Tucson Lifestyle — January 2016
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Mind Games
Anne Kellogg

What if 10 minutes of your time and an Internet connection could help researchers unlock the mysteries behind learning and memory? Log onto MindCrowd.org and take a simple memory test. Your results may hold the answers as to why certain individuals get Alzheimer’s Disease.

HAVE YOU WALKED INTO YOUR kitchen recently but forgotten what you wanted there? Your kids may even have teased you about having “Old-Timers Disease,” but the memory problems that come with advanced age — especially Alzheimer’s Disease — are no laughing matter.

Until the human genome project, it seemed unlikely that anyone would ever be able to “crack the code” to discover why one person gets Alzheimer’s Disease in their 60s while another can be 99 and sharp as a tack. But now, Arizona researchers, including two from The University of Arizona, are hoping to get to the bottom of this mystery.

Dr. Matt Huentelman of the Phoenix-based Tgen is the founder and principal scientist behind the MindCrowd project. It was his idea to use the Internet to test a subject pool from all over the world, and gather demographic data from them. This is the first time online research will be gathered, analyzed and pursued for insight into cognition and memory, and the relationship to Alzheimer’s and other brain disorders through genetics. In later stages of the study, the test results could indicate which subjects he would then ask for saliva samples and brain scans.

“When it comes to things like learning and memory there are many factors that change our performance — maybe half of them are environmental and half are hard-coded into our genes,” Dr. Huentelman explains. “To date we haven’t identified many of these factors and that is primarily because our studies in this area of research are way too small. We are addressing that by reaching out to our study participants on the Internet. Eventually we will be able to explain almost everything that influences how you perform on our specific test, and when we know that, then we can make recommendations about which lifestyle or environmental factors to change. By leveraging genetics we also can start to develop targeted medicines that could improve function in the general population.”

Drs. Lee Ryan and Betty Glisky, University of Arizona professors and researchers, were brought on early in the project to create the memory tests for the MindCrowd program. “I knew Betty and Lee from our many years of working together in the Arizona Alzheimer’s Consortium — a statewide laboratory ‘without walls’ that combines the expertise of several institutes within the state of Arizona,” says Dr. Huentelman. “They have far-reaching expertise in the testing of human memory performance so they were the perfect fit for this work.”

“What we want to understand is what allows people to age successfully,” says Dr. Ryan. “In order to do that, we need huge numbers of test subjects so we can see the breadth of the aging process, from those who are remaining active and sharp throughout their lifespan to others who have more difficulty. We know there are many different factors that influence this: health, genetics, lifestyle, and social interaction. We’ll be able to gather demographic information about the people who take the MindCrowd test, and down the road obtain genetic information so we can understand these individual differences in how people age.”

Thus far, there is no cure for Alzheimer’s or dementia, only certain pharmaceuticals that are designed to slow the process. Dr. Glisky says, “We’re learning that there are things you can incorporate into your lifestyle that can decrease the risk. The big question is whether we can find the ‘magic combination’ of factors. So it’s not just having a glass of red wine a day, or staying physically active, but perhaps we can come up with a ‘cocktail’ of lifestyle choices that could ameliorate the risk you might have because of your family history. We also want to know how early you have to start these interventions … can you start at age 60 or 70?”

Dr. Ryan adds, “There are other forms of dementia that also may be impacted positively through lifestyle factors like exercise and social interaction. This may have implications beyond Alzheimer’s disease — we’re talking about optimal aging and the aging brain. And that’s part of why we created the Annual Conference on Successful Aging, (ACoSA), now going into its fourth year. Its a series of informative seminars that are open to the public.” (See Sidebar for details.)

“We are collaborating with other researchers on drugs that may have some benefit to the brain as people age, particularly if they have health issues like cardiovascular disease, says Dr. Ryan. “Obesity, high blood pressure and diabetes all increase risk for cardiovascular disease, which in turn can increase risk for Alzheimer’s Disease. Pharmaceutical interventions are not a primary focus for the MindCrowd project, but the information the researchers get might help steer them in the right direction for new varieties of medications.

