Brain imaging shows differences in people at risk for Alzheimer's

Using brain imaging, researchers at Columbia University Medical Center (CUMC) have found clear differences in brain function between healthy people who carry a genetic risk factor for Alzheimer's disease and those who lack the factor.

Because researchers believe that Alzheimer's disease starts changing the brain years before any symptoms appear, the disease may be most amenable to treatment in these pre-clinical stages. If so, detecting the early changes will be crucial for future therapies.

People who carry the genetic risk factor, the å 4 allele of the Apolipoprotein (APOE) gene, have higher risk of developing the disease than non-carriers and usually show symptoms earlier.

"It is possible that what we're seeing in the APOE- å4 carriers are early changes in the brain caused by Alzheimer's disease," says the study's senior author, Yaakov Stern, Ph.D., of CUMC's Taub Institute and Sergievsky Center.

But he and the study's first author, Nikolaos Scarmeas, M.D., caution that more research is needed before it's known for certain if the difference is an early sign of Alzheimer's. "It's also possible that the brain differences we see are related to the APOE gene but are not necessarily directly related to incipient Alzheimer's," says Dr. Scarmeas, a neurologist in the Taub Institute, Sergievsky Center and neurology department. "Even so, the differences we've found may provide information on how the å4 allele predisposes carriers to Alzheimer's disease."

The present study appears in the Nov.-Dec. 2004 issue of the American Journal of Geriatric Psychiatry.

The researchers looked at six people who carried the APOE- å4 risk factor and 26 non-carriers.

None of the 32 participants, mostly in their 60s and 70s, had any signs of dementia or memory deficits and the two groups could not be distinguished from one another by standard cognitive tests.

PET scans taken while the subjects were performing a memory task, however, showed clear differences between the two groups. As the participants tried to remember if they'd seen a particular shape before, one pattern of brain activation appeared in the APOE- å4 carriers while a different pattern appeared in the non-carriers.

Dr. Scarmeas says the difference may indicate that APOE- å4 carriers have to compensate for early damage done by Alzheimer's by switching to an alternate brain network to complete the task. It could also be that their different genetic makeup results in different patterns of brain activity.

In previous studies, Dr Scarmeas has demonstrated APOE-related changes in brain activity in patients that already have Alzheimer's disease and in healthy, young, college-age people. Drs Scarmeas, Stern and a large group of other researchers at the Taub Institute are using advanced brain imaging techniques to examine changes in cognition and brain function as a result of normal aging and brain diseases, such as Alzheimer's disease.