
a community-based sample of 62 adults (3572 years) with Down syndrome. They found that the
correlations between the DMR and the DSDS were high suggesting that they measure very similar
constructs and that the level of agreement when diagnosing dementia was also high between these
two measures. However more people were diagnosed with the DMR than with the DSDS and the
authors suggested that as the DMR includes general disability it may overdiagnose while the DSDS is
more specically focused on the symptoms of Alzheimers dementia. The MMSE did not provide a
reliable measure of Alzheimers dementia because it could not be used in 45% of their population. The
authors suggested that a combined approach using observer-rated scales as well as neuropsychological tests may be required for the diagnosis of dementia in people with an intellectual disability.
Stanton and Coetzee (2004) also suggested that the DSDS and DMR could be useful but that an
experienced clinical psychologist with experience in assessing people with IDs should administer
them.
3.2. Assessing emotional/motivational change and changes in daily functioning
Mood and daily functioning changes are crucial aspects of Alzheimers dementia diagnosis in many
classication systems. These have generally been assessed via interview, informant-ratings and/or
questionnaires in the Down syndrome population. Kalsy, Adams, and Oliver (2006) stated that: Early
identication and assessment of dementia in individuals with Down syndrome require consideration
of a wide range of factors not relevant to the general population (pp. 358359). Behavioral changes
(including changes in socialization skills, a relative strength in younger people with Down syndrome)
may come rst accompanied by executive dysfunction. A list of these early behavioral changes derived
from subjective and retrospective reports can be seen in Table 1 below.
Self-initiated referrals are rare in both the general and Down populations and in the latter it may be
behavioral excesses, especially aggression, anxiety and sleep disturbances that prompt carers to refer
their charges to specialists for assessment. These behaviors are all difcult for carers to deal with,
especially if such excesses occur on a daily basis.
A problem when assessing daily functioning in this population is that many people with Down
syndrome live in sheltered accommodation and these can be relatively unstimulating places. This
means of course that the intellectual demands on these people may be few and opportunities to do
daily chores (cooking a meal, etc.) limited. Carers too tend to be used to providing help and may fail to
spot (subtle) decline/s in their charges, while at the same time carers may change their workplaces
frequently. All of these issues can make both noticing and assessing changes in daily functioning and
cognition all the more difcult.
3.3. Assessing neurological/physiological change
Studies by Menendez (2005) and Visser et al. (1997) suggested that mental deterioration due to
Alzheimers dementia is accompanied by a slowing of alpha rhythm in the occipital cortex in people in

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Table 1
Behavioral changes in Down syndrome diagnosed with Alzheimers dementia.
Behavioral changes

Example reference

Apathy
Episodic noisy excitement
Irritability
Wandering & confusion
Destructive, aggressive or difcult behavior

Jervis (1948) and Deb et al. (2007)

Jervis (1948)
Jervis (1948) and Stanton and Coetzee (2004)
Jervis (1948), Prasher and Filer (1995) and Deb et al. (2007)
Jervis (1948), Prasher and Filer (1995), Urv, Zigman, and
Silverman (2008) and Stanton and Coetzee (2004)
Crapper, Dalton, Skoptiz, Scott, and Hachinski (1975)
and Stanton and Coetzee (2004)
Crapper et al. (1975)
Crapper et al. (1975)
Urv et al. (2008) and Stanton and Coetzee (2004)
Crapper et al. (1975)

Lethargy, withdrawal, loss of interest

Silliness
Limited response to people
Social inadequacy, isolation
Extreme changes in appetite
(typically weight loss)
Restlessness
Sleep disturbance
Incontinence
Excessively uncooperative
Anxiety & fearfulness
Sadness
Stealing & general regressive behavior
Personality changes
Increased dependence

Prasher and Filer (1995) and Stanton and Coetzee (2004)

Prasher and Filer (1995), Deb et al. (2007), Urv et al. (2008)
and Stanton and Coetzee (2004)
Prasher and Filer (1995)
Cooper and Prasher (1998) and Stanton and Coetzee (2004)
Urv et al. (2008) and Stanton and Coetzee (2004)
Urv et al. (2008)
Urv et al. (2008)
Stanton and Coetzee (2004)
Stanton and Coetzee (2004)

