Psychiatric Morbidity in Adults with Down's Syndrome
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 Neha Bansal (UK)
Down’s syndrome is the commonest genetic cause of intellectual disabilities (Vicari et al, 2013). Although there is increased prevalence of psychiatric disorders in people with intellectual disabilities as a whole (Mantry et al, 2008; Buckles et al, 2013), certain psychiatric illnesses are more common amongst people with Down’s syndrome (Dykens et al, 2015; Tasse et al, 2016). This article reviews the current literature regarding the types of mental disorders that people with Down’s syndrome may experience during adulthood. Whilst particular attention is given to the association of Alzheimer's dementia with Down’s syndrome, other mental disorders are also discussed (including schizophrenia, affective disorders and obsessive compulsive disorder). The differences in the presentations of such disorders in people with intellectual disabilities 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 disorders and Down’s syndrome.
Prevalence of psychiatric disorders
Prevalence rates for psychiatric disorders have been consistently demonstrated to be higher in adults with Down’s syndrome than in the general population and for the non-Down’s syndrome intellectually disabled population (Prasher, 1995; Vicari et al, 2013). 18-23% of patients with Down’s syndrome show significant psychopathology (Vicari et al, 2013; Tasse et al, 2016). As well as the prevalence rate being greater, there is also a difference in the type of disorders that present in people with Down’s syndrome; Dementia in Alzheimer’s disease (DAD), obsessive-compulsive disorders and depression are more common among people with Down’s syndrome (see Figure 1). Dykens et al (2015) compared rates of various psychiatric disorders in young adults with Down’s syndrome and other intellectual disabilities. In this study, the rates of psychosis were significantly higher in those with Down’s syndrome. However, rates of bipolar and impulse control disorders were lower compared to those with other intellectual disabilities. Rates of psychiatric disorders in Down’s syndrome also change with age, which may be associated with the significant burden of medical and cognitive morbidities as well as social and developmental changes that evolve with age (Alexander et al, 2016).
Specific types of psychiatric disorder
The first reported association between Down’s syndrome and dementia in Alzheimer’s disease 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'. A strong clinical, epidemiological, neuropathological and genetic association has been well established since then (Prasher, 2005).
The high risk of dementia in Alzheimer’s disease 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 (Head et al, 2016). Evidence increasingly suggests that the presence of one or more copies of APOE E4, as in the general population, increases the risk for dementia in Alzheimer’s disease in the Down’s syndrome population (Patel et al, 2011; Ness et al, 2012). 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. A recent review from Schupf et al (2017) reports that reduced levels of oestrogen, for example as seen in early menopause, and variation in genes for oestrogen receptor activity and biosynthesis, are related to early onset of dementia in Down’s syndrome. The neuroprotective effects of oestrogen are well documented; these include increasing cholinergic activity, antioxidant and anti-inflammatory properties, and protection against the toxicity of amyloid beta which are all associated with a protective role against development of dementia in Alzheimer’s disease.
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 dementia in Alzheimer’s disease in the Down’s syndrome population has proved to be difficult, leading to a wider variation in rates (4-55%) (Head et al, 2012). 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 dementia in Alzheimer’s disease is 50-55 years, with onset as young as 30 years. The mean duration of dementia in Alzheimer’s disease is approximately 6 years but can range from a few months to 21 years (Prasher and Krishnan, 1993).
