Nicotine treatment of mild cognitive impairment

Abstract

Objective: To preliminarily assess the safety and efficacy of transdermal nicotine therapy on cognitive performance and clinical status in subjects with mild cognitive impairment (MCI). Methods: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.Results: 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. Conclusion: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. Neurology ® 2012;78:91-101

Therapeutic Potential ofα7 Nicotinic Acetylcholine Receptors

“…In view of the parallel reductions in ACh and nicotine binding sites in cerebral cortex, experiments were conducted to determine if nicotine could be a suitable treatment to restore cognitive function. Exposure to nicotine alleviated deficits in attention and informational processing associated with AD (Wesnes and Warburton, 1984;Sahakian et al, 1989;Newhouse et al, 2012). The positive effects of nicotine treatment observed in these studies were initially attributed to nicotine interacting with the high-affinity a4b2 nAChRs.…”

“…A genetic study suggested that the CHRNA7 might act as a modifier gene in patients with MCI in protection from conversion to AD (Barabash et al, 2009). A recent study demonstrated that in a 6-month study, transdermal nicotine improved measures of attention, memory, and mental processing in nonsmoking MCI patients, although not in the global impression clinical rating scale (Newhouse et al, 2012).…”

Nicotine: Pharmacology, Toxicity and Therapeutic use

“…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).…”

Pharmacological Treatment of Mild Cognitive Impairment as a Prodromal Syndrome of Alzheimer's Disease

“…These include intranasal insulin [37], melatonin [38], nicotine patches [39], Chinese plant extracts [40] and other antioxidants, various nutritional supplements (including vitamins and omega-3 fatty acids), ampakines , testosterone , metformin and levodopa. …”