Universität zu Köln

Richter, Nils ORCID: 0000-0002-3377-5684, Nellessen, Nils, Dronse, Julian, Dillen, Kim, Jacobs, Heidi I. L., Langen, Karl-Josef ORCID: 0000-0003-1101-5075, Dietlein, Markus, Kracht, Lutz, Neumaier, Bernd, Fink, Gereon R. ORCID: 0000-0002-8230-1856, Kukolja, Juraj and Onur, Oezguer A. (2019). Spatial distributions of cholinergic impairment and neuronal hypometabolism differ in MCI due to AD. NeuroImage-Clin., 24. OXFORD: ELSEVIER SCI LTD. ISSN 2213-1582

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Abstract

Elucidating the relationship between neuronal metabolism and the integrity of the cholinergic system is prerequisite for a profound understanding of cholinergic dysfunction in Alzheimer's disease. The cholinergic system can be investigated specifically using positron emission tomography (PET) with [C-11] N-methyl-4-piperidyl-acetate (MP4A), while neuronal metabolism is often assessed with 2-deoxy-2-[F-18]fluoro-D-glucose-(FDG) PET. We hypothesised a close correlation between MP4A-perfusion and FDG-uptake, permitting inferences about metabolism from MP4A-perfusion, and investigated the patterns of neuronal hypometabolism and cholinergic impairment in non-demented AD patients. MP4A-PET was performed in 18 cognitively normal adults and 19 patients with mild cognitive impairment (MCI) and positive AD biomarkers. In nine patients with additional FDG-PET, the sum images of every combination of consecutive early MP4A-frames were correlated with FDG-scans to determine the optimal time window for assessing MP4A-perfusion. Acetylcholinesterase (AChE) activity was estimated using a 3-compartmental model. Group comparisons of MP4A-perfusion and AChE-activity were performed using the entire sample. The highest correlation between MP4A-perfusion and FDG-uptake across the cerebral cortex was observed 60-450 s after injection (r = 0.867). The patterns of hypometabolism (FDG-PET) and hypoperfusion (MP4A-PET) in MCI covered areas known to be hypometabolic early in AD, while AChE activity was mainly reduced in the lateral temporal cortex and the occipital lobe, sparing posterior midline structures. Data indicate that patterns of cholinergic impairment and neuronal hypometabolism differ significantly at the stage of MCI in AD, implying distinct underlying pathologies, and suggesting potential predictors of the response to cholinergic pharmacotherapy.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Richter, Nils UNSPECIFIED orcid.org/0000-0002-3377-5684 UNSPECIFIED Nellessen, Nils UNSPECIFIED UNSPECIFIED UNSPECIFIED Dronse, Julian UNSPECIFIED UNSPECIFIED UNSPECIFIED Dillen, Kim UNSPECIFIED UNSPECIFIED UNSPECIFIED Jacobs, Heidi I. L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Langen, Karl-Josef UNSPECIFIED orcid.org/0000-0003-1101-5075 UNSPECIFIED Dietlein, Markus UNSPECIFIED UNSPECIFIED UNSPECIFIED Kracht, Lutz UNSPECIFIED UNSPECIFIED UNSPECIFIED Neumaier, Bernd UNSPECIFIED UNSPECIFIED UNSPECIFIED Fink, Gereon R. UNSPECIFIED orcid.org/0000-0002-8230-1856 UNSPECIFIED Kukolja, Juraj UNSPECIFIED UNSPECIFIED UNSPECIFIED Onur, Oezguer A. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-160092
DOI:	10.1016/j.nicl.2019.101978
Journal or Publication Title:	NeuroImage-Clin.
Volume:	24
Date:	2019
Publisher:	ELSEVIER SCI LTD
Place of Publication:	OXFORD
ISSN:	2213-1582
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language POSITRON-EMISSION-TOMOGRAPHY; MILD COGNITIVE IMPAIRMENT; ALZHEIMERS-DISEASE; ACETYLCHOLINESTERASE ACTIVITY; EARLY-PHASE; BLOOD-FLOW; PET IMAGES; FDG PET; BRAIN; SEGMENTATION Multiple languages Neuroimaging Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/16009