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Nicotine Patches Improve Memory in Patients with Mild Cognitive Impairment

Buzz surrounding the potential of typical commercially available transdermal nicotine patches (those used as nicotine replacement therapy for smoking cessation) to help those with mild cognitive impairment has been all over the Al Gore for the past week or so.

Researchers from Vanderbuilt University published the results of their 6-month double-blind pilot trial on the effects of nicotine treatment in those with mild cognitive impairment in the prestigious medical journal, Neurology[1], on January 10th of this year.

Before College kids who’re cramming for exams (looking for a nootropic effect) or those who occasionally can’t find their keys in the morning rush off to the drug store to buy some nicotine patches, let’s first consider the population of this study. 

Secondly, let’s also note that researchers believe that studies of nicotine administration to normal, healthy non-smokers tends to have a negative impact on working memory though it also tends to decrease reaction time.

Why Nicotine Patches?

Why nicotine patches?  Alzheimer’s Dementia (AD) is the most common form of dementia.  Since the early 90’s researchers have explored the loss of  nicotinic acetylcholine receptors in the brain and AD.

I can’t believe it’s taken this long for someone to think of putting nicotine transdermal patches on those either at first for or with dementia?  It hasn’t…

Back in 1999, researchers from Durham North Carolina [3] found that nicotine patches had some benefits in improving measures of attention, but not memory in patients with Alzheimer’s Dementia.  Other studies have shown some benefits of nicotine patches in reducing agitation in patients with dementia.

In the same year, other researchers from the University of New England published the results of their study of nicotine patch treatment on patients at risk for dementia [4].  These researchers found mixed results with some indication that nicotine treatment could be beneficial for verbal learning and recall tasks.

Transdermal Nicotine Patches and Mild Cognitive Impairment MCI:  Study

First, let’s simply consider the study population since the results of this study can’t be generalized to college students or normal healthy adults.  In total, the study included 74 subjects who were enrolled.  Of which, the subjects had a mean age of roughly 76 yrs [Nicotine (n=39) 76.2 yrs (+/-8.5); Placebo (n=35)  75.7 ys(+/-6.5)].

Second, the subjects had a confirmed diagnoses of MCI based on the generally accepted criteria for MCI.  The study excluded current smokers, those with Axis I Psychiatric disorders (i.e. Depression) or substance abuse within the last 2 years, and those taking cognitive enhancing medication (among other additional exclusion criteria).

What Is Mild Cognitive Impairment (MCI)?

Simply put, the researchers note that MCI is defined by a subjective and objective decline in cognition and function that does NOT meet the criteria for dementia.  Essentially, it’s a level of cognitive functioning that fills in the gap between dementia and the cognitive decline associated with normal aging.

Those with MCI differ from those with normal age associated memory decline by having prominent symptoms including forgetfulness along with difficulty learning new information or recalling old information.  People with MCI differ from those with Alzheimer’s Dementia in that they can functional normally in other cognitive areas outside of memory tasks such as decision-making and processing information.  However, MCI is a transitional state towards dementia with a rate of roughly 15% per year.

Nicotine Patches

For this particular study, participants randomized to the nicotine group were started on 5 mg nicotine patches for 16 hours per day and were titrated up to 15 mg patches by 21 days into the study.

Study Results

I’d be the first to admit that the tagline “Nicotine Improves Cognitive Performance” is attention grabbing.  However, before you start thinking that slapping on some nicotine patches will turn Grandma into Einstein, let’s note that cognitive performance is a sufficiently vague concept for may of us.

Generally speaking, cognition is comprised of several mental processes including not only short and long-term memory, but also attention, problem-solving ability, planning,  and information processing.

Connors Continuous Performance Measure (CPT)

For this particular study, the primary outcome measure involved assessing the effects of nicotine patches on attention using the Connors Continuous Performance Measure (CPT).

Having worked on a research project just over 10 years ago on Attention Deficit Disorder at the University of Toronto, I’m distantly familiar with many of the cognitive tests used in this study.  The Connors test is a measure of visual motor functioning.

Think of a really old and boring video game (not to mention an expensive one since it costs just under $1000)  with a series of letters that briefly display on your screen over time.  Every time a letter flashes on your screen, you click the space bar unless it’s a letter, “X.”

Basically, it appears this study found that nicotine therapy improved reaction time on this test, but had no effect on errors of omission (not clicking when you should) or commission (clicking when it’s the letter, ‘x’).

So far, not much to get excited about.

Clinical Global Improvement Change – CGIC

Though it sounds impressive, the CGIC is just a subjective rating by physician at the end of the trial that categorizes participants into one of five outcomes – moderate improvement, minimal improvement, no change, minimal improvement, and moderate improvement.  Regardless, there were no statistical differences between the placebo and nicotine treatment groups based on CGIC.

Computerized Cognitive Battery – Memory

Though the study included various memory tests, the only reported statistically significant results were a beneficial effect of nicotine treatment on paragraph recall and delayed word recall accuracy.

Weight Loss, Blood Pressure, Adverse Events:

The nicotine treatment group experienced statistically significant reductions in both weight (-1.3 kg) and systolic blood pressure (-4 mmhg) compared to placebo.

Total adverse events were higher in the nicotine group vs. placebo:

“Total adverse events (AEs) for the double-blind treatment period were 82 for nicotine vs 52 for placebo.”

Conclusions

One of the more interesting results of this study was that individuals with two APOE4 genes responded better to nicotine therapy.  People who have two APOE4 Alleles on Chromosome 19 have 8 x the risk of developing Alzheimer’s disease!

The researchers noted that this is just a pilot study, but that their results provided justification for further research into the use of nicotine for patients with early cognitive dysfunction (read: don’t put the patch on just yet).

 

Sources:

  1. Newhouse P, Kellar K, Aisen P, White H, Wesnes K, Coderre E, Pfaff A, Wilkins H, Howard D, Levin ED.  Nicotine treatment of mild cognitive impairment: A 6-month double-blind pilot clinical trial.  Neurology. 2012 Jan 10;78(2):91-101.
  2. Newhouse PA, Potter A, Singh A.  Effects of nicotinic stimulation on cognitive performance. Curr Opin Pharmacol. 2004 Feb;4(1):36-46.
  3. White HK, Levin ED.  Four-week nicotine skin patch treatment effects on cognitive performance in Alzheimer’s disease.  Psychopharmacology (Berl). 1999 Apr;143(2):158-65.
  4. Howe MN, Price IR.  Effects of transdermal nicotine on learning, memory, verbal fluency, concentration, and general health in a healthy sample at risk for dementia.  Int Psychogeriatr. 2001 Dec;13(4):465-75.

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