Universität zu Köln

Klupp, Elisabeth, Grimmer, Timo, Tahmasian, Masoud ORCID: 0000-0003-3999-3807, Sorg, Christian, Yakushev, Igor, Yousefi, Behrooz H., Drzezga, Alexander and Foerster, Stefan (2015). Prefrontal Hypometabolism in Alzheimer Disease Is Related to Longitudinal Amyloid Accumulation in Remote Brain Regions. J. Nucl. Med., 56 (3). S. 399 - 405. RESTON: SOC NUCLEAR MEDICINE INC. ISSN 1535-5667

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Abstract

In PET studies of patients with Alzheimer disease (AD), prominent hypometabolism can occur in brain regions without major amyloid load. These hypometabolism-only (HO) areas may not be explained easily as a consequence of local amyloid toxicity. The aim of this longitudinal multimodal imaging study was the investigation of locoregional and remote relationships between metabolism in HO areas and longitudinal amyloid increase in functionally connected brain areas, with a particular focus on intrinsic functional connectivity as a relevant linking mechanism between pathology and dysfunction. Methods: Fifteen AD patients underwent longitudinal examinations with C-11-Pittsburgh compound B (C-11-PiB) and F-18-FDG PET (mean follow-up period, 2 y). The peak HO region was identified by the subtraction of equally thresholded statistical T maps (hypometabolism minus amyloid burden), resulting from voxel-based statistical parametric mapping group comparisons between the AD patients and 15 healthy controls. Then functionally connected and nonconnected brain networks were identified by means of seed-based intrinsic functional connectivity analysis of the resting-state functional MRI data of healthy controls. Finally, network-based, region-of-interest-based, and voxel-based correlations were calculated between longitudinal changes of normalized C-11-PiB binding and F-18-FDG metabolism. Results: Positive voxel-based and region-of-interest-based correlations were demonstrated between longitudinal C-11-PiB increases in the HO-connected network, encompassing bilateral temporoparietal and frontal brain regions, and metabolic changes in the peak HO region as well as locoregionally within several AD-typical brain regions. Conclusion: Our results indicate that in AD amyloid accumulation in remote but functionally connected brain regions may significantly contribute to longitudinally evolving hypometabolism in brain regions not strongly affected by local amyloid pathology, supporting the amyloid-and network-degeneration hypothesis.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Klupp, Elisabeth UNSPECIFIED UNSPECIFIED UNSPECIFIED Grimmer, Timo UNSPECIFIED UNSPECIFIED UNSPECIFIED Tahmasian, Masoud UNSPECIFIED orcid.org/0000-0003-3999-3807 UNSPECIFIED Sorg, Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED Yakushev, Igor UNSPECIFIED UNSPECIFIED UNSPECIFIED Yousefi, Behrooz H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Drzezga, Alexander UNSPECIFIED UNSPECIFIED UNSPECIFIED Foerster, Stefan UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-410846
DOI:	10.2967/jnumed.114.149302
Journal or Publication Title:	J. Nucl. Med.
Volume:	56
Number:	3
Page Range:	S. 399 - 405
Date:	2015
Publisher:	SOC NUCLEAR MEDICINE INC
Place of Publication:	RESTON
ISSN:	1535-5667
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language MILD COGNITIVE IMPAIRMENT; FUNCTIONAL CONNECTIVITY; DEFAULT NETWORK; CORTICAL HUBS; DEPOSITION; METABOLISM; BETA; DEMENTIA; PET; VARIABILITY Multiple languages Radiology, Nuclear Medicine & Medical Imaging Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/41084