The results are promising, says Sisodia. He says the findings may also shed light on the earliest progression of the disease. Research from animal studies suggests that synapses—the connections between neurons—are the first part of the brain to suffer. While still just a theory, it’s possible that the brain regions that receive input from the substantia innominata shrink before that region itself does because they are losing their incoming synapses. However, he says, larger studies are needed to determine how accurate a predictor of Alzheimer’s this measure can be.
In a second study, UCLA’s Madsen analyzed MRI scans from 400 elderly individuals, some healthy, some mildly impaired, and some severely impaired, who had previously undergone brain scans, cognitive testing, and other types of medical testing. She focused on a c-shaped region in the center of the brain known as the caudate nucleus, which plays a key role in motor control and attention. Using mathematical tools to compare the size and shape of the caudate nucleus across different groups, she found that the caudate had shrunk most significantly in people with Alzheimer’s disease—it was 7 percent smaller than in healthy people. People with mild cognitive impairment also showed some decline, about 4 percent compared to controls. Within the latter group, those who went on to develop Alzheimer’s within the next year had a smaller caudate than those who did not.
Before drug developers can begin to use markers such as these to select patients for clinical testing, researchers need to better document early changes associated with the disease, says Sisodia. He points to one ongoing trial in Colombia that involves studying families who carry a genetic mutation that guarantees development of Alzheimer’s. Because scientists know approximately when people with the mutation will develop the disease, they can carefully analyze their brains for early changes.
“Before drug trials, we need to better solidify the data,” says Sisodia. “That’s why doing the study in Colombian people to study the natural history of disease is so important. They can study the progression from a normal individual with perfect cognition to abnormal cognition and look for the cellular correlates of behavior.”