Cortical neural synchronization mechanisms in Alzheimer's disease as revealed by resting state EEG rhythms: A window on cholinergic function?

Abstract

Current pharmacological treatments of Alzheimer's disease (AD) include the use of acetylcholinesterase inhibitors (AChEIs), based on the cholinergic hypothesis of the disease. However, converging evidence has shown a strong and unpredictable inter-individual variation in response to AChEI treatment. This motivates a better understanding of the neurophysiological role played by cholinergic neurophysiological systems in subjects with prodromal and overt AD. The present Consortium has probed neurophysiological mechanisms of cortical neural synchronization in pathological aging as revealed by an advanced spectral analysis of resting state eyes-closed electroencephalographic (EEG) rhythms in groups of normal elderly (Nold), amnesic mild cognitive impairment (MCI), cerebrovascular dementia (CVD), Parkinson disease with dementia (PDD), covert hepatic encephalopathy (CHE), and AD subjects. (1) dominant alpha frequencies (8–10 Hz) of EEG rhythms were specifically abnormal in the AD group when compared to the Nold, MCI, CVD, PPD, and CHE groups; (2) delta (2–4 Hz) and alpha rhythms were related to attention and global cognitive status in both MCI and AD groups; (3) power and functional coupling of alpha rhythms were related to white-matter lesions along the cholinergic tracts in the MCI group; (4) long-term (1 year) cholinergic therapy was just able to slow the derangement of alpha rhythms in the AD group. These findings suggest that resting state EEG rhythms may reflect the dysfunction of cholinergic neuromodulation of cortical neural synchronization in the MCI and in the AD group. Future research will have to evaluate the clinical impact of this methodological approach in individual patients.