When Georgetown University neurologist R. Scott Turner, MD, PhD, began enrolling people with mild to moderate Alzheimer's disease into a nationwide study last year, he expected to find only a handful of participants with undiagnosed glucose intolerance; instead, the overall prevalence of impaired glucose tolerance or diabetes was 43 percent - or almost half of the individuals recruited to the study.
By Alzheimer's Reading Room
When Georgetown University neurologist R. Scott Turner, MD, PhD, began enrolling people with mild to moderate Alzheimer's disease into a nationwide study last year, he expected to find only a handful of participants with undiagnosed glucose intolerance, as all the patients were already under a doctor's care and those with known diabetes were excluded.
But Turner says he was "shocked" by how many study participants were found to have pre-diabetes -- a finding that is triggering important questions.
Turner's study examines resveratrol, a compound found in red grapes and red wine, to see if it might change glucose levels in patients with mild to moderate Alzheimer's disease (AD). Turner says resveratrol is thought to act on proteins in the brain in a way that mimics effects of a low-calorie diet.
"We know from animal studies that caloric restriction prevents diseases of aging such as diabetes and Alzheimer's. On the flip side of the coin, having diabetes increases one's risk of developing AD. So perhaps by improving glucose tolerance, we will prevent or delay both diabetes and Alzheimer's," explained Turner, director of the Georgetown University Medical Center's Memory Disorders Program.
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- To join the resveratrol study, participants were first given a fasting glucose tolerance test to obtain a baseline level, and then retested two hours after eating.
- During digestion, the blood sugar level increases, but the pancreas produces insulin to lower it.
- A high sugar level after two hours reveals glucose intolerance (pre-diabetes) or diabetes if the level is very high.
- Five (4 percent) of 128 participants had impaired fasting glucose levels while three others (2 percent) had findings consistent with type 2 diabetes mellitus. Of the 125 subjects who completed the two-hour test, 38 (30 percent) demonstrated glucose intolerance while 16 (13 percent) had results consistent with diabetes.
- Thus, the overall prevalence of impaired glucose tolerance or diabetes at two hours was 43 percent - or almost half of the individuals recruited to the study.
"How does glucose intolerance or diabetes lead to AD? Does the inflammation associated with AD trigger glucose intolerance? Or do both events create a vicious cycle of Alzheimer's and glucose intolerance?"
Turner's study isn't designed to answer these questions, but it might provide important clues.
- Turner says while a glucose tolerance test is not typically ordered by neurologists, "this result suggests that perhaps we should test all our patients with early Alzheimer's.
- It's a simple, inexpensive study that reveals critical health information."
The resveratrol study is sponsored by the Alzheimer's Disease Cooperative Study through a grant from the National Institute on Aging. Turner reports no personal financial interests related to the study.
About Georgetown University Medical Center
Georgetown University Medical Center (GUMC) is an internationally recognized academic medical center with a three-part mission of research, teaching and patient care (through MedStar Health). GUMC's mission is carried out with a strong emphasis on public service and a dedication to the Catholic, Jesuit principle of cura personalis -- or "care of the whole person."
The Medical Center includes the School of Medicine and the School of Nursing & Health Studies, both nationally ranked; Georgetown Lombardi Comprehensive Cancer Center, designated as a comprehensive cancer center by the National Cancer Institute; and the Biomedical Graduate Research Organization, which accounts for the majority of externally funded research at GUMC including a Clinical and Translational Science Award from the National Institutes of Health.
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Alzheimer’s, the most common cause of dementia, currently has no cure, and the number of people with the disease is growing exponentially—from 35.6 million worldwide today to an estimated 115.4 million by 2050. There are four FDA-approved drugs for the symptoms of Alzheimer’s, but nothing yet that can delay or halt its progression in the brain.
At a Dec. 3 panel discussion hosted by GUMC, part of the Doctors Speak Out quarterly lunch education series, experts struck a hopeful chord as they described new research in the lab and in the clinic.
“I am very bullish on the future. I can’t tell you for certain if it’s going to be in 10 or 20 years, but I think … you should be very optimistic that this future is going to be a brighter one for those who are at risk for the disease, and even for those who currently have the disease,” said Howard J. Federoff, MD, PhD, a neurologist who is also executive vice president for health sciences at GUMC, and executive dean of the medical school.Federoff, an Alzheimer’s researcher, joined panelists Kevin FitzGerald, SJ, PhD, associate professor of oncology and the Dr. David P. Lauler Chair for Catholic Health Care Ethics, and R. Scott Turner, MD, PhD, professor of neurology and director of GUMC’s Memory Disorders Program.
Betsy Agnvall, features editor for health at AARP media, moderated the panel.
NEW TREATMENT STRATEGIES
Turner’s Memory Disorders program currently has several studies looking at predictors of the disease as well as clinical trials looking for more effective treatments—as well as a new prevention study. He said that there are some promising new treatment strategies under investigation, including new preclinical research at Georgetown by Charbel Moussa, PhD, MB, who is repurposing cancer drugs for neurodegenerative diseases including Alzheimer’s.
Turner noted that while age and family history and genetics are the biggest risk factors, lifestyle factors within people’s control also play a role, such as maintaining an ideal body weight, avoiding head trauma, doing regular exercise and adhering to a Mediterranean diet.
“Remaining mentally, physically and socially active preserves brain health. There is still a possibility you can get [Alzheimer’s] but this could help delay or even prevent it,” Turner said.PREDICTING THE DISEASE
Researchers are also breaking new ground with predictive technologies.
Federoff described his lab’s groundbreaking research, released in March of this year, which found a new blood test that can predict who will experience cognitive decline or develop Alzheimer’s with 90 percent accuracy. His team is working on moving that accuracy to more than 99 percent for the test, which needs external validation in large-scale clinical studies.
The finding made international news and heralded a new era in which people could know in advance that they will get the disease. It also raised ethical questions regarding what people would do with that information once they have it, in light of the lack of treatment options.
Fitzgerald, the bioethicist, said that this breakthrough and others offer patients, their families and society as a whole “the incentive to start to address some of these ethical issues.” And the ethical conundrum is not unprecedented, he said; we can look to other conditions such as Huntington’s disease and even cancer to see how people who learn of their likelihood of getting a devastating disease handle that information.
“What will we do if we know? How will we treat one another? How can we look at ways we can reduce the stress and the depression? How can we better care for one another now to better prevent the types of decline we want to avoid?” FitzGerald queried.“Here is another opportunity to say: ‘How can we use this information that could possibly be beneficial?’ There is a whole range of possibilities,” he added.
Since advance knowledge of the disease could provoke discrimination in terms of insurance coverage, employment or other areas, it is imperative to get ahead of this discussion, Federoff said.
“It is essential that we ensure there is no overt discrimination. If a test discloses that someone has a risk in a period of time to become an Alzheimer’s patient, we have to make sure they can get long-term care insurance and life insurance,” Federoff said.The Memory Disorders program seeks volunteers who are cognitively normal (especially ages 75-85) or have mild memory problems or early Alzheimer’s to join research studies. For more information, go to memory.georgetown.edu.
By Lauren Wolkoff