Alzheimer's Disease in Down Syndrome

People with Down syndrome have a higher risk of developing Alzheimer's disease.

• Alzheimer's disease (AD) is the most common form of dementia. The disease is progressive, and the brain degenerates. Alzheimer's disease is strongly associated with old age. However, it should not be considered a normal part of aging.
• Down syndrome (DS) is a genetic disorder (the chromosome abnormality is acquired at the time of conception) in which a person has extra genes because of extra chromosome 21 material. The syndrome causes delays and limitations in physical and intellectual development. The extra chromosome material can be inherited from either parent. Common characteristics of the syndrome include:
  • Low muscle tone
  • Flat face (low nasal bridge and small nose)
  • Eye openings that slant downward and inward
  • A single crease across the center of the palm
  • Smaller than normal size
  • Delay of both physical and intellectual development
• People with Down syndrome, also called trisomy 21, develop a syndrome of dementia that has the same characteristics as Alzheimer's disease that occurs in individuals without Down syndrome. The only difference is that Alzheimer's disease occurs much earlier in people with Down syndrome; patients with Down syndrome begin to have symptoms in their late 40s or early 50s.
• Most (and maybe all) people with Down syndrome develop the brain changes associated with Alzheimer's disease. However, Alzheimer's disease is not more common in individuals with intellectual disabilities from causes other than Down syndrome.
• The percentage of people with Down syndrome that have Alzheimer's disease increases with age, with a majority occurring in people older than 60. Alzheimer's disease decreases survival in people with Down syndrome who are older than 45 years of age.

The reason Alzheimer's disease is more common in people with Down syndrome is not completely known. Alzheimer's disease is associated with increased production of a compound called amyloid-beta in the brain. Amyloid-beta accumulates and causes the loss of brain cells called neurons. Exactly how neuron loss occurs is not well understood. The higher risk for Alzheimer's disease in people with Down syndrome may be related to the extra copy of chromosome 21 (which causes Down syndrome) because it leads to increased production of amyloid-beta.

The age when symptoms of Alzheimer's disease actually develop may be related to a person's mental capacity (cognitive reserve) or some anatomic characteristics of the brain. That means people with greater brain weight, more brain cells (neurons), and more education may not have symptoms of Alzheimer's disease as early as people with less cognitive reserve. People with Down syndrome may develop symptoms of Alzheimer's disease earlier in life than other people because of their increased production of amyloid-beta and their smaller cognitive reserve.

The time from the first symptoms of Alzheimer's disease to death is usually about 9 years.

In people with Down syndrome, the first symptoms usually develop at age 50 years, and the disease is usually diagnosed by age 52 years. Death occurs at an average age of 60.11 years. The time from the first symptoms of Alzheimer's disease to death is usually about 9 years.

Symptoms of the early stage of Alzheimer's disease

• The main symptoms are confusion, disorientation, and wandering. These early signs are not usually recognized and are commonly misdiagnosed.
• Behavioral changes also occur.
  • Early behavior changes that are truly related to Alzheimer's disease are often seen as an exaggeration of the person's normal traits. For example, the person may refuse to follow certain directions or to do chores because of Alzheimer's-related mental changes, but this refusal may be perceived as stubbornness.
  • Because these early changes are hard to recognize, only those familiar with the individual notice these changes. Changes can include a change in daily routine, change in sleeping or eating habits, inability to make decisions about clothing, getting lost in familiar environments, and inability to remember the names of familiar people.
  • Another early sign of Alzheimer's disease in highly functional individuals with Down syndrome is the inability to perform job duties.
• Visual problems can develop in the early stages of Alzheimer's disease. Because of these visual problems combined with the cognitive and memory deficits, individuals with Down syndrome:
  • can get lost in familiar environments,
  • may not be able to perform certain activities,
  • may have accidents and falls, and
  • may have difficulty learning new tasks.
• Learning is usually impaired, but it is difficult to demonstrate in people with greater disability related to Down syndrome.
• Other early signs include loss of language and other communication skills, impairment of social skills, and progressive loss of "activities of daily living" (ADL) (for example, personal hygiene, dining skills, bathroom skills).

Symptoms of the middle stage of Alzheimer's disease

• ADL markedly deteriorates. The patient may depend totally on others for activities such as dressing, eating, walking, and toilet needs.
• Communication is reduced.
• Any behavioral problems are usually exaggerated, and psychotic behavior may develop. Social activities are reduced to a minimum.

