Age-related decline in nicotinic receptor availability with [(123)I]5-IA-85380 SPECT.
Neurobiology of aging 2008 Jan 31; In press
Mitsis E EM, Cosgrove K KP, Staley J JK, Bois F F, Frohlich E EB, Tamagnan G GD, Estok K KM, Seibyl J JP, van Dyck C CH
Alzheimer's Disease Research Unit, Yale University School of Medicine, One Church Street, Suite 600, New Haven, CT 06510, USA; Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA; Veterans Affairs Connecticut Healthcare System
Human postmortem studies have reported decreases with age in high affinity nicotine binding in brain. We investigated the effect of age on beta(2)-containing nicotinic acetylcholine receptor (beta(2)-nAChR) availability in eight brain regions of living human subjects using the ligand [(123)I]5-IA-85380 ([(123)I]5-IA) and single photon emission computed tomography (SPECT). Healthy, nonsmokers (N=47) ranging in age from 18 to 85 were administered [(123)I]5-IA using a bolus plus constant infusion paradigm and imaged 6-8h later under equilibrium conditions. The effect of age on regional beta(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 beta(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 beta(2)-nAChRs in cognitive aging.
Keywords: nACh nicotine nicotinic receptors beta2 cognition memory SPECT