the general population and in those with Down syndrome. Replication of these ndings is crucial
however before EEG measures could be recommended as a tool for aiding diagnosis of Alzheimers
dementia in the Down syndrome population. Functional neuroimaging studies have yet to provide
ndings which could aid diagnosis in this population (e.g. Feldman et al., 2008).
4. Potential difculties when trying to diagnose Alzheimers dementia in people with Down
syndrome: a summary
A number of problems arise when one attempts to diagnose Alzheimers dementia in people with
Down syndrome. Firstly, there is currently no gold standard for such diagnosis. Different instruments
and criteria abound making early diagnosis especially difcult. Secondly, underdevelopment of social
and cognitive skills is relatively common in people with Down syndrome (Deb & Braganza, 1999), as is
comorbidity (e.g. depression or hypothyroidism). Both can make assessment difcult, especially if one
uses tests which were originally designed with a different population in mind, while comorbidity can
make it difcult to determine the cause of any impairment seen. A third problem is that there appears
to be a difference in the expression of Alzheimers disease in Down syndrome when these people are
compared to the general population. Frontal symptoms may be more common as opposed to episodic
memory problems. Most classication systems (e.g. DSM-IV, ICD-10) are based on what is typical in
the general population and as such may not be as relevant when attempting to diagnose people with
Down syndrome. Finally, institutionalized people tend to perform at a lower level on standard
neuropsychological test instruments than those with Down syndrome living in the community.
This phenomenon might be for several reasons: (1) it is reasonable to expect that people living in
institutions have more severe forms of functional impairments than those living in the community;
(2) these differences in functional impairments may or may not be due to differently developed brains;
(3) individuals with Down syndrome living in institutions tend to be older on average than those living
in the community and this could obviously hike up the prevalence rates of Alzheimers dementia in
these populations (Tyrrell et al., 2001); and (4) more restricted environments typical in most
institutions may present fewer intellectual challenges and lead these people to rely on different skills
and behaviors than is typical in community populations.

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5. Recommendations
Aylward, Burt, Thorpe, Lai, and Dalton (1995) and Aylward et al. (1997) published the rst
consensus recommendations for the diagnosis of dementia in people with intellectual disabilities and
since then there has been some research carried out in these populations. Diagnosis however remains
a problem, especially in the early stages of dementia. The focus should be centered on recognizing
change and decline in relation to a premorbid baseline. Obtaining a premorbid level of functioning is
not an easy task and therefore, to assist in this, I, along with Burt and Aylward (2000) would
recommend annual screening for people with Down syndrome over the age of 35 years. A short
cognitive screen may be adequate with the option of more extensive neuropsychological testing if
necessary.
Modications of current classication systems in order to include the symptomatology typical in
early Alzheimers dementia in Down syndrome are also strongly recommended. The emphasis should
be on the frontal symptoms and the warning signs of sudden changes in behavior in this population.
Many people with Down syndrome may not be diagnosed early simply because the current
classication systems place the emphasis on memory difculties seen in the general population.
Diagnosis in this population would also be easier if a standard set of tests were used in assessment.
There is no MMSE or equivalent screening instrument which is widely used by all practitioners. Nor
do people with Down syndrome frequent memory clinics the rst sign that something might be
amiss may/may not be spotted by their caregivers or family doctors. Other brief cognitive tests/
screens may prove useful especially in a rst (baseline) assessment (e.g. the DemTect (Kalbe et al.,
2004 or the 7-minute screen, Solomon et al., 1998), however, none of these have been, to my
knowledge found to be superior over other tests in the general never mind in the Down syndrome
population.
I would recommend the CAMDEX-DS (Ball et al., 2004) for use when attempting to assess decline in
the Down population. I would also include an activity in daily living questionnaire both general and
instrumental activities in daily living (ADL and IADL) to assess change in daily functioning over time
(for example the Barthel index, Mahoney & Barthel, 1965 a good measure of ADL; IADL, Lawton &
Brody, 1969). Questionnaires assessing depression (e.g. Geriatric Depression Scale, GDS, Yesavage
et al., 1983), delirium (e.g. Delirium Observation Scale, DOS, Schuurmans, 2001) and other changes in
mood (e.g. Spielberger State-Trait Anxiety Inventory, STAI, Spielberger, Gorsuch, & Lushene, 1970) are
also recommended to be lled in by carers or family members who know the person well (for at least 6
months, Ball et al., 2004). Longitudinal follow-up is crucial in an attempt to detect and monitor
change/decline. Proper training in detection of decline/assessment is also needed for families and staff
members and in multidisciplinary teams of professionals making the ultimate diagnosis
(psychologists, doctors, nurses, etc.).
Of course, the use of the proposed test battery should be examined for its reliability, validity and
feasibility empirically before it can actually be used in clinical practice. In order to assess whether this
battery is workable I would like to suggest that a large population of people with Down syndrome
should be tested in a longitudinal follow-up design. The best studies in the eld of Alzheimers
dementia diagnosis in Down syndrome have included large cohorts from both the general and
institutional populations, equal numbers of males and females, control groups including those with
intellectual dysfunction not due to Down syndrome and a wide variety of cognitive, functional,
behavioral and emotional tests using both client performance, informant checklists and clinical
interviews in their methodology. A consensus with regard to the scoring methods used is also
recommended (as suggested by for example Burt et al., 2005 changing slope scores were found to be
better than difference scores for example). My recommendations when attempting to make a
diagnosis of Alzheimers dementia in the Down population have been summarized in Table 2 below.
The recommendations as set out by Feldman et al. (2008) should also be followed for the Down
syndrome population. These included: a clinical history (from both patient and caregiver), a physical
examination (including standard laboratory tests to rule out other causes of dementia) and a brief
cognitive testing repeated over time. These authors also recommended structural neuroimaging for
some cases but ruled against functional neuroimaging (not widely available, data that exists not yet
conclusive enough to aid diagnosis), measurement of biomarkers (have shown promise but are not yet

