title: Alzheimer disease biomarkers, attentional control, and semantic memory retrieval: Synergistic and mediational effects of biomarkers on a sensitive cognitive measure in non-demented older adults.
abstract: OBJECTIVE
  Past studies have shown that measures of attentional control and semantic memory are sensitive markers of Alzheimer's disease (AD). The effects of established biomarkers of AD (cerebrospinal fluid tau and amyloid-beta42, positron emission tomography Pittsburgh compound-B, and apolipoprotein E [APOE] genotype) on concurrent cognitive performance in cognitively normal individuals have been mixed. The present study examined the utility of combining attentional control with semantic retrieval as a sensitive correlate of AD biomarkers and used mediation analyses to examine possible mechanisms by which the biomarkers influence cognition.
  
  
  METHODS
  Three hundred sixty-three participants completed a category verification task (CVT), and 113 of them concurrently underwent biomarker assessments. On each trial, participants viewed a category (e.g., "unit of time") and verified whether a subsequent target item was an exemplar of the category ("hour") or not ("clock"). Importantly, the nonmembers of the category were associatively related to the category (e.g., "clock" is not "a unit of time," but is highly related), and demanded attentional control to reject.
  
  
  RESULTS
  Accuracy to the foil items was the strongest discriminator between healthy aging and very mild symptomatic AD. Cerebrospinal fluid biomarkers had independent yet synergistic influence on CVT performance in cognitively healthy older adults. Furthermore, the influence of the biomarkers and APOE genotype was mediated primarily through increased levels of PIB.
  
  
  CONCLUSIONS
  The combined influence of attentional control with semantic retrieval is a marker of symptomatic AD and a sensitive correlate of established biomarkers for AD risk in cognitively healthy participants. The biomarkers influenced cognition primarily through increased levels of amyloid in the brain.
authors.affiliation: Department of Psychology, Washington University.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Aschenbrenner
authors.affiliation: Department of Psychology, Washington University.
authors.forename: David A
authors.initials: DA
authors.lastname: Balota
authors.affiliation: Department of Educational Psychology, The Chinese University of Hong Kong.
authors.forename: Chi-Shing
authors.initials: CS
authors.lastname: Tse
authors.affiliation: Department of Neurology, Washington University.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Fagan
authors.affiliation: Department of Neurology, Washington University.
authors.forename: David M
authors.initials: DM
authors.lastname: Holtzman
authors.affiliation: The Knight Alzheimer's Disease Research Center and Department of Radiology, Washington University.
authors.forename: Tammie L S
authors.initials: TL
authors.lastname: Benzinger
authors.affiliation: Department of Neurology, Washington University.
authors.forename: John C
authors.initials: JC
authors.lastname: Morris
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000175:diagnosis* / Q000235:genetics / Q000523:psychology; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D001057:Apolipoproteins E / Q000235:genetics*; D001288:Attention / Q000502:physiology*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D001921:Brain / Q000000981:diagnostic imaging*; D003071:Cognition / Q000502:physiology; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008568:Memory / Q000502:physiology*; D008875:Middle Aged; D009483:Neuropsychological Tests; D010766:Phosphorylation; D011877:Radionuclide Imaging; D016875:tau Proteins / Q000134:cerebrospinal fluid
chemical_list: D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E; D015415:Biomarkers; D016875:tau Proteins