UCI study volunteer Diana Burns (right) keeps an eye on her mother, Irma, who has late-stage Alzheimer's. Burns has experienced episodes of forgetfulness, but researchers found no evidence of dementia in her brain. Steve Zylius/UC Irvine

Distinguishing ‘senior moments’ from Alzheimer’s

UCI scientists locate inner brain pathway they believe is key to memory.

In late 2008, when Diana Burns forgot yet again where she’d put her purse, and then couldn’t remember why she was in the laundry room, she decided she had to know: Was she, like her aging mother, going to be a victim of the debilitating loss of brain function known as Alzheimer’s disease?

“When you’re a caregiver for somebody with Alzheimer’s, you always wonder if it’s going to happen to you,” says Burns, who had quit her job to stay home the day her mother was found unconscious and bleeding half a mile from their house, with no idea how she got there. “I was becoming concerned because I myself was forgetting things, so I thought, ‘Now is the time to find out.’”

Burns, 64, of Anaheim, searched for human clinical trials online and found UC Irvine’s Center for the Neurobiology of Learning & Memory. Soon interim center director Craig Stark and his staff had her ensconced in their big MRI machine.

Now, with the help of Burns and other volunteers aged 18 to 89, the researchers have been able to identify for the first time in humans a long-hidden part of the brain known as the perforant path. The passage is believed to deteriorate gradually as part of normal aging and far more quickly as part of Alzheimer’s. Scientists have struggled for decades to locate the tiny pathway, which is linked to the hippocampus, a well-known center of memory.

The UCI researchers developed and used a new ultrahigh-resolution technique, outlined in a paper published June 28 in the Proceedings of the National Academy of Sciences, to electronically peer through dense matter near the seahorse-shaped hippocampus.

Locating the perforant path and monitoring its deterioration could distinguish normal aging from dementia much sooner than other methods, offering relief to absent-minded folks. The information could also be useful to drug companies and doctors testing Alzheimer’s treatments.

“The nice thing about this is we may be able to predict Alzheimer’s very early,” says Stark, who often inserted his own gleaming bald pate into the MRI to help develop their scanning techniques. “Let’s say you’re a drug company, and you think you’ve got a potentially effective treatment for slowing Alzheimer’s. You want to try it on people in the most preliminary stages of that disease, not those just experiencing normal aging.”

The search for the inner passage was detailed but also involved common sense. The perforant path is basically a bundle of nerve fibers, lined up like straws, connecting an area called the entorhinal cortex to the hippocampus. By monitoring the brains of Burns and others via their ultrahigh-resolution technique – know as diffusion tensor imaging – the team was able to detect water molecules moving in the exact area where they knew the passage had to be. The scientists then painstakingly tracked the progress of the molecules along the length of the fiber bundle, thereby identifying the perforant path.

“There was definitely an ‘aha’ moment when we knew we had finally found it,” says Mike Yassa, postdoctoral researcher and lead author of the paper. They were also able to measure the strength of the passageway, showing that in normal brains it weakens gradually, reducing the capacity to quickly recall details but not wiping out memory.

L. Tugan Muftuler, assistant professor of radiological sciences, also contributed to the study, which was supported by the National Science Foundation and the National Institute on Aging. With additional funding, the UCI researchers are now utilizing the same technique to examine people with mild cognitive impairment – often the first stage of Alzheimer’s. They expect to see precipitous deterioration of the perforant path.

So what about Burns? Fortunately, the scientists detected no signs of dementia. Her data helped create a baseline image of a normal, aging brain. “I’m healthier than a horse,” she jokes, speaking via cell phone from a quilt show, where she was enjoying a rare day off from caring for her mother.

Burns is happy she did the trials – both because she got answers about her own memory and because the research may help others. “I couldn’t donate money,” she says, “but I could donate time.”

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