Signs and symptoms of dementia in Alzheimer’s disease in adults with Down’s syndrome may be difficult to diagnose because of the underlying mental impairment. Patients may have a lengthy prodromal phase, where clinical features do not fulfill criteria for diagnosis of Alzheimer’s disease, making diagnosis more difficult. Nearly all patients with Down’s syndrome, by the age of 50 years, have sufficient senile plaques and neurofibrillary tangles for a neuropathological diagnosis of Alzheimer’s disease (Lautarescu et al, 2017). Studies investigating dementia in Alzheimer’s disease in persons with Down’s syndrome highlight the importance of earlier detection, role of standardized diagnostic criteria and use of recognized measures to follow disease progression (McCarron et al, 2017). Dalton and Crapper-McLachlan (1986) had previously reviewed 35 case reports of people with Down’s syndrome who had received a clinical description relating to the development of dementia in Alzheimer’s disease. 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 dementia in Alzheimer’s disease (DAD):
- 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, 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 dementia in Alzheimer’s disease 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. (Deb S et al 2007; Lautarescu et al, 2017)
Unlike in the general population, in people with intellectual disabilities there are no internationally approved systematic, acceptable, standardized forms of assessment, although several have been proposed (Prasher, 2018). People with Down’s syndrome show lower performances in auditory word span, higher performances in spatio-sequential span and comparable performances in visual span in short-term memory tests compared to people without Down’s syndrome (Frenkel and Bourdin, 2009). Measurements of other intellectual functions (e.g. speech, comprehension and visuo-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). Co-morbid conditions presenting or impacting on dementia in Alzheimer’s disease in adults with Down’s syndrome is not uncommon. In a recent case study by Wark et al (2014), they describe 3 individuals with Down’s syndrome and dementia who appeared to have some recovered functioning after a clear period of decline. They hypothesize that undiagnosed depression may be a factor exaggerating the true level of functional decline associated with dementia and that identification and treatment of depressive symptoms may improve quality of life for these patients. Tsiouris et al (2014) reported that antidepressant use was associated with increased longevity in adults with Down’s syndrome as well as delayed onset of dementia.
The management of dementia in Down’s syndrome is generally 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 dementia in Alzheimer’s disease in both the general population and the Down’s syndrome population. Memantine (NMDA receptor antagonist) has been established as an effective drug in the treatment of dementia in the general population, although not as effective in the treatment of dementia in patients with Down’s syndrome (Hanney et al 2012).
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). 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, advocacy, increased community nursing support and greater involvement of the primary health care and end-of-life services can all enable people with dementia to be managed for longer in their homes and delay necessary admission to a nursing home (Watchman and Janicki, 2017). 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 as a whole, the prevalence of depression is approximately 1-3.5%. Few epidemiological studies of depression or mania in people with Down’s syndrome have been reported. 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% and Walker et al (2011) in their review of the literature reported prevalence rates of depression in Down’s syndrome to range between 0-11.1%. Rates of depression in persons with Down’s syndrome as compared to non-Down’s syndrome persons with intellectual disabilities were recently found to similar in younger adults; however in older adults with Down’s syndrome, the rates of depression are reported to be higher (Dykens et al, 2015).
A number of potential risk factors for depression in Down’s syndrome have been proposed (Walker et al, 2011; Dykens et al, 2015; Foley et al, 2015):
- Studies have shown that whole brain volumes of individuals with Down’s syndrome are smaller compared to the general population. Smaller total brain volume, in particular smaller hippocampal volume, is associated with increased risk of depression
- Gender differences in prevalence of depression are similar in Down’s syndrome compared to the general population, in that there is a higher prevalence amongst women
- Significant life events
- Social isolation
- Physical and/or sexual abuse
- Advancing age
- Lower functioning in activities of daily living
The presentation of depression in adults with Down’s syndrome can differ significantly to 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, fatigue) may be more significant. Decline in adaptive skills (e.g. dressing, washing, feeding), anhedonia, anxiety, agitation are significantly associated with depression.
In adults with Down’s syndrome, the difficulty in not recognizing depression and the lack of reporting of symptoms, as well as inadequate treatment may influence the prognosis. Stein (2017) highlights the challenges of differentiating apparent cognitive decline and developmental regression from depression. We are reminded not to underestimate the impact of psychological stress and to think of wider causes of cognitive decline other than medical, for example, the impact on children of entering puberty and adjustment difficulties as a result of social and environmental changes. Studies have shown the persistence of depressive symptoms from childhood to young adulthood in Down’s syndrome and have emphasized the importance of routine screening for potential depressive symptoms, increasing awareness amongst carers and family members (Foley et al, 2015).
