Effects of 40-Hz transcranial alternating current stimulation on cognition and neural markers in Alzheimer's disease: a randomized, sham-controlled trial.
Level 2 - randomized trial
Individual randomized, double-blind, sham-controlled clinical trial
PubMed 41918026 · doi:10.1186/s13195-026-02033-4
What was done
In a randomized, double-blind, sham-controlled trial, 39 participants with Alzheimer's disease received either 40-Hz transcranial alternating current stimulation (tACS, n = 20) targeting the left dorsolateral prefrontal cortex (2.0 mA, 30 min/day, 2 weeks) or sham stimulation (n = 19). Assessed outcomes included cognitive and mood measures, resting-state electroencephalography (rs-EEG) spectral and connectivity parameters, and plasma phosphorylated tau markers (p-tau217 and p-tau181).
What was found
The abstract reports directional signals without numerical values, confidence intervals, or p-values. Compared with sham, 40-Hz tACS was associated with a trajectory-level signal favoring improved global cognition, reduced depressive symptoms, increased frontal–central theta power, enhanced theta-band hippocampal–prefrontal connectivity, stronger low-gamma connectivity at the region-of-interest level, and exploratory reductions in plasma p-tau217 and p-tau181.
Why it matters
This study provides initial clinical evidence that gamma-band electrical stimulation can engage target prefrontal-hippocampal networks and may favorably modulate Alzheimer's-related cognitive and plasma tau markers.
Limits
The sample size is very small (n = 39) with a short 2-week intervention. The abstract reports no numerical effect sizes or statistical significance values. Biomarker changes were exploratory and post-treatment durability was not evaluated.
Cited by
- supports Exposure to 40 Hz sensory stimulation increases gamma brain wave activity and is associated in early clinical research with a slower rate of cognitive decline.