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Article published Dec 1, 2012
Imaging shows progressive damage by Parkinson's
For the first time, researchers at the Massachusetts Institute of Technology report, brain imaging has been able to show in living patients the progressive damage Parkinson's disease causes to two small structures deep in the brain.
The new technique confirms some ideas about the overall progress of the disease in the brain. But the effects of Parkinson's vary in patients, the researchers said, and in the future, the refinement in imaging may help doctors monitor how the disease is affecting different people and adjust treatment accordingly.
The outward symptoms and progress of Parkinson's disease — tremors, stiffness, weakness — have been well known since James Parkinson first described them in 1817.
But its progress in the brain has been harder to document.
Some of the structures affected by the disease have been buried too deeply to see clearly even with advances in brain imaging. An important recent hypothesis about how the disease progresses was based on the examinations of brains of patients who had died.
Now, a group of scientists at MIT and Massachusetts General Hospital report that they have worked out a way to combine four different sorts of MRI to get clear pictures of damage to two brain structures in people living with Parkinson's. In doing so, they have added support to one part of the recent hypothesis, which is that the disease first strikes an area involved in movement and later progresses to a higher part of the brain more involved in memory and attention.
Suzanne Corkin, a professor emerita of behavioral neuroscience at MIT and the senior author on the paper published online Monday in the Archives of Neurology, said that this progression was part of the hypothesis put forward in 2003 by Heiko Braak, a German neuroscientist, based on autopsies.
But, she said, because of the limits of brain imaging, “nobody could test this in living patients.”
David A. Ziegler, who was at MIT when the research was done and is now a postdoctoral researcher at the University of California, San Francisco, said that the study, of 29 patients with Parkinson's and 27 healthy patients of roughly the same age, showed that the peanut-sized substantia nigra lost volume first, and another structure called the basal forebrain, involved in memory and attention, was struck later.
Glenda Halliday, a neuroscientist at Neuroscience Research Australia and the University of New South Wales, who was not involved in the study, said the paper confirmed “the progression of degeneration in two important affected brain regions in people with Parkinson's.”
Corkin, Ziegler and their colleagues developed a way to use four different varieties of MRI — each using different settings on the same machine — to come up with four different images that could be used to form one image that showed structures deep in the brain like the substantia nigra, long known to be important in Parkinson's.
The disease kills brain cells, shrinking the parts of the brain that it affects, and the comparative study showed that the reduction in size of the substantia nigra showed up in early stage Parkinson's patients, compared with a healthy group.
The reduction in size in the basal forebrain, compared with the healthy group, did not show up in the patients in the early stage but was clear in patients in the later stage.
“This is a project we've been working on in our lab for years,” Corkin said.
A next step, already in progress, is to correlate damage to specific brain structures with symptoms.
Parkinson's, she said, is a disease that shows the same broad outlines of development in most patients but with considerable variation. Dementia may arrive early or may not appear. The MRI technique described in the paper, she said, might help tease out what is going on in the brain in subgroups of Parkinson's patients that show different symptoms and could influence treatment.
One important difference between the two brain structures is that damage to the substantia nigra decreases production of the neurotransmitter dopamine, while a smaller basal forebrain would reduce the production of a different chemical, acetylcholine.
The research is just one step, Ziegler said.
One of the “big outstanding questions,” he said, is whether all patients will eventually get dementia.
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