Summary: WRAP Information Sessions 2006

The WAI recently held information sessions for participants in the Wisconsin Registry for Alzheimer's Prevention (WRAP) and others interested in Alzheimer's research. What follows is a summary of the results of our research so far and a review of the content of the four WRAP informational programs presented in May and June of this year.

Many participants had questions during and after the sessions that we have answered here as well. Questions like, "Will I be told the results of my APOE genotyping?", "Will I receive the results of my neuropsychological testing?" and others are answered on this site (following the summary below).

WRAP volunteers have a high prevalence of a known genetic risk factor for AD, the apolipoprotein ε4 (APOE ε4) gene. Forty-four percent of WRAP participants have this gene compared with only 15% of control subjects (persons without a family history of Alzheimer’s disease). The presence of this gene does not mean that a person will develop AD, but studies suggest that 30-50% of persons who have APOE ε4 will eventually develop AD. Approximately 70% of autopsy-proven cases of persons with AD have this APOE ε4 gene, suggesting that other factors may also place persons at risk for developing the disease.

Neuropsychological test results do not show any difference between WRAP volunteers who have and do not have the APOE ε4 gene or persons without a family history. As described during the informational meetings, there are no differences among these groups in verbal language scores, executive function scores or memory at the present time.

Analyses of the baseline data suggest that lifestyle may be an important factor in the development of AD. Moderate alcohol use and exercise are associated with slightly better performance in the WRAP baseline cognitive testing. One question that will be answered in the second wave is whether these factors as well as other lifestyle measures are protective against abnormal changes in cognitive ability and the eventual development of AD.

Dr. Sterling Johnson, Principal Investigator of the functional magnetic resonance imaging study, for which many of you volunteered, has recently published an important paper in the Journal of Neuroscience (Johnson SC, Schmitz TW, Trivedi MA, Ries ML, Torgerson BM, Carlsson CM, Asthana S, Hermann BP, Sager MA. The influence of AD family history and APOE-4 on mesial temporal lobe activation. J Neuroscience 2006; 26(22)6069-6076.) The paper describes his findings that the brains of persons with a family history of AD (WRAP volunteers) respond differently to cognitive stimuli than the brains of persons without a family history. In this study, areas of the brain known to be affected by AD activated significantly less in persons with a family history than in persons without a family history. This effect was independent of whether a person had the APOE ε4 gene suggesting that an unknown factor embodied in family history is influencing brain function. This may suggest that the unknown family history risk factor could actually be more important in determining AD risk than the APOE ε4 gene. This finding has now been confirmed in a similar study from Johns Hopkins and will become a major focus of our research in the future.

Dr. Cindy Carlsson’s study of the relationship between cholesterol-lowering drugs and the development of Alzheimer’s disease is ongoing and results are pending.

1. Will I receive the results of my APOE genetic testing?

Although the APOE ε4 gene is a known risk factor for Alzheimer’s disease (AD), we are not releasing this information at this time. If the results of the genetic testing were to become known, persons with the APOE ε4 gene could be denied long-term care insurance. Because of this risk of disclosure, we have taken great measures to protect your privacy. Once the blood is drawn, the APOE genetic sample is given a number and then sent to the laboratory for analysis. As a result, there is no indication in the medical record at University Hospital that this test was done or that you are involved in this study. If an insurance company requests copies of your medical record, the APOE test and other findings from this study will not appear in the record. If there is a research breakthrough suggesting that persons with the APOE ?4 gene would benefit from a given treatment, the results of the testing will be released and each person participating in WRAP will be given his or her genotype. APOE genotyping can be obtained through your physician at a cost of approximately $300.

2. Will I get the results of my neuropsychological testing? What will happen if my testing results change?

The neuropsychological testing is a research battery that requires trained personnel to interpret. Because of that, we have not released the results of the cognitive testing, but we will notify persons who show changes in their neuropsychological test scores during the second and subsequent waves of testing. We will contact those of you who show changes in memory and conduct either an over-the-telephone evaluation or ask that you come to the University of Wisconsin Memory Assessment Clinic to see Dr. Sager for evaluation. For those of you who are found to have mild cognitive impairment (often a precursor to AD), you will be given an opportunity to enter a program called “Take Charge.”

