The Generation Program’s Approach to Disclosing Information about Your Risk for Alzheimer’s disease

The Generation Program is made up of two clinical trials: Generation Study 1 and Generation Study 2. The trials will enroll people with a specific gene that may increase the risk of developing Alzheimer’s disease. It is your genes, along with other information about you, which will determine whether you are eligible to take part in either of these studies.

Overview of the Generation Program

The Generation Program focuses on people ages 60-75 who do not have symptoms of Alzheimer’s disease but who have one or both of two factors that are known to increase a person’s risk of developing dementia caused by Alzheimer’s disease. Those factors include:

  • The APOE e4 Gene People who have one or two copies of the gene APOE e4 are more likely to develop dementia due to Alzheimer’s disease. It is important to note that not every person who has the APOE e4 gene will develop dementia caused by Alzheimer’s disease.

  • ·Elevated Amyloid Plaques Amyloid is a protein produced normally in the brain. Recent research studies suggest that people over the age of 65 who have evidence of higher than normal levels of amyloid plaques in their brains are at higher risk for dementia due to Alzheimer’s disease. However, not every person who has higher than normal levels of amyloid plaques will develop dementia due to Alzheimer’s disease.

Frequently Asked Questions

How do doctors determine whether someone has high levels of brain amyloid?

In one of two ways. 1) A PET scan test for brain amyloid (also referred to “brain amyloid scan” or “amyloid PET scan”) allows physicians to detect amyloid plaques in the brain. 2) Amyloid can also be measured through collection of cerebro-spinal fluid from a lumbar puncture. 

Participants in Generation Study 2 will learn whether the level of amyloid in their brain is either “elevated” or “not elevated.” Please note that amyloid tests do not measure whether you have dementia due to Alzheimer’s disease nor can they predict whether you will develop dementia due to Alzheimer’s disease in the future.

How is an amyloid PET scan performed?

The test takes about two hours to complete. First, the person is given an injection of a dye (called a “radiotracer”). About an hour later, the person undergoes a 20-minute scan exam.

During the exam, the radiotracer dye “lights up” where amyloid plaques are located and the PET scan turns this information into images. A qualified expert will then assess the images to determine whether the level of amyloid is “elevated” or “not elevated.”

How is a lumbar puncture performed?

During this procedure, a thin needle is inserted into the lower part of the person’s spinal column to collect spinal fluid. The amount of amyloid in the spinal fluid is then measured to determine whether the level of brain amyloid is “elevated” or “not elevated.”

What does an “elevated” level of brain amyloid mean?

An “elevated” amyloid result means that you have enough amyloid plaques in your brain to meet the criteria that make you eligible to participate in the study. While an “elevated” amyloid result is associated with an increased risk of developing dementia due to Alzheimer’s disease, it does not mean definitively that you will develop dementia due to Alzheimer’s disease.

 Studies suggest that the increased risk of developing dementia due to Alzheimer’s disease associated with an “elevated” amyloid level is spread out over years or even decades. Scientists do not yet know which people with normal memory and thinking ability as well as elevated brain amyloid will develop dementia due to Alzheimer’s disease. Some people with elevated levels of amyloid plaques in their brain may never develop dementia in their lifetimes.

Is an “elevated” level of amyloid similar to other risk factors?

Having an “elevated” level of amyloid plaques may increase the risk of developing memory problems and dementia due to Alzheimer’s disease but it does not mean a person will definitely develop dementia due to Alzheimer’s disease.

Studies suggest the relationship between elevated amyloid plaques and Alzheimer’s disease dementia may be similar to the relationship between cholesterol and heart disease. Having high cholesterol increases the risk of having heart disease, but having high cholesterol does not mean that person will definitely have a heart attack. Years of research involving thousands of people enabled us to calculate a person’s risk of heart disease. There are not yet enough amyloid test research results available to calculate an individual’s risk of developing Alzheimer’s disease-related memory decline.

There are some factors that may protect a person from developing memory or thinking problems, even if they do have elevated levels of amyloid plaques. For example, some protection may come from a person’s genes, but good general health and a healthy lifestyle may also lower the risk of Alzheimer’s disease-related memory decline. 

What does a “not elevated” level of brain amyloid mean?

A “not elevated” amyloid result means you do not have enough amyloid plaques in your brain to be eligible to participate in the Generation Study 2. Having elevated brain amyloid is not an eligibility requirement for Generation Study 1. A “not elevated” amyloid result does not mean that you will never develop dementia due to Alzheimer’s disease.  A person who has a “not elevated” amyloid level at the time of testing could in the future develop an “elevated” level of amyloid or dementia due to Alzheimer’s disease.

Are there other risk factors in addition to the APOE e4 gene and amyloid plaques that can lead to dementia caused by Alzheimer’s disease?

Yes. The greatest risk factor for developing dementia caused by Alzheimer’s disease is advancing age, especially for those who are over 70 years old. However, dementia caused by Alzheimer’s disease is not a normal part of aging.

Another risk factor is having a family history of dementia or Alzheimer’s disease. Some studies also indicate that cardiovascular disease and conditions such as diabetes and high blood pressure are associated with a higher risk of developing dementia due to Alzheimer’s disease as well as other types of dementias. If you have any questions regarding these risk factors, please consult with your study team.

If you are interested in joining the Generations Program, please call (773) 275-3500
or visit our study-specific webpage by clicking here.