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The ultra-slow NAT2*6A haplotype is associated with reduced higher cognitive functions in an elderly study group

  • Molecular Toxicology
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Abstract

N-Acetyltransferase 2 (NAT2) genotype is associated with age-related declines in basic sensory hearing functions. However, the possible modulatory role of NAT2 for higher cognitive functions has not yet been studied. We tested auditory goal-directed behavior and attentional control in 120 NAT2 genotyped subjects (63–88 years), using an auditory distraction paradigm in which participants responded to the duration of long and short tone stimuli. We studied involuntary shifts in attention to task-irrelevant deviant stimuli and applied event-related potentials (ERPs) to examine which cognitive subprocesses are affected by NAT2 status on a neurophysiological level. Relative to the standard stimuli, deviant stimuli decreased performance in the recently described ultra-slow acetylators (NAT2*6A and *7B): The increase in error-corrected reaction times (a combined measure of response speed and accuracy) in ultra-slow acetylators (254 ms increase) was more than twice as high as in the rapid acetylator reference group (111 ms increase; p < 0.01). The increase was still higher than in the other slow acetylators (149 ms increase, p < 0.05). In addition, clear differences were found in the ERP results: Ultra-slow acetylators showed deficits specifically in the automatic detection of changes in the acoustic environment as evidenced by reduced mismatch negativity (MMN, p < 0.005 compared to rapid acetylators). Refocussing of attention after a distracting event was also impaired in the ultra-slow acetylators as evidenced by a reduced re-orienting negativity (RON, p < 0.01 compared to rapid acetylators). In conclusion, the ultra-slow acetylation status was associated with reduced higher cognitive functions.

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    1. Leibniz-Institut für Arbeitsforschung an der TU Dortmund (IfADo), Ardeystr. 67, 44139, Dortmund, Germany

      Silvia Selinski, Stephan Getzmann, Patrick D. Gajewski, Meinolf Blaszkewicz, Jan G. Hengstler, Michael Falkenstein & Klaus Golka

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    1. Silvia Selinski
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    Silvia Selinski, Stephan Getzmann, Michael Falkenstein, and Klaus Golka have contributed equally to this work.

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    Selinski, S., Getzmann, S., Gajewski, P.D. et al. The ultra-slow NAT2*6A haplotype is associated with reduced higher cognitive functions in an elderly study group. Arch Toxicol 89, 2291–2303 (2015). https://doi.org/10.1007/s00204-015-1635-1

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