A team of HMS researchers hopes to decipher Alzheimer’s disease by first understanding how brain systems function in normal aging.
Senior author Randy Buckner, Howard Hughes investigator and HMS lecturer in radiology at Massachusetts General Hospital, lead author Jessica Andrews-Hanna, a graduate student in Buckner’s lab, and colleagues began from the hypothesis that cognitive decline occurs when cerebral regions are disconnected by deteriorating white matter tracts. Their study, published in the Dec. 6 Neuron, tested 93 adults aged 18 to 93 and found that older subjects experienced a cognitive, functional, and structural decline similar to patients with Alzheimer’s, but with milder effects.
“What we found was that networks of brain regions that are correlated in young adults become less integrated with advanced aging, even in individuals who showed no signs of early Alzheimer’s disease,” said Buckner.
Nine randomly selected older individuals tested negative for signs of Alzheimer’s disease in a PET exam to uncover amyloid buildup.
The researchers took an “activity snapshot” of participants’ brains to examine neural crosstalk. Volunteers inside an fMRI scanner were asked to determine whether words represented living or nonliving objects. Buckner and colleagues calculated functional activity correlations from the scans, which showed how different areas of the brain communicated with one another. This may be the first time researchers have used such activity correlations across widely distributed brain regions to study normal aging.
“When we think, we don’t just use one brain region at a time. We use brain regions that are connected to one another and need to interact to communicate with each other to perform the task,” said Andrews-Hanna.
Older patients experienced a marked decline in the brain’s default system, which specializes in internal cognition and is thought to be connected by white matter tracts from the front to the back of the brain.
In addition to the fMRI, 40 older participants completed a variety of cognitive tests that measured executive function, memory, and processing speed. Individuals exhibiting the lowest functional correlations also exhibited the poorest cognitive tests. In spite of this link, depleted neurotransmitters or gray matter atrophy might also contribute to cognitive decline, the researchers said. A longitudinal study will be needed to uncover the causes.
“If we can come up with an understanding of how neural eavesdropping can be predictive of cognitive decline, it might help us understand the changes that occur in normal aging,” said Andrews-Hanna. “And it might help us better predict Alzheimer’s disease.”