The Brain Donation Research Project
One Sunday David Wekstein's home telephone rang at 9 a.m., alerting him that he and other researchers at the University of Kentucky's Alzheimer's Disease Research Center were about to receive a special gift.
"You don't know me," the caller told Wekstein, who is the associate director of the center, "but I'm one of your control subjects. My next-door neighbor is also one of your controls. He just died two minutes ago. Call me back at this number in about five minutes. By then his sister will be here and we'll get this thing going."
Within an hour of that phone call, the neighbor's body was on its way to the University of Kentucky, where researchers would immediately perform an autopsy on the man's brain. Both Wekstein's caller and his neighbor are part of a group of older Fayette County residents who have agreed to donate their healthy brains after they die to help researchers learn more about Alzheimer's disease.
Most agree to participate in the control group because they have personal knowledge of Alzheimer's disease. They've lost a parent, spouse, sibling or another relative or a friend to the disease, which afflicts an estimated four million people in the United States over the age of 65, including an estimated 60,000 Kentuckians. Alzheimer's disease is marked by progressive, irreversible declines in memory, performance of routine tasks, time and space orientation, language and communication skills, abstract thinking, and the ability to learn and carry out mathematical calculations. Other symptoms include personality changes and impairment of judgment.
David Wekstein has directed the brain donation research project since its inception in 1989. "The prime motivation of the volunteers is altruism."
Since it opened in 1985, UK's Alzheimer's Disease Research Center has diagnosed and followed hundreds of older people with non-treatable memory disorders--almost always Alzheimer's disease. The next of kin of many of the patients who are followed by the Memory Disorders Clinic give permission, when the patient dies, for an autopsy, which must be done as quickly as possible because of biochemical changes in the brain after death. The autopsy serves two purposes: it lets the family know for sure if the patient had Alzheimer's disease, which can be definitively diagnosed only through an autopsy, and it allows the center to use the brain for research. "It's a way for us to correlate what we find with the patient clinically with what we find in the brain after death," Wekstein says.
But studying the brains of Alzheimer's patients alone was not enough. Researchers needed a control group. "We can study Alzheimer's brains for the next 20 years and if we don't study brains of people who don't have Alzheimer's disease, we can't draw valid conclusions," Wekstein says.
So in August of 1989 Wekstein began recruiting people for a control group. The Sanders-Brown Center on Aging already had a pool of 1,200 older Fayette County residents who were called on periodically for research projects, and Wekstein began writing letters to those volunteers 10 at a time.
"Basically, it was a polite letter that said, 'When you die, will you give us your brain?'" Wekstein says. Phone calls followed the letters. "Some of the people would pick up the phone and say, 'Hell, no!' And others would politely say, 'Thank you, but this is not my thing,' and about 20 percent said, 'Yes, I would be very much interested,'" Wekstein recalls.
Researchers met with those who were interested, explaining in detail what they were obligating themselves to do and asking them to sign informed consents. The researchers also administered neuropsychological tests to verify the volunteers' normalcy.
From those beginnings in 1989, 499 volunteers were recruited by the end of May 1998, with 380 of them still being followed (81 have died and a few have either moved away or withdrawn from the project). The center has not actively recruited donors for several years because the group is self-generating, with members of the group recruiting their friends, says Gail Cohen, research volunteer coordinator.
To join the control group, individuals must be 60 or older (55 or older for people who have a blood relative with Alzheimer's disease), reside in the greater Lexington area, have normal cognitive function as determined by neuropsychological tests, have no history of neurological or psychiatric disease, and have no history of drug or alcohol abuse.
Researchers telephone the volunteers every six months and ask them to assess their general health and memory. Once a year volunteers undergo neuropsychological testing to determine mental function, and every two years they receive a physical and neurological exam.
Almost two-thirds of the control group subjects are women. About half of the volunteers are in their 70s, a quarter in their 60s and a quarter 80 or older. They are highly educated, with almost nine out of 10 having attended or graduated from college or having done postgraduate work. The majority are married--in fact, several couples are in the group. Most of the volunteers say their health is excellent or good.
The prime motivation of the volunteers is altruism, Wekstein says. They receive no money. "No one is doing this so that every couple of years they get cookies and punch," Wekstein says, referring to the receptions held periodically for control-group members at Spindletop Hall, where researchers update them on the latest findings.
"The tissue received through this program is the central resource at UK for those of us inspecting the molecular mechanisms of Alzheimer's disease," says Rosemary Booze, associate professor of anatomy and neurobiology. "The lack of feasible animal models for the disease heightens the need for a program such as this. The combination of pre-mortem clinical testing and post-mortem pathological confirmation of this disease creates a reliable source of tissue that is indispensable in Alzheimer's research."
Jim Geddes, a UK associate professor of anatomy and neurobiology, says that because the brain deteriorates rapidly after death, it's vital that an autopsy be performed as soon as possible. "The support of families has been tremendous. We are often able to perform the autopsy within three hours of death," Geddes says. "This does mean coming in at all hours of the night sometimes, but luckily we have a dedicated group of neuropathologists and researchers who do that."
Geddes adds that the 60,000 people in Kentucky who have Alzheimer's represents one in nine individuals over age 65 and approximately 45 percent of those who reach 85. "When the baby boomers begin to turn 65 in 2010, the number of elderly will increase dramatically," he says. "In Kentucky, we will have 200,000 people with Alzheimer's by the year 2020 unless a cure or effective treatment is found."
For more on Alzheimer's disease projects at the University of Kentucky: