Nicotine treatment of mild cognitive impairment: A 6-month double-blind pilot clinical trial

Clinical Neuroscience Research Unit, Department of Psychiatry, University of Vermont College of Medicine, Burlington, USA.
Neurology (Impact Factor: 8.29). 01/2012; 78(2):91-101. DOI: 10.1212/WNL.0b013e31823efcbb
Source: PubMed


To preliminarily assess the safety and efficacy of transdermal nicotine therapy on cognitive performance and clinical status in subjects with mild cognitive impairment (MCI).
Nonsmoking subjects with amnestic MCI were randomized to transdermal nicotine (15 mg per day or placebo) for 6 months. Primary outcome variables were attentional improvement assessed with Connors Continuous Performance Test (CPT), clinical improvement as measured by clinical global impression, and safety measures. Secondary measures included computerized cognitive testing and patient and observer ratings.
Of 74 subjects enrolled, 39 were randomized to nicotine and 35 to placebo. 67 subjects completed (34 nicotine, 33 placebo). The primary cognitive outcome measure (CPT) showed a significant nicotine-induced improvement. There was no statistically significant effect on clinician-rated global improvement. The secondary outcome measures showed significant nicotine-associated improvements in attention, memory, and psychomotor speed, and improvements were seen in patient/informant ratings of cognitive impairment. Safety and tolerability for transdermal nicotine were excellent.
This study demonstrated that transdermal nicotine can be safely administered to nonsmoking subjects with MCI over 6 months with improvement in primary and secondary cognitive measures of attention, memory, and mental processing, but not in ratings of clinician-rated global impression. We conclude that this initial study provides evidence for nicotine-induced cognitive improvement in subjects with MCI; however, whether these effects are clinically important will require larger studies. Classification of evidence: This study provides Class I evidence that 6 months of transdermal nicotine (15 mg/day) improves cognitive test performance, but not clinical global impression of change, in nonsmoking subjects with amnestic MCI.

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Available from: Kenneth J Kellar, Jan 21, 2014
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    • "However, few studies have investigated the impact of NIC exposure on METH-induced memory deficits. Among these, in clinical trials, NIC patch application improved recognition memory or attention in patients with schizophrenia or mild cognitive impairment compared with placebo-treated patients (Jubelt et al., 2008; Newhouse et al., 2012). Activation of α4β2 subtypes of nAChRs also improved working memory in rhesus monkeys that self-administered cocaine (Gould et al., 2013). "
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    ABSTRACT: Previous studies have demonstrated that methamphetamine (METH) abuse leads to memory deficits and these are associated with relapse. Furthermore, extensive evidence indicates that nicotine (NIC) prevents and/or improves memory deficits in different models of cognitive dysfunction and these nicotinic effects might be mediated by hippocampal or cortical nicotinic acetylcholine receptors (nAChRs). The present study investigated whether NIC attenuates METH-induced novel object recognition (NOR) deficits in rats and explored potential underlying mechanisms. Adolescent or adult male Sprague-Dawley rats received either NIC water (10-75 μg/ml) or tap water for several weeks. METH (4 x 7.5 mg/kg/injection) or saline was administered either before or after chronic NIC exposure. Novel object recognition was evaluated 6 d after METH or saline. Serotonin transporter function and density, and α4β2 nAChR density were assessed on the following day. Chronic NIC intake via drinking water beginning during either adolescence or adulthood attenuated the NOR deficits caused by a high-dose METH administration. Similarly, NIC attenuated METH-induced deficits in NOR when administered after METH treatment. However, NIC did not attenuate the serotonergic deficits caused by METH in adults. Conversely, NIC attenuated METH-induced deficits in α4β2 nAChR density in the hippocampal CA1 region. Furthermore, NIC increased α4β2 nAChR density in the hippocampal CA3, dentate gyrus and perirhinal cortex (PRh) in both saline- and METH-treated rats. Overall, these findings suggest that NIC-induced increases in α4β2 nAChRs in the hippocampus and PRh might be one mechanism by which NOR deficits are attenuated by NIC in METH-treated rats. © The Author 2015. Published by Oxford University Press on behalf of CINP.
    The International Journal of Neuropsychopharmacology 07/2015; DOI:10.1093/ijnp/pyv073 · 4.01 Impact Factor
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    • "Following this line of thought, nicotine may be particularly effective in populations with decreased cognitive performance . Indeed, a study on patients with minimal cognitive impairment (MCI) showed that nicotine improved attention, memory, and psychomotor speed (Newhouse et al., 2012). So far, only two studies have addressed the effects of nicotine in a normal elderly population. "
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    ABSTRACT: Since cholinergic neurotransmission plays a major role in cognition, stimulation of the nicotinic acetylcholine receptor may be a target for cognitive enhancement. While nicotine improves performance on several cognitive domains, results of individual studies vary. A possible explanation for these findings is that the effect of nicotine administration may be dependent on baseline cognitive function, where subjects with a suboptimal cognitive performance may benefit from nicotine, while subjects who already perform optimally may show a decline in performance after nicotinic stimulation. We conducted a double-blind randomised placebo-controlled crossover trial, examining the effects of placebo, 1, and 2mg of nicotine on cognition in young (n=16, age 18-30 years) and healthy elderly (n=16, age 60-75 years) subjects. We hypothesised that the elderly would benefit more from nicotine compared to young subjects, as normal ageing is associated with decreases in cognitive function. Attention, working memory, visual memory, information-processing speed, psychomotor function, stereotypy, and emotion recognition were assessed. Compared to the young volunteers, the elderly performed significantly worse on psychomotor function and emotion recognition in the placebo condition. Nicotine had no effect in the young volunteers and decreased performance on working memory and visual memory in the elderly. Contrary to our hypothesis, the effect of nicotine was dependent on baseline performance in both the groups, with subjects with lower baseline performance benefiting from nicotine administration, while those with higher baseline performance performed worse after nicotine administration. This suggests that subjects with lower cognitive performance, irrespective of age, may benefit from nicotine.
    European neuropsychopharmacology: the journal of the European College of Neuropsychopharmacology 04/2014; 24(7). DOI:10.1016/j.euroneuro.2014.03.011 · 4.37 Impact Factor
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    • "A good number of NR products have been developed and licensed as effective treatments for tobacco dependence . However, nicotine isolated from tobacco has been tried as a treatment for many conditions and disorders and some positive effects have been observed in preliminary studies in the following conditions: ulcerative colitis (Sandborn, 1999), major depression (McClernon, Hiott, Westman, Rosse, & Levin, 2006), Tourettes's syndrome (Silver et al., 2001), neuroleptic-induced akathisia (Anfang & Pope, 1997), cognition in schizophrenia (Barr et al., 2008), attention deficit hyperactivity disorder (Gehricke Hong, Whalen, Steinhoff & Wigal, 2009), Parkinsons disease (Thiriez et al., 2011) and mild cognitive impairment (Newhouse et al., 2012). The best evidence is available for Parkinson's disease (Fagerström & Pomerleau, 1994; Thiriez et al., 2011) and ulcerative colitis (Green et al., 1997; Sandborn, 1999). "

    The Journal of Smoking Cessation 12/2014; 9(2):53-59. DOI:10.1017/jsc.2014.27
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