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@ARTICLE{Richter:864642,
author = {Richter, Nils and Nellessen, Nils and Dronse, Julian and
Dillen, Kim and Jacobs, Heidi and Langen, Karl-Josef and
Kracht, Lutz and Dietlein, Markus and Neumaier, Bernd and
Fink, Gereon R. and Kukolja, Juraj and Onur, Oezguer A.},
title = {{S}patial distributions of cholinergic impairment and
neuronal hypometabolism differ in {MCI} due to {AD}},
journal = {NeuroImage: Clinical},
volume = {24},
issn = {2213-1582},
address = {[Amsterdam u.a.]},
publisher = {Elsevier},
reportid = {FZJ-2019-04344},
pages = {101978 -},
year = {2019},
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 [11C]N-methyl-4-piperidyl-acetate (MP4A), while
neuronal metabolism is often assessed with
2-deoxy-2-[18F]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.},
cin = {INM-3 / INM-4 / INM-5},
ddc = {610},
cid = {I:(DE-Juel1)INM-3-20090406 / I:(DE-Juel1)INM-4-20090406 /
I:(DE-Juel1)INM-5-20090406},
pnm = {572 - (Dys-)function and Plasticity (POF3-572)},
pid = {G:(DE-HGF)POF3-572},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:31422337},
UT = {WOS:000504663800122},
doi = {10.1016/j.nicl.2019.101978},
url = {https://juser.fz-juelich.de/record/864642},
}