title: The functional tumor necrosis factor-α (308A/G) polymorphism modulates attentional selection in elderly individuals.
abstract: There has been increasing interest in understanding the role of inflammatory processes for cognitive functions in aging using molecular genetic approaches. Though this has mostly been evaluated in pathological aging, little is known about the relevance for cognitive functions in healthy aging in humans. On the basis of behavioral data and neurophysiological data (event-related potentials and time-frequency decomposition) we show that the A-allele of the functional tumor necrosis factor (TNF)-α -308 A/G polymorphism confers dysfunction in a number of cognitive processes: prolonged attentional selection indexed by a delayed P1/N1 complex, an increased P3a, which is interpreted as an enhanced distractibility by nonrelevant stimuli and compromised response selection mechanisms, as indexed by a reduced frontocentral N2. Time-frequency analyses show that allelic variations further exert their effects by modulating alpha and beta frequency oscillations. On a neurobiological level, these effects might be because of the interaction of TNF-α with glutamatergic neural transmission by which TNF-α is known to boost apoptotic mechanisms in elderly individuals.
authors.affiliation: Leibniz Research Centre for Working Environment and Human Factors at the Technical University of Dortmund, Dortmund, Germany. gajewski@uni-duesseldorf.de
authors.forename: Patrick D
authors.initials: PD
authors.lastname: Gajewski
authors.forename: Jan G
authors.initials: JG
authors.lastname: Hengstler
authors.forename: Klaus
authors.initials: K
authors.lastname: Golka
authors.forename: Michael
authors.initials: M
authors.lastname: Falkenstein
authors.forename: Christian
authors.initials: C
authors.lastname: Beste
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics*; D001288:Attention / Q000502:physiology*; D001921:Brain / Q000502:physiology; D001931:Brain Mapping; D004569:Electroencephalography; D005071:Evoked Potentials / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D010364:Pattern Recognition, Visual / Q000502:physiology; D010775:Photic Stimulation; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011569:Psychiatric Status Rating Scales; D017603:Signal Detection, Psychological / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D014409:Tumor Necrosis Factor-alpha
keywords: Aging; Event-related potential; Genetic imaging; TNF-α polymorphism; Time–frequency decomposition; Visual attention; Visual search