Table 3.

Measures of rsEEG rhythms for monitoring AD progression and response to interventions in AD clinical trials. These biomarkers refer to longitudinal rsEEG studies of the so-called “Class A” (see Table 1 for definitions). The qualification of those measures was based on studies showing differences in rsEEG measures at baseline vs. follow-up recordings or before vs. after a pharmacological intervention in relation to placebo. For example, in the PQ912 study, ADMCI and ADD patients formed an experimental group (n=60) receiving an inhibitor of the glutaminyl cyclase enzyme (PQ912) that plays a central role in the formation of synaptotoxic pyroglutamate-A-beta oligomers for 12 weeks, while a placebo group (n=60) received hypocaloric beverage for the same period [181]. In other studies, ADD and ADMCI patients received Acetylcholinesterase inhibitors (AChEIs) for weeks/months. Frequency bands of rsEEG rhythms were standard, namely delta, theta, alpha, beta, and gamma. When the data were available in the “Class-A” paper, the effect and sample sizes of the main rsEEG measures characterizing AD patients over controls are reported. More literature evidence and the meaning of rsEEG measures in the table are reported in the main text.

Purpose	Design	Patient samples	EEG biomarkers	Main findings	Selected References (Class A)
Disease progression and monitoring	Longitudinal	ADMCI (N= 72, age= 69), noADMCI (N= 54, age= 68)	Delta, theta, and alpha source activities	ADMCI patients showed increased limbic theta source activity and greater cognitive decline at a 24-month follow-up in relation to reduced functional connectivity. The output of the Linear Mixed Models was presented in terms of standardized coefficient, corresponding p-value and, for the interaction factor only, effect size (pseudo h2) calculated as ratio of explained variability of interaction effect on total variability of each model.	Jovicich et al., 2019
Disease progression and monitoring	Longitudinal	ADMCI (N= 27, age= 58)	Alpha and theta power density and sources	ADMCI showed increased temporal and occipital theta-delta power density and decreased beta power density at an averaged follow-up of 21 months	Jelic et al., 2000
Assessment of treatment effects	Longitudinal	ADMCI (N= 47, age=70), ADD (N= 56, age= 72)	Delta, theta, alpha, dominant frequency, functional connectivity	ADMCI receiving a glutaminyl cyclase inhibitor involved in the amyloid production (PQ912) showed enhanced interrelatedness of alpha rhythms as revealed by an improved phase lag index.	Briels et al., 2020
Assessment of treatment effects	Longitudinal	ADMCI (N= 60, age= 72), ADD (N= 60, age= 71)	Delta, theta, and alpha source activities	Results showed an improvement of memory and a reduction of global theta power density across all electrodes in the Souvenaid PQ912 as compared with the placebo group. The effect size was 0.37 for theta power, while the sample size was 116 for the protocol group (PP), 0.29 and 188 for the intent to treat (ITT) group, and 0.32 and 155 for the modified ITT group. PQ912 intervention did not affect the “phase lag index” as measure of rsEEG “interrelatedness”	Scheltens et al., 2018
Assessment of treatment effects	Longitudinal	ADD (N= 15, age= 65), ADD placebo (N= 10, age= 61)	Delta and theta GFP	AChEIs (tacrine) reduced theta GFP after 3 and 12 months, while both delta and theta GFP reduced after 6 months	Jelic et al., 1998