Imaging Alzheimer’s Patients’ Brains

by Shauna Kanel

Kaustubh Supekar’s Research Article
The subject of human brain function has long been at the forefront of biological research; now a BMI student is using innovative, computational imaging-based techniques to study abnormal brain function in a neuropsychiatric disorder — one of the leading causes of death and disability in the United States — Alzheimer’s Disease (AD).

Alzheimer’s is a progressive disease. The sign that clues most people in to the fact something is wrong is the loss of memory, so scientists tend to view this loss as the first recognizable symptom of AD. But what if something was going on in the brain before a functional, noticeable, affective loss of memory occurred in an Alzheimer’s patient? It could alert physicians of the disease’s presence before any permanent damage occurs, and could possibly reveal new areas to study, and new treatments to develop.

Kaustubh Supekar, a PhD candidate in the BMI training program (see insert), is utilizing a novel Functional Magnetic Resonance Imaging (fMRI) technique to discover a biomarker for early and accurate diagnosis of AD. fMRI measures the blood flow to areas of the brain, indicating neural activity.

While in an fMRI scanner, participants were asked to rest and keep their eyes closed. The use of resting data gives researchers something with which to compare performance data, and it frees the fMRI data from several pitfalls associated with traditional fMRI techniques where the participants are asked to perform sensory or memory related tasks in the scanner. Patients with cognitive impairments may not be able to perform the same tasks with the same level of competency as unimpaired patients, and so pitfalls resulting from differences in learning effects and variable performance can be avoided in Alzheimer’s patients’ fMRIs by measuring performance data against resting data.

Since AD affects multiple systems and causes a lessening of efficiency in the brain, researchers studied interactions between brain regions, looking at the brain on systemic and global levels to find differences between “normal” and Alzheimer’s-affected brain structure and function. Supekar hypothesized that it was a change in the level of efficiency in brain system interaction causing the abnormal brain function in AD. Perhaps function depreciates before neurons die, Supekar hypothesized.

Findings show that Supekar is right. The memory system fails first, possibly due to decreased interaction with other brain regions, which may lead to cell death in the area responsible for memory – a main hub of many brain networks.

He likens this system to the popular social networking Web sites, such as Facebook and MySpace, and the hippocampus to “popular” people on the site. “We found that in Alzheimer’s disease, these hub regions are targeted first, which may explain memory loss and confusion” characteristic of Alzheimer’s disease.

He is currently studying subsets of this imaging work, searching for common image-based biomarkers of Alzheimer’s, and ruling out biomarkers of dementia alone. This will greatly advance early-stage detection of Alzheimer’s, and will further provide candidates for early treatment. If physicians can pinpoint consistent, functional changes in “social hubs” of the brain that precede neuron death, perhaps they can thwart permanent memory loss.

Supekar was awarded the 2007 Kathryn Grupe Award for excellence in research on Alzheimer’s from the Alzheimer’s Association of Northern California and Northern Nevada.

He collaborated with Vinod Menon, PhD, associate professor of psychiatry & behavioral science; Michael Greicius, MD, assistant professor of neurology; Mark Musen, MD, PhD, professor of biomedical informatics; and Daniel Rubin, MD, clinical assistant professor in radiology (see feature article for more information on this collaboration). The work was funded by grants from the Alzheimer’s Association and from National Institutes of Health.