Nicotine Patches May Slow the Decline of Mild Cognitive Impairment into
Alzheimer’s
Evelyn E. Smith
MS
in Library Science, University of North Texas (2012)
Family members of patients diagnosed with Mild Cognitive Impairment may wish to ask a neurologist about the advisability of outfitting their loved one with a daily nicotine patch at least on a trial basis, perhaps replicating the results of a six-month trial published in 2012 that proved that wearing a nicotine patch under a physician’s supervision for six months eases some of the loss of cognitive functioning of MCI. Although caretakers will also need to weigh this against the increased anxiety that often accompanies a heightened awareness of memory loss, I can certainly testify that family members often try all sorts of alternative cures—from Vitamin E to blueberries and coconut oil--to slow the approach of dementia.
A few years later, what
would the family trade for six extra months of relative normality? Mother was diagnosed with MCI in August 2000
and is now completing her ninth-month in hospice care for Frontaltemporal
Dementia, so looking at her increasingly emaciated body and often
expressionless face, I know that I would certainly call her neurologist about
this finding.
On February 9, 2014, Scientific American published the
following excerpt from Dan Hurley’s book, Smarter:
The New Science of Building Brain Power (2013), which elicited a hunt for
vetted research backing up its claims that nicotine patches can safely
ameliorate some of the memory loss brought about by MCI:
Hurley, Dan. (2014, February 9). Will a Nicotine Patch Make You Smarter?
[Excerpt]. Scientific American.
Retrieved from http://www.scientificamerican.com/article/will-a-nicotine-patch-make-you-smarter-excerpt/?&WT.mc_id=SA_MB_20140212
Smarter:
The New Science of Building Brain Power (2013) details how dozens of human and animal studies
published during the last five years have shown that nicotine in the form of
chewing gum or a transdermal patch may treat or prevent a wide variety of
neurological disorders, including Parkinson’s, Mild Cognitive Impairment (MCI),
Attention Deficit Hyperactivity Disorder (ADHD), Tourette’s, and schizophrenia as well as bring about weight loss with “few known safety risks” (2014,
February 9, para. 1).
The one area where nicotine
patches, however, prove ironically ineffective is quitting smoking since heavy
smokers who use nicotine replacement therapy have the same
long-term relapse rate as those who don’t use nicotine patches, gum, inhalers,
or nasal spray (Hurley, 2014, February 9, para. 2).
Yet for all of
nicotine’s medical usefulness, scientists can’t disassociate it from smoking (Hurley,
2014, February 9, para. 3 & 5). Even so, the first serendipitous hint of
nicotine’s possible health benefits came from a report published in 1966 by the
National Institutes of Health that revealed while smokers were far more likely
to die from various cancers than nonsmokers, nonsmokers were three times more
likely to die from a neurodegenerative disorder, marked by a loss of dopamine-producing
neurons in midbrain (Hurley, 2014, February 9, para. 8). During the 1970s, neuroscientists went on to learn
that nicotine molecules guarded against cognitive disorders by fitting into
receptors for the neurotransmitter acetylcholine (Hurley, 2014, February 9,
para. 9).
Research now hints that
nicotine may protect against the early stages of Alzheimer’s or Mild Cognitive
Impairment: In a recent trial, 67 patients
diagnosed with MCI well-tolerated nicotine treatment and found “significant
nicotine-associated improvements in attention, memory, and psychomotor speed”
(Hurley, 2014, February 9, para. 12). Paul
Newhouse explains, “What we saw was consistent with prior studies showing that
nicotinic stimulation in the short run can improve memory, attention, and
speed.” Although Newhouse admits that the results of these exceedingly small studies weren’t necessarily
replicated in larger ones, participants suffered absolutely no withdrawal
symptoms or any abuse liability when using the nicotine patch (Hurley, 2014, February 9, para. 13-14).
As for the risk of
addicting nicotine patch wearers to nicotine, while nicotine when smoked is one
of the most addictive substances known, “in animal models nicotine appears to
be a weak reinforcer”. To be addictive,
tobacco therefore needs other chemical ingredients to keep smokers hooked (Hurley, 2014,
February 9, para. 15-17).
Thus, during the past
six years, researchers in Europe as well as Paul Newhouse in the United States
have published more than a dozen studies verifying that nicotine temporarily
improves visual attention and working memory.
For example, Jennifer Rusted, of
the University of Sussex, has published a series of reports proving that
nicotine increases by about 15 percent “prospective
memory”, or the ability to remember and put into effect an objective, shutting
out irrelevant stimuli and focusing attention on relevant matters (Hurley,
2014, February 9, para. 20-21).
Even with these
studies, however, physicians and neuroscientists discourage using a nicotine
patch for anything other than its intended use—to quit smoking (Hurley, 2014,
February 9, para. 22).
Using this Scientific American article as a basis for a keyword search verifies that Hurley is just jumping on the nicotine patch band wagon since Time Magazine published a similar article in January 2012.
