AAGP 2009: Nicotine Patch May be Helpful in Mild Cognitive Impairment

Caroline Cassels

March 11, 2009

March 11, 2009 (Honolulu, Hawaii) — Transdermal nicotine treatment may help improve memory in patients with amnestic mild cognitive impairment (MCI), new research suggests.

Presented here at the American Association of Geriatric Psychiatry 2009 Annual Meeting, results from a large, double-blind, multicenter pilot study show that nicotine patches improve attention, memory, and speed, with several other measures showing strong trends toward improvement.

Dr. Paul Newhouse

"There's a strong signal that nicotinic stimulation improves cognitive performance and that transdermal nicotine improves delayed-word-recall accuracy and the speed of memory processes in this patient population," principal investigator Paul Newhouse, MD, from the University of Vermont School of Medicine, in Burlington, told Medscape Psychiatry.

For the past 20 years, Dr. Newhouse and colleagues have been researching nicotine as a possible way of enhancing cognitive function in several different disorders.

During the 1980s, he said, his group and others began looking at stimulating nicotinic-receptor function as a possible method of improving cognitive function in individuals with Alzheimer's disease, other dementia types, and attention-deficit/hyperactivity disorder as well as MCI.

Much of this work, he said, focused on developing novel nicotinic agonists to treat these conditions — a research effort that is ongoing.

Ideal Target

The objective of the current study, which is funded by the National Institute on Aging (NIA), was to determine whether transdermal nicotine could improve cognitive function in MCI, a condition that is widely held to be a transitional stage between normal cognitive function and the subsequent development of dementia.

"We know that nicotinic-receptor function is a critical part of overall cholinergic function. We wanted to see whether we could demonstrate that stimulating nicotinic-receptor function enhances cognition in MCI patients. In many ways, MCI is really the ideal target for nicotine [therapy] because patients with this condition have not yet lost all of their nicotinic receptors," he said.

Investigators at 3 centers — the University of Vermont, Duke University, and Georgetown University — recruited 74 nonsmoking subjects who met the criteria for amnestic MCI.

Participants were randomized to receive either a double-blind nicotine or placebo patch for the first 6 months of the study, followed by a 6-month crossover phase in which all subjects received active treatment.

During the double-blind phase, subjects were cognitively assessed at baseline, 91, and 182 days using the Cognitive Drug Research battery (a computerized assessment), the Conners Continuous Performance Task (CPT), and the Clinical Global Impression of Change (CGIC). Those randomized to receive nicotine had their dose blindly titrated from 5 mg to 15 mg per day over 3 weeks.

"We found that over a 6-month period, 23% of those in the treatment group vs 9% of subjects in the placebo group were improved on the global assessment. This just missed statistical significance, but we believe this is because the study was slightly underpowered to detect statistical significance," said Dr. Newhouse.

In addition, subjects' self-ratings of cognitive impairment and alertness showed a strong trend in favor of nicotine treatment.

Unexpected BP-Lowering Effect

An analysis of treatment effect by subjects' APOE e4 status showed a genotype effect, with a stronger treatment response in CGIC ratings and performance measures in subjects without the allele.

Adverse events, said Dr. Newhouse, were mild and evenly split between the placebo and treatment groups. Not unexpectedly, he said, those in the nicotine group experienced a small but significant decline in weight compared with placebo subjects. Interestingly, he said, those in the active-treatment group experienced a statistically significant reduction in systolic blood pressure — an unexpected finding.

"Normally, you hear that nicotine has an adverse effect on cardiovascular health, so this drop in blood pressure was unexpected. We are at a loss to explain it, except to say it may be a brain-stem mechanism," he said.

Analysis of data from the open-label phase of the study is not yet complete. However, said Dr. Newhouse, the findings from the double-blind phase provide a strong enough signal of efficacy to warrant a larger study.

"We've got enough data now to go forward and propose a much larger study to the NIA to see whether transdermal nicotine may be an appropriate treatment for amnestic MCI. If it works out, we would have a treatment that is safe, cheap, and effective," he said.

The study was funded by the National Institute on Aging.

American Association for Geriatric Psychiatry 2009 Annual Meeting: Abstract NR 89. Presented March 6, 2009.

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