There are 329 genes predicted to be on chromosome 21. Sixteen of these genes play a role in mitochondrial energy metabolism or the generation of free radicals. Abnormalities in these genes are thought to lead to increased free radical production, leading to premature ageing.

At least 10 genes on chromosome 21 play a role in brain development and neuronal loss. Two of these are associated with Alzheimer’s disease, namely the amyloid precursor protein and the S100 calcium-binding protein. Overproduction of amyloid precursor protein and, thus, β-amyloid, is thought to play a key role in the early onset of Alzheimer’s disease in persons with Down syndrome. In addition, excess production of β-amyloid has been shown to lead to problems with learning and memory, which may contribute to the cognitive problems seen in persons with Down syndrome.

There are six genes that are involved in folate and methyl group metabolism on chromosome 21. Elevated levels of homocysteine, which are seen in folate deficiency, are associated with Alzheimer’s disease. In our clinical experience, elevated homocysteine levels are not rare in younger adults with Down syndrome.

Older persons with Down syndrome are usually easily recognized when they present to the physician, because of the classical facial features (brachycephaly, epicanthal folds and flat nasal bridge) and short stature. These persons also often have broad hands, lax ligaments and a wide gap between the first and second toes, brachydactyly and mental retardation. The majority of persons with Down syndrome live in the community. They may live in group housing and work in sheltered workshops. Physicians need to identify the person who accompanies the individual with Down to the office. This person often provides supervisory care for the individual with Down syndrome and can provide useful historical information on behavioural and other changes that may be occurring. We recommend office visits every 6 months for healthy persons with Down syndrome and every 3–4 months when functional or mental decline is present. This allows the patient to become comfortable with the healthcare provider. Many patients enjoy hugging and this can further increase trust in the physician. However, the physician must remember to ask the patient first if they wish to hug. The physician should always discuss the patient’s work and how it is progressing. Also, note should be made of their recreational activities and how they are interacting with other persons within a group home. The quality of life of all patients should be assessed by probing multiple areas such as ‘things you do, your family and friends, your self-image, your leisure time, your employment and help you need’ before exploring the person’s health issues.

Always address the person with Down syndrome directly, before hearing the caregiver’s story. This gains their confidence and allows observation of their language ability. Finally, never assume that changes in persons with Down syndrome are due to the condition itself before excluding other common medical causes. Problems with spatial memory are classical of Down syndrome and so should not be used in the diagnosis of Alzheimer’s disease.3 Aerobic exercise programmes may help improve both psychosocial and physical health.4

For some medical examinations, such as pap smears, and special tests, such as MRI or CT scan, or procedures such as dental care, persons with Down syndrome may require sedation. We have found that 0.5–1 mg of lorazepam orally is usually sufficient for this purpose and produces no adverse effects. Low-dose intravenous lorazepam can also be used in more difficult situations. Others have recommended oral ketamine and midazolam, given under the supervision of an anaesthetist.5 Before undergoing a procedure requiring sedation, a risk–benefit evaluation should always be undertaken. Informed consent needs to be obtained from the patient or, where applicable, the court-appointed guardian.

Preventive measures for Down syndrome patients should be similar to those for the general adult population. This includes screening for hypertension and heart disease. Because obesity is a common problem in this population, regular counselling on the need for exercise is mandatory. Although, in our experience, most Down syndrome patients do not smoke or drink alcohol, this should be confirmed both from the patient and the caregiver.

Down syndrome adults tend to complain of pain, even when present, less often than other persons. Therefore, it is important to utilize facial expressions during the examination to obtain input concerning presence of pain. Also, such patients may stop using a limb when it is painful. Rocking and ‘head banging’ behaviours occur as visceral pain proxies. As is the case with older adults, middle-aged adults with Down syndrome often manifest medical problems as a delirium or other behavioural problem.

Persons with Down are a vulnerable population and therefore, like children and older people, are at increased risk for abuse. When adults with Down syndrome become withdrawn, this may suggest abuse or an unrecognized pain syndrome or depression. The presence of unexplained bruises, skin tears or fractures must increase the physician’s suspicion of abuse. New-onset falls can suggest delirium, functional deterioration or abuse.

Health counselling includes decisions on advanced directives and guardianship. Financial support questions need to be addressed and relatives need to be aware of local resources. Estate planning, for example trusts, need to be created where appropriate, as Down syndrome persons are now regularly outliving their parents and other close relatives. Parent (caregiver) support groups can be invaluable as caregiver stress is common, particularly as the parent ages. Local and national societies for Down syndrome or for persons with developmental disabilities are an important resource. The physician needs to look for excess stress and/or depression in caregivers and advise treatment where appropriate.

Functional ability using at least basic activities of daily living (ADLs) and instrumental activities of daily living (IADLs) should be assessed yearly. Where possible, mental status screening using the Mini Mental Status Examination (MMSE) or the Saint Louis University Mental Status Examination and the Geriatric Depression Scale or the Cornell Depression Inventory should be done yearly.