November 8, 2004

Baycrest study uses advanced PET scanning technique to detect brain deposits associated with Alzheimer's

Washington , DC – Sophisticated brain imaging techniques show that when storing and accessing memories, individuals who carry a genetic variant linked to a heightened risk of Alzheimer Disease “activate” brain functions differently than do non-carriers, even when no outward signs of disease are present, according to a study reported in the November-December issue of the American Journal of Geriatric Psychiatry (AJGP).

The study by investigators at Columbia University is one of two in the current issue of the journal offering new evidence that brain imaging technology known as positron-emission tomography or PET scans has the potential to play an increasingly prominent role in the study and treatment of Alzheimer Disease (AD).

The second report, from researchers at Baycrest Centre for Geriatric Care, the Centre for Addiction and Mental Health PET Center and the University of Toronto, describes an advance in using PET scans to detect the presence of brain deposits known as beta-amyloid plaques, which are believed to be a telltale sign of the disease.

Both studies come in the wake of an October announcement that Medicare, the federal health plan for seniors, will pay for PET scans used to help determine whether certain patients with dementia have AD or another brain disorder. The decision to cover the costs of this relatively narrow application has sparked renewed interest in research to determine whether the technology could have broader uses for AD.

PET scans are already widely used among scientists studying the disease. Researchers led by Nikolaos Scarmeas, M.D., of Columbia University , used PET scans to observe brain activity in a small group of healthy elderly subjects--six of whom carried a genetic variant linked to an increased risk of AD--as they underwent a memory test.

The scientists were not trying to determine whether the carriers were suffering from memory loss. Rather, they wanted to see whether “patterns of brain activation” that occurred while they were taking the test differed from non-carriers. As the study points out, previous research has shown that outward symptoms of AD are “preceded by a period of unknown duration during which” changes occur in the brain though no significant memory loss or other problems with everyday activities are evident.

What the PET scans revealed is that while the carriers had similar cognitive performance to the non-carriers, their brains were processing the tasks differently than non-carriers.

“Our results indicate that elderly persons with a genetic risk for AD have alterations in brain functioning even at a point in time when behavioral, cognitive or clinical evidence of the disease is absent,” Scarmeas said.

However, Scarmeas cautioned that the results could lead to different interpretations.

“It could be that the changes we saw in the way these carriers process memory tasks are evidence that these are people who are destined to get the disease,” he said. “But we also know that not everyone who carries this genotype develops AD. It could be that the gene simply causes the brain to function differently but not in a way that necessarily does damage. So we can't say for sure that what we are observing is early evidence of Alzheimer Disease.”

Scarmeas said the above conundrum could be solved if the PET scans could be paired with tests that would offer some biological evidence of the disease. That's why he's intrigued by another study in this same AJGP issue in which a team headed by Nicolaas Verhoeff, M.D., Ph.D., from the Kunin-Lunenfeld Applied Research Unit at Baycrest Centre for Geriatric Care, the PET Centre at the Centre for Addiction and Mental health, and the University of Toronto, reports that it successfully used a novel PET scan technique to detect beta-amyloid plaques, one of the brain lesions linked to AD. Thus, now we may be able to explore which are the earliest changes that could be detected in AD: changed brain functions during “active” memory processing or deposition of brain chemicals linked to AD.

As it now stands, doctors have no laboratory tests they can use for confirming the existence of AD or for monitoring its progression. Diagnosis is confirmed only after a relatively clear set of symptoms appears. However, autopsies of AD victims have revealed abnormally high levels of what are known as beta-amyloid plaques. Some scientists believe beta-amyloid plays a central role in AD-related brain damage. They also suspect that abnormally high levels of the substance begin accumulating in the brains of AD patients long before symptoms appear. But they have lacked a reliable test for detecting amyloid build-up.

Verhoeff and his colleagues recruited five AD patients and six healthy volunteers. All were injected with a new compound designed to cross from the bloodstream into the brain, attach itself to amyloid deposits and then send out harmless radioactive signals that can be detected with a PET scan. This new compound, which had been originally developed at the University of Pennsylvania in collaboration with the Centre for Addiction and Mental Health PET Centre in Toronto , was compared to another compound that had been developed independently at the University of Pittsburgh . What the study found is preliminary evidence that the new compound or “tracer” may also be effective at allowing the researchers to use PET scans to discriminate between amyloid levels one would expect to see in AD versus non-AD patients.

Researchers report that the amount and location of the amyloid build-up they observed in the test subjects with AD was consistent with what researchers have seen in brain autopsies of AD victims.

Verhoeff said future research should evaluate both tracers in a larger group of AD patients and in subjects who are experiencing relatively minor memory loss of an undetermined cause. As it now stands, doctors face a significant quandary in determining which patients reporting memory loss are in the early stages of AD and which ones are suffering from a different disorder. A test that is very sensitive to brain amyloid levels could enable doctors to identify the subgroup of patients more likely to be suffering from AD.

“The test would allow for a more timely initiation of preventative treatment strategies aimed at delaying the onset and decreasing the severity of AD,” Verhoeff reports.

The American Journal of Geriatric Psychiatry is the official journal of the American Association for Geriatric Psychiatry and can be found online at http://ajgp.psychiatryonline.org.

CONTACT:
American Association for Geriatric Psychiatry
Joe Sutherland (301) 652-1558
jsutherland@burnesscommunications.com
Kate McDuffie (301) 654-7850, ext. 113
kmcduffie@aagponline.org