Symptoms of the advanced stage of Alzheimer's disease

• People with Down syndrome and advanced Alzheimer's disease seem almost to be in a coma.
• They totally depend on others and interact minimally with the environment.

Physical symptoms of Alzheimer's disease are similar to those in people without Down syndrome and include the following:

• Motor disorders may be observed in the early stage but become obvious in the middle stage of the disease. Walking becomes difficult, and in the advanced stage, the person is confined to bed and has almost no voluntary movements.
• Eating disorders may be observed at the beginning of the disease but are more obvious in the middle stage. The person has problems swallowing and frequently chokes.
• Epileptic seizures can develop.

Recognizing the early stages of Alzheimer's disease is difficult in people with Down syndrome. People with Down syndrome have a wide range of health problems as they age, and some of these may mimic or hide the presence of Alzheimer's disease. Also, the usual diagnostic tests used for the diagnosis of Alzheimer's disease in people without Down syndrome do not take into account the existing disabilities of the person with Down syndrome. Many people with Down syndrome cannot be evaluated by standard psychological tests. Finally, some people with Down syndrome have limited verbal and other communication skills that may make assessment difficult. For these reasons, the methods used for testing for Alzheimer's disease in people without Down syndrome (for example, Mini-Mental Status Examination) are unreliable in people with Down syndrome.

Tests for Alzheimer's disease in people with Down syndrome

Several clinical tools have been designed that are more appropriate for diagnostic use in people with Down syndrome. Many of these tests focus on changes related to a decline in activities of daily living (ADL) such as eating, dressing, and bathing. Most of this information can be obtained by interviewing relatives or caregivers. The following are some tests appropriate for people with Down syndrome:

• Alzheimer's Functional Assessment Tool - Useful for follow-up
• Dementia Scale for Down syndrome (DSDS) - Useful for screening, especially in the middle or late stage of Alzheimer's disease
• The Dementia Questionnaire for Mentally Retarded Persons - Useful for screening for Alzheimer's disease

The medical work-up for the diagnosis of Alzheimer's disease, that is, blood tests and neuroimaging studies (CT scan, MRI), is the same as for individuals without Down syndrome. The three tests mentioned above are questionnaires or scales to assess or document the evolution of dementia. Blood tests may be obtained to rule out certain other causes of dementia, such as infection, metabolic disorders (like thyroid imbalance), or medication effects.

There is no cure for Alzheimer's disease. The disease progresses and becomes worse, despite treatment. The medications listed below have been used for or found to be useful to slow Alzheimer's disease progression, but few studies have been done with donepezil (Aricept) and rivastigmine (Exelon), in individuals with Down syndrome; and it is not clear how useful these drugs are in persons with Down syndrome. For more information on these medications see Alzheimer's Disease Medications.

Medical treatment is directed toward treating the signs and symptoms of dementia or treating coexisting behavioral changes such as psychosis, anxiety, or depression.

Two types of drugs have been studied enough to gain approval by the United States Food and Drug Administration (FDA) and may provide modest improvement.

• Acetyl cholinesterase (AChE) inhibitors, such as tacrine (Cognex), donepezil (Aricept), galantamine (Reminyl), and rivastigmine (Exelon)
• N-methyl-D-aspartate (NMDA) blockers, such as memantine (Namenda, Axura)

Treatment for coexisting behaviors may include antipsychotics, antidepressants, or antianxiety drugs. Data continue to emerge regarding other potential drugs that may treat or decrease the risk of developing dementia. For a complete discussion of medications for dementia, see the article Dementia Medication Overview.

This is a summary of scoring for the Alzheimer's Functional Assessment Tool. This tool can be used to document the progression of the symptoms, and it can also be helpful to evaluate the usefulness of any drug treatment or behavioral intervention. It is not intended to make the diagnosis of Alzheimer's disease.

Toileting

1. Can use the bathroom in familiar and unfamiliar environments independently
2. Goes to the toilet independently or asks for assistance; may need reminders to use toilet paper and wash hands
3. Has occasional toileting accidents; needs verbal reminders
4. Needs assistance going to the bathroom on a schedule (does not go to the bathroom independently); remains continent 90% of the time
5. Needs assistance going to the bathroom on a schedule (does not go to the bathroom independently); remains continent 50% of the time or less
6. No bowel or bladder control; may require frequent changing or special clothing (for example, pads, diapers)

