Boston researchers have reported a new method for detecting subtle brain changes in people who have no memory problems but who may already be in the earliest stages of Alzheimer’s disease.
The findings, published online today in the medical journal Neurology, may help speed clinical trials for potential Alzheimer’s treatments, according to Dr. Bradford Dickerson, an associate professor of neurology at Harvard Medical School and lead author of the study. “We need efficient, cost-effective ways to screen people for research,” said Dickerson, who also is a brain specialist at Massachusetts General Hospital. “This will potentially give us a tool that will help identify people in a more efficient manner.”
Dickerson explained that his method is not ready for use in physicians’ offices. Researchers and the medical community still must pinpoint reliable markers for the disease that could be used much the same way doctors now measure early signs of heart disease by monitoring patients’ cholesterol levels.
For screening the team used brain scans to measure the thickness in nine specific areas of the brain in 159 people who did not show signs of dementia or other cognitive problems. The brain regions were chosen based on prior studies that showed they shrink in patients with Alzheimer’s. The median age of the participants was about 76 years. Of the 159 people, 19 were classified as high risk, meaning that they likely were undergoing the earliest stages of Alzheimer’s disease because of the smaller size of their brain regions that corresponded to areas typically affected by the illness. Another 116 were deemed to be at average risk for the disease, and the remaining 24 at low risk.
At the beginning of the study and over the next three years, participants were also given tests that measured their memory and problem-solving abilities. The cerebral cortex is the outer layer of the cerebrum, the most highly developed part of the brain. It consists of grey matter - the cell bodies of neurons where processing of muscle control, sensory perceptions, memory, emotions and speech take place.
The researchers also looked at cerebrospinal fluid (CSF) samples from 84 participants after three years to check levels of amyloid protein, a hallmark of Alzheimer's.
They found that 60% of people with a thinner cortex had abnormal CSF amyloid levels similar to those seen in the brains of Alzheimer's patients. This compared with 36% of those with average cortical thickness and 19% of those with an unusually thick cortex.
There is no known cure for Alzheimer’s disease. But a growing number of researchers believe that the lack of progress may be because the drugs are now tested only in people whose Alzheimer’s is too advanced. Researchers are searching for ways to detect the disease at its earliest stages, before it damages critical brain cells, because they believe that’s when potential treatments would be most effective.
Many believe that an accumulation of a specific protein, known as beta amyloid, in the brains of Alzheimer’s patients may be a reliable marker to identify the disease early on. Dickerson’s study found that 60 percent of the group of participants identified at high risk for Alzheimer’s because of their smaller brain regions also had abnormal levels of amyloid in the fluid of their brains and spinal cord. In comparison, the abnormal amyloid levels were detected in 36 percent of those deemed to be at average risk, and 19 percent at low risk.
Susan Resnick, chief of the behavioral neuroscience laboratory at the National Institutes of Health, said Dickerson’s new method could give researchers a more accurate tool for pinpointing from the people with amyloid plaques those who would most likely go on to suffer an Alzheimer’s decline. This would be the group most likely to benefit from potential treatments, and would be the type of participants researchers need to find, Resnick said. “This is a disease that we believe starts 10 to 15 years before we see clinical symptoms,” Resnick said, “so we need these kinds of tools to try to understand the disease at the earliest possible stage.”
Dickerson said he hopes his method could be used to lower the costs for screening participants in upcoming clinical trials of potential Alzheimer’s treatments, such as one Brigham and Women’s Hospital researcher Dr. Reisa Sperling plans to start next year. Sperling hopes to begin a three-year study of an amyloid-clearing medication on as many as 1,000 people, 70 years old and older, whose brains show an accumulation of amyloid plaques but who don’t appear to be impaired. She said that the cost of the research is expected to be in the range of $100 million but that she hoped to lower that amount by finding more efficient ways to screen participants.
Dr Simon Ridley, from the charity Alzheimer's Research UK, said, “The ability to predict who will develop Alzheimer's disease is a key target for dementia research, as it would allow new treatments to be trialed early, when they are more likely to be effective. These findings add weight to existing evidence that Alzheimer's begins long before symptoms appear, although it's important to note that the study did not assess who went on to develop the disease. This research provides a potential new avenue to follow, but we need to see larger and longer-term studies before we can know whether this type of brain scan could accurately predict Alzheimer's.”
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