Paul Newhouse, M.D., Director of the Vanderbilt Center for Cognitive Medicine talks about his history of successful trials using nicotine patches on patients with early stage memory loss.
Can you tell me a little bit on the mind study? Where did the idea come about?
Newhouse: I’ve been studying the effects of nicotine on the brain since the 1980s. We have been exploring whether nicotine might be helpful for patients with memory loss. We’ve done that in a lot of different ways, but more recently, we had done a smaller study in the mid-2000s where we had three centers and we treated patients with memory loss for up to six months. We found that the patients improved with a measurable and sustained improvement in memory and attention functioning over that six month period. We were very encouraged by that. We went to the National Institutes of Health and asked them to fund this large multicenter national trial, which they agreed to do. That allowed us to start the MIND study.
Why nicotine? In particular, where did the concept of nicotine helping with memory come about?
Newhouse: Since the early 1980s, it’s been known that there are specific cellular structures (receptors) in the brain that bind nicotine. That’s not terribly surprising since we know that a lot of plant substances are active in our bodies and our brains. Many of our medicines come from plants. That receptor is lost in patients with Alzheimer’s disease. We thought by stimulating the remaining receptors, we might be able to amplify the effects and improve brain function. What nicotine does is it imitates the action of a normally occurring chemical in the brain that’s important for signaling.
What’s that naturally occurring chemical?
Newhouse: It’s called acetylcholine. It signals information between nerve cells and it seems to be common throughout the brain. It is important for memory and for attention. Without acetylcholine, our brain cannot function properly. Nicotine can help imitate the actions of acetylcholine when it’s being degraded by Alzheimer’s disease.
How did you go about this study? How many patients did you have? What did you have them do?
Newhouse: In the preliminary study that we published back in 2012, we studied 74 patients at three sites, and treated them with a skin patch version of nicotine. It is very similar to the patch that smokers use, and we administered it on a daily basis for six months. We saw sustained improvements in attention, learning, and memory. In this new study we are treating patients on a daily basis with a skin patch of nicotine or a placebo for up to two years. This is a longer-term study that will really attempt to define whether nicotine can help people sustain their memory function, or improve their memory function, or attention function over a long period of time.
How many people do you have in the larger study?
Newhouse: We’re hoping to recruit 300 patients nationwide for up to two years of treatment. We will also be offering them very close follow-up. Patients get seen by us every three months. We are doing brain scans on a number of patients evaluate the effects of treatment on the structure of their brain over time. We are also sampling bodily fluids to see if there’s any change in the biological markers for memory loss. We will be tracking people in multiple different ways as well as testing their memory periodically.
Do you currently have people enrolled that have already started?
Newhouse: Yes. We have about 180 patients enrolled so far and we’re hoping to get another 120. The National Institute on Aging has been very helpful in helping us move this project forward. We also have funding from the Alzheimer’s Drug Discovery Foundation.
For the smaller study that you did before, are there numbers to show the difference in how much their memory improved or how much they felt better?
Newhouse: We found that a higher proportion of patients who are on nicotine were rated by their doctors as improved compared to those on placebo. When you do a trial for a memory agent, you have to really show two things. You have to show that patients perform better on tests, but you also have to show that this difference can be detected by patients, families and doctors. Although that wasn’t really the focus of the pilot study, we did see an improvement in the number of patients who were rated as better by their doctors. Patients themselves detected a difference as well.
You collected data from the patient’s doctor, the patient’s family, and the patient themselves. Did you test the patients afterwards?
Newhouse: We tested them every three months at month three and at month six. Then we offer people an opportunity to continue to take nicotine for up to another six months. A whole year of safety data indicated that there were not any nicotine-related serious adverse side effects. Another thing that people always ask about nicotine, “isn’t it addictive or habit forming?” Our experience seems to be that if you give nicotine through the skin (as opposed to inhaling), you don’t have see these problems in nonsmokers. Therefore, using a transdermal patch, which is what we’re using in this study, seems to be very safe. No one in our prior studies has shown any withdrawal symptoms.
For this current study right now, can you walk me through what kind of tests you give them every three months?
Newhouse: We perform a series of computerized cognitive tests as well as paper and pencil memory tests. Some of those tests are focused on attention, such as how attentive people will be to information that’s coming at them, because one of the things we know about nicotine and nicotinic stimulation is that it really enhances attentional functioning. That’s important because attention is a critical first step for memory. If you don’t attend to something, you’re not going to remember it. We also assess memory abilities. We interview the patient and their caregiver or family member or partner to find out what their opinions are about how they are doing. We assess their functional abilities in terms of everyday life, and we also, for a subset of patients, we also offer brain scans where we actually measure the functional activity in the brain as well as the structure. For a few patients who want to volunteer for it, we are also doing spinal taps as well.
It is restricted to patients that just have mild cognitive decline or can they have maybe advanced dementia or something of that sort?
Newhouse: This trial is restricted to what we call MCI patients, which is mild cognitive impairment. That’s the preliminary stage of Alzheimer’s disease. Many patients with MCI will go on to progress to develop Alzheimer’s disease or dementia. We are not testing this in patients with late stage dementia because we think it’s less likely to be helpful to those patients. We think that treatment is best started when patients are very early on in this disease.
What impact do you think this research would have for the medical field?
Newhouse: If we were successful at showing that nicotine was helpful over the long haul, what’s exciting about this is that this is an inexpensive, widely available, over the counter treatment that could be rolled out very quickly. Patients could start taking this without enormous expenses or limited availability. We think that it could have substantial impact on the treatment of early memory loss if it proves to be successful.
For the people that hear nicotine, they think of cigarettes, of all the chemicals that cigarettes have, and what that does to the lungs. What would you say to people that have only heard bad things about nicotine and are unaware of how it actually helps?
Newhouse: What I say to people is that this is nicotine used in a completely different way. A lot of times we can use plant-derived chemicals, molecules, and medicines, but we can use them in a safe way. If we simply inhale them, that brings in a lot of other chemicals that are not related to nicotine at all, and it causes damage to the lungs. However, if we give just nicotine through the skin directly into the bloodstream with no effect on the lungs or inhaling, then very little habit-forming characteristics to it. You can tell that nicotine is not habit forming as a patch because they sell it over the counter. If it was thought to be addictive or abusable in that form it likely would not be sold over the counter. It doesn’t have the characteristics that things like vaping or cigarette smoking do. In our pilot studies, we didn’t see any withdrawal, we didn’t see any habit-forming properties, and we didn’t see anybody wanting to go back to taking it themselves.
For family members that have someone who they believe might be starting to experience the early signs of MCI, what do you believe this will mean for them?
Newhouse: We always encourage people to get their memory assessed. We encourage families, if they notice a change in people’s memory, the sooner they can get that evaluated, the better. We encourage people to get assessed, get a doctor to take a look, get them referred to a memory clinic if that’s available to them, or come to see one of our centers around the country that is running the MIND trial for an assessment. We think it’s very important that early intervention and early assessment be a part of any consideration for memory loss. People can check out our website to find where the mind study site is nearest to them.
Our website is: https://mindstudy.org/ and people can see where the nearest site to them is for an assessment.
How many sites do you guys have around the country?
Newhouse: We have about 40 sites now.
Anything else that you think people should know?
Newhouse: I think we’re excited about this study because it is easy to take and to test whether transdermal nicotine may be an effective early intervention for mild memory loss. We are hopeful about the likelihood that it will have a benefit for patients.
END OF INTERVIEW
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