title: Effects of Beta-Amyloid on Resting State Functional Connectivity Within and Between Networks Reflect Known Patterns of Regional Vulnerability.
abstract: Beta-amyloid (Aβ) deposition is one of the hallmarks of Alzheimer's disease (AD). However, it is also present in some cognitively normal elderly adults and may represent a preclinical disease state. While AD patients exhibit disrupted functional connectivity (FC) both within and between resting-state networks, studies of preclinical cases have focused primarily on the default mode network (DMN). The extent to which Aβ-related effects occur outside of the DMN and between networks remains unclear. In the present study, we examine how within- and between-network FC are related to both global and regional Aβ deposition as measured by [(11)C]PIB-PET in 92 cognitively normal older people. We found that within-network FC changes occurred in multiple networks, including the DMN. Changes of between-network FC were also apparent, suggesting that regions maintaining connections to multiple networks may be particularly susceptible to Aβ-induced alterations. Cortical regions showing altered FC clustered in parietal and temporal cortex, areas known to be susceptible to AD pathology. These results likely represent a mix of local network disruption, compensatory reorganization, and impaired control network function. They indicate the presence of Aβ-related dysfunction of neural systems in cognitively normal people well before these areas become hypometabolic with the onset of cognitive decline.
authors.affiliation: Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
authors.forename: Jeremy A
authors.initials: JA
authors.lastname: Elman
authors.affiliation: Helen Wills Neuroscience Institute, University of California, Berkeley, CA 94720, USA.
authors.forename: Cindee M
authors.initials: CM
authors.lastname: Madison
authors.affiliation: Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
authors.forename: Suzanne L
authors.initials: SL
authors.lastname: Baker
authors.affiliation: Helen Wills Neuroscience Institute, University of California, Berkeley, CA 94720, USA.
authors.forename: Jacob W
authors.initials: JW
authors.lastname: Vogel
authors.affiliation: Helen Wills Neuroscience Institute, University of California, Berkeley, CA 94720, USA.
authors.forename: Shawn M
authors.initials: SM
authors.lastname: Marks
authors.affiliation: Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
authors.forename: Sam
authors.initials: S
authors.lastname: Crowley
authors.affiliation: Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
authors.forename: James P
authors.initials: JP
authors.lastname: O'Neil
authors.affiliation: Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA Helen Wills Neuroscience Institute, University of California, Berkeley, CA 94720, USA.
authors.forename: William J
authors.initials: WJ
authors.lastname: Jagust
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000000981:diagnostic imaging / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000814:Aniline Compounds / Q000493:pharmacokinetics; D001921:Brain / Q000098:blood supply / Q000000981:diagnostic imaging / Q000378:metabolism*; D001931:Brain Mapping; D002247:Carbon Isotopes / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D009415:Nerve Net / Q000000981:diagnostic imaging; D010100:Oxygen / Q000097:blood; D049268:Positron-Emission Tomography; D012044:Regression Analysis; D012146:Rest; D013844:Thiazoles / Q000493:pharmacokinetics; D055815:Young Adult
chemical_list: C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D002247:Carbon Isotopes; D013844:Thiazoles; D010100:Oxygen
keywords: PIB-PET; aging; beta-amyloid; functional connectivity; resting-state fMRI