PET plus new brain marker could assess Alzheimer's risk

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A new PET imaging technique developed at the University of California at Los Angeles (UCLA), along with patient-specific information on Alzheimer's disease risk, can help diagnose and track brain aging before symptoms appear, according to research published in the January issue of the Archives of General Psychiatry.

Researchers used PET imaging, which reveals plaques and tangles, the hallmarks of neurodegeneration. The PET scans were complemented by information on patients' age, cognitive status and a genetic profile.

“Combining key patient information with a brain scan may give us better predictive power in targeting those who may benefit from early interventions, as well as help test how well treatments are working,” said study author Gary Small, MD, who holds UCLA’s Parlow-Solomon Chair on Aging and is a professor at the Semel Institute for Neuroscience and Human Behavior at UCLA.

The researchers took PET brain scans of 76 non-demented volunteers after they had been intravenously injected with a new chemical marker called FDDNP, which binds to plaque and tangle deposits in the brain. The investigators were then able to pinpoint where the abnormal protein deposits were accumulating.

The authors reported that older age correlated with higher concentrations of FDDNP in the medial and lateral temporal regions of the brain, areas involved with memory, where plaques and tangles usually collect. The average age of study volunteers was 67.

They found that 34 of the 76 volunteers carried the APOE-4 gene allele, which heightens the risk for developing Alzheimer's disease. This group demonstrated higher FDDNP levels in the frontal region of the brain, also involved in memory, than study participants without allele.

“We found that for many volunteers, the imaging scans reflected subtle brain changes, which take place before symptoms manifest,” Small said. He noted that the brain will try to compensate for any problems, which is why cognitive symptoms may not become apparent until much later.

“This type of scan offers an opportunity to see what is really going on in the brain,” Small said.

Another subset of the volunteers had mild cognitive impairment (MCI), a condition that increases the risk of developing Alzheimer's disease. The 36 volunteers had higher measures of FDDNP in the medial temporal brain regions than normal volunteers. Those who had both MCI and the APOE-4 gene had higher concentrations of FDDNP in the medial temporal brain regions than volunteers who had MCI but not APOE-4.

“We could see more advancing disease in those with mild cognitive impairment, who are already demonstrating some minimal symptoms,” Small said. “Eventually, this imaging method, together with patient information like age, cognitive status and genetics, may help us better manage brain aging.”

In the future, brain aging may be controlled similarly to high cholesterol or high blood pressure, according to Small. Patients would receive a brain scan and perhaps a genetic test to predict their risk. Medications and other interventions could be prescribed, if necessary, to prevent or delay future neurodegeneration, allowing doctors to protect a healthy brain before extensive damage occurs. The brain scans may also prove helpful in tracking the effectiveness of treatments, he concluded.