Assessment tools and treatment regimens may need to be modified but with careful and detailed psychiatric evaluation virtually all disorders can be detected. It is important that all psychiatrists are aware of the increased psychiatric morbidity in adults with Down's Syndrome.

Vee P Prasher (UK) and Sunil K Routhu (UK)

There is an increased prevalence of psychiatric disorders in people with intellectual disabilities (Mantry et al 2008). However, certain types of disorder are more common amongst people with Down’s syndrome, compared to other adults with intellectual disabilities: Alzheimer's, dementia, depression, and obsessive-compulsive disorder. This article reviews the current literature regarding the main types of mental illness that people with Down’s syndrome may experience during their lifespan. Whilst particular attention is given to the association of Alzheimer's dementia with Down’s syndrome, other mental disorders are also discussed (including schizophrenia and anxiety disorders). The differences in the presentations of such disorders in people with intellectual disability are discussed, together with the challenges that face clinicians in detecting these illnesses. This article is particularly helpful for medical students, trainee psychiatrists, and general practitioners wanting an overview of the association between mental illness and Down’s syndrome.

Prevalence of psychiatric disorders

An increase in the prevalence of psychiatric disorders in people with intellectual disability has been reported (Mantry et al 2008). Prevalence rates have been consistently demonstrated to be higher in adults with Down’s syndrome than in the general population, with overall rates similar to those for learning-disabled adults who do not have Down’s syndrome. Although the overall rates are similar, there is a difference in the type of disorders present in people with Down’s syndrome: dementia of Alzheimer’s type (DAT), obsessive-compulsive disorders and depression are more common among people with Down’s syndrome (see Figure 1).

Specific types of psychiatric disorder

Dementia:

The first reported association between Down’s syndrome and DAT was made by Fraser and Mitchell in 1876. Commenting on people with Down’s syndrome, they wrote: 'in not a few instances, however, death was attributed to nothing more than general decay - a sort of precipitated senility'. The association has been well established since then.

Aetiology:

The high risk of DAT in adults with Down’s syndrome is principally due to the triplication and over-expression of the gene for amyloid precursor protein (APP) located on chromosome 21. Evidence increasingly suggests that the presence of one or more copies of APOE E4, as in the general population, increases the risk for DAT in the Down’s syndrome population. The presence of the APOE E2 allele possibly increases longevity and reduces the risk. A family history of dementia, sex differences and the effects of oestrogen in Down’s syndrome are yet to be fully investigated.

Prevalence:

The prevalence rate of dementia of all types in the general population varies from 0.6% to 21%, depending on the age of the sample studied. Identification of DAT in the Down’s syndrome population has proved to be difficult, leading to a wider variation in rates of 15-45%.  In a study by Coppus A et al., (2006), the prevalence of dementia doubled with each 5-year interval up to the age of 60 years. Above the age of 60 years, there is a small decrease in prevalence of dementia to 25.6%. This may be explained by the increased mortality among elderly demented Down’s syndrome patients (44.4%) in comparison with non-demented patients (10.7%). There was no decrease in incidence of dementia in the age group of 60 and above. The mean age of onset of DAT is 50-55 years, with onset as young as 30 years. The mean duration of DAT is approximately 6 years but can range from a few months to 21 years (Prasher and Krishnan, 1993).

Psychopathology:

Signs and symptoms of DAT in adults with Down’s syndrome may be difficult to diagnose because of the underlying mental impairment. Dalton and Crapper-McLachlan (1986) reviewed 35 case reports of people with Down’s syndrome who had received a clinical description relating to the development of DAT. The most frequently occurring symptom/sign was the presence of epilepsy (88% of cases), followed by focal neurological signs (46%) and personality change (46%). See Figure 2 for other symptoms/signs, in order of frequency.

Lai and Williams (1989) described three phases of DAT:

  • In the initial phase memory impairment, temporal disorientation, and reduced verbal output were evident in higher-functioning individuals with Down’s syndrome. For those with more severe learning disability, the first indications of dementia were apathy, inattention and reduced social interactions.
  • In the second phase, there was loss of self-help skills such as dressing, toileting and use of food utensils. The gait was often slowed and shuffling.
  • In the final phase the patients were non-ambulatory and bed-ridden, and often assumed flexed postures. Sphincter incontinence was present and pathological reflexes such as sucking, palmar grasp, palmomental and glabellar reflexes were prevalent. Park­insonism developed in 20% of cases. Seizures developed in 41 of the 49 demented patients, and occurred in all 23 who died. Ten patients had the flexed posture, bradykinesia, masked face and cogwheel rigidity of Parkinsonism.

