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.