People with Down’s syndrome or trisomy 21 (a genetic disorder causing mental retardation in which there are 3 copies of chromosome 21 instead of the normal 2 copies) are at greater risk of developing a dementia that is like Alzheimer’s disease as early as 30 years of age. In fact, the neuropathologic findings related to Alzheimer’s disease have been described in all Down’s syndrome individuals older than 35, yet not everyone with Down’s syndrome develops the accompanying clinical symptoms needed for a diagnosis of dementia.
Alzheimer’s disease is a progressive degenerative disease of the brain that causes the most common form of dementia, and is strongly associated with advanced age. However, Alzheimer’s disease should NOT be considered a part of the normal aging process.
Scientific studies of people with Down’s syndrome find the risk of developing an Alzheimer’s-like dementia doubles with each 5-year interval after age 30, and range from 10-25% when aged 40-49 years, 20-50% when aged 50-59 years, 60-75% when older than 60, and close to 100% in people with Down’s syndrome who are older than 70. Therefore, the average age of onset of Alzheimer’s-like dementia is considerably younger in the Down’s syndrome population, and it appears to be independent of living arrangement, degree of mental retardation and gender. However, there is a subset of Down’s syndrome individuals who do NOT appear to develop Alzheimer’s-like dementia, even in old age.
People with Down’s Syndrome Are More Susceptible to Common Health Problems
It has been known for many years that people with Down’s syndrome are more susceptible to common health problems such as obesity, cataracts, and congenital heart conditions. In addition, with aging, people with Down’s syndrome are more susceptible to thyroid and cardiovascular dysfunction, skeletal problems such as osteoporosis, arthritis and muscular disorders, and depression (this process of early aging is referred to as “precocious aging”).
Life Expectancy and Down’s Syndrome
For the majority of human history, people with Down’s syndrome died at an early age, and in the 1920s, life expectancy for people with Down’s syndrome was just 9 years. This increased to 12 years by 1949 and 35 years of age by 1985. Now, people with Down’s syndrome, live an average of 55 years or more; so, their increased life span has increased their susceptibility to conditions that are associated with aging, including Alzheimer’s disease.
People with Down’s syndrome Have Increased Levels of B-amyloid in the Brain
Interestingly, people with Down’s syndrome have increased levels of B-amyloid in the brain, with deposits of B-amyloid in the cerebral cortex beginning as early as age 8, and these B-amyloid deposits increase with age. It is thought that this B-amyloid forms senile plaques that cause Alzheimer’s disease.
Anatomical and Chemical Differences in the Brains of People with Down’s Syndrome
People with Down’s syndrome have anatomical and chemical differences in their brains compared to persons without Down’s syndrome. For example, people with Down’s syndrome already have a reduced brain volume, especially in the hippocampus, and people with Down’s syndrome have other developmental abnormalities, such as reduced dendritic arborizations, and abnormalities of pyramidal neurons. Therefore, it is not difficult to see that the dementia associated with Down’s syndrome is NOT an exact biological replica of Alzheimer’s disease, and Down’s syndrome dementia is often considered by many researchers as a different entity.
Mental Retardation and Alzheimer’s-like Dementia
Individuals with mental retardation from causes other than Down’s syndrome do NOT have Alzheimer’s-like dementia more commonly than individuals without mental retardation. Also, mental retardation is universally seen in Down’s syndrome, but the development of Alzheimer’s-like dementia in people with Down’s syndrome appears to be unrelated to the degree of mental retardation.
Amyloid Precursor Protein Gene is on Chromosome 21
All recognized mutations for Alzheimer’s disease are associated with increased deposition of B-amyloid, a peptide fragment from 39-43 amino acids long, which are products of the catabolism of the amyloid precursor protein (APP) molecule. The discovery that the amyloid precursor protein gene is on the 21st chromosome led to the hypothesis that the early and universal development of Alzheimer’s disease-like pathology in people with Down’s syndrome is due to a third copy of the amyloid precursor protein gene (one on each of the three copies of chromosome 21).
Superoxide Dismutase Gene is on Chromosome 21
There are several other genes that might play a role in the development of Alzheimer’s disease-like pathology that are found on chromosome 21. Among them are superoxide dismutase genes important in the production of hydrogen peroxide (H 2 O 2 ), a potentially toxic metabolite that causes cell death. The excess activity of superoxide dismutase is not limited to the brain and has also been observed in erythrocytes, B and T lymphocytes, and fibroblasts of people with Down’s syndrome. Therefore, an alternative hypothesis suggests that increased oxidative stress leads to structural damage to the membranes and DNA of brain cells.
Symptoms of People with Down’s Syndrome and Dementia
The symptoms of people with Down’s syndrome and dementia include: memory and weight loss, apathy, personality changes, loss of conversation skills, poor mobility and increasing dependency on others in activities of daily living. People with Down’s syndrome and dementia show a higher prevalence of mood changes, overactivity, auditory hallucinations, disturbed sleep, and less aggression than people who have dementia alone. 84% of people with Down’s syndrome develop epilepsy (seizures) in the later stages of their Alzheimer’s-like dementia.