Friday, February 12, 2016

Alzheimer's and seizures

Until a few months ago, I was not aware that seizures were a relatively common aspect of Alzheimer’s—about 10 to 20 percent with the disease experience them, according to Dr. Keith Vossel, a neurologist at the University of California at San Francisco. I linked up with Dr. Vossel at the suggestion of my high school classmate and football teammate Steve DeWitt, who some years back suffered a seizure that appeared to be Alzheimer’s-related. Vossel is one of Steve’s doctors.
During a recent phone conversation, Vossel illuminated the overlap between the two disorders and suggested that the real figure for seizures may be a good deal higher, on account of many minor seizures going unnoticed. More than half of the seizures that people with Alzheimer’s experience lack the classic feature of seizures: violent shaking. These episodes, he said, can be as subtle as “a metallic taste in the mouth or  experiencing déjà vu, or sometimes a sudden feeling of dread.”
Often an EEG [electroencephalgram] is taken. “But,” Vossel noted, “a lot of the time, it’s just clinical judgment, and we often put patients on anti-seizure medications when we suspect that seizures are happening.”
Vossel is particularly interested in a medication called Levetiracetam, an anti-seizure drug that has been on the market for nearly two decades. “The idea is that it quiets the neurons that are firing excessively, and now it is one of the more common drugs to treat seizures.”
How the drug works remains somewhat of a mystery.
“We’re basically finding that really low doses of this medication may actual be helpful with cognition,” Vossel said. “But particularly in Alzheimer’s disease models, it seems to have some specific action that clamps down on excess brain activity caused by the amyloid-beta protein”—not in the plaque form but the soluble form.
“When amyloid-beta is floating around, it can potentially wreak more havoc than it can when it’s bound up in these plaques. In animal models of Alzheimer’s disease, they don’t develop a lot of amyloid plaques until later in life, but they actually have memory loss at a young ages.”
 Vossel and his fellow researchers believe that memory loss, at least in part, is a consequence of amyloid peptides disrupting the brain’s network activity. “Essentially, what it can do is lead to excess activity in the brain, manifesting as seizures.
 “We’ve been able to dissect out part of the cause of the seizures, and also how to suppress the seizures, in a number of different ways,” Vossel said. “And by doing that, we’ve found that seizures are very tightly linked to the cognitive deficits and even the synaptic changes, the connections between the neurons. It seems to be very related to amyloid peptide changes” — a key component of plaque that builds up in the brains of those with Alzheimer’s.
In research involving mice, the seizures “can also be quite subtle ….Essentially, the brain is raising its defenses against these seizures, and by doing so, the brain is less able to attend to normal functions such as learning and memory. We think that the drugs need to suppress the seizures for several weeks for the brain to recover and regain normal function.
“Surprisingly, to us, we can make genetic modifications in the brain like lowering tau,” the component of tangles that form in the brain. “By doing this, we can also prevent seizures,” Vossel said.

My thanks to Steve DeWitt for suggesting that I interview Dr. Vossel. I learned a lot.

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