Ageing and Dementia

Overview

Adults who have Down Syndrome are enjoying increasingly longer lives – with many surviving beyond their 50th and 60th birthdays. This is partly due to our increased understanding of the medical conditions seen in Down Syndrome, as well as improvement in health surveillance, intervention and management of comorbidities throughout childhood and beyond.

The most notable association of Down Syndrome in older age is Alzheimer Disease – with increasing acknowledgement that Down Syndrome is a genetic form of this dementia. However, adults with Down Syndrome are no different to other members of the population when it comes to getting older. They will face the same medical issues and are also entitled to the same provision of healthcare. However, it is important to note that the presence of an extra chromosome leads to an “accelerated” ageing process in Down Syndrome and more rapid cognitive and functional decline with advancing age.

Because of their underlying learning disability and communication difficulties in articulating how they are feeling or describing symptoms, many adults who have Down Syndrome will be reliant on family members or carers to interpret changes in their behaviour or recognise symptoms of deteriorating health. Carers and involved  professionals need to be mindful of “diagnostic overshadowing” – whereby clinical signs, symptoms or new behaviours are attributed to the learning disability or other pre-established medical condition. Although Alzheimer Disease and symptoms of dementia are known to affect adults from an earlier age, it is still important to assess for other conditions that can cause decline in skills or apparent cognitive or personality changes including sensory impairment, thyroid dysfunction, depression, menopause or even musculoskeletal  conditions, such as cervical spinal instability. Social isolation or life changing events, such as moving into care or loss of a parent, are also considerations during this same assessment.

Where possible, all adults should be empowered to take ownership of their own health (with appropriate support) and for them to be accessing the “Annual Health Check” from the age of 14 years old – offered by most UK General Practitioners (https://www.nhs.uk/conditions/learning-disabilities/annual-health-checks/). Young people and adults have their own personal copy Health Book (https://www.downs-syndrome.org.uk/download-package/health-book/) produced by the Down’s Syndrome Association.

General Health:

All adults should continue to adopt a healthy lifestyle that started in early childhood. Regular exercise and a diet that involves making good food choices e.g. high fibre, adequate fluid intake and calcium and vitamin D rich sources (or supplementation) especially in the winter months, will help to prevent obesity (and possibly type 2 diabetes) as well as reduce the risk of constipation and osteoporosis – all of which occur with increased frequency in adults who have Down Syndrome.

Specific Medical Issues:

Thyroid:

The risk of thyroid dysfunction persists from childhood into adulthood. This requires lifelong surveillance, which in practice comprises at least annual T4 and TSH measurement. There is a tendency for the thyroid gland to be underactive rather than overactive in later life – with onset of symptoms being insidious. Typical symptoms include weight gain, general and physical “slowing”, increased cold intolerance, dry skin and brittle hair, and there is usually a good response to thyroxine replacement therapy. Although symptoms of hypothyroidism can be mistaken for depression (and vice versa), hypothyroidism does not cause depression.

Hyperthyroidism is much less common in Down Syndrome, with symptoms including weight loss, poor heat tolerance, irritability. Sometimes a goitre will be present as will exophthalmos. Hyperthyroidism is usually treated with carbimazole, but sometimes “block and replace” therapy is used – carbimazole is used to block thyroid hormone production and thyroxine is used to replace the deficit.

For more information on thyroid issues in Down syndrome see here

Sensory Impairment:

It is important that hearing and vision continue to be monitored regularly beyond childhood. Deterioration in these sensory domains can present with behavioural changes, confusion, apparent social withdrawal and decline in self-care skills. If the adult already has a hearing aid or wears prescription glasses, these also need to be checked to ensure that they are fitted appropriately.

Hearing:

A common causes of impaired hearing includes conductive hearing loss due to build up of wax or otitis media with effusion (glue ear). Sensorineural hearing is usually an age related phenomenon, or deterioration of an established disorder during childhood. Assessment of hearing should take place at least 2 yearly with an audiological scientist/physician, or if necessary, an ENT surgeon.

Vision:

There is an increased incidence of visual problems in adults with Down Syndrome. Refractive errors occur frequently (recent studies suggests it affects at least 50%) and will require correction with glasses. Cataracts, glaucoma and Age-Related Macular Degeneration (AMD) are also commonly seen in adults with Down Syndrome.

