May 19, 2017 -- Judy Culbertson gets lost sometimes. She might be on her way home from the grocery store or some other place she’s been dozens of times, when she suddenly finds herself on a street she doesn’t recognize.
“Then I call somebody and they tell me which way to go,” says Culbertson, 74. “It’s scary.”
Incidents like these pushed Culbertson to attend a “Meet the Memory Doctor” town hall in Columbus, GA, last month. Culbertson, who lives just across the border in Phenix City, AL, was among 184 older adults who crowded into a packed conference room to hear neurologist Jonathan Liss, MD, speak. His pitch: “Make Columbus, GA, the focal point of the world’s effort to cure Alzheimer’s disease.”
The meeting is part of a 3-year citywide initiative, The Columbus Memory Project, intended to prevent memory loss and prevent or delay the start of Alzheimer’s disease. Based at the Columbus Memory Center, the project aims to make the city the first to screen every senior citizen for memory loss and thousands more for their chance of getting Alzheimer's disease from their genes.
“If we start taking memory as seriously as we take heart disease, we will take a massive leap both in our ability to prevent Alzheimer’s disease and in our ability to treat it as soon as there’s even that earliest detection, which we now know for certain is the key to defeating this disease,” Liss said. He is funding the project with $100,000 of his own money.
Through advertising, frequent town halls, and word of mouth, the project has recruited 1,600 people so far. The goal is to test 20,000 area residents ages 65 and older for memory loss and genetic risk and offer them free yearly memory testing. Adults 55 to 75 are eligible for genetic screening tests, but memory tests typically aren’t useful until age 65.
Genes and Alzheimer's
Culbertson is among those who agreed to get a free cheek swab -- a DNA test -- to find out if she has the ApoE e4 gene. This gene variant raises the chance of having Alzheimer’s disease, but it's not a guarantee that those who have it will develop the condition. One copy of the e4 variant moderately raises the odds of having late-onset Alzheimer’s disease. Two copies raise the risk more.
“I’m certain that I want to know the results of my cheek swab,” Culbertson said. “I don’t know what the options would be, but I’m already having problems with memory, so I want to know.”
Melissa Hill, 64, of Columbus is not so sure. Watching her mother decline into dementia in the last few years has left her frightened about her own future.
“I would be more afraid of an Alzheimer’s diagnosis than anything else. If I do find out [my ApoE e4 status], I would like to know what I can do, but I have to decide if I want to know that,” she said.
People who agree to submit their DNA can decide if they want to learn their test results.
“There are many people who don’t want to know,” said Dorene Rentz, a neuropsychologist who is not involved with the Columbus Memory Project.
“What will you do if you find out?” said Rentz, co-director of the Center for Alzheimer Research at Brigham and Women’s Hospital in Boston. “Will you then restructure your life in such a way that you’re worried about yourself for the rest of your life?”
Project participants who want to know their ApoE e4 status must meet via Skype with a certified genetic counselor, who won’t yet know their results either. The counselor must verify that the participant is emotionally stable enough and understands enough to learn their genetic risk. “They have to know what it means to know this stuff,” Liss said. “We can’t just jump into it.”
Rufus Riggs, who lost his mother and a paternal aunt and uncle to Alzheimer’s disease, wants to know where he stands. At 74 years old, he hasn’t noticed any signs of memory loss, but he knows the risk might be in his genes.
“If so, I want to know. Whatever I can do to be active and self-sufficient, I will do, because if you don’t do anything, it’s like putting your head in the sand, which is not very smart in my estimation.” Riggs and his wife attended the town hall together, and both planned to get the cheek swab.
It’s not only about whether a person wants to know their status, Rentz said. “How much does the spouse want to know whether their loved one is likely to get Alzheimer’s disease? I would think it’s a family decision. These are questions that the field is still grappling with.”
Testing Your Memory
Project participants ages 65 and over can also take a memory test. Test scores on the Self-Administered Gerocognitive Examination can pick up signs of memory loss ranging from mild cognitive impairment -- which may come just before Alzheimer's dementia -- to full-fledged dementia. The aim is to give every participant what Liss calls a “memory number.” He describes it as another vital sign for seniors -- a number they should know as well as their cholesterol level and blood pressure.
The idea, he says, is to monitor memory over the years, just like cholesterol, so that doctors can step in at the first, smallest signs of memory loss. By the time a person has severe cognitive impairment, it’s usually too late to do anything to slow the disease down. “We feel pretty convinced as a research community, not just me, that the key to defeating this disease, is finding it early,” he says.
Fifty-five out of 112 people tested during the first town hall showed that they had either mild cognitive impairment or dementia. This is a far higher percentage than you would expect in the general population, Liss said. Maybe people came to the meeting because they suspect they have memory loss, or maybe the group tended to be older, he says. The project staff have not yet broken the scores down by age.
Benefits and Risks
Today, there isn’t a prescription medication that people with the ApoE e4 gene can take to prevent Alzheimer’s disease. Nor is there a pill you can take at the earliest sign of memory loss. But one day, there could be.
For people who are interested, the project connects them with clinical trials that test such treatments, among them the Generation and EARLY trials. In the Generation trial, people with two copies of ApoE e4 who have no signs or symptoms of disease can take a drug called CNP520, designed to lessen beta-amyloid plaque in the brain. Buildup of this protein in the brain advances Alzheimer’s disease. The trial aims to discover whether CNP520 can prevent it. Similarly, the EARLY trial offers an experimental drug to people who either have the ApoE e4 gene or beta-amyloid plaque in their brain with no other symptoms of disease.
In the best-case scenario, participants get personal health benefits from the project or a clinical trial while helping advance research. But taking part in the studies can be risky. “These treatments are all experimental and have risks that we don’t know about,” said Rentz.
Screening tests may bring unexpected risks and consequences, too. “One of the things about screening is that it tends to lead to subsequent testing,” said Gilbert Welch, a professor of medicine at the Dartmouth Institute for Health Policy and Clinical Research in Hanover, NH. His research focuses on how finding disease early can affect people.
“For real people, suddenly that starts to involve real anxiety and real money, which comes out-of-pocket and only adds to anxiety,” he says.
Welch wonders whether the benefits of early detection, based on the non-experimental treatments that doctors now have for Alzheimer’s disease, outweigh the psychological cost. “This is a really powerful disease for people, and I certainly don’t want to know about it 10 years before it happens, particularly since it’s not actionable.”
But before doctors can take action against the disease, volunteers will have to be willing to take part in experimental research.
“If Columbus, GA, can be the first city in the world to get everybody 65 and older to know their memory number, I think we will have developed a paradigm for the prevention of Alzheimer’s disease that will be copied throughout the world and will keep the cost of the disease dramatically lower,” Liss said.