TY  - JOUR
AU  - Richter, Nils
AU  - Beckers, Nora
AU  - Onur, Özgür
AU  - Dietlein, Markus
AU  - Tittgemeyer, Marc
AU  - Kracht, Lutz
AU  - Neumaier, Bernd
AU  - Fink, Gereon Rudolf
AU  - Kukolja, Juraj
TI  - Effect of cholinergic treatment depends on cholinergic integrity in early Alzheimer’s disease
JO  - Brain
VL  - 141
IS  - 3
SN  - 1460-2156
CY  - Oxford
PB  - Oxford Univ. Press
M1  - FZJ-2018-00261
SP  - 903–915
PY  - 2018
AB  - 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.
LB  - PUB:(DE-HGF)16
UR  - <Go to ISI:>//WOS:000426813600032
C6  - pmid:29309600
DO  - DOI:10.1093/brain/awx356
UR  - https://juser.fz-juelich.de/record/841974
ER  -