3. What is “Take Charge?”

Too often, persons who develop cognitive impairment or AD become victims of the disease and often feel that nothing can be done. We believe that current science and the results of this project so far suggest that non-pharmacologic interventions (e.g., exercise, diet) may be useful in altering the course of pre-clinical AD (before symptoms arise) and possibly prevent or delay the onset of AD. The ability to slow cognitive decline in persons who are asymptomatic has not been well studied because there has never been a study like WRAP. Dr. Asenath La Rue, Senior Scientist at the Wisconsin Alzheimer’s Institute, is in the process of developing “Take Charge,” a program that will incorporate the latest findings from this study and other studies from around the world in an effort to slow or prevent the emergence of AD.

4. If I am over 65 at the time of the second wave of testing, am I still eligible?

Yes. Once you are enrolled in this study, it is critical that you participate in subsequent waves of testing regardless of age.

5. I would like to understand the MRI study results better.

Dr. Sterling Johnson’s MRI study suggests that the brains of persons with a family history of AD are functioning differently from persons who do not have a family history and that this is occurring regardless of the presence or absence of the APOE ε4 gene. This has never been noted before. Although we know that family history is a risk factor for AD, we have never understood why. It is possible that Dr. Johnson’s findings will open an entirely new area of research that will improve our understanding about why persons with a family history are at increased risk of developing this disease. His findings have now been confirmed by a study from Johns Hopkins and our future research will attempt to understand what fact or factors constitute the genetic or lifestyle risk embodied by a family history of AD.

6. My mom was on Aricept. Has it been proven to aid memory?

Aricept belongs to a class of medications commonly used to treat AD. Aricept does not result in dramatic improvements in memory, and in fact, most people on these medications gradually deteriorate over time. The major benefit of Aricept and other AD treatments may be that it will slow, but not reverse, gradual progression of the disease in some persons.

7. Will testing in Green Bay in the future be a possibility?

Many persons attending the informational meetings asked about the possibility of having testing done closer to home, thus eliminating the need to drive to Madison. We understand the sacrifice and inconvenience that many WRAP participants have made by coming to Madison for a half day of testing. Currently, we have persons who have flown in from 18 states and who have driven from over 60 counties to come to Madison for participation in this study. Unfortunately, this study currently does not have adequate funding to allow us to set up recruitment sites at different locations around the state. If additional funding becomes available, we would envision having testing sites in Green Bay or Oshkosh, Milwaukee, Madison and La Crosse.

8. When is the timeline for a second wave of testing and when should I plan another trip to Madison?

The second wave of testing will begin in September, 2006, and it will occur at approximately 4-year intervals after your first assessment. We expect to begin contacting persons who were initially assessed in 2001-2002 this fall. We appreciate your willingness to participate and will do whatever is necessary to accommodate your schedule, including doing testing on weekends.

9. Could a volunteer RN collect lab specimens in the Green Bay area?

Yes, this is an excellent idea that we would like to act upon if funds become available. We would need a cooperating laboratory to process the specimens and a mechanism for transporting the samples to Madison.

10. Would an autopsy of my parents brain be useful for the WRAP study?

Yes. Currently, there are no blood tests or x-rays that can be done to verify the diagnosis of AD in a parent. An autopsy will verify the diagnosis and allow us to better understand the factors that make family history a risk factor for AD.

11. Does tobacco have any affect on the risk of AD?

There is no data that ties tobacco to the development of AD. Tobacco does increase a person’s risk of cerebrovascular and cardiovascular disease, both of which may have an impact on the development of AD.

12. What is the relationship between hormone replacement therapy and Alzheimer’s disease? Is there a safe estrogen preparation?

The findings of the Women’s Health Initiative Study suggested that taking conjugated estrogen (Premarin or Prempro) increased a person’s risk of developing dementia. Although the exact mechanism of this was unknown, it was thought that women taking these preparations were developing small blood clots that went to the brain and produced small strokes. Because of that, the Women’s Health Initiative Memory Study was discontinued and the recommendations were to not take these preparations for hormone replacement therapy. One form of estrogen, 17-beta estradiol, is available in a patch form and is not thought to result in the production of blood clots or increase the risk of dementia.

13. What is the best way to make sure that a person’s brain will be donated for research?

The University of Wisconsin is currently developing a program for brain donation and autopsy for the purposes of AD research. The policies and procedures are currently being developed and once finalized, will be made available on this website.

