, Salem, MA

November 15, 2013

Alzheimer's research focusing on the 'before'

By Gary Rotstein
The Salem News

---- — Anne Kolesar’s father, aunt and grandmother all had dementia before they died — a knowledge that shakes her as she contemplates her future at age 61.

The Indiana, Pa., hospice volunteer has no signs of Alzheimer’s disease and no way of knowing if she’ll get it, but she’s aware that she carries a gene that increases her risk. It means she spends more time than her peers thinking about the disease, and she’s joined a national registry of healthy people willing to be studied long term in trials aimed at preventing Alzheimer’s.

Kolesar and her sister “inspect ourselves minutely to make sure that we haven’t got it yet. I know that’s the way all children of all Alzheimer’s sufferers are — you’re just waiting for it to hit.”

Kolesar, who is married and has an adult son, supports a growing trend in Alzheimer’s research, which until now has been dominated by studies of people already diagnosed with some level of the disease that gradually and devastatingly robs them of their memory and cognitive function.

So little has come of efforts to undo those effects in drug trials that more money and emphasis is being put into lengthy monitoring of adults without any dementia symptoms, to see if drugs can postpone their getting the disease or even prevent it. For such studies to be practical and cost-effective, researchers need participants who, like Kolesar, are known to be at higher risk than the general population.

The primary risk factor for Alzheimer’s is age, with an estimated 5 million Americans over age 65 carrying the disease. Kolesar knows from participation in a prior study in New York, however, that she inherited a gene known as ApoE4, which increases her risk by about fourfold.

That makes her a relatively valuable person among some 20,000 nationally who have signed up for the Alzheimer’s Prevention Registry since its creation in May 2012. The Banner Alzheimer’s Institute, based in Phoenix, coordinates the registry, hoping ultimately to create a list of 250,000 people making themselves available for study by researchers across the nation.

Jessica Langbaum, Banner associate director, said people 18 or older can join the registry, and they will be emailed updates on Alzheimer’s findings and studies. The target population, however, is anyone 50 and older who has shown no problems yet with memory or mental functioning.

About 70 percent of those who have signed up for the registry thus far have some family history of Alzheimer’s.

“People certainly feel a personal connection to the disease, and that’s often what’s motivating them to get involved,” Langbaum said.

The registry has not been used for any studies yet. One of the first will be for a Banner-led trial funded in part by $33 million from the National Institutes of Health that will begin tracking the progress in 2015 of some 650 people who carry two copies of the ApoE4 gene.

Only 2 to 3 percent of the population are in that category, and such individuals have about a 20 times higher risk than the rest of the population of developing Alzheimer’s, said Eric Reiman, a brain-imaging researcher who is Banner’s executive director.

The idea is to begin following those 650 people when they’re still healthy after age 65 and track them for a five-year period, while administering a drug that has shown potential in preliminary trials to inhibit formation of amyloid plaque. The presence and growth of amyloid in the brain has been linked to Alzheimer’s, though researchers have not concluded whether amyloid causes the diminishing mental abilities or are just a visible sign of them.

In a separate long-term prevention trial where the registry won’t be needed, Banner is heading a study of hundreds of members of an extended family in Colombia who have a genetic mutation far more serious than carrying the ApoE4 gene. The mutation virtually guarantees that individuals will develop the early-onset version of Alzheimer’s in their 30s, 40s or 50s. The family members participating in the study will receive an anti-amyloid drug called crenezumab, or a placebo, while monitored for five years for any preventive effects.

“The hypothesis is that some of these treatments may need to be started before amyloid ravages the brain in order to have the most effect,” Reiman said. “It’s been suggested that even a modestly effective treatment could have a profound public health effect. ... A procrastination treatment that delays onset of the disease by five years could cut the number of people diagnosed with Alzheimer’s in half.”

To get more information or join the Alzheimer’s Prevention Registry, go to For the Alzheimer’s Association Trial Match, visit