The effects of nicotine on cognition are dependent on baseline performance.

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.

Acute nicotine improves social decision-making in non-smoking but not in smoking schizophrenia patients.

Schizophrenia patients are characterized by severe social impairments. Recently, social cognition has been put forward as an important mediator in schizophrenia between the often-reported neurocognitive deficits and functional outcome and is thus an important target for treatments. Nicotine has been reported to improve neurocognitive processes in schizophrenia patients but no studies have investigated possible nicotine-induced facilitation of social cognition. The current placebo-controlled crossover study aimed at bridging this gap by investigating whether the administration of active (1 mg or 2 mg) or placebo oromucosal nicotine spray resulted in improved social decision-making in non-smoking (N = 15) and smoking (N = 16) schizophrenia patients. All patients played the role of responder in a variant of the ultimatum game that allowed detailed measurements of fairness and intentionality considerations. The results showed impaired social decision-making in the non-smoking patients under placebo, but not in the smoking patients. Interestingly, this impairment normalized after administration of 1 mg of nicotine, but not after 2 mg of nicotine. Nicotine had no effect on performance in the smoking patients. The present study indicates that nicotine improves social decision-making in non-smoking patients. The present results suggest that acute nicotine effects may result in a facilitation of proactive control through improved attentional processes. However, the efficacy seems limited and although nicotine may thus be an interesting target for (social) cognitive enhancement in the subset of patients that do not smoke, more research is needed on the long-lasting effects of nicotine-based treatments.