By the time a person begins to experience symptoms of Alzheimer’s disease, several brain structures already are dotted with the plaques and tangles that characterize the illness. Research teams are working to identify changes in brain structures as early as possible in the course of the disease — at a time when it might soon be possible to halt its progress before people become severely impaired.
A team of neuroscientists at the Silvio Conte Center for Neuroscience Research and the Alzheimer’s Disease Research Center at the University are working with state-of-the-art imaging techniques to see whether they can identify subtle changes in brain structures that are present in the earliest stages of the disease.
Reporting online and in an upcoming issue of the journal NeuroImage, Lei Wang, Ph.D., research associate in psychiatry, and his colleagues have identified changes in the brain that appear to distinguish Alzheimer’s disease from healthy aging. Because learning and memory are greatly affected by Alzheimer’s disease, the team focused on a structure important for learning and memory: the hippocampus, a seahorse-shaped structure deep inside the brain.
The researchers compared healthy people with those in the early stages of Alzheimer’s disease. To identify differences, they conducted magnetic resonance imaging scans two years apart on 18 patients with mild Alzheimer’s disease and 26 healthy individuals about the same age.
The team measured differences in the volume and shape of the hippocampus and the differences in the way the volume and shape became more abnormal over time.
In people without Alzheimer’s disease, hippocampal volume decreased by about 4 percent over two years. But in people with early Alzheimer’s disease, volume decreased by 10 percent.
In addition, the changes in shape in healthy people tended to be confined to a small part of the structure. But in Alzheimer’s patients, shape changes involved larger parts of the hippocampus, including an area where plaques and tangles are known to appear.
“There were changes in normal people, too,” Wang said, “but the changes were more pronounced in people with mild Alzheimer’s disease. At the start of the study, there were some differences between the two groups, but at the two-year follow-up, the changes had spread to a wider region of the hippocampus in people with Alzheimer’s disease.”
Much of the Conte center’s research uses imaging to try to identify subtle anatomical differences that demonstrate a person is at risk for a particular disease. In diseases like schizophrenia or autism, researchers believe differences in the shape of various brain structures probably show up very early — perhaps even at birth.
“But in Alzheimer’s disease, presumably brain structures have a normal size and shape until the disease cascade begins,” said John G. Csernansky, M.D., the Gregory B. Couch Professor of Psychiatry and director of the Conte Center. “Changes in hippocampal shape represent early evidence of damage to a part of the brain that previously was normal. Those changes in shape happened as patients were first showing symptoms of Alzheimer’s disease, so that provides strong evidence the shape changes we observed in the hippocampus may be actually causing at least some of the symptoms of Alzheimer’s disease.”
Alzheimer’s disease also causes volume changes, which can be difficult to interpret because people of various sizes tend to have different sized brains. By using imaging scans to measure subtle changes in shape, the researchers believe they have a more sensitive indicator of the presence of disease.
“Tangles and plaques occur early in a part of the hippocampus called the CA1 region and in another sub-field of the hippocampus called the subiculum,” Wang said. “In our study, we were able to see changes occurring in those same sub-fields as the disease progressed over time. Our findings seem to correspond to what others have found in post-mortem studies.”
The ultimate goal is to identify shape and volume differences that can predict the future onset of the disease. Detecting the disease before clinical symptoms appear will be critical when treatments become available to prevent more extensive damage and halt the progression of the disease.