The early presentation of Alzheimer's dementia in Down’s syndrome is characterized by prominent personality and behaviour changes, associated with executive dysfunction, providing support for the notion that the functions of the frontal lobes may be compromised early in the course of the disease in this population. (Ball SL et al 2006, Deb S et al 2007)

Diagnosis: unlike in the general population, in people with intellectual disabilities there are no approved systematic, acceptable, standardized forms of assessment. People with Down’s syndrome showed lower performances in auditory word span, higher performances in spatio-sequential span and comparable performance in visual span in short-term memory tests compared to people without Down’s syndrome (Frenkel S and Bourdin B, 2009). Measurements of other intellectual functions (e.g. speech, comprehension and visio-spatial function) remain elusive. However, a number of assessment measures have been proposed to detect dementia in people with Down’s syndrome (see Figure 3).

Management:

the management of dementia in Down’s syndrome is similar to that for the general population. Once the diagnosis has been made there are four main areas of management.

1. Treat the underlying disease process - anticholinesterase (AChE) inhibitors (donepezil, rivastigmine, galantamine) have now been established as drugs that can slow down the rate of deterioration of DAT in both the general population and the Down’s syndrome population.

2. Treat associated symptoms - many of the clinical symptoms of dementia can be treated. Seizures should be treated with standard anticonvulsant therapy; insomnia with mild night sedation; aggression, irritability and psychotic features with neuroleptic medication; and low mood with antidepressants.

3. Psychological intervention - although not fully researched in the field of learning disability there is growing evidence that psychological/behavioural intervention can benefit adults with dementia in the general population (Hollins and Sinason, 2000) (see also Banks 2003, pp.62-65). Reminiscence therapy, reality-orientation therapy and behavioural therapy (including occupational therapy) can maintain current skills and reduce deterioration.

4. Support for carers - most Down’s syndrome adults with dementia reside in the community, either with family carers or with paid carers. Education, increased community nursing support and greater involvement of the primary health services can all enable people with dementia to be managed for longer in their homes and delay necessary admission to a nursing home. Carers can also receive considerable support from charities such as the Down’s Syndrome Association and the Alzheimer's Society (see Figure 4 for contact details).

Affective disorders

In the general population, the prevalence of affective disorders varies depending on the diagnostic criteria used, but the rate of depression is in the order of 2-10%. Among people with intellectual disabilities the prevalence of depression is approximately 1-3.5%. There have been few epidemiological studies of depression in people with Down’s syndrome. Myers and Pueschel (1991), in their study of 497 people with Down’s syndrome found depression in 10 adults (2%). Prasher (1995), in a study of 201 adults with Down’s syndrome, found a point prevalence of 5.0%.

Presentation: The presentation of depression in adults with Down’s syndrome differs from that in the general population. Cognitive features (e.g. disturbance of memory, loss of concentration, suicidal ideation) may not be apparent. Biological features (psychomotor retardation, disturbed sleep, loss of appetite, loss of weight) may be more significant. Decline in adaptive skills (e.g. dressing, washing, feeding) is significantly associated with depression.

Management: the assessment and treatment of affective disorders should follow the same clinical guidelines as for the general population. Drug treatments (neuroleptic medication, antidepressants, and mood stabilizers), psychotherapy and electroconvulsive therapy all have a role to play and have been reported to be of benefit in the treatment of depressive episodes in adults with Down’s syndrome. Further research investigating the value of diagnostic instruments and rating scales, outcome post-illness and response to treatment is required.

Schizophrenia

Prevalence rates of schizophrenia of around 3-6% have been demonstrated in people with intellectual disabilities (compared with 0.5-0.8% for the general population). Although case reports of schizophrenia in people with Down’s syndrome have been described there has been little investigation of the prevalence and/or possible association between schizophrenia and Down’s syndrome.

There are considerable difficulties in diagnosing an episode of schizophrenia in adults with Down’s syndrome: eliciting abnormalities of thought and of psychotic experiences in people with severe intellectual impairment is difficult (Prasher 2003, p.10), and so standard diagnostic criteria may not be applicable. To date there is no strong evidence to suggest that people with Down’s syndrome are particularly susceptible to schizophrenia. However, considerable methodological difficulties still need to be overcome before any firm conclusions can be drawn.

Obsessive-compulsive disorder

The prevalence of obsessive-compulsive disorder (OCD) is reported to be 1.65-2.5% in the general population. Myers and Pueschel (1991) found that 4 (1.7%) of 236 Down’s syndrome individuals had OCD, and Prasher (1995) found OCD in 9 (4.5%) of 201 subjects. Ordering is the most common type of action/obsession, along with ritualistic touching and cleaning.
It can be difficult to distinguish compulsive disorders from stereotypes in people with intellectual disabilities, and this must be borne in mind before a diagnosis of OCD is made. Obsessional repetitive thoughts can occur in people with Down’s syndrome but may be difficult to diagnose. Obsessive-compulsive acts are probably more likely to be detected.