New developments in the management of keratoconus (thinning of the cornea) with collagen cross linking therapy (CXL or C3R) which strengthens the cornea using vitamin B2 and ultraviolet light) means that earlier detection by an optometrist experienced in retinoscopy, can stop further deterioration (Stephanie Campbell, Cardiff 2017 DSA website). Currently only a few specialist ophthalmological services in the UK offer CXL on the NHS.

Vision should be checked at least 1-2 yearly and this can be done by any experienced local optician or optometrist. Adults who remain under the care of a hospital ophthalmologist will be guided by their own specialist regarding the frequency of follow up.

For more information on ocular disorders in Down Syndrome see here

Musculoskeletal Disorders:

Musculoskeletal disorders in adults who have Down Syndrome occur more frequently and often at an earlier age than the general population. Causes include hypermobility at the joints, ligamentous laxity as well as the “accelerated ageing” process seen in Down Syndrome. Hip abnormalities occur in almost 30% of adults – instability and potential for (recurrent dislocation) being a feature from early childhood. Osteoarthritis (which tends to affect other large joints as well e.g. spine, shoulders, knees) is a common sequelae of any hip condition with damage to the joint sometimes requiring total hip replacement because of pain and decreased mobility.

Inflammatory arthritis in adults, can be a delayed diagnosis of a process that commenced in mid-childhood. Childhood arthritis in Down Syndrome has historically been underreported – usually presenting as a polyarticular (mostly small joints in the hands and wrists) that is usually rheumatoid factor negative (Foley 2019). Diagnostic overshadowing, misinterpretation of how a child communicates pain, or total lack of awareness of arthritic conditions in children, means that the disease process remains undetected until irreversible joint damage has occurred.

It is therefore important that musculoskeletal health assessment is routinely incorporated into the annual health check for adults (and children) to facilitate  early identification and management of any problems, to ensure good functional and achieve pain free outcomes.

Other musculoskeletal issues seen in adults who have Down Syndrome are outlined below – but the list is not exhaustive:

Cranial-Vertebral Instability (CVI):

Reduced tone and ligamentous laxity at the cranio-vertebral junction – atlas (C1) and axis (C2) – allows for excessive movement and potential for the spinal cord to be compressed or “bruised” as it exits the foramen magnum. The incidence of asymptomatic CVI is around 10-24% – but very few cases (<1%) are symptomatic. Any general anaesthetic procedure will therefore pose a risk of CVI.

Typical symptoms are a deterioration in fine motor or self care skills, changes in mobility or gait, torticollis, occipital or neck pain with an extended neck position and recent onset incontinence. There is no benefit for radiological screening of CVI. However, lifelong vigilance for this possibility is vital to avoid potentially catastrophic consequences – but there needs to be a balance regarding risk and quality of life.

Cervical Arthropathy:

As people who have Down Syndrome demonstrate “accelerated ageing”, there is increased likelihood of arthritic and degenerative changes (including osteophyte formation, cystic changes, subarticular sclerosis, fusion and disk narrowing) occurring throughout the cervical spine, at a much younger age than the general population. The prevalence of cervical arthropathy may be as high as 50% by the 4th decade and most will have some degree of arthropathy by their 50th birthday. Symptoms are similar to those observed in CVI.

For more information on musculoskeletal issues in Down Syndrome please see here

Sleep:

Sleep difficulties are seen commonly in Down Syndrome and usually begins in early childhood. The causes are often behavioural, but medical problems e.g. gastroesophageal reflux disease or obstructive sleep apnoea (OSA). These difficulties can present as behavioural problems e.g. aggression and irritability with a negative impact on learning

Poor sleep patterns can persist beyond adolescence into adulthood, with approximately 20% young people reporting sleep difficulties in their late teens (Wood and Sacks 2004). A detailed systemic review can identify and respond to medical conditions. Strict sleep hygiene and routine are hugely beneficial from early childhood.

For more information on sleep disorders in Down Syndrome please see here

Obstructive Sleep Apnoea:

Adults with Down Syndrome are prone to obstructive sleep apnoea (35-42% – Hill 2016) and this risk is increased with a tendency to overweight and obesity. Symptoms of snoring, restless and fragmented sleep, daytime somnolence as well as behavioural changes should be sought during the history taking. Untreated, OSA is associated with increased cardiovascular morbidity including hypertension and ischaemic stroke. Once identified with these symptoms, the GP can make a referral to specialist services.