Szalavitz, Maia. (2012,
January 9). Nicotine Patch May Improve Memory. Aging. Health & Family. Time. Retrieved from http://healthland.time.com/2012/01/09/nicotine-patch-may-improve-memory/
A study led by Dr. Paul
Newhouse of Vanderbilt University and published in Neurology has determined that the nicotine found in cigarettes may
treat mild cognitive impairment (MCI), a precursor to Alzheimer’s and other
dementias, as shown by the results of a randomized, controlled trial of 74
individuals diagnosed with MCI. Six
months of treatment with nicotine patches restored some long-term memory to 46
percent of normal in non-smoking patients while a control group treated with a
placebo experienced a 26 percent decline in cognitive functioning. Approximately half the participants were
previous smokers (Szalavitz, 2012, January 9, para. 1-2).
Participants receiving
nicotine patches experienced improved attention, memory, and reaction time on
several objective tests while the patients themselves as well as their family
members also noted their partial recovery. Nicotine’s positive effects didn’t decline
over time. However, clinical experts didn’t see a significant difference
between the behavior in the patients outfitted with nicotine patches and their
controls (Szalavitz, 2012, January 9, para. 3).
Wearing a nicotine
patch had the most effect on individuals with two copies of the APOE4 gene,
which increases the risk of Alzheimer’s by a factor of 20 or higher. Since the brains of Alzheimer’s patients have a
reduced number of nicotine receptors, some evidence indicates that nicotine
could possibly protect these neurons even as other research suggests that nicotine
might increase the cancer-causing properties of other substances (Szalavitz,
2012, January 9, para. 4).
Proof thus exists
for nicotine-induced cognitive improvement in MCI patients; however,
additional, larger studies are needed to determine if this partial recovery of
memory, attention span, and reaction time is “clinically important”(Szalavitz,
2012, January 9, para. 5). However, the
research funded by the National Institute on Aging, the pharmaceutical
industry, and the tobacco company Philip Morris found no problematic side
effects or withdrawal symptoms, although patients did lose some weight. Pfizer supplied the nicotine patches (Szalavitz,
2012, January 9, para. 6).
All of which lead to Google Scholar and PubMed searches for clinical trials that verify the results touted by the Time and Scientific American articles:
Newhouse, Paul A.,
Potter, Alexandra, & Singh, Abhay.
(2004). Effects of nicotinic stimulation on cognitive performance. Current
Opinion in Pharmacology, 4, 36–46.
Retrieved from http://www.gwern.net/docs/nicotine/2004-newhouse.pdf
Newhouse and his
fellow researchers certainly prove that using nicotine patches to ameliorate
the effects of MCI and Alzheimer’s isn’t new if the dates of the clinical
trials they mention are any indication.
In this 2004 article, which serves as a basis for further research, they
emphasize that successful trials of nicotine treatment in Alzheimer’s patients
preceded trials of nicotine patches for patients diagnosed with Mild Cognitive
Impairment (Newhouse, 2004, p. 38). The
articles referenced in this article also clearly show that that medical science has long recognized the short-term positive
effect of nicotine patches for treating memory loss and dementia:
White, H. K. and Levin,
E. D. (2004, February). Chronic transdermal nicotine patch treatment
effects on cognitive performance in age-associated memory impairment. Psychopharmacology,
171(4):465-71. [Abstract only]. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/14534771
This double-blind, placebo-controlled,
cross-over study determined the clinical and neuropsychological effectiveness of
chronic transdermal nicotine for treating Age Associated Memory Impairment
(AAMI), otherwise sometimes known as Mild Cognitive Impairment. Participants wore a nicotine patch for 16
hours daily, dispensed and tested in an outpatient setting. A two-week washout period followed the wearing
of the patch (White, 2004, para. 1-3).
Individuals diagnosed with AAMI wore Nicotrol patches dispensing 5
milligrams of nicotine during the first week, 10 milligrams of nicotine during
the second week, and five milligrams of nicotine during the third week (White,
2004, para. 4).
Using the Clinical Global
Impressions Questionnaire, the Conners’ Continuous Performance Test (CPT), and
a computerized neuropsychology battery, known as the Automated
Neuropsychological Assessment Metrics (ANAM), researchers determined that
nicotine “significantly improved” the participants’ clinical Global Impressions
Questionnaire scores as well as their attention function and decision reaction
time, but it didn’t improve motor and memory function (White, 2004, para. 5-6).
Researchers concluded that transdermal
nicotine treatment of AAMI patients resulted in sustained improvement of
clinical symptoms, thereby supporting further investigation (White, 2004, para.
7).
However, before clinical trials fitted nicotine patches on MCI patients, researchers first administered intravenous injections of nicotine to Alzheimer’s patients in 1988 and first outfitted them with nicotine patches in 1995 and 1999:
Newhouse, P. A.,
Sunderland, T., Tariot, P. N. et al.
(1988). Intravenous nicotine in
Alzheimer’s disease: A pilot study. Psychopharmacology,
95, 171-175. [Abstract and first page only].
Retrieved from http://link.springer.com/article/10.1007/BF00174504#page-1
Six-non-smoking
Alzheimer’s patients with the mean age of 66.8 received three successive amounts
of low (0.125 kilograms), middle (0.25 kilograms), and high (0.5 kilograms)
intravenous nicotine or a placebo over an unspecified period of time [that
didn’t appear in the abstract or the first page] whereupon they took cognitive
tests that showed a decrease in intrusion errors. However, an increase in anxiety and depression
accompanied this increase in cognitive function.
