title: Alzheimer's Biomarkers are Correlated with Brain Connectivity in Older Adults Differentially during Resting and Task States.
abstract: β-amyloid (Aβ) plaques and tau-related neurodegeneration are pathologic hallmarks of Alzheimer's disease (AD). The utility of AD biomarkers, including those measured in cerebrospinal fluid (CSF), in predicting future AD risk and cognitive decline is still being refined. Here, we explored potential relationships between functional connectivity (FC) patterns within the default-mode network (DMN), age, CSF biomarkers (Aβ42 and pTau181), and cognitive status in older adults. Multiple measures of FC were explored, including a novel time series-based measure [total interdependence (TI)]. In our sample of 27 cognitively normal older adults, no significant associations were found between levels of Aβ42 or pTau181 and cognitive scores or regional brain volumes. However, we observed several novel relationships between these biomarkers and measures of FC in DMN during both resting-state and a short-term memory task. First, increased connectivity between bilateral anterior middle temporal gyri was associated with higher levels of CSF Aβ42 and Aβ42/pTau181 ratio (reflecting lower AD risk) during both rest and task. Second, increased bilateral parietal connectivity during the short-term memory task, but not during rest, was associated with higher levels of CSF pTau181 (reflecting higher AD risk). Third, increased connectivity between left middle temporal and left parietal cortices during the active task was associated with decreased global cognitive status but not CSF biomarkers. Lastly, we found that our new TI method was more sensitive to the CSF Aβ42-connectivity relationship whereas the traditional cross-correlation method was more sensitive to levels of CSF pTau181 and cognitive status. With further refinement, resting-state connectivity and task-driven connectivity measures hold promise as non-invasive neuroimaging markers of Aβ and pTau burden in cognitively normal older adults.
authors.affiliation: Department of Behavioral Science, University of Kentucky College of Medicine, Lexington, KY, USA; Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA; The Magnetic Resonance Imaging and Spectroscopy Center, University of Kentucky, Lexington, KY, USA.
authors.forename: Yang
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: J Crayton Pruitt Family Department of Biomedical Engineering, University of Florida , Gainesville, FL , USA.
authors.forename: Haiqing
authors.initials: H
authors.lastname: Huang
authors.affiliation: Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA; Department of Epidemiology, University of Kentucky College of Public Health, Lexington, KY, USA.
authors.forename: Erin
authors.initials: E
authors.lastname: Abner
authors.affiliation: Department of Behavioral Science, University of Kentucky College of Medicine , Lexington, KY , USA.
authors.forename: Lucas S
authors.initials: LS
authors.lastname: Broster
authors.affiliation: Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA; Department of Neurology, University of Kentucky College of Medicine, Lexington, KY, USA.
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Jicha
authors.affiliation: Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA; Department of Neurology, University of Kentucky College of Medicine, Lexington, KY, USA.
authors.forename: Frederick A
authors.initials: FA
authors.lastname: Schmitt
authors.affiliation: Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA; Department of Biostatistics, University of Kentucky College of Public Health, Lexington, KY, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Kryscio
authors.affiliation: The Magnetic Resonance Imaging and Spectroscopy Center, University of Kentucky, Lexington, KY, USA; Department of Anatomy and Neurobiology, University of Kentucky College of Medicine, Lexington, KY, USA.
authors.forename: Anders
authors.initials: A
authors.lastname: Andersen
authors.affiliation: The Magnetic Resonance Imaging and Spectroscopy Center, University of Kentucky, Lexington, KY, USA; Department of Anatomy and Neurobiology, University of Kentucky College of Medicine, Lexington, KY, USA.
authors.forename: David
authors.initials: D
authors.lastname: Powell
authors.affiliation: Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA; Department of Anatomy and Neurobiology, University of Kentucky College of Medicine, Lexington, KY, USA.
authors.forename: Linda
authors.initials: L
authors.lastname: Van Eldik
authors.affiliation: Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA; The Magnetic Resonance Imaging and Spectroscopy Center, University of Kentucky, Lexington, KY, USA; Department of Anatomy and Neurobiology, University of Kentucky College of Medicine, Lexington, KY, USA.
authors.forename: Brian T
authors.initials: BT
authors.lastname: Gold
authors.affiliation: Sanders-Brown Center on Aging, University of Kentucky , Lexington, KY , USA.
authors.forename: Peter T
authors.initials: PT
authors.lastname: Nelson
authors.affiliation: Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA; The Magnetic Resonance Imaging and Spectroscopy Center, University of Kentucky, Lexington, KY, USA; Department of Neurology, University of Kentucky College of Medicine, Lexington, KY, USA.
authors.forename: Charles
authors.initials: C
authors.lastname: Smith
authors.affiliation: J Crayton Pruitt Family Department of Biomedical Engineering, University of Florida , Gainesville, FL , USA.
authors.forename: Mingzhou
authors.initials: M
authors.lastname: Ding
keywords: Aβ42 peptides; CSF biomarkers; default-mode network; global cognitive status; pTau181; predictors of AD; short-term memory task