2016 Global Research & Medical Care Roundtable Q&A

Down Syndrome and Alzheimer’s Disease questions

  1. What is the latest update regarding the link between Down syndrome and Alzheimer’s?

    It continues to be clear that people with Down syndrome begin to develop Alzheimer’s amyloid deposits in their brain in the teenage years, which progresses through the 20’s and 30’s such that by the age of 40 they have the full apology of Alzheimer’s disease including plaques, tangles, inflammation, and nerve cell loss. Interestingly some 32 is much as possibly 40% of people with down syndrome do not develop Alzheimer’s disease like dementia by the age of 60 suggesting that some may be partially protected from the clinical manifestations of the brain pathology. Current research is directed at understanding how to recognize Alzheimer’s disease development early in both typical people and people with Down syndrome, how to prevent the development of dementia and pathology and hopefully how to reverse them once they have been established.

  2. What new research has potential to help people with Down syndrome not get Alzheimer’s disease?

    Thus far no new drugs have been approved by the FDA for the treatment of Alzheimer’s disease either in typical people or in people with Down syndrome. However several clinical trials are currently underway to test new drugs that may achieve this goal. We expect the results of some of these trials within the next few years and the approval process may take a few years more.

  3. Is Alzheimer’s disease the same in people with DS as in typical people?

    Yes, the biochemical and clinical features of Alzheimer’s disease in people with Down syndrome appears to be the same as in people with typical age-related Alzheimer’s disease and therefore it is expected that any treatments that will be appropriate for one population will also be appropriate for the other.

  4. What are some of the signs of early Alzheimer’s in people with DS and is there anything that can deter it?

    Unfortunately, it is not now possible to clearly deter the development of Alzheimer’s disease in people with Down syndrome, but as indicated above there are clinical trials of new treatments that may be successful. It is likely, as has been found in animal models and in typical people with mild cognitive impairment, that exercise may delay the development of symptoms but the mechanism is still unclear and it cannot be considered a true sure.

  5. How can you detect Alzheimer’s in a person with DS?  Is there such a thing as early detection?

    The pathology of Alzheimer’s disease that occurs in the brain in the form of for example amyloid deposits can be detected early in people with Down syndrome by an experimental technique called a PET brain scan. However this is quite expensive and is not approved for general use. Furthermore it only detects the amyloid deposits and cannot predict when or if a person will develop Alzheimer’s disease clinical symptoms. Several laboratories around the world are working to develop a blood test that may provide an early diagnosis or at least an indication of increased risk of developing dementia, but thus far such investigations have not provided a definitive result.

  6. How can you tell the difference between an adult with DS who is depressed versus one who has dementia?

    While it is true that depression can often exacerbate or even induce symptoms that are similar to those of Alzheimer’s disease, depression and Alzheimer’s disease are quite different and can be distinguished by an expert clinician. Furthermore the treatment of depression is in most cases quite successful and should be tried if there are indications of depression in any person including a person with Down syndrome.

  7. Are there any medications that slow the progression of Alzheimer’s?

    The current drugs that have been approved by the FDA for the treatment of Alzheimer’s disease can also be prescribed four people with Down syndrome who also have Alzheimer’s disease although there are insufficient data to indicate how well they slowed the progression in this special population. In the typical population these drugs appear to slow the progression of Alzheimer’s disease by about one year. There first century two classes of such drugs one of which reduces the degradation of the neurotransmitter acetylcholine, thus allowing this neurotransmitter that is important for memory to work longer, and the other of which allows the neurotransmitter glutamate to work better. Both of these classes of drug do not attack the underlying disease process which is why they cannot be considered the best potential treatment and have only relatively short-term benefits.

  8. What can we do to decrease the chances of our loved ones with DS from getting Alzheimer’s?

    See above. At this time there are no clear preventative measures that can be taken except possibly increased exercise and generally reducing the risk of vascular problems by keeping blood pressure and blood cholesterol levels in a safe, usually lower, level.

  9. Are there any vitamin/supplement therapies given to small children that help decrease the odds of a person with DS from getting Alzheimer’s?

    There are no vitamins or other over-the-counter therapies that are known to reduce the risk of developing Alzheimer’s disease in either people with Down syndrome or typical people. A very large and expensive trial of typical people with Alzheimer’s disease or mild cognitive impairment was carried out to investigate the potential benefit of ginkgo biloba, but the results were clear that it had no benefit.

