TY - JOUR

T1 - Cholinergic dysfunction, neurodegeneration, and amyloid-beta pathology in neurodegenerative diseases

AU - Petrova, Teodora

AU - Orellana, Camila

AU - Jelic, Vesna

AU - Oeksengaard, Anne-Rita

AU - Snaedal, Jon

AU - Hogh, Peter

AU - Andersen, Birgitte Bo

AU - Naik, Mala

AU - Engedal, Knut

AU - Wahlund, Lars-Olof

AU - Ferreira, Daniel

PY - 2020

Y1 - 2020

N2 - 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.

AB - 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.

KW - Dementia

KW - Alzheimer's disease

KW - Electroencephalography

KW - Acetylcholine

KW - Magnetic resonance imaging

KW - Amyloid-beta

KW - Neurodegeneration

U2 - 10.1016/j.pscychresns.2020.111099

DO - 10.1016/j.pscychresns.2020.111099

M3 - Journal article

C2 - 32505903

VL - 302

JO - Psychiatry Research: Neuroimaging

JF - Psychiatry Research: Neuroimaging

SN - 0925-4927

M1 - 111099

ER -