Down Syndrome and Alzheimer’s 

About

Down syndrome, also known as trisomy 21, is a genetic condition in which individuals are born with an additional copy of chromosome 21. This extra genetic material affects the development and health of individuals with Down syndrome. Learning, language, and memory are commonly affected, but the severity varies among individuals. Additionally, individuals with Down syndrome often experience other health issues such as heart defects, musculoskeletal problems, and sensory impairments. Researchers are actively studying the mechanisms by which the extra copy of chromosome 21 leads to these challenges.

As people with Down syndrome live longer and experience improved quality of life, another health risk emerges: a significantly increased likelihood of developing dementia that closely resembles or matches Alzheimer’s disease.

Autopsy studies have shown that nearly all individuals with Down syndrome have notable levels of beta-amyloid plaques and tau tangles in their brains, which are hallmark characteristics of Alzheimer’s disease. However, not all individuals with Down syndrome exhibit symptoms of Alzheimer’s.

Researchers are striving to understand why some individuals with Down syndrome develop dementia while others do not. Similarly, they are investigating why some individuals without Down syndrome exhibit brain changes associated with Alzheimer’s but do not develop symptoms of the disease.

Prevalence

The risk of developing Alzheimer’s disease increases with age for all individuals, including those with Down syndrome. According to the National Down Syndrome Society, approximately 30% of individuals with Down syndrome in their 50s have Alzheimer’s dementia, and this percentage rises to around 50% for individuals in their 60s.

Causes and Risk Factors

Scientists believe that the increased risk of dementia in individuals with Down syndrome is attributed to the additional genes present in chromosome 21. One gene of particular interest in the connection between Down syndrome and Alzheimer’s is the amyloid precursor protein (APP) gene.

While the function of APP is not fully understood, researchers have observed that daily brain activity involves the continuous processing of APP, which results in the production of beta-amyloid. Beta-amyloid is a fragment that plays a crucial role in the formation of plaques and is considered a primary contributor to Alzheimer’s-related brain changes. The presence of an extra copy of the APP gene in individuals with Down syndrome may lead to increased beta-amyloid production, triggering the cascade of events associated with Alzheimer’s.

The APP gene is also associated with rare inherited forms of Alzheimer’s disease. Specific variations in the chemical code of the APP gene guarantee the development of Alzheimer’s when inherited. However, these variations are extremely rare and are not commonly found in individuals with Down syndrome.

The strong connection between APP and Alzheimer’s through two different mechanisms – one involving an extra copy of the gene and the other involving specific variations in its chemical code – underscores the importance of studying the intersection of Down syndrome and Alzheimer’s.

Symptoms

In individuals with Down syndrome, changes in overall function, personality, and behavior are often early signs of Alzheimer’s, rather than memory loss and forgetfulness.

Early symptoms may include:
• Reduced interest in socializing, conversing, or expressing thoughts.
• Decreased enthusiasm for regular activities.
• Decline in attention span.
• Feelings of sadness, fear, or anxiety.
• Irritability, uncooperativeness, or aggression.
• Restlessness or sleep disturbances.
• Adult-onset seizures.
• Changes in coordination and gait.
• Increased excitability or vocalization

 

Diagnosis

Diagnosing dementia in individuals with Down syndrome can be challenging due to the difficulties in assessing changes in thinking skills in individuals with intellectual disabilities. Most adults with Down syndrome do not self-report concerns about memory.

To ensure a person-centered diagnosis in individuals with Down syndrome, experts recommend the following principles:
• Establish a baseline of adult function by age 35. Detailed information on an individual’s adult abilities should be documented in their medical record by this age. The person with Down syndrome, family members, and reliable sources can provide valuable information.
• Observe changes in day-to-day function. Reduced enthusiasm for daily activities, loss of interest in social interactions, and changes in personality and behavior are often early indicators of declining thinking skills.
• Consider professional assessment by a dementia expert. Various cognitive tests are available for evaluating thinking changes in adults with Down syndrome, but it is important not to rely solely on these tests for diagnosing dementia.
• Rule out other possible causes. It is essential to investigate and eliminate other medical conditions commonly associated with Down syndrome that may cause changes in thinking and function, such as thyroid problems, depression, chronic infections, vision loss, and sleep apnea.

Prognosis

Despite advancements in quality of life and lifespan for individuals with Down syndrome, their average lifespan is still shortened compared to the general population. Individuals with Down syndrome typically experience an earlier onset of age-related conditions, including Alzheimer’s disease. On average, individuals with Down syndrome live to around 60 years, with some living into their seventies or even eighties, albeit rarely.

Outcomes and Treatment

Currently, the U.S. Food and Drug Administration (FDA) has not approved any drugs specifically for treating dementia associated with Down syndrome. In the United Kingdom, cholinesterase inhibitors, which are approved for Alzheimer’s treatment in several countries, are also approved for treating dementia in people with Down syndrome. However, conclusive evidence regarding the benefits of cholinesterase inhibitors in individuals with Down syndrome is lacking.

A randomized trial has shown no benefit of the Alzheimer’s drug memantine in adults with Down syndrome. Further research and clinical studies are necessary to identify effective treatments for dementia in individuals with Down syndrome. Caution is advised when considering medications not specifically tested for safety and effectiveness in this population due to potential differences in how individuals with Down syndrome metabolize drugs.