For more information on sleep apnoea in Down Syndrome please see here

Cancer:

In childhood, Down Syndrome is associated with an increased risk of leukaemia and germ cell tumours such as testicular cancer. However, in adulthood, the incidence of solid organ tumours is much lower compared to adults who do not have Down Syndrome. Presumably the gene dosage imbalance in Trisomy 21 affords some kind of protection against certain malignancies.

Despite this apparent protection, adults with Down Syndrome should have access to the universal cancer screening programmes available in the UK – for breast, bowel and cervical cancer. In addition, men with Down Syndrome should be taught testicular self-examination (if their cognitive ability allows this) from the age of 15 years old, as currently there is not enough evidence to support annual testicular ultrasound screening. Enquiries about possible testicular lumps should be included in the annual health check with Primary Care Professionals.

Menopause

The menopause is mentioned briefly here, as it is often overlooked when assessing women with learning disability who might be presenting present with behavioural  changes, lethargy, low mood and weight change. The symptoms, stages and formal diagnosis of the menopause are the same in women with Down Syndrome as for the rest of the population. However, there is a tendency for it to occur earlier – median age of 46 years – and with this comes the increased risk of osteoporosis. There is no evidence that hypothyroidism influences the age at which the menopause occurs. Clearly there is a great deal of symptom overlap between menopause, thyroid dysfunction and mental health conditions such as depression or dementia, so a careful history and examination is essential to identify the true cause.

Skin Conditions:

More is known about dermatological conditions in children with Down Syndrome than in adulthood. However adults are prone to the same skin problems as others, although conditions such as seborrhoea, alopecia, and infections are more common. Due to the “accelerated ageing” process, greying and thinning of the hair, skin atrophy and lentigines formation are also seen prematurely.

For more information on skin disorders please see here

Mental Health:

Mental health disorders are reported to be more prevalent in adults with Down Syndrome than those in the general population (comprehensive review in Prasher & Bansal 2017) with depression, obsessive compulsive disorder and dementia (Alzheimer Disease) among the most common psychiatric conditions seen.

However, there is a risk that these psychiatric conditions are missed. Alzheimer Disease is the most notable association of the ageing process in Down Syndrome, but it is important to exclude depression, thyroid dysfunction, hearing and visual impairment, should functional or cognitive decline be observed.

Therefore, a focused history and use of appropriate screening questionnaires to look for symptoms and signs of psychopathology, should form part of the annual health review, to avoid diagnostic overshadowing. Wider family history of mental health conditions, as well as life events such as bereavement, change in housing situation or care provision, are also important factors that can precipitate anxiety or depression. Most Learning Disability Teams have screening programmes for dementia and it is advisable for a baseline assessment to be undertaken before the age of 30 years, so that a comparison can be made with any further assessments, if cognitive decline is reported.

For more information on mental health disorders in Down Syndrome please see here

Depression:

Although there have been limited studies looking at depression in people with Down Syndrome, work from the early 90s suggests it may affect 2-5%. Symptoms of depression in adults with Down Syndrome may differ to the general population, with biological features e.g. sleep disturbance, weight loss, tiredness and “slowing down” being more prominent than cognitive decline e.g. impaired concentration and memory, suicidal ideation. More significant signs of depression in adults with Down Syndrome include anxiety and reduced enjoyment, as well as deterioration in activities of daily living – washing, dressing etc.

Due to the underlying learning disability, the first signs of depression may be overlooked and attributed to “challenging behaviour”. Once the correct diagnosis is made, depression can be treated successfully with standard treatment and interventions.

Obsessive Compulsive Disorder:

Obsessive compulsive disorder (OCD) has been reported in 1.7-4.5% of adults with Down Syndrome. It is characterised by intrusive thoughts, images or urges (obsessions) leading to compulsions (can be mental or physical) in order to help reduce the anxiety associated with the obsession (Prasher & Bansal 2017).

Typical features in adults with Down Syndrome are ordering, ritualistic touching, opening/ closing doors and cleaning. Caution needs to be exercised as differentiating between the stereotypies observed in adults with learning disability and compulsive urges of OCD, can make the diagnosis more challenging. OCD can be treated effectively with selective serotonin-reuptake inhibitors (SSRI).

Dementia and Alzheimer Disease:

The term dementia is used to describe a number of different, progressive neurological conditions, that result in cognitive and functional decline. Alzheimer Disease is the most common form of dementia in the general population but also in adults with Down Syndrome.

