The heterogeneous functional architecture of the posteromedial cortex is associated with selective functional connectivity differences in Alzheimer's disease
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Dec 19, 2019
- Source ID
- 10.1002/hbm.24894
Entities
People
- Ali Amad
- Amy Brodtmann
- Emilio Werden
- Eric Westman
- For The Alzheimer’s Disease Neuroimaging Initiative*
- Jonathan O'Muircheartaigh
- Owen O'daly
- Sara De Simoni
- Steve C. R. Williams
- Vincent Giampietro
- Wasim Khan
Organizations
- Austin Hospital, Melbourne
- Imperial College London
- Karolinska Institutet
- King's College London
- Monash University
- National Health and Medical Research Council
- National Institutes of Health
- United States Department of Defense
- University of Lille Nord de France
- University of Melbourne