Alzheimer Disease in Individuals With Down Syndrome

Alzheimer disease (AD) is the most common form of dementia (see Dementia Overview for more information). The disease is progressive, and the brain degenerates (see Alzheimer Disease). Alzheimer disease is strongly associated with old age. However, it should not be considered a normal part of aging. The symptoms progress, and the disease is associated with changes of the brain (neuropathologic changes).

Down syndrome (DS) is a genetic disorder (you have it from birth) 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 downwards and inwards
  
  
• Single crease across the centre 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 of the Alzheimer disease that occurs in individuals without Down syndrome. The only difference is that Alzheimer 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 disease. Alzheimer disease is not more common in individuals with mental retardation from other causes. An estimated 10-25% of patients with Down syndrome have Alzheimer disease at age 40-49 years, 20-50% have Alzheimer disease at age 50-59 years, and 60-75% have Alzheimer disease when older than 60 years. Alzheimer disease decreases survival in people with Down syndrome who are older than 45 years, but not every person with Down syndrome will develop symptoms of Alzheimer disease, even if the brain changes of Alzheimer disease occur.

The reason Alzheimer disease is more common in people with Down syndrome is not completely known. Alzheimer disease is associated with increased production of a compound called amyloid beta in the brain. Amyloid beta accumulates and causes loss of brain cells called neurons. Exactly how neuron loss occurs is not well understood. The higher risk for Alzheimer 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 disease actually develop may be related to a person’s mental capacity (cognitive reserve). That means people with greater brain weight, more brain cells (neurons), and more education may not have symptoms of Alzheimer disease as early as people with less cognitive reserve. People with Down syndrome may develop symptoms of Alzheimer disease earlier in life than other people because of their increased production of amyloid beta and their smaller cognitive reserve.

Recognizing the early stages of Alzheimer 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 disease. Also, the usual skill tests used for diagnosis of Alzheimer 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 disease in people without Down syndrome (eg, Mini Mental Status Examination) are unreliable in people with Down syndrome. 

Tests for Alzheimer disease in people with Down syndrome

Several tests have been designed that are more appropriate 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 Functional Assessment Tool - Useful for diagnosis and follow-up
  
  
• Dementia Scale for Down Syndrome (DSDS) - Useful for screening, especially in the middle or late stage of Alzheimer disease
  
  
• The Dementia Questionnaire for Mentally Retarded Persons - Useful for screening for Alzheimer disease

Other tests for Alzheimer disease in people with Down syndrome, such as CT scanning and MRI, are the same as in people without Down syndrome. Blood tests may be obtained to rule out certain other causes of dementia, such as infection, metabolic disorders (like thyroid imbalance), or medication effects (see Alzheimer Disease).

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 disease to death is usually about 9 years.

• Symptoms of the early stage of Alzheimer 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 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-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 change in daily routine, change in sleeping or eating habits, inability to make clothing decisions, getting lost in familiar environments, and inability to remember the names of familiar people.
      
      
    • Another early sign of Alzheimer 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 disease. Because of these sight problems, individuals with Down syndrome can get lost in familiar environments, they may not be able to perform certain activities, they may have accidents and falls, and they 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 ADL (eg, personal hygiene, dining skills, bathroom skills).
    
    
• Symptoms of the middle stage of Alzheimer disease
  
  
  • ADL markedly deteriorate. 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 disease
  
  
  • People with Down syndrome and advanced Alzheimer disease seem almost to be in a coma.
    
    
  • They totally depend on others and interact minimally with the environment.

Physical symptoms of Alzheimer 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.

There is no cure for Alzheimer 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 disease progression, but only one (donepezil) was evaluated in individuals with Down syndrome.

Medical treatment is directed toward treating dementia, treating coexisting behavioral changes such as psychosis, anxiety, or depression, and evaluating the benefit other therapeutic interventions. 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 continues to emerge regarding other potential drugs that may treat or decrease the risk of developing dementia. For a complete dementia medication discussion, see Dementia Medication Overview. 

This is a summary of scoring for the Alzheimer Functional Assessment Tool.

• Toileting
  
  
  1. Can use 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 (eg, pads, diapers)
  
  
• Dining
  
  
  1. Can prepare simple food (eg, sandwich, toast); can set table and clean up after 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 down stairs; 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 (eg, another person to hold, walker) to walk; "cruises" around using structures such as furniture and walls as support; unable to leave premises independently
     
     
  6. Needs 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 not necessary; may use toiletries inappropriately
     
     
  4. Requires continuous staff supervision at shower time to ensure complete bathing and safety (eg, 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 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 (eg, places dirty clothes in 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 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 (eg, puts 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 routine is changed (eg, 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 (eg, 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 to familiar people and situations but shows a delayed or inappropriate response to unfamiliar people and situations
     
     
  4. Cognizant and responsive to stimuli, but 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

Alzheimer’s Association
919 North Michigan Avenue, Suite 1100
Chicago, IL 60611-1676
(800) 272-3900
 
Alzheimer’s Disease Education & Referral Center
P.O. Box 8250
Silver Spring, MD 20907-8250
(301) 495-3311
(800) 438-4380
 
Alzheimer’s Information, Fisher Center for Alzheimer’s Research Foundation
(800) 259-4636
 
 Family Caregiver Alliance, National Center on Caregiving
(800) 445-8106

|Web Links|

Alzheimer’s Association

Alzheimer’s Disease Education & Referral Center, National Institute on Aging, National Institutes of Health

Alzheimer’s Information Site, Fisher Center for Alzheimer’s Research Foundation

Family Caregiver Alliance, National Center on Caregiving

National Institute on Aging, National Institutes of Health

National Institute of Neurological Disorders and Stroke, National Institutes of Health, NINDS Alzheimer's Disease Information Page

Better Health Channel, Down syndrome and Alzheimer's

Familydoctor.org, Down Syndrome in Adults: Staying Healthy

Alzheimer’s Disease and Down Syndrome

Media file 1: A brain in Alzheimer disease.

Media type:  Illustration

Alzheimer disease in individuals with Down syndrome, Alzheimer's, Alzheimer dementia, presenile dementia, dementia presenilis, primary neuronal degeneration, primary senile dementia, trisomy 21, trisomy 21 syndrome, Down's syndrome, DS, mental retardation, activities of daily living, ADLs, acetylcholine, AD, Alzheimer disease, Alzheimer's disease, amyloid protein, apoE, apolipoprotein E, caregiver, caregiving, cholinesterase, cognitive disorder, degenerative brain disease, minimal cognitive impairment, senile dementia, senile plaques, dementia, neurofibrillary tangles, neurotransmitter, mild cognitive impairment, memory loss, glutamate, dementia medications

Author: Norberto Alvarez, MD, Medical Director, Shriver Clinical Services Corporation; Assistant Professor, Department of Neurology, Boston Children's Hospital, Harvard Medical School.

Coauthor(s): Jessica B Johnson, Medical Writer, .com, Inc.

Editors: Nicholas Y Lorenzo, MD, Chief Editor, Neurology; Consulting Staff, Neurology Specialists and Consultants; Mary L Windle, Pharm D, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Pharmacy Editor, .com, Inc; Helmi L Lutsep, MD, Associate Director, Oregon Stroke Center; Associate Professor, Department of Neurology, Oregon Health and Science University.