Experts caution that it’s still too soon to say if any of these drugs will prove successful enough to make it to market. “There have been nicotinic drugs studied clinically, but there is still a question of whether they are really effective,” says Steven Ferris, an Alzheimer’s expert at New York University Medical Center. He adds that such drugs are likely to have a high safety hurdle. “People who are going to take a cognitive enhancer because they are forgetful due to aging are going to want a very safe drug,” he says.
But there are plenty of reasons to believe the drugs could be effective. Nicotine stimulates neurons by mimicking acetylcholine, one of the brain’s major signaling molecules. When acetylcholine binds to specific receptors on brain cells, it triggers an electrical message that travels down the neuron and throughout the brain. Smoking a cigarette shoots a wave of nicotine into the brain, activating a subset of these receptors, known as the nicotinic acetylcholine receptors. The resulting jump in neural activity is the likely source of cigarettes’ concentration-boosting quality. “Things that enhance nicotinic receptor function may enhance overall synaptic function,” says Adam Boxer, a neurologist at the Memory and Aging Center at the University of California, San Francisco.
A shortage of acetylcholine could account for the cognitive problems seen in Alzheimer’s patients, according to one theory. Acetylcholine works in the brain to enhance information flow from the senses into the cortex, says Boxer, so a shortage of this neurotransmitter may block the brain’s ability to properly encode information into short-term memory. Scientists know from post-mortem studies that Alzheimer’s patients have fewer nicotinic acetylcholine receptors in their brains, though scientists aren’t sure how this deficit relates to the buildup of abnormal proteins that is the disease’s hallmark.
Alzheimer’s is currently treated with drugs known as cholinesterase inhibitors, which block the breakdown of acetylcholine so that more of the neurotransmitter is available to stimulate the neurons. These drugs can help some of the cognitive symptoms of Alzheimer’s, but it’s unclear whether they can slow or stop the progression of the disease. Worse, cholinesterase inhibitors have a relatively modest effect and don’t work for all patients.
Scientists studying nicotine say that selectively activating the nicotinic acetylcholine receptors might provide a more effective way to treat memory problems. “This is a very important target for early Alzheimer’s disease,” says Ken Kellar, a neuroscientist at Georgetown University in Washington, D.C. “It might slow down the progression of the disease and allow whatever function is there to be maintained, though it’s probably not going to reverse full-blown Alzheimer’s.”
Others, however, are skeptical that any cognitive enhancers are the best route for treatment. “Even if you find something that enhances the ability to form memories, damage from Alzheimer’s disease is still going on,” says Boxer. “If a large portion of cells die out or stop working, cognitive enhancers might stop working.”