Using innovative new technology, scientists have discovered brain plaques are associated with future declines on cognitive tests — the first solid confirmation that the plaques are pathologic.
The finding is insightful because brain plaques have been discovered in autopsies of people with no signs of mental impairment. However, for years, scientists have assumed amyloid brain plaques were harmful and cause Alzheimer’s disease as they are classically found in autopsies of Alzheimer’s patients.
In two studies published in the Archives of Neurology, scientists report that volunteers with brain plaques were more likely to have declining scores on annual cognitive tests, to show signs of shrinkage in a key brain area affected by Alzheimer’s and to eventually be diagnosed with the disease.
“We don’t have enough data yet to definitively say that people who scan positive for these brain plaques have presymptomatic Alzheimer’s disease, but something is clearly going on that does not bode well for the health of their aging brains,” says John C. Morris, the director of Washington University’s Alzheimer’s Disease Research Center (ADRC) and the Friedman Center for Aging.
Morris and others at the ADRC have previously found evidence that Alzheimer’s disease harms the brain for years prior to typical diagnosis. They are pushing for earlier diagnosis as an essential step to successful treatment of Alzheimer’s disease, but to do that they first have to seek earlier indicators of disease and then wait years to see if people with the indicators later develop symptomatic Alzheimer’s.
According to Morris, the new papers are early and encouraging indicators that scientists are on track to pushing back the time at which diagnosis can be made.
“We only have a very small number of subjects to date, but what we’re learning so far has been consistent with our predictions,” he says.
The new studies were made possible by the development of an imaging agent, Pittsburgh Compound B (PiB), that lets scientists use positron emission tomography (PET) scans to detect amyloid plaques in living brains for the first time. Prior to PiB, clinicians could only verify the presence of brain plaques during autopsies.
PiB scanning of ADRC research participants is directed by Mark Mintun, M.D., vice chair for research in radiology and professor of radiology at the University’s Mallinckrodt Institute of Radiology.
Martha Storandt, Ph.D., professor of psychology and of neurology, led one of the studies, which compared a variety of factors in plaque-positive and plaque-negative subjects.
“One of the main things we wanted to know was whether people who scanned positive for brain plaques scored abnormally low on cognitive tests,” she says.
“They didn’t, but when we looked at their annual testing records over a period of years, we saw that the scores of the plaque-positive group were declining, while those of the plaque-negative group were not.”
Magnetic resonance imaging (MRI) scans analyzed by Denise Head, Ph.D., assistant professor of psychology, revealed that brain areas hit hard by Alzheimer’s disease, such as the parahippocampal gyrus, were smaller in subjects with plaques.
In a second study, led by Morris, researchers tracked a group of 159 volunteers, ages 51 to 88, who were scanned using PiB between 2004 and 2008. At the time of the scans, none of the participants showed signs of mental impairment. Twenty-three of the volunteers later developed mild impairment, and nine members of that group were diagnosed with Alzheimer’s disease.
Those who stayed mentally healthy did not scan positive for plaques, but volunteers later diagnosed with problems did. Comparisons of the volumes of key brain structures revealed the same disparities seen in the other study: subjects who developed mental impairment had significant reductions in their parahippocampal gyrus and other structures affected by Alzheimer’s.
Morris speculates that earlier diagnosis and testing of new treatments may be possible within the next 10 years.
“There are risks inherent in Alzheimer’s treatments, so we have to be careful that healthy people who are selected to receive these treatments to prevent dementia caused by Alzheimer’s disease really do have presymptomatic disease,” he says.