The Acetylcholine Index: An Electroencephalographic Marker of Cholinergic Activity in the Living Human Brain Applied to Alzheimer's Disease and Other Dementias

Abstract

Background: The cholinergic hypothesis is well established and has led to the development of pharmacological treatments for Alzheimer's disease (AD). However, there has previously been no physiological means of monitoring cholinergic activity in vivo. Methods: An electroencephalography (EEG)-based acetylcholine (Ach) index reflecting the cholinergic activity in the brain was developed using data from a scopolamine challenge study. The applicability of the Ach index was examined in an elderly population of healthy controls and patients suffering from various causes of cognitive decline. Results: The Ach index showed a strong reduction in the severe stages of AD dementia. A high correlation was demonstrated between the Ach index and cognitive function. The index was reduced in patients with mild cognitive impairment and prodromal AD, indicating a decreased cholinergic activity. When considering the distribution of the Ach index in a population of healthy elderly subjects, an age-related threshold was revealed, beyond which there is a general decline in cholinergic activity. Conclusions: The EEG-based Ach index provides, for the first time, a physiological means of monitoring the cholinergic activity in the human brain in vivo. This has great potential for aiding diagnosis and patient stratification as well as for monitoring disease progression and treatment response. © 2014 S. Karger AG, Basel

EEG machine learning for accurate detection of cholinergic intervention and Alzheimer’s disease

“…A similar analysis using machine learning for classifying scopolamine effects on the EEG has been developed in the past 45 ; however, with different features and analysis methods used and without reporting the classification performance of the index; therefore, it cannot readily be compared with our findings. Our cross-validation (training and testing on different data) resulted in a remarkable performance (Fig.…”

Electroencephalography Is a Good Complement to Currently Established Dementia Biomarkers

“…This is presumably due to overlapping in CSF tau levels as well as coexistence of atrophy in similar sites in both disorders. The two qEEG-SPR indices used in the current study correlate with a third classifier that reflects cholinergic neurotransmission [17]. These indices thus allow investigation of cholinergic derangement in the human brain in vivo.…”

“…Interestingly, a recent study demonstrated that the qEEG-SPR method allows investigation of cholinergic derangement in the human brain in vivo. This is relevant for disorders involving cholinergic deficit such as AD, DLB, and PDD [17]. …”

Fabrication of peptide-linked albumin nanoconstructs for receptor-mediated delivery of asiatic acid to the brain as a preventive measure in cognitive impairment: optimization, in-vitro and in-vivo evaluation

“…However, multiple neurotransmitters are supposed to be deregulated due to the neurodegeneration in basal forebrain which is involved in memory and learning ability. The precise aetiology of the AD has yet not been elucidated but the cholinergic hypothesis has been well established and it reveals that hyperactivated acetylcholinesterase (AChE) enzyme hydrolyses the acetylcholine (ACh) leading to the scarcity of the neurotransmitter in the synaptic cleft which leads to dementia by adversely affecting learning ability and acquisition of reference memory [3]. Currently, acetylcholinesterase inhibitors like donepezil (DPZ) and galanthamine are the first-line drugs for symptomatic treatment of dementia.…”