Patients' offspring have memory loss

Children of parents with Alzheimer's disease can develop memory problems in their 50s or even younger - much earlier than previously thought - according to a large study released yesterday by researchers at Boston University School of Medicine.

The study subjects, who carried a gene strongly linked to Alzheimer's, performed worse in memory tests, on average, than other middle-aged people who had the same gene but did not have a parent diagnosed with Alzheimer's. The difference in memory between the two groups was equivalent to approximately 15 years of brain aging, researchers found.

"How big an effect we saw was surprising," said Dr. Sudha Seshadri, a BU associate professor of neurology and senior author of the study. "It was like you were comparing two groups, 55-year-olds to 70-year-olds."

Researchers not involved with the study say the findings have broad implications because they are the first to demonstrate changes in cognitive abilities years before the age at which the degenerative brain disease is diagnosed. By the time the most common form of Alzheimer's is confirmed, usually around age 75, it has irreparably damaged large sections of the brain's memory center.

The BU findings do not suggest that everyone with the gene, known as APOE-e4, will develop Alzheimer's, said Seshadri. The gene is believed to play a role in about 50 percent of Alzheimer's cases. The study also did not address whether the people showing early memory impairment were destined to develop Alzheimer's.

The memory of the affected group was diminished, but still within a broad range considered normal, researchers said. The deficits would not be noticeable to the average person, researchers said.

"These people are not having trouble at work," Seshadri said.

As scientists race to find Alzheimer's treatments, the latest findings may help researchers one day pinpoint when medical interventions should be started to halt the brain-ravaging process before it takes hold. Alzheimer's afflicts roughly 5 million Americans and has no known cure.

The BU study, which included 715 participants ages 37 to 80, has been accepted for presentation at the annual meeting in April of the American Academy of Neurology, the nation's premier organization of brain specialists. However, the study has not yet gone through the traditional scientific vetting process, which includes other scientists reviewing the data before it is published in a journal.

The BU participants come from the Framingham Heart Study, which has tracked three generations. It started in 1948 to study cardiovascular risks and later expanded to include other diseases.

In the latest research on Alzheimer's, participants were separated into two groups. Participants in both groups carried the APOE-e4 gene, but in one group, participants also had at least one parent with Alzheimer's or dementia. The other group had parents who did not have the disease.

Both groups were given visual and verbal memory tests, in which participants were shown complex images and also were told short stories. Twenty minutes later, they were asked to draw the figures and recite the stories as precisely as they could recall. The group with a parental history of Alzheimer's disease scored, on average, significantly worse than the one with no parental Alzheimer's.

Other research has shown that significant changes, such as the buildup of amyloid plaques in the brain, take place at least a decade before Alzheimer's disease is diagnosed. But the BU study is the first to demonstrate that measurable changes in memory may also be happening.

"If that bears out, it appears that Alzheimer's starts years before it's diagnosed," said Dr. Randy Bateman, assistant professor of neurology at Washington University School of Medicine in St. Louis. Bateman is conducting a separate, large-scale Alzheimer's study that is measuring brain fluid and plaques of middle-aged participants as well as testing for memory impairment.

Bateman said that if other studies replicate BU's findings, the confirmation of very early symptoms could provide physicians with a "window of opportunity" to treat patients before the brain is severely damaged. Currently there are a few approved medications to slow the mental decline from Alzheimer's, but they are given only after the disease has been diagnosed.

There is a genetic test to detect the APOE-e4 gene studied by the BU researchers, used by physicians to help diagnose Alzheimer's in patients who already are displaying symptoms. With scientists still unraveling the connections between APOE-e4 and Alzheimer's - some believe there may be up to a dozen more unidentified genes that play a role in the disease - none are recommending that healthy people seek such testing.

"I wonder about genetic discrimination," said Dr. Rudy Tanzi, a neurology professor at Harvard Medical School who co-discovered three other genes that have been linked to early-onset Alzheimer's, a more rare form of the disease that typically strikes before 65.

"If it's out there that my parents have APOE-e4, there is a chance my employer might know and wonder, 'Should I promote this guy?' " Tanzi said.

The BU findings, he added, increase the urgency for stronger genetic nondiscrimination laws. Tanzi said that even though a federal law - The Genetic Information Nondiscrimination Act, enacted last year - protects against employment discrimination, he worries about subtle discrimination in the workplace.

"I am not sure how wise it is to have genetic information about your cognitive function when you don't have the disease," Tanzi said. "People risk discrimination for something they can't help."