title: Age-related differences in working memory deficits during nicotine withdrawal.
abstract: Nicotine withdrawal is associated with subtle working memory deficits that predict subsequent relapse. We examined the neural substrates underlying these processes in treatment-seeking smokers, and explored the moderating influence of age on abstinence-induced alterations in brain activity and performance. Sixty-three smokers participated in two blood oxygen level-dependent (BOLD) functional magnetic resonance imaging scans while performing a visual N-back task on two separate occasions: smoking as usual and after 24 hours of biochemically confirmed abstinence (order counterbalanced). Abstinence (versus smoking) led to reduced accuracy, slower median correct response time and reduced BOLD signal change in the three a priori regions of interest: medial frontal/cingulate gyrus and right and left dorsolateral prefrontal cortex. Significant age × session effects were found for BOLD signal change in all three regions, as well as for withdrawal and craving; for all measures, abstinence effects were attenuated in smokers aged ≥50 years compared with those <50 years old. These results suggest that abstinence effects on neurocognitive function may be more pronounced for younger smokers, and may indicate a new avenue for research exploring mechanisms underlying age differences in smoking cessation success.
authors.affiliation: Department of Pharmacology, University of Pennsylvania, Philadelphia, PA, USA; Center for Interdisciplinary Research on Nicotine Addiction, Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Mary
authors.initials: M
authors.lastname: Falcone
authors.forename: E Paul
authors.initials: EP
authors.lastname: Wileyto
authors.forename: Kosha
authors.initials: K
authors.lastname: Ruparel
authors.forename: Raphael T
authors.initials: RT
authors.lastname: Gerraty
authors.forename: Leah
authors.initials: L
authors.lastname: LaPrate
authors.forename: John A
authors.initials: JA
authors.lastname: Detre
authors.forename: Ruben
authors.initials: R
authors.lastname: Gur
authors.forename: James
authors.initials: J
authors.lastname: Loughead
authors.forename: Caryn
authors.initials: C
authors.lastname: Lerman
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008569:Memory Disorders / Q000209:etiology* / Q000503:physiopathology; D008570:Memory, Short-Term / Q000502:physiology*; D008875:Middle Aged; D017397:Prefrontal Cortex / Q000502:physiology; D011597:Psychomotor Performance / Q000502:physiology; D012907:Smoking / Q000503:physiopathology*; D016540:Smoking Cessation / Q000523:psychology; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology / Q000523:psychology*; D014029:Tobacco Use Disorder / Q000503:physiopathology / Q000523:psychology*; D055815:Young Adult
keywords: Addiction; age; cognition; fMRI; nicotine; withdrawal