- Written by Megan Joyce Megan Joyce
Nowadays, it’s difficult to hear the word “nicotine” without immediately conjuring up an image of a cigarette.
Nicotine may be in need of a PR overhaul, to be sure. Its potential use as a medicinal agent has been on researchers’ radar for decades; nicotine has demonstrated effectiveness in the treatment of Parkinson’s disease, depression, ADHD, anxiety, and other disorders.
A stimulant found naturally in the nightshade family of plants — which includes tobacco — nicotine is now also the focus of a two-year nationwide study, funded by the National Institutes of Health, that looks at nicotine and its potential to improve memory in adults diagnosed with mild cognitive impairment, or MCI.
The MIND Study comprises data collected from 400 individuals diagnosed with MCI from 32 sites across the country, including Penn State Health Milton S. Hershey Medical Center in Hershey.
Researchers have used nicotine in memory studies for more than three decades, according to the NIH, and the MIND Study is the largest and longest running of its kind.
Researchers hope to establish whether the safe use of nicotine, delivered via patch, can improve memory and functioning in people diagnosed with MCI.
“MCI is a bit of a broad umbrella term that refers, in most cases, to short-term memory loss that starts to become noticeable to an individual in their daily activities,” Dr. Paul Eslinger, neurologist with Penn State Neuroscience Institute at Penn State Health Milton S. Hershey Medical Center, said.
MCI, which occurs in about 20% of people 65 and older, goes beyond what is considered a normal level of cognitive decline associated with aging.
“MCI is usually diagnosed if they tend to fall a certain degree below what’s typical for an individual of their background, such as their educational and occupational level,” Eslinger said.
People with MCI will report not only misplacing objects and forgetting aspects of conversations, but also trouble retrieving names of people or objects they would usually know and difficulty keeping track of scheduled activities.
“Most often, individuals don’t have noticeable changes in their neurologic exams, such as their cranial nerves or reflexes,” Eslinger added.
People with MCI can generally use effective strategies — such as calendars, alarms, and other reminders — to compensate for their memory issues.
“Most often, they’ll be able to be fully independent and continue managing their affairs and their social and recreational activities, but they need extra attention, often double checking specifics,” Eslinger noted.
Eslinger said about half of individuals with MCI will remain stable, meaning their memory loss will not progress further; but the other half will develop more symptoms over time, leading to conditions such as Alzheimer’s disease.
And it’s here, in the mild stages of impairment, that Eslinger and other MIND Study researchers hope to be able to slow or even stop memory decline — using nicotine.
Studies of Alzheimer’s disease have shown that one of the brain’s neurotransmitters, acetylcholine, has become deficient in disease sufferers. Acetylcholine sends signals from cell to cell and activates entire groups of cells, Eslinger explained. It is a key neurotransmitter for memory and thinking.
And nicotine, a natural stimulant, acts very similarly to acetylcholine, stimulating the nicotinic receptors in the brain and in areas close to the memory structures of the limbic system.
“So [nicotine use] is a way for us to potentially stimulate some cells that may be underactive in the memory areas in a way that can bolster functioning of these memory structures in the brain and hence improve individuals’ memory functions on a day-to-day basis,” Eslinger said.
Administering nicotine via a patch on the skin bypasses all the problems associated with cigarettes, he added.
“In its pure form, [nicotine] can actually be used by the brain quite well,” Eslinger said. “The problem with cigarettes is all the carcinogens that cause all the lung disease, and the other anoxic effects of the smoke. And all that is completely taken out of the equation.”
In a preliminary six-month study of 74 people with MCI, individuals using nicotine patches showed improvement in both attention and memory versus those who had placebo patches. The two-year, double-blind MIND Study looks to extend the confirmation of nicotine’s benefit.
Study participants must be healthy, nonsmoking adults 55–90 years old who have been diagnosed with MCI. Participants must commit to applying a fresh patch each morning and to visiting their research site every three months for two years to have their progress documented.
All studies to date have shown no risk of addiction — even for former smokers — to the patch’s nicotine, which is released in a dose considerably lower than that found in cigarettes.
The nicotine is also absorbed more slowly, over the course of a 12- to 15-hour day, and is gradually titrated up in each participant until a therapeutic dose is reached.
Past participants have occasionally reported minor side effects, such as nausea, dizziness, or headache, but “when they do occur, they tend to be upon first having the patch, and they tend to resolve rapidly,” Eslinger said. “We have not seen any side effects that have been lingering or that have caused anyone to drop out of the study.”
Eslinger sees the potential advantages of nicotine use for both halves of the population with MCI, those whose problems will progress no further — and those whose symptoms signal the beginnings of dementia or Alzheimer’s.
“For those individuals … this will be a stage at which we could slow that progression, and we may be able to slow it by several years if the nicotine patch ends up being very helpful in improving the memory function and slowing progression of the disease,” Eslinger said.
“For those individuals who have MCI as really their only manifestation of change in the brain, it will help them, we believe, function better in their daily activities,” he added. “They’ll be less stressed and harried in trying to keep up with notes and providing reminders all the time.”
The MIND Study has already begun, but additional participants are still needed. Individuals interested in more information should call (866) MIND-150 or visit www.mindstudy.org.