Nicotine Patch Showing Promise in Mild Cognitive Impairment

Allison Shelley

January 10, 2012

January 10, 2012 ( UPDATED January 18, 2012 ) — The nicotine patch, best known as a smoking cessation aid, is now showing benefit as a treatment for mild cognitive impairment. New class I evidence suggests the patch (Nicotrol, Pfizer) improves cognitive test performance in older adults with early memory loss.

"This is a promising treatment," lead investigator Paul Newhouse, MD, from Vanderbilt University in Nashville, Tennessee, told Medscape Medical News. "It is well tolerated with minimal side effects."

Results from the pilot clinical trial appear in the January 10 issue of Neurology.

The study included 74 nonsmokers with mild cognitive impairment. Half of the participants received a nicotine patch of 15 mg/day, and half received a placebo.

The primary outcome variables were attentional improvement, assessed with the Connors Continuous Performance Test, and improvement measured by clinical global impression and safety measures. Secondary measures included computerized cognitive testing and patient and observer ratings.

After 6 months of treatment, the nicotine-treated group regained 46% of normal performance for age on long-term memory. In contrast, patients in the placebo group declined by 26% during the same period.

More Study Needed

The study demonstrated that nicotine improved primary and secondary cognitive measures of attention, memory, and mental processing, but not ratings of clinician-rated global impression.

"We will need larger, longer-term studies to confirm clinical efficacy," Dr. Newhouse pointed out. "This study provides strong justification for further research into the use of nicotine for people with early signs of memory loss."

Nicotine treatment was associated with a modest reduction in systolic blood pressure. Many patients also experienced a reduction in weight with no significant medical consequences. There were no problems in withdrawing treatment, and no participants continued nicotine use.

The transdermal administration probably contributed to improved tolerability, the authors note, particularly reducing the incidence of gastrointestinal adverse effects.

The results are consistent with prior studies. Nicotine has been shown to improve cognitive performance in smokers who have stopped smoking, and previous short-term studies with nicotine have shown attention and memory improvement in patients with Alzheimer's disease. Nicotinic stimulation appears to alter receptors in the brain involved in thinking and memory; patients with Alzheimer's typically lose some of these receptors.

Asked by Medscape Medical News to comment on the study, Ronald Petersen, MD, from the Mayo Clinic in Rochester, Minnesota, said, "I think it is interesting and makes some pharmacological sense, since cholinergic receptors in the brain are involved in cognitive function. There are 2 types of receptors, muscarinic and nicotinic, and while we usually think muscarinic receptors are most relevant, nicotinic receptors play a role as well."

Serge Gauthier, MD, from the McGill Center for Studies in Aging in Montreal, Quebec, Canada, says the study is interesting; however, not all evaluations of nicotinic agents in mild Alzheimer's disease have been promising. "Some have been tried before with little effects," he noted.

Both physicians agree the study was relatively small, with a short length of follow-up, and will require additional investigation.

Dr. Newhouse emphasized that people with early memory loss should not start smoking or using nicotine patches by themselves. "Smoking is a terrible delivery system for nicotine, and is filled with carcinogens," he said, "and a medication such as nicotine should only be used with a doctor's supervision."

This study was supported by the National Institute on Aging and the National Institute of General Medical Sciences. Pfizer provided the transdermal nicotine patches. Dr. Newhouse has served as a consultant for AstraZeneca, Gerson Lehrman Group, Guidepoint Global, Summer Street Research Partners, and Biotechnology Value Fund, LP. He also receives research support from Eli Lilly and Targacept. Dr. Petersen and Dr. Gauthier have disclosed no relevant financial relationships.

Neurology. 2012;78:91-101. Abstract

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