Age-related decline in nicotinic receptor availability with [(123)I]5-IA-85380 SPECT.
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.
Mitsis
Effie M
EM
Yale University School of Medicine, New Haven, CT 06510, USA.
Cosgrove
Kelly P
KP
Staley
Julie K
JK
Bois
Frederic
F
Frohlich
Erin B
EB
Tamagnan
Gilles D
GD
Estok
Kristina M
KM
Seibyl
John P
JP
van Dyck
Christopher H
CH
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism*; D001384:Azetidines; D001921:Brain / Q000033:anatomy & histology / Q000378:metabolism* / Q000503:physiopathology; D001923:Brain Chemistry / Q000502:physiology*; D003072:Cognition Disorders / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000503:physiopathology; D015536:Down-Regulation / Q000502:physiology*; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D011725:Pyridines; D011978:Receptors, Nicotinic / Q000032:analysis / Q000378:metabolism*; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods; D055815:Young Adult
D001384:Azetidines; D007457:Iodine Radioisotopes; D011725:Pyridines; D011978:Receptors, Nicotinic; C426745:5-iodo-3-(2-azetidinylmethoxy)pyridine