PET imaging of cortical 11C-nicotine binding correlates with the cognitive function of attention in Alzheimer's disease

Rationale Patients suffering from Alzheimer's disease (AD) experience a marked reduction in cortical nicotinic acetylcholine receptors (nAChRs). In particular, selective loss of the alpha(4)beta(2) nAChR subtype was observed in postmortem AD brain tissue. The alpha(4) and alpha(7) nAChR subunits were suggested to play an important role in cognitive function. Positron emission tomography (PET) has so far been used to visualize neuronal nAChRs in vivo by C-11-nicotine binding. Objectives To investigate the relationship between measures of cognitive function and in vivo C-11-nicotine binding in mild AD brain as assessed by PET. Materials and methods Twenty-seven patients with mild AD were recruited in this study. A dual tracer model with administration of O-15-water for regional cerebral blood flow and (S)(-)C-11-nicotine was used to assess nicotine binding sites in the brain by PET. Cognitive function was assessed using neuropsychological tests of global cognition, episodic memory, attention, and visuospatial ability. Results Mean cortical C-11-nicotine binding significantly correlated with the results of attention tests [Digit Symbol test (r=-0.44 and p=0.02) and Trail Making Test A (TMT-A) (r=0.42 and p=0.03)]. No significant correlation was observed between C-11-nicotine binding and the results of tests of episodic memory or visuospatial ability. Regional analysis showed that C-11-nicotine binding in the frontal and parietal cortex, which are the main areas for attention, correlated significantly with the Digit Symbol test and TMT-A results. Conclusion Cortical nicotinic receptors in vivo in mild AD patients are robustly associated with the cognitive function of attention.