Phobias/anxiety

Studies in the intellectual disability population as a whole have reported increased rates of anxiety disorders. However, anxiety-related disorders appear to be uncommon in the Down’s syndrome population. Lund (1988) found neurotic traits in 25 (57%) of 44 adults but, using diagnostic criteria, none was diagnosed as suffering from a neurosis. Myers and Pueschel (1991) found that 5 (1.0%) of 497 people with Down’s syndrome had a phobia disorder. Further research in this area is required.

Other psychiatric disorders

Psychiatric disorders found in the general population, such as somatoform disorders, drug abuse and personality disorders, are also found in people with Down’s syndrome. However, limited evidence suggests that they do not have an increased susceptibility to developing these disorders. Case reports of rarer disorders have been described, including paraphilias, Tourette syndrome and eating disorders.

Conclusion

Overall, the prevalence rates of psychiatric disorders in adults with Down’s syndrome are similar to rates in people with non-Down’s syndrome intellectual disability, but are increased compared with the general population. DAT and possibly depression and OCD are particularly associated with Down’s syndrome. There is strong evidence for a genetic predisposition to developing DAT, although not all adults with Down’s syndrome will do so, and there have been several reports of adults surviving into the seventh decade of life. The diagnosis and subsequent treatment of any given disorder should follow guidelines used in the general population. Assessment tools and treatment regimens may need to be modified but with careful and detailed psychiatric evaluation virtually all disorders can be detected. It is important that all psychiatrists are aware of the increased psychiatric morbidity in adults with Down’s syndrome.

FIGURE 1: Studies investigating psychiatric comorbidity in adults with Down’s syndrome

Investigators

Age group (years)

Sample size (n)

Findings

Lund (1988)

-

44

  • Psychiatric diagnosis in 11 people: dementia in 4
  • Infantile autism in 5
  • Behavioural disorders in

Myers & Pueschel (1991)

20-72

236

  • For adults, 1.3% had an attention deficit disorder or a hyperactivity disorder
  • 1.3% conduct or oppositional disorder
  • 1.2% aggressive behaviour
  • 4.1% compulsive behaviour
  • 1.3% eating problems
  • 4.1% elimination difficulties
  • 5.5% self-injurious behaviour
  • 1.3% affective syndromes
  • 6.1% dementia
  • Overall, 27% of the 72 adult residents had a psychiatric disorder

Collacott (1992)

16-78

371

  • No disorder was found in 275 (74%)
  • depression in 42 (11.3%)
  • manic-depressive psychosis in 2 (0.5%)
  • pre-senile dementia in 16 (4.3%)
  • autism in 8 (2.2%)
  • conduct disorder in 23 (6.2%)
  • personality disorder in 0 (0%)
  • neurosis in 1 (0.3%)
  • phrenia/paranoid states in 6 (1.6%)
  • other diagnoses in 4 (1.1%)

Prasher (1995)

16-76

201

  • 58 (29%) suffered from a menal disorder
  • The commonest was dementia, in 27 (13%)
  • followed by depression, in 10 (5%)
  • and obsessive compulsive disorder (OCD), in 9 (4.5%)

Mantry (2008)

Above 16

186

  • Point prevalence of mental illness excluding specific phobias –

23.7% Clinical

19.9% by DC-LD

11.3% by DCR-ICD-10

10.8% by DSM – IV – TR

  • Two year mental illness incidence –

14.9% by DC-LD

9.0% by DCR-ICD-10

3.7% by DSM – IV – TR

  • Highest Incidence –

Depressive Episode (5.2%)

Dementia/Delirium (5.2%)

  • Standardized rate for prevalence of mental ill-health – 0.6 (0.4- excluding Organic Disorders)
  • Standardized incidence ratio for mental ill-health – 0.9 (0.7- excluding Organic Disorders)

FIGURE 2: Symptoms and signs of dementia of Alzheimer's type (DAT)

  • Incontinence
  • Apathy/inactivity
  • Loss of conversation
  • EEG changes
  • Loss of self-help skills
  • Seizures/myoclonus
  • Visual/auditory effects
  • Walking impairment
  • Stubbornness/lack of cooperation
  • Depression
  • Memory loss
  • Increased muscle tone
  • Disorientation
  • Hallucinations/delusions

FIGURE 3: Differing measures of dementia in people with Down’s syndrome

Measure

Findings

Neuropsychological tests

 

