Effects of acetylcholinesterase inhibitors and memantine on resting-state electroencephalographic rhythms in Alzheimer’s disease patients

Acetylcholinesterase inhibitors (AChEIs) are the most widely used symptomatic treatment for mild to severe Alzheimer’s disease (AD) patients, while N-methyl-d-aspartic acid (NMDA) receptor antagonist memantine is licensed for use in moderate to severe AD patients. In this article, the effect of these compounds on resting state eyes-closed electroencephalographic (EEG) rhythms in AD patients is reviewed to form a knowledge platform for the European Innovative Medicine Initiative project “PharmaCog” (IMI Grant Agreement No. 115009) aimed at developing innovative translational models for drug testing in AD. Indeed, quite similar EEG experiments and the same kind of spectral data analysis can be performed in animal models of AD and in elderly individuals with prodromal or manifest AD. Several studies have shown that AChEIs affect both resting state EEG rhythms and cognitive functions in AD patients. After few weeks of successful treatment, delta (0–3 Hz) or theta (4–7 Hz) rhythms decrease, dominant alpha rhythms (8–10 Hz) increase, and cognitive functions slightly improve. Beneficial effects of these rhythms and cognitive functions were also found in AD responders to the long-term successful treatment (i.e. 6–12 months). In contrast, only one study has explored the long-term effects of memantine on EEG rhythms in AD patients, showing reduced theta rhythms. The present review enlightens the expected effects of AChEIs on resting state EEG rhythms in AD patients as promising EEG markers for the development of translational protocols both within the PharmaCog project and for wider use.

► Symptomatic treatment options for Alzheimer’s disease (AD) are currently limited to two therapeutic classes namely, acetylcholinesterase inhibitors (AChEIs) and memantine. ► The present review clarifies the effects of AChEIs and memantine on resting-state electroencephalographic (EEG) rhythms and cognitive function in AD patients to identify EEG markers useful for drug development. ► Based on the field literature, the patient’s EEG rhythms most reactive to AChEIs are those at delta (0–3 Hz), theta (4–7 Hz) and alpha (8–12 Hz); the effects of memantine generate a reduction of pathological theta rhythms.