Amyloid causes intermittent network disruptions in cognitively intact older subjects

  • Susanne G. Mueller
Original Research


Recent findings in AD models but also human patients suggest that amyloid can cause intermittent neuronal hyperactivity. The overall goal of this study was to use dynamic fMRI analysis combined with graph analysis to a) characterize the graph analytical signature of two types of intermittent hyperactivity (spike-like (spike) and hypersynchronus-like (synchron)) in simulated data and b) to attempt to identify one of these signatures in task-free fMRIs of cognitively intact subjects (CN) with or without increased brain amyloid. The toolbox simtb was used to generate 33 data sets with 2 short spike events, 33 with 2 synchron and 33 baseline data sets. A combination of sliding windows, hierarchical cluster analysis and graph analysis was used to characterize the spike and the synchron signature. Florbetapir-F18 PET and task-free 3 T fMRI was acquired in 49 CN (age = 70.7 ± 6.4). Processing the real data with the same approach as the simulated data identified phases whose graph analytical signature resembled that of the synchron signature in the simulated data. The duration of these phases was positively correlated with amyloid load (r = 0.42, p < 0.05) and negatively with memory performance (r = −0.43, p < 0.05). In conclusion, amyloid positivity is associated with intermittent hyperactivity that is caused by short phases of hypersynchronous activity. The negative association with memory performance suggests that these disturbances have the potential to interfere with cognitive processes and could lead to cognitive impairment if they become more frequent or more severe with increasing amyloid deposition.


Amyloid Intermittent Functional connectivity Cognitively intact Hyperactivity Resting state fMRI 



The study was supported by a NIH grant R01 AG010897 (PI Michael Weiner) and a UCSF grant REAC/CTSI 37785-525205 to SGM. SGM would like to thank Dr. Weiner for making his data available. Thanks also to A.M.M for the critical reading of an early draft of the manuscript.


The study was supported by NIH grant R01 AG010897 (PI Michael Weiner) and a UCSF grant REAC/CTSI 37785–525205 to SGM.

Compliance with ethical standards

Conflict of interest

The author has no conflict of interest to declare.

Ethical approval

This study was done with human participants after obtaining informed consent. All procedures performed in this study were in accordance with the ethical standards of the committees of human research at the University of California, San Francisco (UCSF) and VA Medical Center San Francisco, and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.


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Authors and Affiliations

  1. 1.Center for Imaging of Neurodegenerative Diseases, Department of Veterans Affairs (DVA) Medical Center, VAMCSan FranciscoUSA
  2. 2.Department of Radiology and Biomedical ImagingUniversity of CaliforniaSan FranciscoUSA

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