Loss of intranetwork and internetwork resting state functional connections with Alzheimer's disease progression

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Abstract

Alzheimer's disease (AD) is the mostcommoncause of dementia. Much is known concerningADpathophysiology 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 defaultmode 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 CDR0 andCDR0.5. However, atCDR1, 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 thatADis 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.

Original languageEnglish
Pages (from-to)8890-8899
Number of pages10
JournalJournal of Neuroscience
Volume32
Issue number26
DOIs
StatePublished - Jun 27 2012

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