title: Task-evoked fMRI changes in attention networks are associated with preclinical Alzheimer's disease biomarkers.
abstract: There is a growing emphasis on examining preclinical levels of Alzheimer's disease (AD)-related pathology in the absence of cognitive impairment. Previous work examining biomarkers has focused almost exclusively on memory, although there is mounting evidence that attention also declines early in disease progression. In the current experiment, 2 attentional control tasks were used to examine alterations in task-evoked functional magnetic resonance imaging data related to biomarkers of AD pathology. Seventy-one cognitively normal individuals (females = 44, mean age = 63.5 years) performed 2 attention-demanding cognitive tasks in a design that modeled both trial- and task-level functional magnetic resonance imaging changes. Biomarkers included amyloid β42, tau, and phosphorylated tau measured from cerebrospinal fluid and positron emission tomography measures of amyloid deposition. Both tasks elicited widespread patterns of activation and deactivation associated with large task-level manipulations of attention. Importantly, results from both tasks indicated that higher levels of tau and phosphorylated tau pathologies were associated with block-level overactivations of attentional control areas. This suggests early alteration in attentional control with rising levels of AD pathology.
authors.affiliation: Department of Radiology, Washington University in St Louis, St Louis, MO, USA; Knight Alzheimer's Disease Research Center, Washington University in St Louis, St Louis, MO, USA. Electronic address: bagordon@wustl.edu.
authors.forename: Brian A
authors.initials: BA
authors.lastname: Gordon
authors.affiliation: Department of Radiology, Washington University in St Louis, St Louis, MO, USA; Department of Psychology, Washington University in St Louis, St Louis, MO, USA.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Zacks
authors.affiliation: Division of Biology and Biomedical Sciences, Washington University in St Louis, St Louis, MO, USA.
authors.forename: Tyler
authors.initials: T
authors.lastname: Blazey
authors.affiliation: Department of Radiology, Washington University in St Louis, St Louis, MO, USA; Knight Alzheimer's Disease Research Center, Washington University in St Louis, St Louis, MO, USA; Division of Biology and Biomedical Sciences, Washington University in St Louis, St Louis, MO, USA; Department of Neurological Surgery, Washington University in St Louis, St Louis, MO, USA.
authors.forename: Tammie L S
authors.initials: TL
authors.lastname: Benzinger
authors.affiliation: Knight Alzheimer's Disease Research Center, Washington University in St Louis, St Louis, MO, USA; Department of Neurology, Washington University in St Louis, St Louis, MO, USA.
authors.forename: John C
authors.initials: JC
authors.lastname: Morris
authors.affiliation: Knight Alzheimer's Disease Research Center, Washington University in St Louis, St Louis, MO, USA; Department of Neurology, Washington University in St Louis, St Louis, MO, USA; The Hope Center for Neurodegenerative Disorders, Washington University in St Louis, St Louis, MO, USA.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Fagan
authors.affiliation: Knight Alzheimer's Disease Research Center, Washington University in St Louis, St Louis, MO, USA; Division of Biology and Biomedical Sciences, Washington University in St Louis, St Louis, MO, USA; Department of Neurology, Washington University in St Louis, St Louis, MO, USA; The Hope Center for Neurodegenerative Disorders, Washington University in St Louis, St Louis, MO, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Holtzman
authors.affiliation: Knight Alzheimer's Disease Research Center, Washington University in St Louis, St Louis, MO, USA; Department of Psychology, Washington University in St Louis, St Louis, MO, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Balota
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000175:diagnosis* / Q000473:pathology* / Q000523:psychology; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D001288:Attention / Q000502:physiology*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D001921:Brain / Q000473:pathology* / Q000502:physiology*; D003071:Cognition / Q000502:physiology; D018450:Disease Progression; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D016875:tau Proteins / Q000134:cerebrospinal fluid
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins
keywords: Alzheimer; Alzheimer's disease; Amyloid; Attention; Biomarkers; Dementia; fMRI; ptau; tau