Universität zu Köln

Myers, Nicholas, Pasquini, Lorenzo ORCID: 0000-0002-7899-7061, Goettler, Jens, Grimmer, Timo, Koch, Kathrin, Ortner, Marion, Neitzel, Julia, Muehlau, Mark, Foerster, Stefan, Kurz, Alexander, Foerstl, Hans, Zimmer, Claus, Wohlschlaeger, Afra M., Riedl, Valentin ORCID: 0000-0002-2861-8449, Drzezga, Alexander and Sorg, Christian (2014). Within-patient correspondence of amyloid-beta and intrinsic network connectivity in Alzheimer's disease. Brain, 137. S. 2052 - 2065. OXFORD: OXFORD UNIV PRESS. ISSN 1460-2156

Full text not available from this repository.

Abstract

There is striking overlap between the spatial distribution of amyloid-beta pathology in patients with Alzheimer's disease and the spatial distribution of high intrinsic functional connectivity in healthy persons. This overlap suggests a mechanistic link between amyloid-beta and intrinsic connectivity, and indeed there is evidence in patients for the detrimental effects of amyloid-beta plaque accumulation on intrinsic connectivity in areas of high connectivity in heteromodal hubs, and particularly in the default mode network. However, the observed spatial extent of amyloid-beta exceeds these tightly circumscribed areas, suggesting that previous studies may have underestimated the negative impact of amyloid-beta on intrinsic connectivity. We hypothesized that the known positive baseline correlation between patterns of amyloid-beta and intrinsic connectivity may mask the larger extent of the negative effects of amyloid-beta on connectivity. Crucially, a test of this hypothesis requires the within-patient comparison of intrinsic connectivity and amyloid-beta distributions. Here we compared spatial patterns of amyloid-beta-plaques (measured by Pittsburgh compound B positron emission tomography) and intrinsic functional connectivity (measured by resting-state functional magnetic resonance imaging) in patients with prodromal Alzheimer's disease via spatial correlations in intrinsic networks covering fronto-parietal heteromodal cortices. At the global network level, we found that amyloid-beta and intrinsic connectivity patterns were positively correlated in the default mode and several fronto-parietal attention networks, confirming that amyloid-beta aggregates in areas of high intrinsic connectivity on a within-network basis. Further, we saw an internetwork gradient of the magnitude of correlation that depended on network plaque-load. After accounting for this globally positive correlation, local amyloid-beta-plaque concentration in regions of high connectivity co-varied negatively with intrinsic connectivity, indicating that amyloid-beta pathology adversely reduces connectivity anywhere in an affected network as a function of local amyloid-beta-plaque concentration. The local negative association between amyloid-beta and intrinsic connectivity was much more pronounced than conventional group comparisons of intrinsic connectivity would suggest. Our findings indicate that the negative impact of amyloid-beta on intrinsic connectivity in heteromodal networks is underestimated by conventional analyses. Moreover, our results provide first within-patient evidence for correspondent patterns of amyloid-beta and intrinsic connectivity, with the distribution of amyloid-beta pathology following functional connectivity gradients within and across intrinsic networks.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Myers, Nicholas UNSPECIFIED UNSPECIFIED UNSPECIFIED Pasquini, Lorenzo UNSPECIFIED orcid.org/0000-0002-7899-7061 UNSPECIFIED Goettler, Jens UNSPECIFIED UNSPECIFIED UNSPECIFIED Grimmer, Timo UNSPECIFIED UNSPECIFIED UNSPECIFIED Koch, Kathrin UNSPECIFIED UNSPECIFIED UNSPECIFIED Ortner, Marion UNSPECIFIED UNSPECIFIED UNSPECIFIED Neitzel, Julia UNSPECIFIED UNSPECIFIED UNSPECIFIED Muehlau, Mark UNSPECIFIED UNSPECIFIED UNSPECIFIED Foerster, Stefan UNSPECIFIED UNSPECIFIED UNSPECIFIED Kurz, Alexander UNSPECIFIED UNSPECIFIED UNSPECIFIED Foerstl, Hans UNSPECIFIED UNSPECIFIED UNSPECIFIED Zimmer, Claus UNSPECIFIED UNSPECIFIED UNSPECIFIED Wohlschlaeger, Afra M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Riedl, Valentin UNSPECIFIED orcid.org/0000-0002-2861-8449 UNSPECIFIED Drzezga, Alexander UNSPECIFIED UNSPECIFIED UNSPECIFIED Sorg, Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-435185
DOI:	10.1093/brain/awu103
Journal or Publication Title:	Brain
Volume:	137
Page Range:	S. 2052 - 2065
Date:	2014
Publisher:	OXFORD UNIV PRESS
Place of Publication:	OXFORD
ISSN:	1460-2156
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language DEFAULT-MODE NETWORK; INDEPENDENT COMPONENT ANALYSIS; MILD COGNITIVE IMPAIRMENT; RESTING-STATE NETWORKS; FUNCTIONAL CONNECTIVITY; BRAIN ACTIVITY; CORTICAL HUBS; DEPOSITION; MRI; DEMENTIA Multiple languages Clinical Neurology; Neurosciences Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/43518