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@ARTICLE{Richter:841974,
author = {Richter, Nils and Beckers, Nora and Onur, Özgür and
Dietlein, Markus and Tittgemeyer, Marc and Kracht, Lutz and
Neumaier, Bernd and Fink, Gereon Rudolf and Kukolja, Juraj},
title = {{E}ffect of cholinergic treatment depends on cholinergic
integrity in early {A}lzheimer’s disease},
journal = {Brain},
volume = {141},
number = {3},
issn = {1460-2156},
address = {Oxford},
publisher = {Oxford Univ. Press},
reportid = {FZJ-2018-00261},
pages = {903–915},
year = {2018},
abstract = {In early Alzheimer’s disease, which initially presents
with progressive loss of short-term memory,
neurodegeneration especially affects cholinergic neurons of
the basal forebrain. Pharmacotherapy of Alzheimer’s
disease therefore often targets the cholinergic system. In
contrast, cholinergic pharmacotherapy of mild cognitive
impairment is debated since its efficacy to date remains
controversial. We here investigated the relationship between
cholinergic treatment effects and the integrity of the
cholinergic system in mild cognitive impairment due to
Alzheimer’s disease. Fourteen patients with high
likelihood of mild cognitive impairment due to Alzheimer’s
disease and 16 age-matched cognitively normal adults
performed an episodic memory task during functional magnetic
resonance imaging under three conditions: (i) without
pharmacotherapy; (ii) with placebo; and (iii) with a single
dose of rivastigmine (3 mg). Cortical acetylcholinesterase
activity was measured using PET with the tracer
11C-N-methyl-4-piperidyl acetate (MP4A). Cortical
acetylcholinesterase activity was significantly decreased in
patients relative to controls, especially in the lateral
temporal lobes. Without pharmacotherapy, mild cognitive
impairment was associated with less memory-related neural
activation in the fusiform gyrus and impaired deactivation
in the posterior cingulate cortex, relative to controls.
These differences were attenuated under cholinergic
stimulation with rivastigmine: patients showed increased
neural activation in the right fusiform gyrus but enhanced
deactivation of the posterior cingulate cortex under
rivastigmine, compared to placebo. Conversely, controls
showed reduced activation of the fusiform gyrus and reduced
deactivation of the posterior cingulate under rivastigmine,
compared to placebo. In both groups, the change in neural
activation in response to rivastigmine was negatively
associated with local acetylcholinesterase activity. At the
behavioural level, an analysis of covariance revealed a
significant group × treatment interaction in episodic
memory performance when accounting for hippocampal grey
matter atrophy and function. Our results indicate that
rivastigmine differentially affects memory-related neural
activity in patients with mild cognitive impairment and
cognitively normal, age-matched adults, depending on
acetylcholinesterase activity as a marker for the integrity
of the cortical cholinergic system. Furthermore, hippocampal
integrity showed an independent association with the
response of memory performance to acetylcholinesterase
inhibition.},
cin = {INM-3 / INM-5},
ddc = {610},
cid = {I:(DE-Juel1)INM-3-20090406 / 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},
UT = {WOS:000426813600032},
pubmed = {pmid:29309600},
doi = {10.1093/brain/awx356},
url = {https://juser.fz-juelich.de/record/841974},
}