TESTING …TESTING …

How can a simple word-pair memory test show how a person’s memory is affected by age? Dr. Glisky explains, “These tests have been used in psychological circles for many years. The word pairs are either related to each other or not. For example, one pair might be related, like ‘Rain – Wet,’ while the others might read something like, ‘Hydrant – Teacher.’ Relational memory is very sensitive to aging and, generally, as people age they do more poorly in this test. Yet, others do phenomenally well. The test was chosen for that reason — it can show different cognitive or neuropsychological factors. Also, it had to be easy enough that no one would fail it. Subjects go through the test three times and we can see how or if they improve over the course of the test, learning from trial to trial.

“There are many reasons someone could do poorly on this test. They were tired, distracted, not ‘with it,’ or they didn’t pay attention. We’ll be studying all of the data, but we’re particularly interested in the people who do well, in the top tier, and compare them to the average.”

It is important to note that your test score, and the comparison to others in your age group, by itself, is not meaningful and should not be considered an indicator of Alzheimer’s risk. “It’s really our gateway into a larger round of testing later on that will presumably tell us a lot about how people are doing with their memory and in other areas,” says Dr. Ryan. “What does it take to get to this top level? In Phase Two of the study we’ll be asking the subjects for more information that we didn’t ask for the first time around. There were very few demographic questions in Phase One, such as gender and age.”

As of this writing, the Phase One test was only available in English. Dr. Huentelman is working with a company to translate the entire test into Russian, Spanish, Mandarin, Arabic, and Hindi to increase their ability to reach out to people all over the world and make it truly global. This also will help hone the statistics.

“We want to make sure that a language barrier wasn’t the reason the test subjects weren’t doing well,” Dr. Ryan notes. “In Phase Two, we’ll have nonverbal tests and go into other tasks that won’t be language-based, such as visual pairs.

“We don’t know a lot about how the aging process progresses across ethnic groups,” she says. “Are those differences related to genetics or lifestyle? We don’t know. This is a great opportunity to look at these large samples of people of varying backgrounds.”

WHAT’S NEW FOR PHASE TWO

This next phase is critical for us,” Dr. Ryan states. “We’ll have additional tests available for people to do, and we’ll be asking them more information about aspects of their lives and health, backgrounds, family histories, etc. Besides memory, we’ll also look at what we call executive functions — all of those cognitive abilities that allow us to control what’s happening in our minds. There also will be perceptual tasks that will create a better, broader picture of how someone is aging, and different aspects of memory as well.

Dr. Huentelman is enthusiastic about the scope of the project. “My group already is analyzing the Phase One data on an almost daily basis. We continually look for new statistical associations and trends. It is an interesting study because each week we have more test takers and therefore increased statistical power to discover new things. Normally, data sets don’t continue to grow in science — they have a clear start and stop, but with the MindCrowd project, we wake up each morning and have more data points.”

When asked how long the project is slated to continue, Dr. Ryan states, “It’s taken us a little longer than we thought to get to Phase Two. We’re doing this on a shoestring budget right now, so we’re doing what we can as we cobble together resources to go to the next step. We’ll continue until we get the information we want.”

Dr. Glisky continues, “On Mind-Crowd’s website it says we’re aiming to get data from one million people. So far we’ve had 150,000 subjects take the test but only 64,000 have left their information so we can follow up. (A graph on MindCrowd.Org’s home page shows how many people have completed the test and left data.)

As a follow-up to the Phase Two results, the researchers will want to obtain brain scans and saliva tests from certain indivduals .

“We’ll probably concentrate on those people with the highest scores, as well as the average,” says Dr. Glisky. “We’d like to get them from as many people as possible, but there are constraints based on how much it’ll cost to test them. The saliva test is simply a little tube the person spits into, puts into an envelope and sends back to Tgen. Getting the samples won’t be as difficult as the analysis will be. How do you analyze that much data? Dr. Huentelman is an expert in these massive genetic analyses … that’s what Tgen does best.”

