Acute nicotine enhances strategy-based semantic processing in Parkinson's disease.

Nicotinic mechanisms may play a role in the cognitive deficits of Parkinson's disease (PD). Recently, on a cognitively demanding strategy-based priming task, nicotine selectively affected controlled semantic processing in young adult non-smokers as reported by Holmes et al. (International Journal of Neuropsychopharmacology 11, 389-399, 2008). Such controlled semantic processing is compromised in PD. This study investigated the effects of acute transdermal nicotine on controlled semantic processing in non-smokers with PD (n = 10) and non-smoking matched controls (n = 16) using a strategy-based semantic priming paradigm. Transdermal nicotine patches (7 mg/24 h) were administered in a double-blind, placebo-controlled, crossover design. Participants were instructed to expect target words from specified semantic categories based on the primes, while unexpected targets were also presented. Priming conditions included those concurring with trained expectations (expected-related and expected-unrelated), those which did not (unexpected-related and unexpected-unrelated), and neutral-baseline conditions. Controls evidenced significant expectancy effects (i.e. reaction-time differences for expected vs. unexpected conditions) under both drug states. An expectancy effect was not evident for PD under placebo due to a lack of reaction-time slowing for unexpected conditions. However, under nicotine an expectancy effect was present for PD at a level comparable to controls. Overall the findings indicate that nicotine can improve impaired controlled semantic processing in PD possibly via enhanced expectancy or inhibitory mechanisms.