Alzheimer Disease is characterised by the presence of amyloid beta plaques and tau neurofibrillary tangles in the brain. It is believed that genes including the Amyloid precursor protein (APP) gene on chromosome 21, work together to increase the formation of these plaques and tangles (amyloid cascade hypothesis leads to increased deposition of amyloid-?). Much of our understanding of Alzheimer Disease has been based on studies of Down Syndrome. As most people (>95%) with Down Syndrome have an extra, third copy of chromosome 21 i.e. trisomy 21, there is overexpression of the APP and other implicated genes, with resultant increase in amyloid-? deposition in the brain and subsequent cognitive deterioration. Down Syndrome is therefore recognised as a genetic form of Alzheimer Disease.

Another important feature of Alzheimer Disease in Down Syndrome is that the age of diagnosis of occurs earlier than the rest of the population – the mean age being 55 years old (Hithersay et al, 2019). Therefore, as adults with Down Syndrome are living for longer, there is an increased expectation that they will get dementia, with recent estimates suggesting a lifetime risk of ~90%. Alzheimer Disease is now the major cause of morbidity and mortality in older adults with DS, with a mean age of death of 60 years (Strydom et al. 2018).

Clinical Features:

Typical signs of Alzheimer Disease include loss of short term memory, decreased interest in activities, loss of adaptive skills, reduced social interest and desire to communicate. However these features may be more subtle in Down Syndrome and can be overlooked. Diagnosis of Alzheimer Disease is usually made earlier when an adult with Down Syndrome is living at home with their family or familiar caregivers who can recognise these changes. Many studies suggest that changes in personality and behaviour occur before memory impairment in adults with Down Syndrome (Annus et al 2015). Seizures (seen in 40%) may be the first manifestation of Alzheimer Disease and usually presents as myoclonic or generalised tonic clonic seizures. However, the median time of onset of seizures is usually 2 years after the diagnosis of Alzheimer Disease is made.

As the disease progresses, there is more obvious deterioration in general functioning, memory, poor spontaneous recognition of familiar people, with obvious confusion and disorientation and eventually incontinence. The end stages of Alzheimer Disease is heralded by the complete loss of self care and inability to recognise familiar people or their surroundings.

Management:

Correct diagnosis at the earliest possible stage of the disease by the GP or community learning disability team is imperative. Ongoing management is a multidisciplinary affair – including identification of a lead clinician to coordinate care and involvement of Adult Social Care to review the long term needs and current placement (Strydom 2019). Careful evaluation by a psychiatrist will also determine if medication is indicated, and early discussions between the multidisciplinary team, patient and family will help optimise the quality of life, as well facilitate advanced care planning.

Drug Therapy:

Although there are several drugs in clinical use for the treatment of established Alzheimer Disease, no drug has been found to reverse or prevent disease progression. Cholinesterase inhibitors such as donepezil, rivastigmine and galantamine all work to increase the concentration of the neurotransmitter acetylcholine in the brain and facilitate effective communication between neurones. However, as Alzheimer Disease advances, production of acetylcholine diminishes, and therefore the potency of the cholinesterase inhibitor will similarly reduce.

Another excitatory neurotransmitter, glutamate, is also implicated in Alzheimer Disease, where it is usually present in excess concentrations leading to neuronal toxicity. This neurotoxicity is principally mediated by excessive Ca2+ entry, primarily through the N-methyl-D-aspartate (NMDA) receptors in the brain, which glutamate binds to. Memantine is a NMDA receptor antagonist that blocks the receptor, therefore reducing calcium entry through the glutamatergic pathway. Memantine tends to be reserved for moderate to severe Alzheimer Disease.

A longitudinal study of >300 affected adults with Down Syndrome and Alzheimer Disease showed that that those prescribed with anti-dementia drugs had prolonged survival compared to those not prescribed medication. The effect of medication appeared to be more pronounced in those taking cholinesterase inhibitors than memantine. Although the study was not a randomised controlled trial, the data suggests that treatment of dementia in Down Syndrome is not associated with worse outcomes than those in the general population (Eady et al. 2018).

