The heterogeneous functional architecture of the posteromedial cortex is associated with selective functional connectivity differences in Alzheimer's disease

Wasim Khan, Ali Amad, Vincent Giampietro, Emilio Werden, Sara De Simoni, Jonathan O'Muircheartaigh, Eric Westman, Owen O'Daly, Steve C.R. Williams, Amy Brodtmann, for the Alzheimer's Disease Neuroimaging Initiative

Research output: Contribution to journalArticleResearchpeer-review

4 Citations (Scopus)

Abstract

The posteromedial cortex (PMC) is a key region involved in the development and progression of Alzheimer's disease (AD). Previous studies have demonstrated a heterogenous functional architecture of the region that is composed of discrete functional modules reflecting a complex pattern of functional connectivity. However, little is understood about the mechanisms underpinning this complex network architecture in neurodegenerative disease, and the differential vulnerability of connectivity-based subdivisions in the PMC to AD pathogenesis. Using a data-driven approach, we applied a constrained independent component analysis (ICA) on healthy adults from the Human Connectome Project to characterise the local functional connectivity patterns within the PMC, and its unique whole-brain functional connectivity. These distinct connectivity profiles were subsequently quantified in the Alzheimer's Disease Neuroimaging Initiative study, to examine functional connectivity differences in AD patients and cognitively normal (CN) participants, as well as the entire AD pathological spectrum. Our findings revealed decreased functional connectivity in the anterior precuneus, dorsal posterior cingulate cortex (PCC), and the central precuneus in AD patients compared to CN participants. Functional abnormalities in the dorsal PCC and central precuneus were also related to amyloid burden and volumetric hippocampal loss. Across the entire AD spectrum, functional connectivity of the central precuneus was associated with disease severity and specific deficits in memory and executive function. These findings provide new evidence showing that the PMC is selectively impacted in AD, with prominent network failures of the dorsal PCC and central precuneus underpinning the neurodegenerative and cognitive dysfunctions associated with the disease.

Original languageEnglish
Pages (from-to)1557-1572
Number of pages16
JournalHuman Brain Mapping
Volume41
Issue number6
DOIs
Publication statusPublished - 15 Apr 2020

Keywords

  • Alzheimer disease
  • fMRI
  • magnetic resonance imaging
  • multivariate analysis
  • posterior cingulate cortex
  • precuneus

Cite this