Wilson, A. Lynn,
Langley, L.K., & Monley, J., et al.
(1995, June-July). Nicotine patches in
Alzheimer's disease: Pilot study on learning, memory, and safety. Pharmacology Biochemistry and
Behavior, 51(2-3), 509-514.
doi: 10.1016/0091-3057(95)00043-V.
[Abstract only]. Retrieved from http://www.sciencedirect.com/science/article/pii/009130579500043V
This double-blind,
placebo-controlled trial evaluated the effects of sustained nicotine
administration on behavior, cognition, and physiology in six patients diagnosed
with Alzheimer’s, who were exposed to seven days of a placebo, eight days of
wearing a nicotine patch, and seven days of washing out its effects
respectively while daily sessions evaluated their learning, memory, and
behavior, and physicians also monitored
their global cognitive functioning, rest and activity levels, cardiac activity
and blood levels. Researchers found the
participants improved learning skills while they wore the nicotine patch, and
this enhanced ability to learn continued through the washout period. However, nicotine didn’t significantly affect
memory, behavior, and global cognition.
Administration of nicotine over the week appeared to be safe, although
participants showed a significant decrease in sleep.
White, H. K. and Levin,
E.D. (1999, April). Four-week nicotine
skin patch treatment effects on cognitive performance in Alzheimer's disease. Psychopharmacology
(Berl), 143(2):158-65. [Abstract only].
Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/10326778
White and Levin
undertook a four-week, double-blind, placebo-controlled cross-over study to
evaluate the clinical and neuropsychological effects of chronic transdermal
nicotine in eight otherwise healthy Alzheimer’s patients since although
researchers knew that nicotine injections improved attention, they didn’t know
much about the effects of the use of chronic nicotine. For sixteen hours a day, patients wore a
Nicotrol patch containing five milligrams of nicotine for the first week, a 10
milligram nicotine patch during the second and third week, and a five milligram
patch during the four week.
Wearing a nicotine
patch significantly improved attention span, errors of omission, and reaction
time for correct responses as measured by the Conners’ Continuous Performance
Test (CPT). But it didn’t improve motor and memory function. The participants' sustained attention
encouraged researchers, but nicotine’s inability to influence other cognitive
and behavioral domains as well as the
modest size of the study left the positive effects of using nicotine patches as
a treatment for Alzheimer’s open to question.
Nevertheless, White and Levin suggested that higher doses of nicotine,
the possible use of other nicotine ligands, or nicotine treatment combined with
other therapies might produce more comprehensive therapies.
____________
These references, in turn, leads to the most recent clinical trial conducted by Newhouse and colleagues:
Newhouse, P., Kellar,
K., Aisen, P., et al. (2012, August 11). Nicotine treatment of mild
cognitive impairment: A 6-month double-blind pilot clinical trial. Neurology,
78;91. doi: 10.1212/WNL.0b013e31823efcbb.
Retrieved from http://www.gwern.net/docs/nicotine/2012-newhouse.pdf
Newhouse and his
fellow researchers randomly administered 15 milligrams of transdermal nicotine daily
to non-smoking trial participants diagnosed with amnestic Mild Cognitive
Impairment over a six-month period. Of
the original 39 participants wearing nicotine patches, 34 completed the study
while 33 of the 35 participants wearing placebo patches finished it. Those wearing the nicotine
patches showed signs of nicotine-induced improvement in attention, memory, and
psychomotor speed but no enhanced cognitive functioning measured by the Clinical Global
Impressions Questionnaire. The
researchers thus concluded that attention, memory, and mental processing
improve when non-smoking MCI patients are outfitted with transdermal nicotine
patches.
Stay tuned to further results by regularly searching PubMed with the keywords “mild cognitive impairment” AND “nicotine”; but in the meanwhile, nicotine patches just might prove beneficial:
Cooper, C., Li, R., & Lyketsos, C, et al. (2013). Treatment for mild cognitive impairment: systematic
review. The British Journal of Psychiatry, 203-255-65. doi:
10.1192/bjp.bp.113.127811. [Abstract
only]. Retrieved from
http://www.ncbi.nlm.nih.gov/pubmed/24085737
Cooper and associates
reviewed 41 studies, assessing their validity and determined that
cholinesterase inhibitors have proved ineffective
in preventing dementia. However,
preliminary evidence suggests that heterogeneous psychological group
interventions enhance thinking skills over a six-month period, Piribedil, a
dopamine agonist, augments cognition over three months, and Donepezil betters
brain functioning over 48 weeks. Clinical
trials have also shown that nicotine improves attention for six months. Equivocal evidence also indicates that Huannao
Yicong capsules boost cognition and social functioning. Nevertheless, no replicated evidence existed
that any intervention was effective.
Bottom Line: Nicotine patches may be another tool in an increasing set of pharmaceutical options that improves cognitive functioning and delays the onset of Alzheimer’s and other dementias.
____________
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