To this end, researchers at UCLA (Los Angeles, CA) have developed a PET tracer called FDDNP that binds specifically to such plaque and tangle deposits in the brain. By using FDDNP-PET in tandem with patient-specific information on Alzheimer's disease risk - including age, cognitive status and genetic profile - they hope to develop a means to diagnose brain aging before any symptoms appear (Arch. Gen. Psychiatry 66 81).
"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, professor at UCLA's Semel Institute and director of the UCLA Center on Aging.
"The fact that we can see tau tangles as well as amyloid plaques is critically important in early detection of brain aging, since the tangles are the first abnormal proteins that appear in the brain, long before dementia is clinically obvious to the physician," added co-author Jorge R. Barrio, professor of molecular and medical pharmacology at UCLA's David Geffen School of Medicine.
Related risks
The UCLA team recorded PET brain scans of 76 middle-aged and older volunteers without dementia, following intravenous injection of FDDNP. The scans revealed a correlation between older age and increased FDDNP binding 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.
Thirty-four of the volunteers carried the APOE-4 gene, which increases the risk of developing Alzheimer's disease. This group demonstrated higher FDDNP levels in the frontal region of the brain, also involved with memory, than study participants without the gene.
"We found that for many volunteers, the imaging scans reflected subtle brain changes, which take place before symptoms manifest," said Small. 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."
Another subset of volunteers had mild cognitive impairment (MCI), a condition that's considered a risk factor for developing Alzheimer's disease. These 36 subjects had increased FDDNP binding in the medial temporal brain regions. Those with both MCI and the APOE-4 gene had higher concentrations of FDDNP in the medial temporal brain regions than volunteers with MCI alone.
"We could see more advancing disease in those with mild cognitive impairment, who are already demonstrating some minimal symptoms," said Small. "Eventually, this imaging method, together with patient information like age, cognitive status and genetics, may help us better manage brain aging."
According to Small, the future could see brain aging controlled in a similar manner to high cholesterol or high blood pressure. Patients would receive a brain scan and perhaps a genetic test to predict their risk, then medications and other interventions could be prescribed where necessary to prevent or delay future neurodegeneration. The brain scans may also prove helpful in tracking the effectiveness of treatments.
FDDNP-PET scanning is currently being used in a research setting, with clinical trials under development to bring the technology to wider patient use.