The trend of disruption in the functional brain network topology of Alzheimer’s disease
Alireza Fathian, Yousef Jamali, Mohammad Reza Raoufy, for the Alzheimer’s Disease Neuroimaging Initiative, Michael W. Weiner, Norbert Schuf, Howard J. Rosen, Bruce L. Miller, Thomas C. Neylan, Jacqueline Hayes, Shannon Finley, Paul Aisen, Zaven S. Khachaturian, Ronald G. Thomas, Michael Donohue, Sarah Walter, Devon Gessert, Tamie Sather, Gus Jiminez, Leon J. Thal, James B. Brewer, Helen Vanderswag, Adam Fleisher, Melissa Davis, Rosemary Morrison, Ronald Petersen, Cliford R. Jack, Matt A. Bernstein, Bret Borowski, Jef Gunter, Matthew L. Senjem, Prashanthi Vemuri, David T. Jones, Kejal Kantarci, Chad Ward, Sara S. Mason, Colleen S. Albers, David S. Knopman, Kris Johnson, William J. Jagust, Susan Landau, John Q. Trojanowki, Leslie M. Shaw, Virginia Lee, Magdalena Korecka, Michal Figurski, Steven E. Arnold, Jason Karlawish, David A. Wolk, Arthur W. Toga, Karen Crawford, Scott Neu, Lon S. Schneider, Sonia Pawluczyk, Mauricio Beccera, Liberty Teodoro, Bryan M. Spann, Laurel Beckett, Danielle Harvey, Evan Fletcher, Owen Carmichael, John Olichney, Charles DeCarli, Robert C. Green, Reisa A. Sperling, Keith A. Johnson, Gad A. Marshall, Meghan Frey, Barton Lane, Allyson Rosen, Jared Tinklenberg, Andrew J. Saykin, Tatiana M. Foroud, Li Shen, Kelley Faber, Sungeun Kim, Kwangsik Nho, Martin R. Farlow, AnnMarie Hake, Brandy R. Matthews, Scott Herring, Cynthia Hunt, John C. Morris, Marc Raichle, Davie Holtzman, Nigel J. Cairns, Erin Householder, Lisa Taylor‐Reinwald, Beau M. Ances, Maria Carroll, Sue Leon, Mark A. Mintun, Stacy Schneider, Angela Oliver, Lisa Raudin, Greg Sorensen, Lew Kuller, Chet Mathis, Oscar L. Lopez, MaryAnn Oakley
Abstract
Alzheimer's disease (AD) is a progressive disorder associated with cognitive dysfunction that alters the brain's functional connectivity. Assessing these alterations has become a topic of increasing interest. However, a few studies have examined different stages of AD from a complex network perspective that cover different topological scales. This study used resting state fMRI data to analyze the trend of functional connectivity alterations from a cognitively normal (CN) state through early and late mild cognitive impairment (EMCI and LMCI) and to Alzheimer's disease. The analyses had been done at the local (hubs and activated links and areas), meso (clustering, assortativity, and rich-club), and global (small-world, small-worldness, and efficiency) topological scales. The results showed that the trends of changes in the topological architecture of the functional brain network were not entirely proportional to the AD progression. There were network characteristics that have changed non-linearly regarding the disease progression, especially at the earliest stage of the disease, i.e., EMCI. Further, it has been indicated that the diseased groups engaged somatomotor, frontoparietal, and default mode modules compared to the CN group. The diseased groups also shifted the functional network towards more random architecture. In the end, the methods introduced in this paper enable us to gain an extensive understanding of the pathological changes of the AD process.