Journal Article

FZJ-2019-04344

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Spatial distributions of cholinergic impairment and neuronal hypometabolism differ in MCI due to AD

Richter, N. (Corresponding author)FZJ* ; Nellessen, N.FZJ* ; Dronse, J.FZJ* ; Dillen, K.FZJ* ; Jacobs, H.FZJ* ; Langen, K.-J.FZJ* ; Kracht, L. ; Dietlein, M. ; Neumaier, B.FZJ* ; Fink, G. R.FZJ* ; Kukolja, J.FZJ* ; Onur, O. A.

2019
Elsevier [Amsterdam u.a.]

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Please use a persistent id in citations: http://hdl.handle.net/2128/22682  doi:10.1016/j.nicl.2019.101978

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.

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Contributing Institute(s):

1. Kognitive Neurowissenschaften (INM-3)
2. Physik der Medizinischen Bildgebung (INM-4)
3. Nuklearchemie (INM-5)

Research Program(s):

1. 572 - (Dys-)function and Plasticity (POF3-572) (POF3-572)

Appears in the scientific report 2019

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Database coverage:
; ; ; ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; DOAJ Seal ; IF < 5 ; JCR ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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