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 (Torr and D’Abrera, 2014). Further research investigating the value of diagnostic instruments and rating scales, outcomes post-illness and response to treatment is required.
3. Regression in young adults with Down’s syndrome
Prasher, in 2002, was the first to describe the condition where young adults with Down’s syndrome present with cognitive decline, language regression, loss of adaptive and social skills and behavioural changes. He termed this “Young Adults with Disintegrative Syndrome (YADS)”. Subsequently other authors have confirmed the presence of this condition, albeit using different terminology to describe it (Capone et al, 2006; Stein et al, 2017; Akahoshi et al, 2012; Ghaziuddin et al, 2015). In addition, these patients may also experience sleep disorders, psychomotor slowing, loss of speech, anxiety and mood disorders, new onset or worsening of existing repetitive thoughts and behaviours. There have also been reports of aggression, psychosis and catatonia.
In some cases this regression may be triggered by a significant life event or emotional stressor, but in others, the condition may occur seemingly unprovoked (Jacobs et al, 2016). Stein et al (2017) described the significant psychological impact on children with Down’s syndrome entering adolescence, which may serve as a trigger for development of regression. Interestingly, regression may not necessarily be associated with the level of intellectual disability. Mircher et al (2017) identified in a study of 30 patients with history of regression and Down’s syndrome that regression occurred regardless of the cognitive level (severe, moderate or mild intellectual disability). In this study, all patients experienced severe emotional stress prior to regression. Further research into this relatively new disorder, particularly regarding successful treatments, is required.
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 very little investigation of the prevalence and/or possible association between schizophrenia and Down’s syndrome. Dykens et al (2015) in their study compared psychiatric disorders in adolescents/young adults with Down’s syndrome to those with other intellectual disabilities. Of the 119 participants, 35% of those with Down’s syndrome (N=49; mean age 21 years) had psychosis NOS (not otherwise specified) compared to 13% in those with other intellectual disabilities. An additional 8% of those with Down’s syndrome had depression with psychotic features. The authors concluded further research was still required in this field.
There are considerable difficulties in diagnosing an episode of schizophrenia in adults with Down’s syndrome. In those with severe intellectual impairment, standard diagnostic criteria may not be applicable, further compounding the challenges of diagnosis as well as the practical difficulties of eliciting abnormalities of thought and of psychotic experiences (Prasher 2003, p.10). To date there is no strong evidence to suggest that people with Down’s syndrome are particularly susceptible to schizophrenia per se.
5. Obsessive compulsive disorder
Obsessive-compulsive disorder (OCD) is characterized by the presence of intrusive thoughts, images or urges (obsessions) which lead to compulsions (physical or mental) in order to help reduce the anxiety associated with the obsession. The prevalence of 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. In adults with Down’s syndrome, ordering is the most common type of action/obsession, along with ritualistic touching, cleaning, frequently altering light switches and opening/closing doors.
It can be difficult to distinguish compulsive disorders from stereotypies 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. The first line treatment for OCD is a serotonin-reuptake inhibitor (SSRI) which has been reported to give a good response in the treatment of OCD in adults with Down’s syndrome. Risperidone may also be used in conjunction with SSRI in treatment of OCD (Sutor et al, 2006). Interestingly, in a case report of an adolescent with Down’s syndrome and treatment-resistant OCD, treatment with Memantine (NMDA receptor antagonist) helped markedly to improve his symptoms over a period of 4 months, with compulsive behaviours significantly reducing and being reported as “rare” (Pekrul et al, 2015).
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; however, using diagnostic criteria, none were 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 but generally phobias/anxiety disorders can occur in persons with Down’s syndrome and should be managed as per the general population.
7. 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.
