The nicotine patch designed to help people quit smoking can also improve memory in older adults with mild cognitive impairment, or MCI, a small clinical trial found.
The trial included 67 non-smokers with MCI, which is considered an intermediate between normal aging and dementia. People with MCI are more likely to develop Alzheimer's disease. Half of the patients wore a skin patch that delivered 15 milligrams of nicotine per day; the other half wore a placebo or dummy patch. The study was double-blinded, meaning both the patients and the researchers were unaware who was getting the drug.
After six months, patients who wore the nicotine patch regained 46 percent of their age-adjusted “normal performance” on long-term memory tests, whereas patients in the placebo group worsened by 26 percent. “We're pretty excited that we got a strong sign of improvement, and we think it has great implications going forward,” said Dr. Paul Newhouse, director of Vanderbilt University's Center for Cognitive Medicine and lead author of the study published today in the journal Neurology.
Nicotine stimulates receptors on neurons involved in learning and memory, called cholinergic neurons. In Alzheimer's disease, those neurons die off. In an earlier study, Newhouse showed intravenous nicotine could improve memory in Alzheimer's patients. Drugs approved to treat the symptoms of Alzheimer's disease, such as Aricept, act by inhibiting the breakdown of acetylcholine, a neurotransmitter that stimulates nicotine receptors as well as other kinds of receptors. Nicotine has just the right shape to mimic acetylcholine and fit snugly into some of the same receptors that the neurotransmitter does. “We reasoned that if it helps in early Alzheimer's, we might be able to move back even further into patients with mild memory loss,” he said.
“Theoretically, the nicotine receptors are more closely related to the changes that occur in the brain in Alzheimer's disease,” said Dr. Peter Whitehouse, a neurologist at University Hospitals Case Medical Center in Cleveland and one of the first to investigate the role of nicotine receptors in Alzheimer's. “Basically, it's more focused, more specific.” By specifically activating those remaining receptors, nicotine can boost the function of surviving neurons. And research done in cells suggests it might even protect neurons from Alzheimer's disease.
“The jury's still out on whether nicotine is disease-modifying,” said Newhouse, describing the ability of a drug to actually slow the progression of a disease rather than merely treat symptoms. “But there's never going to be one single silver bullet. We're going to have to treat patients with a complex brain disease with multiple approaches.”
The six-month trial suggested the nicotine was safe. But Newhouse cautioned that smoking or unsupervised use of the patch is not. “People with mild memory loss should not start smoking or using nicotine patches by themselves, because there are harmful effects of smoking and a medication such as nicotine should only be used with a doctor's supervision,” he said. “But this study provides strong justification for further research into the use of nicotine for people with early signs of memory loss.”
Newhouse is conducting a one-year follow-up study of the same MCI patients. He hopes to publish the results later this year. In the next two years, other researchers will reveal the results of two clinical trials of disease-modifying drugs targeting beta-amyloid, a protein that builds up in the brains of Alzheimer's patients.
“Those are very important studies,” said Dr. William Thies, chief medical and scientific officer of the Alzheimer's Association. “We've known for a long time that the cholinergic drug system is important in Alzheimer's. But eventually, the impact of these drugs is overwhelmed by disease. They don't change the outcome.”
Dr. Frank Leone was surprised to see that the low doses of nicotine in patches were enough to tune up people’s brains. “I think it’s pretty cool,” said Leone, an associate professor of medicine and director of the comprehensive smoking treatment program at the University of Pennsylvania.
It does make sense that nicotine might help, Leone said. “Nicotine is a mild stimulant and presumably any stimulant has the ability to activate a person’s brain and to potentially improve cognition.” The Vanderbilit research is limited and needs to be replicated in larger studies before doctors should start prescribing patches to alleviate MCI, Leone said. Fortunately, smoking cessation programs have shown that patches can be used safely for years.
While patches haven’t been shown to be addictive, epidemiologist Steven Stellman has some words of caution for healthy adults who might try to use the patch to tune up their brains, rather than just kicking cigarettes. “Nicotine is the addicting ingredient in cigarettes,” said Stellman, professor at the Mailman School of Public Health at Columbia University. “People become addicted because nicotine gives them pleasure.”
Dr. Jeremy Koppel, a geriatric psychiatrist at Zucker Hillside Hospital in Glen Oaks, Queens, said the results are intriguing on their face because mild cognitive impairment is “a syndrome without a treatment.” “What needs to be done is a prevention study to see whether these nicotine patches can reduce the risk of Alzheimer’s disease,” said Koppel, who was not involved in the study.