By Marina Murphy and Lindsay Reese 

For years, scientists have searched for ways to slow or prevent Alzheimer’s disease, a condition that robs millions of their memories and independence. Among the most intriguing ideas was the use of nicotine—a compound long associated with smoking-related harm—but also known to interact with brain receptors involved in learning and memory.

The MIND Study (Memory Improvement Through Nicotine Dosing) set out to test whether nicotine patches (an FDA-approved nicotine replacement therapy) could help older adults with mild cognitive impairment (MCI), a stage often considered a precursor to Alzheimer’s. 

The trial, led by Dr. Paul Newhouse of Vanderbilt University Medical Center and Dr. Paul Aisen of the University of Southern California, was ambitious: a 2-year, randomized, double-blind, placebo-controlled study involving 348 non-smoking adults over 55. Participants wore either a nicotine patch or a placebo patch daily, with doses starting at 3.5 mg and increasing to 21 mg (corresponding to the nicotine delivered by a pack of cigarettes). Researchers measured memory, attention, mood, and functional outcomes. 

The hope was clear: if nicotine could safely stimulate nicotinic acetylcholine receptors—critical for cognitive function—it might offer a low-cost, widely available intervention to slow decline. 

A previous smaller study had shown promise, and the stakes were high. Alzheimer’s disease currently affects 7.2 million Americans aged 65 and older, a number projected to nearly double by 2060. Existing treatments offer only modest benefits, and no therapy has yet proven capable of halting progression. 

The Results—and the Reality 

Before a clinical study begins, scientists identify specific outcomes (endpoints) to determine whether a treatment works. They are the yardsticks that measure the success or failure of a study. In this case, the primary endpoint was a word list learning test designed to assess episodic memory. 

While participants in the nicotine group outperformed the placebo group at the end of the study, these differences were not statistically significant. In short, nicotine did not meaningfully slow the trajectory of cognitive decline in MCI in this study design. 

Unfortunately, the MIND Study did not deliver the breakthrough many hoped for. However, nicotine was well tolerated and participants did not experience serious adverse events.

This outcome is disappointing, but not surprising. Alzheimer’s research is littered with failed trials—over 200 in the past two decades—underscoring the complexity of the disease. It is not caused by a single factor but by a cascade of changes in the brain, including amyloid buildup, tau tangles, inflammation, and neurotransmitter deficits. Targeting one pathway, even one as important as the cholinergic system, may simply not be enough. 

Why This Still Matters 

Does this mean nicotine has no role in cognitive health? Not necessarily. These are the topline results, and further analyses need to be done for brain imaging, biomarker, and behavioral endpoints. The results presented at CTAD confirm that transdermal nicotine can be administered safely over long periods without addiction risk or cardiovascular effects—a valuable insight for future research.

This ambitious study also reinforces the importance of exploring unconventional ideas. Science advances through bold hypotheses, even when they fail. 

Moreover, the trial highlights a sobering truth: we have few effective therapies for Alzheimer’s disease. Current treatments for Alzheimer’s offer modest benefits at best. In contrast, nicotine is inexpensive, widely available, and—when delivered via patch—free from the harmful chemicals in tobacco smoke.

Unfortunately, it’s not a silver bullet. When presenting the study results, Dr. Newhouse noted that “nicotine treatment may have short-term benefits on cognition in MCI, but these appear to not be sustained.”

Looking Ahead 

The topline results of the MIND Study should not discourage innovation in this field. Instead, it should sharpen our focus on combination strategies—pairing pharmacological interventions with lifestyle changes like exercise, diet, and cognitive training. It should also accelerate research into early detection, when interventions may have the greatest impact. 

As Dr. Newhouse has said in the past, the question has always been whether we can harness nicotine’s cognitive benefits without the toxicity of smoke. The answer in this case appears to be no—but the pursuit of that answer has deepened our understanding of both nicotine and Alzheimer’s disease. 

There is still promise for the use of nicotine in other conditions. For example, transdermal nicotine has been shown to decrease the severity of late-life depression.

In the end, the MIND Study is a reminder that progress in Alzheimer’s research is incremental, hard-won, and often humbling. But every trial, successful or not, brings us closer to the day when memory loss is not an inevitable part of aging.

 Dr. Marina Murphy is the Senior Director of Scientific Affairs at Haypp Group and its subsidiary Nicokick.com. Dr. Lindsay Reese is Senior Scientific Content Manager at Haypp Group.

References 

1. ClinicalTrials.gov – MIND Study NCT02720445 
2. National Institute on Aging – Mild Cognitive Impairment 
3. https://www.latimes.com/la-he-nicotine1mar01-story.html (from 2004) 
4. https://www.alz.org/getmedia/ef8f48f9-ad36-48ea-87f9-b74034635c1e/alzheimers-facts-and-figures.pdf (Alzheimer disease facts and figures) 
5. Newhouse P et al. Nicotine treatment of mild cognitive impairment: A 6-month double-blind pilot clinical trial. Neurology 2012;78:91-101 
6. https://static1.squarespace.com/static/5631328be4b0ebf91a669d8d/t/69322568af9daf4de3a1a3c9/1764894056773/MIND+Topline+Results+CTAD+12-04-25+FINAL.pdf
7. Andrews P et al. Effects of open-label transdermal nicotine antidepressant augmentation on affective symptoms and executive function in late-life depression. J Affect Disord 2024;362:416-424.