Ghaziuddin et al (2015) described catatonia in Down’s syndrome in his case series of 4 adolescent patients, who all experienced regression and symptoms consistent with catatonia. He showed that whilst they had affective symptoms, they did not respond to antidepressant treatment or mood stabilisers, but responded to treatments for catatonia (electroconvulsive therapy and benzodiazepines), resulting in recovery of their baseline functioning. There have also been studies on the prevalence of attention deficit hyperactivity disorder (ADHD) and obstructive sleep apnoea syndrome (OSAS) amongst patients with Down’s syndrome, with prevalence of 34% for ADHD, suggesting that screening should be introduced in early school years (Oxelgren et al, 2017). Other studies have reported figures to be as high as 43.9% for ADHD in Down’s syndrome (Ekstein et al, 2011). Interestingly in Ekstein’s study, no significant correlation was found between ADHD symptoms and the level of mental retardation. Capone et al (2013) reported an increase in OSAS in adolescents and younger adults with Down’s syndrome and depression, compared to controls. He suggested that further understanding of this association may be helpful in management of mood disorders and functional decline in patients with Down’s syndrome. As well as OSAS, another study found that behavioural sleep disturbances (delayed sleep onset, night time awakening) were associated with anxiety, depression and dementia (Esbensen, 2016). Case reports of rarer disorders have also been described, including paraphilias, Tourette’s syndrome and eating disorders.
Overall, the prevalence rates of psychiatric disorders in adults with Down’s syndrome are similar to rates in people with other intellectual disability; however the rates are increased compared with the general population. Dementia in Alzheimer’s disease and possibly depression and OCD are particularly associated with Down’s syndrome. There is strong evidence for a genetic predisposition to developing dementia in Alzheimer’s disease, although not all adults with Down’s syndrome will do so, and there have been several reports of adults surviving into their 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
Age group (years)
Sample size (n)
Myers & Pueschel (1991)
The commonest was dementia, in 27 (13%)followed by depression in 10 (5%),
and obsessive compulsive disorder (OCD) in 9 (4.5%)
19.9% by DC-LD
11.3% by DCR-ICD-10
10.8% by DSM – IV – TR
14.9% by DC-LD
9.0% by DCR-ICD-10
3.7% by DSM – IV – TR
Depressive Episode (5.2%)
Akahoshi et al (2012)
Hanney et al (2012)
Capone et al (2013)
Tsiouris et al (2014)
Dykens et al (2015)
18% anxiety disorders
Tasse et al (2016)
McCarron et al (2017)
Mircher et al (2017)
FIGURE 2: Symptoms and signs of dementia in Alzheimer's disease (DAD)
- Loss of conversation
- EEG changes
- Loss of self-help skills
- Visual/auditory effects
- Walking impairment
- Stubbornness/lack of cooperation
- Memory loss
- Increased muscle tone
FIGURE 3: Differing measures of dementia in people with Down’s syndrome
· Dementia Questionnaire for Mentally Retarded Person update-DLD
Screening tool for dementia
Screening tool for dementia
Screening tool for dementia
Screening tool for dementia
Screening tool for dementia
Diagnosis of Dementia
Activities of Daily Living
Screening for Alzheimer’s Dementia
Significant decline in adaptive behaviour in adults with DAT
Diffuse slow wave and loss of alpha activity in demented subjects
Low amplitude and delayed P100 latencies
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: 0333 1212 300
General Email: firstname.lastname@example.org
43-44 Crutched Friars
London EC3N 2AE
Royal Mencap Society
123 Golden Lane
Tel: 020 7454 0454
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Wark S, Hussain R, Parmenter T. Down’s syndrome and dementia: Is depression a confounder for accurate diagnosis and treatment? J Intellect Disabil. 2014 18:305-14. https://www.ncbi.nlm.nih.gov/pubmed/25249377
Watchman K, Janicki MP; Members of the International Summit on Intellectual Disability and Dementia; The Intersection of Intellectual Disability and Dementia: Report of The International Summit on Intellectual Disability and Dementia. Gerontologist. 2017 Nov 2.
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, and further updated and revised in 2017.