Age- and sex-related differences in human α4β2* nicotinic acetylcholine receptor binding evaluated with [¹⁸F]nifene...

Neuronal α4β2* nicotinic acetylcholine receptors (nAChRs) are stimulated by nicotine and are associated with tobacco dependence. [¹⁸F]Nifene is a PET radiotracer with high specificity for α4β2* nAChRs that can be used to investigate nAChR distribution in the human brain in vivo. In this study, we investigate the dependence of sex and age on the binding of [¹⁸F]nifene in nonsmoking healthy human participants. Cognitively normal participants (n = 31) were recruited into older versus younger and male versus female cohorts to investigate sex and age differences in [¹⁸F]nifene binding. Distribution volume ratios (DVRs) were calculated for brain regions with known nAChR expression and compared using a multiparameter linear regression model. There was a significant association between age and decreasing thalamic DVR (p = 0.01), with the most notable difference coming from the anterior nucleus of the thalamus (p < 0.001). Outside of the thalamus, a higher [¹⁸F]nifene DVR was observed with increasing age in the cerebellar grey matter (p = 0.01). No significant sex differences were observed using our linear model after multi-comparison correction. These results support including age in the experimental design and analysis of the α4β2* nAChR system in research and clinical applications.