  10. What are the current screening guidelines for Alzheimer’s in people with DS?

    There are no specific screening guidelines for Alzheimer’s disease in people with Down syndrome. Because of their other challenges people with Down syndrome very often are unable to complete the tests used to determine whether a typical person has Alzheimer’s disease, but several laboratories are trying to develop better neuropsychological tests for this purpose.

  11. What is the effect of diet regarding Alzheimer’s in people with DS?

    There is no indication that diet affects Alzheimer’s disease development in people with Down syndrome or in typical people and it may be many years before we know much about this because it takes so long and so much money to determine the long-term potential benefit of dietary changes.

  12. I have recently read and heard that medications used to treat GERD symptoms may actually contribute to dementia.  Is this true?

    There are some recent studies that suggest that the use of proton pump inhibitors, which are commonly used to treat GERD may slightly increased the risk of dementia in typical people over a long period of time. However the increase is not large and there are no data collected thus far in people with Down syndrome.

  13. Alzheimer’s is already present on both sides of my family. Is my child with DS therefore more predisposed to Alzheimer’s because of the family link? Down syndrome? Both?

    In studying large numbers of people with a family history of Alzheimer’s disease does increase an individual’s risk a little, primarily due to the increased genetic risk of the Apolipoprotein E4 gene.  Furthermore there is an increased risk of dementia in people with Down syndrome who carry the Apolipoprotein E4 gene by one study. We and others are working to develop treatments that may reduce this increased risk.

  14. My paternal grandmother died from Alzheimer’s.  Does that mean my daughter with DS has a great chance of developing dementia associated with Alzheimer’s?

    A family history of Alzheimer’s disease does increased one’s risk a little but in your case the distance between your paternal grandmother and your child is probably too great to have much effect.

  15. What medications have been used in people with DS who have Alzheimer’s and what are the pros and cons to these medications?

    In general the approve medications for Alzheimer’s disease in typical people have been tried in people with Down syndrome you have Alzheimer’s disease but the carefully perform clinical trials needed to prove that they are beneficial have not been done.

  16. What is the effect of physical activity (fitness, training) on the development of medical problems, including Alzheimer’s, associated with DS?

    Physical activity has been shown to slow the development of Alzheimer’s disease symptoms in typical people with mild cognitive impairment and in animal models of Alzheimer’s disease. We assume event physical activity will similarly benefit people with Down syndrome but the experiment has not been done.

  17. As a parent of a 6 year old with DS, what actions would you recommend I take to help ensure a cure for Alzheimer’s is found? What other activities would you recommend the parent community embrace to better assist ongoing research?

    The most important contribution a family with a member with Down syndrome, or any individual, can do to increase the chances that a drug for Alzheimer’s disease will be developed is to inform your state and federal representatives that such research is essential.

  18. What research is being done on young adults with DS looking at Alzheimer’s?

    We and other research groups are actively investigating adults with Down syndrome to try to determine oh is at risk for developing Alzheimer’s disease clinical symptoms and what the time course of the development of Alzheimer’s disease is. Thus far the data indicate that all people with Down syndrome develop the brain pathology of Alzheimer’s disease and some 60 to 70% develop dementia by the age of 60.

Down Syndrome and Cancer Questions

  1. What is the effect of diet regarding leukemia in people with Down syndrome?

    There are no well established effects of diet on the incidence of leukemia specifically in people with Down syndrome.

  2. Is leukemia the same in people with Down syndrome as typical people? Is it treated the same?

    There are similarities and differences. As for leukemia in typical people, leukemia in people with Down syndrome is fundamentally the same phenomenon, i.e. uncontrolled proliferation of specific cells in the blood. However, there are important differences. Unlike leukemia cells in typical people, the leukemia cells in people with Down syndrome have an extra copy of chromosome 21, which may impact on the behavior of the leukemia. While treatment options are very similar, there are some differences in the way these types of leukemia respond. For example, the toxicity of standard chemotherapy is greater in people with Down syndrome, which leads to more intensive monitoring of these toxic effects and increased palliative care. Also, the so called ‘immunotherapies’ such as ‘CAR-T cell therapy’ are less effective in people with Down syndrome. On the other hand, the response to treatment in the case of Acute Megakaryoblastic Leukemia (AMKL) is better in people with Down syndrome.

  3. What is the latest research regarding leukemia in people with Down syndrome? Why are people with Down syndrome more at risk and is there anything to be done in this regard?

