By Elizabeth Head, Ph.D. and Frederick Schmitt, Ph.D., University of Kentucky
People with Down syndrome are living long, productive and healthy lives. However, although many people remain healthy as they get older, there is an increasing risk for developing Alzheimer’s disease. In people with Down syndrome, this risk is much higher because of the extra copy of a gene for the amyloid precursor protein on chromosome 21. Alzheimer’s disease is the most common form of dementia in the elderly and the earlier one is diagnosed, the more options are available for managing symptoms of the disease. The good news is, not everyone with Down syndrome will develop dementia even in their later years. Our goal is to identify ways to help people with Down syndrome age gracefully and enjoy their older years.
There are several approaches being proposed and tested in clinical studies. These include pharmacological interventions, vaccines and modifying risk factors for Alzheimer’s disease. One of the best ways to keep the brain functioning optimally is a healthy lifestyle. By doing this, many of the risks associated with developing Alzheimer’s disease (examples are diet, obesity, cardiovascular problems, diabetes) can potentially be modified to reduce the impact that genetics have on developing the disease. There is an abundance of information from studying aging and the risk of Alzheimer’s disease in people without Down syndrome suggesting several consistent findings. We hope in future that some of these most promising lifestyle changes can be encouraged in older adults with Down syndrome.
A healthy diet, rich in fruits and vegetables that contain lots of antioxidants is associated with a reduced risk of developing Alzheimer’s disease. It is interesting to note that eating well provides greater benefits than taking supplements or higher doses of vitamins, which may be associated with side effects. There is also solid evidence suggesting that a Mediterranean diet (including foods like fruits, vegetables, nuts and grains) also appears to lower risk of disease. A healthy diet may be particularly beneficial for people with Down syndrome as several genes on chromosome 21 can lead to higher levels of oxidative stress in the brain, which is modifiable with a diet rich in antioxidants. Benefits of antioxidants may be greater when ingested in food as studies looking at the effects of antioxidant supplements in older people with Down syndrome leads to limited if no improvements in function. It is useful to think that many antioxidants interact and recycle each other leading to a greater impact. The best way to do this is by diet.
Physical exercise is another lifestyle habit that can lead to tremendous benefits both for the heart and for the brain. Indeed, a healthier heart is also strongly linked to a healthier brain. Physical exercise can also promote a healthy body weight, which is ideal given recent studies that higher body mass index is associated with a higher risk of type II diabetes, which in turn is associated with higher risk of Alzheimer’s disease. A recent study suggests that extra weight in midlife may lead to an earlier age of onset of Alzheimer’s disease. Walking, running, playing sports, dancing and strength training all come with tremendous benefits to brain health. There are several studies in younger people with Down syndrome showing benefits to function with the use of an exercise program. Although no studies have been done in older people, we know from research in other groups of older people and in animal models that exercise can lead to increased levels of growth molecules in the brain, which in turn, support the health of cells in the brain. Another good side effect of physical exercise is that improving cardiovascular function can lead to better blood flow to the brain. Your brain uses the most oxygen of the entire body and providing more blood that carries oxygen to the brain can lead to healthier neurons and better cognition.
Using your brain! The more active your brain is, the greater your protection from Alzheimer’s disease. Published reports suggest that activities like reading, playing games, solving puzzles, cognitive training all can slow the development of Alzheimer’s disease or reduce risk. The brain responds to cognitive training by growing more connections, growing new neurons and releasing growth molecules that keep neurons in the brain working well.
Keeping socially active also appears to be protective against Alzheimer’s disease and associated with healthy brain aging. People who have lots of friends, interact frequently with friends and family, are engaged in social groups (e.g. church) tend to have less of a risk for developing disease and also have a fuller, richer life as they get older. The molecular benefits in the brain of social enrichment have not been well characterized but often times being socially active are also associated with physical exercise and cognitive engagement, both of which can improve brain function.
Given the higher prevalence of obesity in Down syndrome along with orofacial anatomical variations, it is not surprising that the frequency of obstructive sleep apnea is also high. The incidence of obstructive sleep apnea (OSA) in children 2 to 4 years of age with Down syndrome is 57% based on polysomnography alone in one study and was shown to increase to 80% when the criterion also included an arousal index that was found to be elevated in 61% of the children who were evaluated. In some studies, the frequency of OSA can be as high 94% with people with Down syndrome showing varying levels of OSA severity with 69% in the severe range based on their apnea-hypopnea index. Interestingly, different studies report either a negative or a positive association between OSA and age and similarly with body mass index. There can be a significant impact of OSA on cognition both in childhood that extends to the older years in Down syndrome that could adversely affect brain aging. Repeated episodes of depriving the brain of oxygen can lead to problems with a part of the brain called the hippocampus, which is critically involved with memory. Thus, OSA is a risk factor that can be modified to the benefit of the brain.
Pharmacological interventions to slow or prevent Alzheimer’s disease in people with Down syndrome are also either actively being tested or have been proposed. For example, because of the extra copy of chromosome 21, there is too much of the amyloid precursor protein being made in Down syndrome. This amyloid precursor protein gets cut into smaller pieces called beta-amyloid peptide that leads to plaques in the brain and is thought to be a cause of Alzheimer’s disease. We may be able to clear this beta-amyloid protein and plaques using a vaccine. Perhaps it will be possible to reduce or prevent plaques in the brain by administering medicines that slow down the production of the beta-amyloid peptide from being cut from the amyloid precursor protein. These are still unanswered questions that require systematic clinical trials once we know that they are safe to test. Indeed, people with Down syndrome may be more vulnerable to some adverse effects of vaccines or drugs that may slow or halt Alzheimer’s disease because of additional genes on chromosome 21 that involve factors such as inflammation (involved with our responses to vaccines), and pathways that involve other molecules that are not the targets of the drug. We cannot necessarily assume that Alzheimer’s disease in people with Down syndrome is identical to sporadic Alzheimer’s disease, which may be why some of the clinical trials in Down syndrome have led to modest or no benefits to cognition. This is a key point that families, clinicians and researchers need to consider when identifying ways in which to provide interventions for healthy brain aging in adults with Down syndrome.
For our friends and family members with Down syndrome, the future is looking brighter every day. Although we may as yet, not have a treatment for Alzheimer’s disease, simple lifestyle changes that can be introduced slowly may have a powerful impact on when and if a person will develop Alzheimer’s disease.