Dining

1. Can prepare simple food (for example, sandwich, toast), can set table and clean up after a meal, uses knife and fork to cut food, may or may not use adaptive equipment to eat independently
2. Can use fork and spoon to eat independently but needs food to be cut
3. Eats independently with the help of adaptive equipment
4. Can use fork and spoon to eat independently but may need occasional prompts to start or continue eating, may finger feed, needs food to be cut
5. Needs physical assistance to complete the meal
6. Develops swallowing problems, needs change in consistency of food or thick drinks
7. Completely dependent on assistance, may need specialized feeding program

Walking/motor

1. Independent walking (ambulation), able to walk steadily, able to start-stop - and change direction without falling, able to walk fast or run, able to ascend and descend stairs, capable of leaving premises without assistance
2. Independent ambulation for short distances walks up and down the stairs one step at a time by holding rails, able to leave premises without assistance
3. Independent but cannot go up or downstairs, unable to leave premises without assistance
4. Can walk without support but requires supervision, may be unsteady, requires supportive measures at times
5. Needs assistance (for example, another person to hold, a walker) to walk, "cruises" around using structures such as furniture and walls as support, unable to leave premises independently
6. Needs a wheelchair but can move independently
7. Needs an adapted wheelchair and cannot move independently, needs to be pushed

Bathing

1. Can independently carry out an appropriate bathing routine (disrobing, washing, drying, and dressing)
2. Can carry out an appropriate bathing routine with occasional reminders to do a step or wash more thoroughly
3. Needs verbal prompts to initiate and/or complete some steps in the bathing process (because of low-level confusion and/or fear), continuous staff supervision at shower time is not necessary, may use toiletries inappropriately
4. Requires continuous staff supervision at shower time to ensure complete bathing and safety (for example, problems due to confusion and/or fear), hand-over-hand assistance may be necessary at times, alternatives to showering or a specialized program may be recommended because of fear of showering, safe use of hot and cold water needs monitoring
5. Primarily passive during bathing, requires some form of assistance for all steps, may be able to stand and move a body part when given a verbal or touch cue, fear of water may be present
6. Physically and cognitively unable to participate actively in the bathing process, may respond to stimulation during bathing with vocalizations or changes in facial expressions

Dressing (skills and appropriate dress)

1. Dresses independently or with physical assistance due to handicap can choose appropriate clothing (for weather or activity of the day) and cares for own clothing (for example, places dirty clothes in the hamper, hangs clothing, stores properly)
2. Occasionally needs reminders to dress appropriately ("It's cold out today") and to care for clothes ("Remember where your dirty socks go?")
3. Dresses with minimal assistance or verbal prompts
4. Dresses inappropriately for the weather (layers clothing and/or puts clothing on inappropriately), may undress at an inappropriate time and/or place may benefit from adaptive clothing to retain dressing skills; makes no attempt to care for own clothing
5. Needs assistance in dressing (50% or more of task) and may be resistive; may assist when compliant (for example, puts an arm through sleeve)
6. Lies passively during dressing; does not respond to dressing or undressing

Personal/oral hygiene (hair brushing, teeth brushing, sanitary pad, shaving)

1. Able to perform all personal hygiene tasks
2. Able to perform all personal hygiene tasks within regular routines, may show difficulty in performing tasks if the routine is changed (for example, hospitalized, moved)
3. Able to perform all personal hygiene tasks but requires occasional reminders from staff to complete the task
4. Able to perform personal hygiene tasks but requires frequent reminders from staff to complete the task, may need staff guidance (verbal and point cues) in some parts of some tasks (for example, may forget steps), may still be proficient in one area and lose ability in another area
5. Requires staff supervision (verbal and point cues) to complete some personal hygiene tasks and staff assistance (light, moderate physical cues) to complete others
6. May still be able to perform some steps of some personal hygiene tasks with staff assistance but depends on staff to meet other personal hygiene needs
7. Depends on staff to meet all personal hygiene needs

Environmental awareness

1. Aware (cognizant) and responsive, in a relevant way, to familiar and unfamiliar people and other environmental stimuli
2. Generally responsive to familiar and unfamiliar people and situations but seems self-absorbed and/or confused most of the time
3. Cognizant and responsive in a relevant way too familiar people and situations but shows a delayed or inappropriate response to unfamiliar people and situations
4. Cognizant and responsive to stimuli, but the response is often inappropriate, even in familiar situations
5. Mostly awake but seems self-involved, showing little or inconsistent response to the environment
6. Sometimes awake but shows little interest in surroundings, sleeps at other times
7. Sleeps most of the day, needs to be aroused repeatedly to maintain interaction