Age-related decline in nicotinic receptor availability with [ 123I]5-IA-85380 SPECT

Abstract

Human postmortem studies have reported decreases with age in high affinity nicotine binding in brain. We investigated the effect of age on β 2-containing nicotinic acetylcholine receptor (β 2-nAChR) availability in eight brain regions of living human subjects using the ligand [ 123I]5-IA-85380 ([ 123I]5-IA) and single photon emission computed tomography (SPECT). Healthy, nonsmokers ( N = 47) ranging in age from 18 to 85 were administered [ 123I]5-IA using a bolus plus constant infusion paradigm and imaged 6–8 h later under equilibrium conditions. The effect of age on regional β 2-nAChR availability ( V T, regional brain activity/free plasma parent, a measure proportional to the binding potential) was analyzed using linear regression and Pearson's correlation ( r). Age and regional β 2-nAChR availability were inversely correlated in seven of the eight brain regions analyzed, with decline ranging from 32% (thalamus) to 18% (occipital cortex) over the adult lifespan, or up to 5% per decade. These results in living human subjects corroborate postmortem reports of decline in high affinity nicotine binding with age and may aid in elucidating the role of β 2-nAChRs in cognitive aging.