Alzheimer’s disease has always been difficult to diagnose — the only way to identify it definitively is by autopsying the brain after death — but scientists may now have an easier way to spot the degenerative brain disease long before that, even before symptoms appear, using brain scans.
People who go on to develop symptoms of memory loss and cognitive deficits are more likely to show shrinkage in certain areas of the brain early on, compared with those who don’t develop Alzheimer’s, and such changes can be seen in MRI scans of the brain, report Dr. Bradford Dickerson at the Harvard Medical School and Massachusetts General Hospital and colleagues in the journal Neurology. The team worked with hundreds of brain scans of patients at various stages of Alzheimer’s disease, collected by the Alzheimer’s Disease Neuroimaging Initiative database.
Dickerson’s team had previously identified nine regions of the cortex of the brain that seem to be most affected by the amyloid plaque deposits and disintegration of nerve networks that are the hallmark of Alzheimer’s disease. By studying people’s brain scans over time, they were able to see that these nine brain regions appear to be thinner in people who eventually go on to develop Alzheimer’s — but that it takes many years for this structural difference to show up as symptoms of memory loss or cognitive problems.
Using this brain-size signature as a yardstick, the researchers decided to confirm the correlation by testing the patients’ cognitive abilities three years after a baseline brain scan. Indeed, they found that 21% of participants, who had the thinnest Alzheimer’s-related brain regions but showed no signs of memory problems or other cognitive deficits at the start of the study did show signs of cognitive decline three years later, compared with none of the subjects who did not have the same brain thinning and 7% who showed moderately thinner brain areas.
The brain regions in question are responsible for functions such as higher-level cognition, memory and language, which are all affected by Alzheimer’s, so it makes sense that they would shrink in those developing the disease.
“We’ve known for years that there are certain areas that are affected by the amyloid plaques and tangles that damage the brain,” says Dickerson. “It’s not as if the whole brain is damaged at first; much of the brain is fine at the early stages. But if you just looked at the whole forest, you might miss the signature brain areas affected by the disease. So you have to zoom in and specifically focus on the areas that are affected in people with known dementia.”
The results are critical for helping doctors identify patients earlier in the course of the disease, and that’s important since many experts now believe that intervening at the beginning stages may offer patients the best chance for controlling the brain degeneration that causes symptoms. Many of the drugs that have failed to help patients in the advanced stages of Alzheimer’s, for example, may benefit those who are in the first weeks or months of the condition.
But in order to test that idea, says Dickerson, it will become more and more important to have a reliable way to identify those who are on the road to Alzheimer’s. Previous studies have suggested that elevated levels of amyloid protein in the spinal fluid are a marker of the disease, for example, but this measure alone isn’t enough, Dickerson says, because some people have naturally higher levels of the protein but no Alzheimer’s. (In fact, about 30% of people over age 65 will show high levels of amyloid, not all related to Alzheimer’s.) But combining amyloid tests with brain scans that check for the Alzheimer’s brain signature could be an effective screen to identify those at highest risk of developing the condition.
As the disease progresses, however, and as more amyloid builds up in the brain, less of the protein leaks out in the spinal fluid, so advanced patients have lower levels of the protein than healthy ones do. That’s exactly what Dickerson and his team found in their study: they measured levels of amyloid in the patients’ cerebrospinal fluid and found that indeed the patients who showed shrinkage in the Alzheimer’s signature brain regions also showed the lowest levels of amyloid in the spinal fluid.
The findings are especially important since the proportion of elderly in the U.S. population is expected to balloon in coming decades. Along with the increasing rolls of seniors, cases of neurodegenerative diseases such as Alzheimer’s and dementia will also mount, and doctors want to catch as many of these cases as early as possible. “My thought is to use something like cognitive tests as a first level screen, to identify as many people as possible who might be at risk. Then to winnow that number down, an MRI could help doctors to determine if someone needs further evaluation from a specialist. Or if they don’t appear to have brain changes typical of Alzheimer’s, they can go for another year or so without a screen,” says Dickerson.
Early identification could mean more years of good function for many aging people. “It’s surprising the number of people coming in with mild symptoms who are still functioning very well,” says Dickerson. “It’s not until you look at their brains, and see the real shrinkage in these key areas, that you get concerned. In casual encounters they are quite normal and highly functioning. That’s why we need better ways to screen for the earliest signs of Alzheimer’s.”