·         Dementia Questionnaire for Mentally Retarded Person

Screening tool for dementia

  • Dementia Scale for Down’s Syndrome

Screening tool for dementia

  • Test for Severe Impairment

Screening tool for dementia

  • Early Signs of Dementia Checklist

Screening tool for dementia

  • Prudhoe Cognitive Functioning Test

Screening tool for dementia

  • CAMDEX-Ds

Diagnosis of Dementia

Neuropsychiatric Assessment

 
  • Down’s Syndrome Mental State Examination

Dementia Symptoms

  • Psychopathology Instrument for Mentally Retarded Adults

Psychiatric Problems

Activities of Daily Living

 
  • Vineland Adaptive Behaviour Scales

Adaptive Behaviour

  • AAMD – Adaptive Behaviour Scale I and II

Adaptive Behaviour

  • Aberrant Behaviour Checklist

Behaviour Disturbances

  • Adaptive Behaviour Dementia Questionnaire

Screening for Alzheimer’s Dementia

  • Adaptive behaviour assessment

Significant decline in adaptive behaviour in adults with DAT

Electroencepalography

Diffuse slow wave and loss of alpha activity in demented subjects

Evoked potentials

 
  • Visual

Low amplitude and delayed P100 latencies

  • Auditory

Increase in latency of P300 in demented DS subjects

Computed tomography (CT)

Cerebral atrophy and ventricular dilation in demented subjects

Single photon emission computerized tomography (SPECT)

Reduced perfusion in demented DS subjects

Positron emission tomography (PET)

Reduced glucose metabolism in demented DS subjects

Magnetic resource imaging (MRI)

Reduced total brain volume and ventricular dilation in demented subjects

FIGURE 4: USEFUL ADDRESSES

Down’s Syndrome Association
The Langdon Down Centre
2a Langdon Park
Teddington TW11 9PS

Tel: 0845 2300 372
Fax: 0845 2300 373

General Email: info@downs-syndrome.org.uk

Website: www.downs-syndrome.org.uk

Alzheimer's Society
Devon House
58 St Katharine's Way
London E1W 1LB

Tel: 020 7423 3500
Fax: 020 7423 3501
Email: enquiries@alzheimers.org.uk
Website: www.alzheimers.org.uk

REFERENCES

Banks R. Psychological Treatments for People with Learning Disabilities. Psychiatry 2003; 2(9): 62-65.
Collacott R A. The effect of age and residential placement on adaptive behaviour of adults with Down’s syndrome. Br J Psychiatry 1992; 161: 675-9.
Dalton A J, Crapper-McLachlan D R. Clinical expression of Alzheimer's disease in Down’s syndrome. Psychiatr Clin North Am 1986; 9: 659-70.
Fraser J, Mitchell A. Kalmuc idiocy: report of a case with autopsy with notes on 62 cases. J Ment Sci 1876; 22: 161.
Hollins S, Sinason V. Psychotherapy, learning disability and trauma: new perspectives. Br J Psychiatry 2000; 177: 201-6.
Lai F, Williams R S. A prospective study of Alzheimer’s disease in Down’s syndrome. Arch Neurol 1989; 46: 849-53.
Lund J. Psychiatric aspects of Down’s syndrome. Acta Psychiatr Scand 1988; 78: 369-74.

Mantry D, Cooper SA, Smiley E, Morrison J, Allan L, Williamson A, Finlayson J, Jackson A. The prevalence and incidence of mental ill-health in adults with Down’s syndrome. J Intellect Disabil Res. 2008; 52 (Pt 2):141-55.

Myers B A, Pueschel S M. Psychiatric disorders in a population with Down’s syndrome. J Nerv Ment Dis 1991; 179: 609-13.
Prasher V P. Epidemiology of Learning Disability. Psychiatry 2003; 2(8): 9-11.
Prasher V P, Krishnan V H R. Age of onset and duration of dementia in people with Down’s syndrome. Int J Geriatr Psychiatry 1993; 8: 915-22.
Prasher V P. Prevalence of psychiatric disorders in adults with Down’s syndrome. Eur J Psychiatry 1995; 9: 77-82.

FURTHER READING

Berg J M, Karlinsky H, Holland A. J. Alzheimer’s disease, Down’s syndrome, and their relationship. Oxford: Oxford University Press, 1993.
(Textbook which reviews all aspects of Alzheimer's disease in Down’s syndrome.)
Pueschel S M, Pueschel J K. Biomedical Concerns in Persons with Down’s syndrome. Baltimore, MD: Paul H Brookes, 1992. (Detailed textbook which highlights important physical and psychiatric conditions associated with the Down’s syndrome population).

Vee P Prasher. Alzheimer’s Disease and Dementia in Down’s Syndrome and Intellectual Disabilities. Radcliffe Publishing Ltd, 2005. (Textbook which reviews aspects of Alzheimer's disease in Down’s syndrome and Intellectual Disabilities.)

First published in Psychiatry, Volume 2:8, August 2003 and reprinted with the kind permission of The Medicine Publishing Company.

This article was updated in 2011.