Prognosis:

As in the general population, survival rates for people with Down Syndrome and Alzheimer Disease is longer if the diagnosis is made earlier. The mean survival after diagnosis of dementia is 4.44 years (mean age at death of 59.98 years, SD 5.98, range 46.9 – 75.0 years). However, if the diagnosis is made before the 50th birthday, the median survival increases to 4.94 years, but this reduces to a median survival of 2.56 years (95% CI 1.56 – 3.58) if Alzheimer Disease is diagnosed after the 60th birthday (Sinai et al 2018). The improved survival rate in younger patients with Down Syndrome and Alzheimer Disease, may be due to having fewer age-related medical comorbidities, the severity of learning disability, use of anti-dementia medication as well as a prior history of epilepsy.

Future Research:

There is active research into identifying and validating biomarkers associated with the development of Alzheimer Disease; the design of sensitive tools to measure changes in cognitive function before the onset of dementia symptoms; as well as alternative genes on chromosome 21 that may be implicated in dementia or influence selection for treatment. Studies are already underway, to develop and validate clinical outcome measures, with a view to using this combined knowledge to facilitate trials of treatment to prevent dementia in Down Syndrome (Horizon21 European Down Syndrome Consortium – Strydom et al. 2018).

Summary:

Adults with Down Syndrome are enjoying increasingly longer lives, and are likely to experience the same medical issues associated with older age, as seen in the general population. This article highlights some of the more common or important conditions seen, and also emphasises the need for clinicians to be aware of diagnostic overshadowing.

Our increased knowledge of Alzheimer Disease in Down Syndrome has highlighted the significant dementia burden, mediated through over expression of the APP gene on Chromosome 21. The lifetime risk of Alzheimer Disease in Down Syndrome may be as high as 90%, with a mean age of diagnosis being 55 years – due in part to the “accelerated ageing” process. Therefore, Alzheimer Disease is now the major cause of morbidity and mortality in older adults with DS, with a mean age of death of 60 years. Earlier diagnosis is associated with longer survival rates, however there are no drugs currently on the market that cure or reverse the disease process. Much work is needed to address this – particularly focused on preventative treatment modalities, but also to improve the quality of life for adults living with dementia, post-diagnosis.

Where possible, all adults should be empowered to take ownership of their own health (with appropriate support) and for them to be accessing the “Annual Health Check” offered by most GPs, with all relevant information documented in their “Health Book”. The purpose of the Health Book becomes more relevant if there are changes in care givers or home situation. Multidisciplinary support from GP, community learning disability team, carers and social care is vital to optimise the care of adults with Down Syndrome throughout adulthood.

Additional Resources

Annual Health Check https://www.nhs.uk/conditions/learning-disabilities/annual-health-checks/

Adult Health Book https://www.downs-syndrome.org.uk/download-package/health-book/ produced by the Down’s Syndrome Association.

Aging and Down Syndrome, 2017, National Down Syndrome Society http://www.ndss.org/wp-content/uploads/2017/11/Aging-and-Down-Syndrome.pdf

Health Series Down’s syndrome association (England Wales and N.Ireland)

Getting Older
https://www.downs-syndrome.org.uk/download-package/getting-older/

Dementia – Alzheimer’s Disease
https://www.downs-syndrome.org.uk/download-package/alzheimers-disease-2/

Psychiatric Morbidity in Adults with Down’s Syndrome, Prasher VP & Bansal, N. Psychiatry, Volume 2:8, August 2003 – revised for University of Hertfordshire Intellectual Disability & Health Website in 2017 http://www.intellectualdisability.info/mental-health/articles/psychiatric-morbidity-in-adults-with-downs-syndrome

Mental Health and Dementia in Adults with Down Syndrome, Annus, T et al. in Down Syndrome Current Perspectives, Mackeith 2015, edited by Richard Newton , Shiela Puri and Liz Marder

Alzheimer’s disease in Down syndrome: An overlooked population for prevention trials, Strydom, A. et al Alzheimers Dement (N Y). 2018; 4: 703–713.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6296162/

Association of Dementia With Mortality Among Adults With Down Syndrome Older Than 35 Years, Hithersay, R et al. JAMA Neurol 2019; 76 (2):152-160
https://jamanetwork.com/journals/jamaneurology/fullarticle/2714719

Impact of cholinesterase inhibitors or memantine on survival in adults with Down syndrome and dementia: clinical cohort study, Eady, N. et al Br J Psychiatry. 2018 Mar;212(3):155-160. DOI: https://doi.org/10.1192/bjp.2017.21