title: Loss of intranetwork and internetwork resting state functional connections with Alzheimer's disease progression.
abstract: Alzheimer's disease (AD) is the most common cause of dementia. Much is known concerning AD pathophysiology but our understanding of the disease at the systems level remains incomplete. Previous AD research has used resting-state functional connectivity magnetic resonance imaging (rs-fcMRI) to assess the integrity of functional networks within the brain. Most studies have focused on the default-mode network (DMN), a primary locus of AD pathology. However, other brain regions are inevitably affected with disease progression. We studied rs-fcMRI in five functionally defined brain networks within a large cohort of human participants of either gender (n = 510) that ranged in AD severity from unaffected [clinical dementia rating (CDR) 0] to very mild (CDR 0.5) to mild (CDR 1). We observed loss of correlations within not only the DMN but other networks at CDR 0.5. Within the salience network (SAL), increases were seen between CDR 0 and CDR 0.5. However, at CDR 1, all networks, including SAL, exhibited reduced correlations. Specific networks were preferentially affected at certain CDR stages. In addition, cross-network relations were consistently lost with increasing AD severity. Our results demonstrate that AD is associated with widespread loss of both intranetwork and internetwork correlations. These results provide insight into AD pathophysiology and reinforce an integrative view of the brain's functional organization.
authors: Department of Neurology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
authors: Mathew R
authors: MR
authors: Brier
authors: Jewell B
authors: JB
authors: Thomas
authors: Abraham Z
authors: AZ
authors: Snyder
authors: Tammie L
authors: TL
authors: Benzinger
authors: Dongyang
authors: D
authors: Zhang
authors: Marcus E
authors: ME
authors: Raichle
authors: David M
authors: DM
authors: Holtzman
authors: John C
authors: JC
authors: Morris
authors: Beau M
authors: BM
authors: Ances
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000473:pathology*; D001921:Brain / Q000098:blood supply / Q000473:pathology*; D001931:Brain Mapping; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D009415:Nerve Net / Q000098:blood supply / Q000473:pathology*; D009434:Neural Pathways / Q000098:blood supply / Q000473:pathology*; D010100:Oxygen / Q000097:blood; D011569:Psychiatric Status Rating Scales; D012146:Rest; D013223:Statistics as Topic
chemical_list: D010100:Oxygen