title: Frontotemporal network connectivity during memory encoding is increased with aging and disrupted by beta-amyloid.
abstract: Approximately 30% of cognitively normal older adults harbor brain β-amyloid (Aβ), a prominent feature of Alzheimer's disease associated with neural alterations and episodic memory decline. We examined how aging and Aβ deposition affect neural function during memory encoding of visual scenes using functional magnetic resonance imaging (fMRI) in humans. Thirty-six cognitively normal older people underwent fMRI scanning, and positron emission tomography with [(11)C] Pittsburgh compound B to measure fibrillar brain Aβ; 15 young subjects were studied with fMRI. Older adults without Aβ deposition showed reduced regional brain activation (compared with young subjects) with decreased task-independent functional connectivity between parahippocampal gyrus and prefrontal cortex. In this network, task-related connectivity was increased compared with young subjects, and the degree of connectivity was related to memory performance. In contrast, older individuals with Aβ deposition showed no such increased task-related network connectivity, but did display increased regional activity unassociated with performance. These findings suggest that network connectivity plays a significant role in compensating for reduced regional activity during successful memory encoding in aging without Aβ deposition, while in those with Aβ this network compensation fails and is accompanied by inefficient regional hyperactivation.
authors.affiliation: Helen Wills Neuroscience Institute, University of California, Berkeley, California 94720 and Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720.
authors.forename: Hwamee
authors.initials: H
authors.lastname: Oh
authors.forename: William J
authors.initials: WJ
authors.lastname: Jagust
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000814:Aniline Compounds / Q000378:metabolism; D053327:Apolipoprotein E4 / Q000235:genetics; D001931:Brain Mapping; D002247:Carbon Isotopes; D005260:Female; D005625:Frontal Lobe / Q000098:blood supply / Q000000981:diagnostic imaging / Q000378:metabolism*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008568:Memory / Q000502:physiology*; D008609:Mental Status Schedule; D009415:Nerve Net / Q000000981:diagnostic imaging / Q000378:metabolism; D010100:Oxygen / Q000097:blood; D049268:Positron-Emission Tomography; D013702:Temporal Lobe / Q000098:blood supply / Q000000981:diagnostic imaging / Q000378:metabolism*; D013844:Thiazoles / Q000378:metabolism; D055815:Young Adult
chemical_list: C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D053327:Apolipoprotein E4; D002247:Carbon Isotopes; D013844:Thiazoles; D010100:Oxygen