title: The ultra-slow NAT2*6A haplotype is associated with reduced higher cognitive functions in an elderly study group.
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.
authors.affiliation: Leibniz-Institut für Arbeitsforschung an der TU Dortmund (IfADo), Ardeystr. 67, 44139, Dortmund, Germany. selinski@ifado.de.
authors.forename: Silvia
authors.initials: S
authors.lastname: Selinski
authors.affiliation: Leibniz-Institut für Arbeitsforschung an der TU Dortmund (IfADo), Ardeystr. 67, 44139, Dortmund, Germany. getzmann@ifado.de.
authors.forename: Stephan
authors.initials: S
authors.lastname: Getzmann
authors.affiliation: Leibniz-Institut für Arbeitsforschung an der TU Dortmund (IfADo), Ardeystr. 67, 44139, Dortmund, Germany. gajewski@ifado.de.
authors.forename: Patrick D
authors.initials: PD
authors.lastname: Gajewski
authors.affiliation: Leibniz-Institut für Arbeitsforschung an der TU Dortmund (IfADo), Ardeystr. 67, 44139, Dortmund, Germany. blaszkewicz@ifado.de.
authors.forename: Meinolf
authors.initials: M
authors.lastname: Blaszkewicz
authors.affiliation: Leibniz-Institut für Arbeitsforschung an der TU Dortmund (IfADo), Ardeystr. 67, 44139, Dortmund, Germany. hengstler@ifado.de.
authors.forename: Jan G
authors.initials: JG
authors.lastname: Hengstler
authors.affiliation: Leibniz-Institut für Arbeitsforschung an der TU Dortmund (IfADo), Ardeystr. 67, 44139, Dortmund, Germany. falkenstein@ifado.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Falkenstein
authors.affiliation: Leibniz-Institut für Arbeitsforschung an der TU Dortmund (IfADo), Ardeystr. 67, 44139, Dortmund, Germany. golka@ifado.de.
authors.forename: Klaus
authors.initials: K
authors.lastname: Golka
mesh_terms: D000107:Acetylation; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics / Q000502:physiology*; D001191:Arylamine N-Acetyltransferase / Q000235:genetics*; D003071:Cognition / Q000502:physiology*; D005071:Evoked Potentials / Q000235:genetics / Q000502:physiology*; D005260:Female; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged
chemical_list: D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human
keywords: Aging; Auditory distraction; Cognitive flexibility; Event-related potentials; N-Acetyltransferase 2