Monday, February 24, 2014

Using Keyword Searches to Find Treatments for Mild Cognitive Impairment

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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The links furnished on this Web page represent the opinions of their authors, so they complement—not substitute—for a physician’s advice.

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