    Research in this area is still ongoing. Research in Dr. John Crispino’s lab has led to the identification of specific genes on chromosome 21 that seem to drive the increase risk of leukemia, such as the DYRK1A gene. Research in Dr. Espinosa’s lab has identified the Interferon molecular pathway as deregulated in people with DS, which could affect the bone marrow in a way that increases the risk of leukemia and autoimmune disorders.

  4. What clinical trials are going on regarding leukemia and people with Down syndrome?

    To our knowledge there are no open clinical trials for the treatment of leukemia specifically in people with Down syndrome. Unfortunately, some clinical trials for novel leukemia therapies, such as JAK inhibitors that shut down the Interferon pathway, exclude children with Down syndrome.

  5. What is leukemia up and cancer down in people with Down syndrome?

    This is unknown. Several hypotheses are being tested in the field. For example, it is hypothesized that chromosome 21 carries genes that promote the proliferation of certain cell types in the blood (e.g. DYRK1A) and other genes that impair the proliferation of cells within tumors (e.g. Interferon receptors).

Autoimmune Disorder Questions

  1. What are the most common autoimmune diseases affecting people with T21? Is there some sort of statistical graph I can look at?

    Autoimmune thyroid disease (Hashimoto’s disease/hypothyroid ism and Graves’ disease/hyperthyroidism) ~35%; Celiac disease 1.4-5 %; Vitiligo ~3%; type 1 diabetes mellitus ~1%; rheumatoid arthritis ~ 0.87%.

  2. My child has normal thyroid and blood work but premature hair loss. What treatments are there for this?

    You should consult a pediatric dermatologist.

  3. What is the effect of diet on development of autoimmune disorders in people with Down syndrome?

    There is no known relationship of diet to development of autoimmune disorders

  4. Do people with Down syndrome get arthritis? How can I tell if my adult child has a high threshold for pain and can’t communicate well?

    Yes. Anyone can get osteoarthritis. The frequency of rheumatoid arthritis in people with Down syndrome is estimated at ~0.87%.  If you are concerned about possible arthritis, you should consult a rheumatologist.

  5. With the “symptoms” of thyroid disease & Down syndrome so similar, why is TSH not treated at a lower high-threshold than the typical population?

    The diagnostic criteria of autoimmune thyroid disease are the same in people with Down syndrome and in the general population. Inappropriate treatment of people with normal TSH would inappropriately function of a normal thyroid.

General Research Questions

  1. What new updates are there in terms of cognition research?

    Unfortunately, the news isn’t all good.  The Roche trial was halted when they unblinded it and discovered that, while the drug was safe, it didn’t result in improved cognition.  There is a recent report in Lancet that EGCG, an ingredient in green tea, improves cognition in some tests, but not others.  This paper suffers from some statistical errors, and so we feel it must be repeated before it can be believed.  On the other hand, drinking tea is safe, so there is no good reason not to do it.

  2. Will there be any clinical trials looking into vitamin/supplement therapies?

    We don’t know of any.  The problem is that vitamins and supplements are already available over the counter and they are relatively inexpensive, so it doesn’t pay a company to fund the clinical trial.  This is especially true since clinical trials are very expensive to perform.

  3. What is the benefit from a Down  syndrome perspective, tracking all the genes in a family, like in gene mail out kits and they mail you info?

    The benefit is the same as for a family entirely made of typical individuals. One may learn about the presence of gene variants that predispose to certain diseases. With that being said, the interpretation of such probabilities may be qualified for the person for trisomy 21. For example, it is not clear how the presence of a mutation predisposing to breast cancer (eg BRCA1 gene) would manifest in a person with trisomy 21, who is naturally protected from developing breast cancer.

  4. What do we know about changes in life expectancy for people with Down syndrome?

    Life expectancies have been increasing for many years. Currently a child born with Down syndrome can expect to live for 50-60 years or more.

  5. What will research on pregnant women and testing fetuses with Down syndrome lead to?

    I assume this question is about the proposal to test the effects of drugs on fetuses by giving the drug to the pregnant mother? Depending on the drug, this could be safe or have an element of danger.  For example, it is presumably safe to have pregnant mothers drink green tea.  In contrast, there are medical professionals who are concerned about the current Prozac trial, since it is unknown what effect this might have on a fetus with Down syndrome. It is crucial to provide evidence for the safety of any drug before embarking on an extensive in utero clinical trial.

  6. How would families become involved with research studies?

    First, sign up for DS connect at https://dsconnect.nih.gov/. That’s a start, but please also sign up for research studies when requested by your physician or clinic representative.