14. Is there a relationship between depression and stress and Alzheimer’s disease?

There is a definite relationship between stress and depression and the development of AD. Stress and depression can cause deterioration in the hippocampus, an area of the brain known to be affected early in AD. The good news is that treatment of depression and control of stress will significantly reduce, if not eliminate, the effect of depression on AD risk.

15. Are there any pharmaceutical companies involved with this research?

No. This project is supported by the Wisconsin Alzheimer’s Institute through private donations and by grants from the Helen Bader, Northwestern Mutual and Extendicare Foundations in Milwaukee and the State of Wisconsin.

16. How is the genetic sample in the second wave of testing done?

Blood will be drawn, and white blood cells will be saved for storage of genetic material.

17. What studies other than the first and second wave of testing, Dr. Carlsson’s statin study and Dr. Johnson’s fMRI study, are being conducted?

Currently, we are planning a minimum of 3 additional waves of neuropsychological and laboratory testing which will begin in September and continue through 2018. In addition, there are other studies that will soon begin. One will involve the Pittsburgh Compound which allows the detection of beta amyloid in the brain, a compound known to accumulate in the brains of persons with AD. This PET study will hopefully begin in fall of 2006 and interested persons in WRAP may participate. The Pittsburgh Compound will be used to determine the presence of abnormal amyloid deposits in persons who may be at risk for AD, but who are currently without symptoms.

18. If I get it correctly, should I take vitamin E with red wine after biking 20 miles? (to reduce my risk of AD)

You should eat a diet high in vitamin E and drink a glass of grape juice (or red wine) after biking 20 miles. Research suggests that exercise, moderate alcohol consumption, diet and other lifestyle factors (like leisure activities) influence a person’s risk of developing AD.

19. My father was diagnosed with AD about 5 years ago and now he has symptoms that are consistent with Lewy body disease. If his autopsy indicates he has Lewy body instead of Alzheimer’s, how would that affect your findings and my participation?

The clinical diagnosis of AD is correct 90-95% of the time. It can only be verified at autopsy. If a WRAP participant’s parent has an autopsy indicating a cause other than AD, then we would like to know this fact which will be taken into consideration during the analyses. Lewy body dementia differs from AD in that hallucinations, changes in walking ability, falls and symptoms of Parkinson’s disease appear early in the course. In addition, many patients with Lewy body dementia will have a vacillating course (i.e., good days and bad days) that are more pronounced than in AD. Persons with Lewy body dementia also respond well to treatment with drugs like Aricept.

20. Is there any type of hormonal study planned for the future?

Dr. Sanjay Asthana is currently conducting studies of 17-beta estradiol in persons with AD. You can learn more about this study by contacting the Wisconsin Comprehensive Memory Research Program at (608) 263-2582 or (866) MEM-PROG (866-636-7764).

21. Are you still enrolling in WRAP?

Yes, interested persons should call Janet Rowley at (608) 829-3306 or (800) 417-4169.

22. Does epilepsy play a part in AD?

There are little data about the relationship between epilepsy and AD. AD patients do develop epilepsy at an increased rate relative to the general population. However, many patients with epilepsy have not been followed for sufficient periods of time to determine whether epilepsy is a risk factor for AD.

23. Where abnormal declines in cognitive abilities are noted, will different interventions be used for participants and will these become secondary studies of the success/failure of different interventions?

Yes, we expect that people will be offered different interventions based upon their lifestyle and interests. Although we are still in the planning stages for developing “Take Charge,” we are hoping to develop at least 2 different interventions that will be tested for their ability to slow or delay the onset of AD.

24. My mother died of Alzheimer’s disease. Should I be taking Aricept?

At the present time, there is no proven medication that individuals could take to reduce their risk of developing AD.

25. Can someone new still enroll in WRAP?

Yes. We expect to enroll an additional 200 adult children of persons with AD in WRAP. We are also interested in persons who have parents who lived until the age of 70 without a history of dementia.

26. Can someone enroll in the fMRI studies?

Yes. If interested, please call the Comprehensive Memory Research Program at (608) 263-2582 or (866) MEM-PROG (866-636-7764).

27. Is Zocor at 20 mg/day protective?

There is some evidence that statins like Zocor, cholesterol-lowering drugs, may reduce a person’s risk of developing AD. This is an area of intense study, but no recommendations can be made at this time.

Questions? Phone: 608-829-3306 or 1-800-417-4169 or Email: jsrowley@wisc.edu