“If we wanted to test the genetics on the entire study cohort it would be cost prohibitive, but running genetics on a select set of individuals is quite possible,” says Dr. Huentelman. “The key thing is that we have now essentially pre-screened this group for performance. If we wanted, we could study the outliers and focus on them. For example, those rare individuals who are in their 60s or above who perform like an 18 year old. Funding for the next phase will likely come from a combination of philanthropic donations as well as federal grant money. We will begin applying for grants to support the work during the next quarter.

“We would like to obtain brain scans from certain test subjects in the future, but that will require additional grant funding as well as wide-ranging collaborations to be able to refer members of our study to specific facilities to receive a brain scan.”

Dr. Ryan notes, “For the brain scans , we’ll most likely start with individuals who live around Tucson but also get those in and around the Phoenix are a , then move out from there.

“You can’t get the kind of brain scan we’re looking for just anywhere. It’s important that they’re performed on the same kind of machine and that the scan is collected in exactly the same way. It will be easier getting subjects scanned here in Arizona. We’ll need help from other large centers where we have collaborators to get the scans done.”

That worry seems a long way off, considering that many people haven’t even logged onto MindCrowd.org to take the word pair test yet.

“We need help from everyone,” says Dr. Huentelman. “The test is short, fun and anonymous, and we would love for people reading this article to participate in our study and tell their social networks about it. We are still looking for our social ‘angel’ who can help our study go viral so we can reach our one million participant goal. At that point we will know more about how the brain functions on this particular memory task than we could ever dream of.”

THE RESEARCHERS

Matthew Huentelman, Ph.D.

Dr. Huentelman is Associate Professor in the Neurogenomics Division at the Translational Genomics Research Institute (TGen), and the head of its Neurobehavioral Research Unit, as well as the PrincipalInvestigator of the MindCrowd Project. “My main interest in this area of work is the very clear impact Alzheimer’s Disease will have on our society if it remains unchecked, as well as my deep-rooted interest in better understanding how the brain works. I consider the brain to be one of the last biophysicalfrontiers in our world.”

Lee Ryan, Ph.D.

Dr. Ryan is Head of Psychology at the University of Arizona and the Associate Director of the Evelyn F. McKnight Brain Institute. A neuropsychologist, she uses Magnetic Resonance Imaging methods to learn about the factors that influence brain health as we age, including genetic markers, cardiovascular health (such as obesity and hypertension), over-the-counter and prescription drug use, lifestyle choices like exercise and diet, and cognitive activities. Her goal is providing a better understanding of how older adults can maintain optimal brain health.

Betty Glisky, Ph.D.

Dr. Glisky is Professor of Psychology, with a primary focus on cognitive psychology, neuropsychology and gerontology. “I teach in the areas of memory and memory disorders. My research focuses on changes in memory that occur as a result of normal aging and brain injury, and on developing methods of rehabilitation to reduce the impact of memory impairment in everyday life.”

Drs. Ryan and Glisky are funded through the Evelyn F. McKnight Foundation, which focuses specifically on understanding and finding ways to decrease memory problems in normal aging. This multidisciplinary model includes researchers from branches of psychology, physiology, neurology and neuroscience, as well as researchers from the University of Arizona Colleges of Science and Medicine. Although these researchers arespread over the campus, they work together, sharing new information and research on the aging brain, memory problems associated with aging, and how we can make them better. Only three other universities have similar programs: the University of Alabama at Birmingham, the University of Miami and the University of Florida at Gainesville.

ACOSA CONFERENCE DETAILS

The Joan Kaye Cauthorn Annual Conference on Successful Aging (ACoSA)

Mar. 1, 2016, 7:30 a.m.-12:30 p.m. North Grand Ballroom, Student Union Memorial Center, University of Arizona

For the past three years, the University of Arizona has given the Annual Conference On Successful Aging, or AcoSA. “This conference is for the general community to come here for the day to hear about the latest scientific information on this topic. “This year’s theme is Technology and Successful Aging — how technology can be used not only in research but also in your daily life so you can age successfully,” says Dr. Ryan. “From using a device like fitbit to increase awareness of and engagement in exercise all the way to having the whole house wired so you can get feedback on your hypertension and other health monitoring. We’ll even delve into how these new technologies can be used to maintain independence.” For more information on the AcoSA Conference, visit Psychology.arizona.edu/ACOSA
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