Sterling Johnson Talks About the Wisconsin Registry for Alzheimer's Prevention
The Wisconsin Registry for Alzheimer’s Prevention (WRAP) began collecting data from participants in 2001 and is now the largest and Alzheimer’s prevention program in the country.
The 1,500 volunteers from 32 states and three countries – most of them children of Alzheimer’s patients - have given blood and taken cognitive tests at regular intervals.
Some participants have also had spinal taps to test for evidence of the plaques and tangles that are hallmarks of the disease, and brain MRI scans to look for signs of neurodegeneration and also activity levels in the hippocampus - the brain’s memory center - or PET scans to look non-invasively for amyloid plaque.
The new Wisconsin Technology Innovation Initiative (Wi2), together with the Wisconsin Economic Development Corporation (WEDC), have announced that one of its first investments will be to devote $1 million to expand research using the WRAP data, in the hopes it will speed up research on Alzheimer’s disease.
Dr. Sterling Johnson, professor of medicine (geriatrics) and WRAP principal investigator, explained how the new investment in extending the Wisconsin Registry for Alzheimer's Prevention dataset and “mining” the existing data could spur discoveries.
How can the data collected by WRAP help solve the puzzle of Alzheimer’s disease?
As the disease develops, there are three phases: the pre-symptomatic phase, the mild cognitive impairment phase and the dementia phase. It turns out that the best of the known markers of the disease – the amyloid plaque and neurofibrillary tangles – begin to manifest in the pre-symptomatic phase – in people who don’t yet show any outward signs of impairment. The field is just now learning this. Just how early we can detect such signal is something WRAP can help us learn.
WRAP is the most mature, well-developed cohort for the pre-symptomatic phase because its enriched with children of Alzheimer’s patients, who themselves are at higher risk of AD, before they were showing symptoms. The longitudinal cognitive data can be used to define the earliest symptoms and the genetic, imaging and fluid data can more accurately define the presymptomatic disease profile.
Can we identify with greater certainty the people who are likely to develop the disease?
This is the question we must address first. It’s an expensive undertaking but it is likely to be extremely productive. In doing so, we will have identified the right population to include in clinical trials of potential therapies - enabling quicker answers.
What still needs to be done?
We have to intensify biomarker investigations. With the new funding, we will be able to conduct more comprehensive assessments with fluid and imaging biomarkers to define the presymptomatic phase. Also, the massive dataset needs to be mined in an integrated way for new discoveries. All of this is geared to the earliest possible detection of Alzheimer’s disease pathology and prevention.
When discoveries are ready to bring to the community, the Wisconsin Alzheimer’s Institute, which specializes in public health and education, and which has cultivated a network of 44 specialized AD clinics throughout the State of Wisconsin, stands ready to implement them.
Is there any good news about Alzheimer’s?
One fortunate problem is that the brain is highly resilient. Some people are more resilient than others for unknown reasons - they can harbor a great amount of AD pathology in the brain and may not ever show impairment. So they may provide clues to prevention.
For example, Dr. Ozioma Okonkwo, assistant professor of medicine, has observed that moderate frequent physical exercise is associated with reduced atrophy of the brain, reduced amyloid plaque burden, and better memory scores. Exercise may not be the end-all, be-all, but a hypothesis we are testing is that it may confer some number of years of protection against the disease in someone who is destined to develop it.
Other lifestyle features, and genetic markers of resilience and risk are certainly also at work, and are active topics of investigation by our collective group.
How does the Wi2 investment help?
This will accelerate the pace of discovery. It allows us to dig deeper, into things like genomics, "big data" mining approaches enabling better prediction algorithms, and to develop more sophisticated measurement tools. It will also help us develop new collaborations within UW, bringing new expertise to the problem.
One already existing internal partner is the Wisconsin Alzheimer’s Disease Research Center, which has developed research service cores (including imaging and spinal fluid collection) to assist projects like WRAP.
It is already a goal and mindset of WRAP to collaborate and share data. New collaborations with drug developers and other biotech stakeholders will allow us to bring our expertise in early detection to designing optimal clinical trials in people at risk. This will include both ways to enrich trials with those participants who are most likely to have underlying AD, and develop more precise outcome measures using our techniques.
This approach will reduce the number of people needed for a trial and give us the tools to implement trials in the presymptomatic phase, when imaging or other biomarker outcomes become the effect of interest, because cognition is still normal.
Will it change anything for participants the WRAP study?
We may wish to enrich the data set with more people who are biomarker-positive. Right now we’ve enriched the cohort with people who are family-history positive, which increases their chances of developing AD by three-fold.
This means we’re going from a lifetime risk of developing the disease at age 65 of 10 percent in the general population to a risk of 30 percent. That’s not efficient. We need to find presymptomatic AD with 100 percent certainty. So we will likely invite more of the current participants to participate in studies to define the asymptomatic phenotype of AD.
The WRAP participants have an overwhelming culture of volunteerism. It’s so gratifying; they’re a wonderful cohort to work with. We are partners in this together and all committed to slowing or preventing AD.
Date Published: 06/26/2014