The Race Against Alzheimer’s
Want to keep your aging brain in tip-top shape? The best advice might be the simplest, if not the most obvious: don’t get too excited.
That appears to be one of many lessons learned from a series of studies conducted by Michela Gallagher, Krieger-Eisenhower Professor of Psychology and Neuroscience.
Drawing upon years of research, Gallagher and her colleagues recently demonstrated that older people suffering from a form of memory impairment that can lead to Alzheimer’s disease showed clear improvement on memory tests after taking a drug to dampen overactivity in a particular part of the brain.
Researchers already knew that the condition in question—amnestic mild cognitive impairment, or aMCI—was associated with elevated levels of activity among neurons in the hippocampus, a region of the brain that is crucial to learning and memory. (People with aMCI have worse-than-normal memories for their age, and 15 percent of them go on to develop Alzheimer’s.) There was speculation, however, that this neuronal overexcitement represented a kind of coping mechanism—a way of revving up the brain’s memory circuit to compensate for flagging performance.
Gallagher proved the opposite. By administering low doses of the anti-epileptic drug levetiracetam to individuals with aMCI, she was able to drive activity in their hippocampi down to normal levels. As a result, their performance on memory tests actually improved.
That finding has all kinds of implications. If aMCI is a way station on the road to Alzheimer’s disease, then treating it could help stave off or at least slow the progression of full-blown dementia. That would be especially welcome given the recent failure of several drugs designed to combat late-stage Alzheimer’s, and would provide much-needed ammunition in the war against an affliction that is expected to affect as many as 16 million Americans by the year 2050.
But as Gallagher points out, an overexcited hippocampus goes hand in hand with several other risk factors for Alzheimer’s, including a particular gene that is the single greatest predictor of dementia aside from aging itself. And excess activity in this small, curved structure located in the medial temporal lobe appears to have negative effects elsewhere in the brain, as well.
“It’s like a cascade,” Gallagher says. “This overactivity appears to be remodeling other circuits that are trying to cope with it.” But Gallagher found that once those elevated levels of activity were reduced, other affected systems saw relief, too.
Gallagher hopes to run a long-term clinical trial to determine if levetiracetam can indeed help prevent Alzheimer’s in people with aMCI. And she is exploring additional therapies for aMCI, and for other conditions linked to overactivity in the brain.
Her work could improve life for the average aging person. “There is a kind of continuum of this condition that does occur in normal aging,” says Gallagher. And if the same mechanism drives both normal and abnormal memory decline in the aging brain, then therapies that work on one ought to work on the other, as well.