TY - JOUR
T1 - Memory performance-related dynamic brain connectivity indicates pathological burden and genetic risk for Alzheimer's disease
AU - Quevenco, Frances C.
AU - Preti, Maria G.
AU - Van Bergen, Jiri M.G.
AU - Hua, Jun
AU - Wyss, Michael
AU - Li, Xu
AU - Schreiner, Simon J.
AU - Steininger, Stefanie C.
AU - Meyer, Rafael
AU - Meier, Irene B.
AU - Brickman, Adam M.
AU - Leh, Sandra E.
AU - Gietl, Anton F.
AU - Buck, Alfred
AU - Nitsch, Roger M.
AU - Pruessmann, Klaas P.
AU - Van Zijl, Peter C.M.
AU - Hock, Christoph
AU - Van De Ville, Dimitri
AU - Unschuld, Paul G.
N1 - Funding Information:
PCMvZ is a paid lecturer for Philips Healthcare and is the inventor of technology that is licensed to Philips. XL’s salary is supported in part by a grant from Philips Healthcare. This arrangement has been approved by The Johns Hopkins University in accordance with its Conflict of Interest policies. The remaining authors declare that they have no competing interests.
Funding Information:
This work was funded by the Swiss National Science Foundation (Schweizerischer Nationalfonds, SNF), the Clinical Research Priority Program (CRPP) of the University of Zurich on Molecular Imaging (MINZ), a grant from the National Institutes of Health (NIBIB) P41 EB015909, the Mäxi Foundation, the Center for Biomedical Imaging (CIBM) in the Lemanic Region, and institutional support from the Division of Psychiatry Research and Psychogeriatric Medicine, University of Zürich, and Institute for Biomedical Engineering, University of Zürich and ETH Zürich, Switzerland.
Publisher Copyright:
© 2017 The Author(s).
PY - 2017/3/31
Y1 - 2017/3/31
N2 - Background: The incidence of Alzheimer's disease (AD) strongly relates to advanced age and progressive deposition of cerebral amyloid-beta (Aβ), hyperphosphorylated tau, and iron. The purpose of this study was to investigate the relationship between cerebral dynamic functional connectivity and variability of long-term cognitive performance in healthy, elderly subjects, allowing for local pathology and genetic risk. Methods: Thirty seven participants (mean (SD) age 74 (6.0) years, Mini-Mental State Examination 29.0 (1.2)) were dichotomized based on repeated neuropsychological test performance within 2 years. Cerebral Aβ was measured by 11C Pittsburgh Compound-B positron emission tomography, and iron by quantitative susceptibility mapping magnetic resonance imaging (MRI) at an ultra-high field strength of 7 Tesla (7T). Dynamic functional connectivity patterns were investigated by resting-state functional MRI at 7T and tested for interactive effects with genetic AD risk (apolipoprotein E (ApoE)-ϵ4 carrier status). Results: A relationship between low episodic memory and a lower expression of anterior-posterior connectivity was seen (F(9,27) = 3.23, p < 0.008), moderated by ApoE-ϵ4 (F(9,27) = 2.22, p < 0.005). Inherent node-strength was related to local iron (F(5,30) = 13.2; p < 0.022). Conclusion: Our data indicate that altered dynamic anterior-posterior brain connectivity is a characteristic of low memory performance in the subclinical range and genetic risk for AD in the elderly. As the observed altered brain network properties are associated with increased local iron, our findings may reflect secondary neuronal changes due to pathologic processes including oxidative stress.
AB - Background: The incidence of Alzheimer's disease (AD) strongly relates to advanced age and progressive deposition of cerebral amyloid-beta (Aβ), hyperphosphorylated tau, and iron. The purpose of this study was to investigate the relationship between cerebral dynamic functional connectivity and variability of long-term cognitive performance in healthy, elderly subjects, allowing for local pathology and genetic risk. Methods: Thirty seven participants (mean (SD) age 74 (6.0) years, Mini-Mental State Examination 29.0 (1.2)) were dichotomized based on repeated neuropsychological test performance within 2 years. Cerebral Aβ was measured by 11C Pittsburgh Compound-B positron emission tomography, and iron by quantitative susceptibility mapping magnetic resonance imaging (MRI) at an ultra-high field strength of 7 Tesla (7T). Dynamic functional connectivity patterns were investigated by resting-state functional MRI at 7T and tested for interactive effects with genetic AD risk (apolipoprotein E (ApoE)-ϵ4 carrier status). Results: A relationship between low episodic memory and a lower expression of anterior-posterior connectivity was seen (F(9,27) = 3.23, p < 0.008), moderated by ApoE-ϵ4 (F(9,27) = 2.22, p < 0.005). Inherent node-strength was related to local iron (F(5,30) = 13.2; p < 0.022). Conclusion: Our data indicate that altered dynamic anterior-posterior brain connectivity is a characteristic of low memory performance in the subclinical range and genetic risk for AD in the elderly. As the observed altered brain network properties are associated with increased local iron, our findings may reflect secondary neuronal changes due to pathologic processes including oxidative stress.
KW - Alzheimer's disease
KW - Amyloid beta
KW - Dynamic functional connectivity
KW - Episodic memory
KW - Iron
KW - Oxidative stress
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U2 - 10.1186/s13195-017-0249-7
DO - 10.1186/s13195-017-0249-7
M3 - Article
C2 - 28359293
AN - SCOPUS:85016445194
SN - 1465-5411
VL - 9
JO - Breast Cancer Research
JF - Breast Cancer Research
IS - 1
M1 - 24
ER -