Staff photo Justin Ide/Harvard News Office


Finding the start of Alzheimer’s disease

6 min read

Faces are hard to remember. Even harder are the names that go with them. It’s one of the most common problems people face as they get older.

In puzzling over why that is, Reisa Sperling and her colleagues at Harvard Medical School have discovered startling things about how memories are made and why people lose them, particularly those on the way to Alzheimer’s disease.

“Names and faces are so difficult to put together because there’s no obvious connection between them,” says Sperling, who is an associate professor of neurology. “There’s no ‘Bill look,’ or ‘Mary face.’”

Working at Brigham and Women’s and Massachusetts General, two Harvard-affiliated hospitals in Boston, she and her team did brain scans of 52 elders, who included normal individuals, those with mild memory problems, and those impaired with Alzheimer’s disease. While their brain activity was being scanned, these people tried to match unfamiliar faces with fictional names.

The results were surprising. The brain’s memory center, a tiny, sea horse-shaped bit of tissue deep in the brain, was more active in the mildly impaired individuals than in those with no obvious mental problems. Their brains seemed to need to work harder than normal to make new memories.

But in those at later stages of impairment, brain activity slowed down. It slipped below normal levels, then began to slide down the slope to Alzheimer’s. Sperling’s team discovered that changes in memory-related brain activity may be an early warning sign for impending Alzheimer’s.

Last month, the Alzheimer’s Association reported that 5 million people now wrestle with that mind-numbing problem. About half of them are in the early stages of it. Most, but not all of them, are 65 and older. As baby boomers move from the 60s to the 80s, Alzheimer’s toll is expected to rise to more than 25 million by the middle of the century. If the numbers are right, one in every eight people over 65 years old will be robbed of part of their ability to understand what is going on around them.

So, can doctors use Sperling’s methods to determine who that one in every eight people will be? “I honestly don’t believe that brain scanning is the best way to screen millions of people,” she cautions. “The functional magnetic resonance imaging [fMRI] technique we used is too expensive and it requires a large facility. What is really needed is a simple blood or urine test.”

Sperling believes that images of what’s going on in the brain could be more useful for testing drugs being developed to slow or stop the advance of Alzheimer’s. At present, five drugs approved by the Food and Drug Administration can ease symptoms of the disease for about a year in half the people who take them, according to the Alzheimer’s Association. Newer drugs that may actually slow the progress of brain dysfunction are in advanced trials. Results from fMRI scans, perhaps used with other types of scanning, show promise for sharply reducing the tens of millions of dollars it costs for a drug trial and for speeding up discovery of the most effective drugs.

A head for memories

The other thing scanning is good for is to find out exactly what happens in the brain when its owner can’t remember a face or name. Sperling’s group has taken a critical step in that direction.

Their research produced clear evidence that storing memories is not confined to a small S-shaped area in the depths of a brain. That area is known as the “hippocampus,” Latin for “sea horse.” (See Gazette, May 25, 2006, page 5.)

The activity imaged as people try to learn a new face and put a name on it includes not only the hippocampus but other areas in the front of the brain where attention and organization of information take place. Called the prefrontal cortex, this region is just behind nerves that operate the eyes. Making memories, then, involves nerve cells in both the front and back of the brain, as well as places in-between.

Also, the Harvard experiments reveal that memories are made not just by what you turn on, but by what you turn off. Even when people are resting, not trying to concentrate on anything, parts of their brain stay active.

These busy regions must be turned off in order to learn new information most efficiently.

“Both these regions and the hippocampus need to be turned on and off in a coordinated way to form a memory,” Sperling explains. “And our research shows that, as memories deteriorate in Alzheimer’s, problems occur in both areas.”

What causes that dysfunction? Genes are certainly involved. People who carry certain genes are at a greater risk for Alzheimer’s, just as people with other genes and mutations of those genes are at greater risk for breast cancer. People with such genes are more likely to develop the hyperactivity present in mildly impaired men and women who are driving their brains harder than normal to remember a name and face.

When Alzheimer’s patients die and undergo autopsy, researchers find their brains overloaded with ugly plaques known as amyloid and unwanted tangles in nerve cells. This stuff, experts say, interferes with memory making and retrieval.

“We don’t know which comes first,” Sperling admits. “Does amyloid in areas that need to be turned off interfere with activity in the hippocampus, or does the hippocampus start to go first? Maybe they both fail together.”

What to do while waiting

Suppose a scan shows that a brain is working overtime to capture a memory. What can someone do to slow the inevitable slide into Alzheimer’s dementia? “Strategies to hold on to your brain-health include staying socially active, engaging with other people, and being as physically active as possible,” Sperling advises.

More specifically, other researchers have proved the value of association in forming memories. In the case of names and faces, try connecting names with physical features. Associate “Fred” with the mole on his chin, or “Susan” with striking blue eyes.

Also, experiments confirm the value of repetition. People shown name and face pairs three times, as you would guess, remember them better than with a single sighting. Repeating facts and face-name pairs several times to yourself should help keep memory areas intact.

All this is temporary, of course, to help keep people going better until those miracle drugs make it to market. “Several drugs now under test aim at slowing or preventing formation of amyloid,” Sperling notes. “With our new knowledge about early changes seen in brain scans, we should be able to run more efficient human tests and do them more quickly. We don’t have to wait until memories are almost gone.

“These are provocative new findings, it’s a very exciting time to be looking into the ‘why’ and ‘how’ of remembering names and faces.”