Cholinergic dysfunction, neurodegeneration, and amyloid-beta pathology in neurodegenerative diseases. (30th August 2020)

• Record Type: Journal Article
• Authors: Petrova, Teodora; Orellana, Camila; Jelic, Vesna; Oeksengaard, Anne-Rita; Snaedal, Jon; Høgh, Peter; Andersen, Birgitte Bo; Naik, Mala; Engedal, Knut; Wahlund, Lars-Olof; Ferreira, Daniel
• Is Part Of: Psychiatry research. Volume 302(2020)
• Publication Date: 2020-08-30
• Subjects: Dementia -- Alzheimer's disease -- Electroencephalography -- Acetylcholine -- Magnetic resonance imaging -- Amyloid-beta -- Neurodegeneration; Psychiatry -- Periodicals; Brain -- Imaging -- Periodicals; Psychiatry -- Periodicals; Diagnostic Imaging -- Periodicals; Psychiatrie -- Périodiques; Cerveau -- Imagerie pour le diagnostic -- Périodiques; 616.890754
• DOI: 10.1016/j.pscychresns.2020.111099
• Languages: English
• ISSNs: 0925-4927

Abstract

Highlights: Cholinergic dysfunction measured by the Electroencephalography-Acetylcholine index correlates with reduced hippocampal volume and thinner cortex in several frontal, temporal, and occipital regions. Cholinergic dysfunction seems to be downstream to biomarkers of amyloid-beta pathology (CSF Aβ) and neurodegeneration (CSF total tau and hippocampal volume). The Electroencephalography-Acetylcholine index is a useful biomarker for cholinergic dysfunction in vivo, with value for differential diagnosis of dementia and monitoring patients at the dementia stage. The Electroencephalography-Acetylcholine index could be used to monitor treatment with cholinesterase inhibitors. Abstract: Cholinergic dysfunction is central in Alzheimer's disease (AD) and dementia with Lewy bodies (DLB). The electroencephalography-based acetylcholine index (EEG-Ach index) has been proposed as a biomarker of cholinergic dysfunction . However, it is unclear how the EEG-Ach index relates to amyloid-beta pathology and neurodegeneration. We investigated the association between the EEG-Ach index and cerebrospinal fluid (CSF) amyloid-beta, CSF total tau, cortical thickness, and hippocampal volume from magnetic resonance imaging (MRI), and cognition. A total of 127 patients with different neurodegenerative diseases were studied. The EEG-Ach index was calculated from quantitative EEG using statistical pattern recognition. The EEG-Ach index was associated with hippocampal volume and cortical thickness in frontal, temporal, and occipital cortices. Cross-sectional sub-analyses based on a small sample suggests that the EEG-Ach index increases the closest to AD dementia, downstream to amyloid-beta pathology, CSF total tau, and hippocampal volume. We conclude that cholinergic dysfunction correlates with atrophy in brain areas important for AD pathogenesis, and this association is more prominent in the dementia stage. These results together with previous studies from this project suggest that the EEG-Ach index may be a useful biomarker for cholinergic dysfunction, with value for differential diagnosis of dementia and monitoring patients at the dementia stage.