title: Interactive effects of APOE and CHRNA4 on attention and white matter volume in healthy middle-aged and older adults.
abstract: In the present study, we investigated age-related changes in interactions between efficiency of neuronal repair mechanisms and efficiency of cholinergic neurotransmission in the context of attentional orienting. In addition, we explored white matter volume changes as possible neuronal underpinnings. A sample of 230 healthy middle-aged (53-64 years) and older (65-75 years) adults was genotyped for polymorphisms of APOE and CHRNA4, a nicotinic receptor subunit gene. Participants were administered a visuospatial attention task involving letter discrimination with location cues of varying validity. Genotype effects on white matter volume were also investigated in a subset of participants who received MRI scans. APOE interacted with CHRNA4, such that APOE-epsilon4 carriers who were also CHRNA4 TT homozygotes showed disproportionately slowed reaction time (RT) following invalid location cues. The interaction was stronger in the middle-aged participants than in the older participants. There was also a trend for individuals with combined APOE-epsilon4/CHRNA4 TT genotypes to show both lower white matter volume and slower overall RT on the attention task The interaction of a neurotransmission gene (CHRNA4) and a susceptibility gene (APOE) suggests that the efficiency of neuronal repair mechanisms may modulate the cholinergic system to influence attentional function.
authors.affiliation: University of Oslo, Oslo, Norway.
authors.forename: Thomas
authors.initials: T
authors.lastname: Espeseth
authors.forename: Pamela M
authors.initials: PM
authors.lastname: Greenwood
authors.forename: Ivar
authors.initials: I
authors.lastname: Reinvang
authors.forename: Anders M
authors.initials: AM
authors.lastname: Fjell
authors.forename: Kristine B
authors.initials: KB
authors.lastname: Walhovd
authors.forename: Lars T
authors.initials: LT
authors.lastname: Westlye
authors.forename: Eike
authors.initials: E
authors.lastname: Wehling
authors.forename: Astri
authors.initials: A
authors.lastname: Lundervold
authors.forename: Helge
authors.initials: H
authors.lastname: Rootwelt
authors.forename: Raja
authors.initials: R
authors.lastname: Parasuraman
mesh_terms: D000368:Aged; D000375:Aging / Q000235:genetics*; D000704:Analysis of Variance; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics*; D001288:Attention / Q000502:physiology*; D001921:Brain / Q000033:anatomy & histology*; D003463:Cues; D004192:Discrimination, Psychological / Q000502:physiology; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D010364:Pattern Recognition, Visual / Q000502:physiology; D010775:Photic Stimulation / Q000379:methods; D011110:Polymorphism, Genetic / Q000235:genetics; D011930:Reaction Time / Q000235:genetics; D011978:Receptors, Nicotinic / Q000235:genetics*
chemical_list: D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D011978:Receptors, Nicotinic