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835

Table 2
Making a diagnosis of Alzheimers dementia in the Down syndrome population: recommendations.
1. Clinical interviews
Establish premorbid level of functioning, possible comorbities,
intellectual abilities, any signs of change
2. Standard laboratory tests and neuroimaging
Including serum B12 levels and test for thyroid stimulating hormone,
genetic testing, structural (and/or) functional neuroimaging
(fMRI, PET, EEG) if there is a good reason to do it
3. Cognitive testing

Repeated testing using parallel versions

4. Activities in daily living
5. Mood/emotion
6. General measurements
Informant must know the person well for at least 6 months With
objective measures focus on change (slopes) rather than raw
scores. Consensus among specialists w.r.t which tests to use
is highly desirable
7. General recommendations
(a) Introduce a clause into standard classication systems of dementia
to include the Down syndrome population
(b) Educate carers, families and specialists on how to recognize change
in individuals with Down syndrome
(c) Follow up patients over the long term (begin at age 35 at yearly intervals)
(d) Assess cognition, emotion, personality and daily living changes
(e) Recognize that those living in institutions may not be intellectually
stimulated making change even harder to detect
(f) Recognize that memory problems may not be the rst sign of dementia
in this population (frontal signs and personality changes may/may not
be more common)
(g) Clinical judgment and (neuropsychological) testing are both important
because clinicians tend to overestimate dementia in this population
(Burt et al., 2005)
(h) Be aware that informants also age and that this can affect their judgment
(Bush & Beail, 2004)

With patient, close family and carers

Blood work-ups and neuroimaging

Short screen and when decline

is indicated a more comprehensive
neuropsychological assessment
using for example the CAMDEX-DS
(Ball et al., 2006)
Measure both ADL and IADL (see text)
Measure depression, anxiety, delirium
(see text)
Both informant and objective measures

routinely used) and extensive neuropsychological testing (on the grounds that this is typically too
expensive and can take 24 h of the patients time while acknowledging that such testing is much
more sensitive than are brief cognitive tests).
6. Conclusion
There is unfortunately no gold standard by which to diagnose Alzheimers dementia in Down
syndrome. This, in my opinion, needs to change and I have provided recommendations in this review
in an attempt to aid both clinicians and carers to this end. Longitudinal studies using multiple tests
assessing cognitive, emotional, motivational and daily functioning in individuals are recommended as
is focus on change in functioning, bounce patterns, and multidisciplinary diagnosis. Cost is likely to
be a factor. However, when you compare potential costs for research against how much this aging
population is likely to cost governments in health care if early diagnosis is not attempted, then a strong
case can be made for adequate funding for long-term, multi-task and multi-disciplinary studies. The
focus should ultimately be on the individual and their changing needs while studies should utilize
large populations to assess possible subgroups and compare them with matched control and other
populations with intellectual disabilities not due to Down syndrome. Environmental factors are very
likely to have an impact on the risk for developing Alzheimers dementia. Researchers and clinicians
should also be aware that Alzheimers dementia is not the only type of dementia people with Down

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R.E. Nieuwenhuis-Mark / Research in Developmental Disabilities 30 (2009) 827838

syndrome can suffer from while the terms dementia and Alzheimers are used interchangeably in the
literature (Bush & Beail, 2004).
While there is no space here to discuss implications for treatment improving attention and
planning in the Down syndrome population with early Alzheimers dementia (assuming executive
dysfunction is the rst sign) is worth pursuing. Frequent reminders may also help these people focus
on tasks they must perform and when routines must be disrupted, supervision is recommended
because they will have trouble learning new things/plans. Patience is required from carers as
articulation problems and slow speech is common in this population and even more so in those with
early Alzheimers dementia. Interventions to reduce behavioral disturbance is necessary not only to
minimize caregiver burden but also to increase the individual with Down syndromes quality of life
(Ball et al., 2006). The goal is to maximize the individuals strengths thereby enabling them to live with
dignity for as long as possible and allow carers to adjust to the individuals changing abilities and
needs. Carers and physicians alike should be made aware of the importance of recognizing changes in
the individual with Down. Further recommendations for treatment can be found in Stanton and
Coetzee (2004).
With both the general and the Down syndrome population living longer than ever before the
likelihood that more people will suffer from Alzheimers dementia in the future is a major cause for
concern. Establishing a reliable procedure for dementia diagnosis is therefore crucial for public health
planning. I would like to end this paper with a quote from Margallo-Lana et al. (2007): In people with
DS surviving to middle and old age, the development of dementia of Alzheimer type is frequent but not
inevitable, and some people with DS reach old age without clinical features of dementia (p. 483).
There is therefore hope for this population not everyone will develop Alzheimers dementia in old
age, while at the same time procedures for (early) diagnosis become ever more important.
Acknowledgment
I would like to thank Anja Visser for her initial help in obtaining some of the references used in this
paper.
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