Michael Falkenstein

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.

Cognitive control functions decline with increasing age. The present study examines if different types of group-based and trainer-guided training effectively enhance performance of older adults in a task switching task, and how this expected enhancement is reflected in changes of cognitive functions, as measured in electrophysiological brain activity (event-related potentials). One hundred forty-one healthy participants aged 65 years and older were randomly assigned to one of four groups: physical training (combined aerobic and strength training), cognitive training (paper–pencil and computer-aided), relaxation and wellness (social control group), and a control group that did not receive any intervention. Training sessions took place twice a week for 90 min for a period of 4 months. The results showed a greater improvement of performance for attendants of the cognitive training group compared to the other groups. This improvement was evident in a reduction of mixing costs in accuracy and intraindividual variability of speed, indexing improved maintenance of multiple task sets in working memory, and an enhanced coherence of neuronal processing. These findings were supported by event-related brain potentials which showed higher amplitudes in a number of potentials associated with response selection (N2), allocation of cognitive resources (P3b), and error detection (Ne). Taken together, our findings suggest neurocognitive plasticity of aging brains which can be stimulated by broad and multilayered cognitive training and assessed in detail by electrophysiological methods.