Long-term study aims to connect Alzheimer’s dots

CU study looks beyond amyloid beta to try and predict disease onset
March 23, 2016

The Rocky Mountain Alzheimer’s Disease Center at the Anschutz Medical Campus has launched a study so far-reaching that it hopes to help answer not only some of today’s biggest questions relating to the disease, but also ones that Alzheimer’s and other memory-disorder researchers have yet to formulate.

“The whole goal is to be able to predict who’s at risk before there are any clinical symptoms,” said Huntington Potter, PhD, the RMADC’s director.

Brianne Bettcher, PhD, a neuropsychologist with the Rocky Mountain Alzheimer’s Disease Center at the University of Colorado, is helping lead a long-term study to understand the roots and development of Alzheimer’s disease.

The Longitudinal Biomarker and Clinical Phenotyping Study, launched in January, follows a line of inquiry that has become an RMADC calling card: to better understand two very different but in fact closely related conditions – Alzheimer’s disease and Down syndrome – through the strategic study of both under one roof.

The study itself aims to establish a repository of blood, cerebral spinal fluid, imaging and clinical data from about 400 patients over the course of five years. Brianne Bettcher, PhD, a CU School of Medicine neuropsychologist, is leading the study as well as neuropsychology research at the RMADC.

“As a neuropsychologist, I’m very interested in assessing patients’ cognition over time and relating it to their brain and physiological states,” Bettcher said.

The Memory Disorders Clinic at the UCHealth University of Colorado Hospital Neurosciences Center will serve as the study’s main source of consenting patients, Bettcher says. CU neurologist Jonathan Woodcock, MD, who serves as the clinic’s as well as the RMADC’s clinical director, is a study co-investigator, as is Potter.

One of four

Bettcher and colleagues are enrolling four types of patients in the study: those who are healthy, those with mild cognitive impairment, those with Alzheimer’s disease, and adults with Down syndrome. They hope to recruit and study roughly 100 people from each category over time, Bettcher says. Patients who join the study will undergo an annual evaluation, including cognitive testing, a physical and neurological exam, a brain MRI, bloodwork and the option of a cerebral spinal fluid draw, Bettcher says. While the study aims to advance science in the long-term, the workups may also identify treatable health problems that crop up with patients, she adds.

On the scientific front, Bettcher aims to link long-term changes in factors such as blood proteins not only to Alzheimer’s disease, but also to other cognitive disorders, vascular diseases and more, she says. The long-term evolution of a given patient’s brain scans could offer clues as to the timing of disease onset, which probably happens well before cognitive symptoms manifest, she says.

Part of what drives the need for the new study is that the amyloid beta plaques linked so strongly to Alzheimer’s disease remain an imperfect proxy. Some people have a lot of amyloid beta in their brains but no symptoms for years; others with lesser amounts of plaque have severe cognitive impairment.

“Hunt and I are very interested in understanding the heterogeneity,” Bettcher said. “Are there things that reflect resilience in the face of pathology, and how can we better predict that? Are there lifestyle factors that predict resilience with respect to Alzheimer’s disease?”

Potter is also interested in studying the ApoE genes – certain forms of which boost Alzheimer’s disease risk – from DNA collected from the samples’ white blood cells. But both he and Bettcher stressed that the samples they collect will help future scientists answer questions that crop up well after today’s inquiries have answers.

“We’re trying to be thoughtful about what we capture,” Bettcher said. “It definitely requires some forethought about what you think you’re going to need.”

High stakes

The stakes – both personal and societal – in getting answers to such questions are enormous. In 2014, Alzheimer’s disease was the sixth-leading cause of death, according to the U.S. Centers for Disease Control and Prevention. About 5.3 million people in the United States had Alzheimer’s disease in 2015, and it and other dementias cost about $226 billion, according to the Alzheimer’s Association. Without a medical breakthrough, those numbers are expected to rise to about 14 million patients and $1.1 trillion by 2050, the Association says.

For Bettcher, who arrived at CU from a faculty position at the University of California San Francisco in 2015, the study augments her work with the UCH Memory Disorders Clinic, where she sees patients one day a week. That’s especially important in Colorado and surrounding states, where Alzheimer’s is common and care is lacking, she adds.

“It takes a special team to work this context. You’re working with people during a potentially very vulnerable time in their lives,” Bettcher said.”We are all very passionate about this work.”

She and others on the team hope the new study and others at the RMADC help bring answers – and therapies based on them – to a disease that has yielded little to science.

For more information on the study or the UCH Memory Disorders Clinic, contact the Neurosciences Center at 720.848.2080.

About the author

Todd Neff has written hundreds of stories for University of Colorado Hospital and UCHealth. He covered science and the environment for the Daily Camera in Boulder, Colorado, and has taught narrative nonfiction at the University of Colorado, where he was a Ted Scripps Fellowship recipient in Environmental Journalism. He is author of “A Beard Cut Short,” a biography of a remarkable professor; “The Laser That’s Changing the World,” a history of lidar; and “From Jars to the Stars,” a history of Ball Aerospace.