RESTING-STATE EEG MARKERS OF CORTICAL SLOWING AND EXPLORATORY PROBIOTIC EFFECTS IN MILD ALZHEIMER’S DISEASE

Cortical network slowing, characterised by increased low-frequency and reduced higher-frequency EEG activity, is a hallmark of Alzheimer’s disease (AD). Modulation of brain function via the gut-brain axis has emerged as a potential therapeutic strategy, yet its effects on electrophysiological markers of AD remain unclear.
Methods: In this double-blind, placebo-controlled randomised trial, 40 patients with mild AD were enrolled; 33 completed baseline and follow-up assessments and were analysed (probiotic = 18, placebo = 15). Participants received a multi-strain probiotic (≈2 x 10¹⁰ CFU/day) or placebo for 16 weeks. Resting-state EEG was recorded under eyes-open and eyes-closed conditions, band-pass filtered and artefact-corrected using conservative epoch rejection. Spectral power (1-40 Hz) was estimated with Welch’s periodogram and expressed as relative band power using a linked-mastoids (A1/A2) reference. Regional spectral power and physiologically motivated spectral ratios were examined. Group-by-time effects were assessed using linear mixed-effects models with difference-in-differences contrasts and false discovery rate (FDR) correction.
Results: At baseline, posterior EEG spectra showed dominant delta-theta with reduced alpha-beta power, consistent with cortical slowing in mild AD. Exploratory analyses suggested very small, state- and region-dependent trends in frontal and fronto-temporal theta and alpha power during eyes-closed rest, and in related spectral ratios, but confidence intervals were wide and no probiotic effects survived FDR correction.
Conclusions: Resting-state EEG provides sensitive markers of cortical dysfunction in mild AD. In this pilot randomised trial, probiotic supplementation did not produce robust, FDR-corrected electrophysiological treatment effects, although exploratory regional patterns motivate further investigation in larger studies.