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-ε4 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-ε4/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.
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This research was supported in part by Norwegian Research Council Grant 154313/V50 to I.R. and by U.S. National Institute on Aging Grant AG19653 to R.P. The contribution from Marit Hansen Hallberg and the staff at the Department of Medical Biochemistry in the Rikshospitalet University Hospital is gratefully acknowledged.
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Espeseth, T., Greenwood, P.M., Reinvang, I. et al. Interactive effects of APOE and CHRNA4 on attention and white matter volume in healthy middle-aged and older adults. Cognitive, Affective, & Behavioral Neuroscience 6, 31–43 (2006). https://doi.org/10.3758/CABN.6.1.31
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DOI: https://doi.org/10.3758/CABN.6.1.31