The Impact of Brain Auditory Stimulation in the Gamma Band on Cognitive Functions in Early-stage Alzheimer Patients

Introduction: Alzheimer disease (AD), a progressive neurodegenerative disorder marked by deterioration in cognitive abilities, currently affects around 24 to 50 million individuals worldwide. However, effective non-invasive therapeutic options are still unavailable. Disruption of gamma-band neural oscillations (~40 Hz), which underlie higher-order cognitive processes such as working memory and executive function, has been repeatedly documented in both human and animal models of AD. Targeted auditory stimulation at gamma frequencies has recently emerged as a potential neuromodulatory strategy for mitigating these deficits. Methods: In a controlled experimental framework, 30 individuals clinically diagnosed with early-stage AD, confirmed via functional magnetic resonance imaging (fMRI), and exhibiting mini-mental state examination (MMSE) scores between 10 and 20, were randomly divided into two groups: the intervention (n=15) and control (n=15) groups using a quasi-experimental parallel-group pre–post design. The intervention group received 30 sessions of auditory stimulation using binaural beats centered at 40 Hz over 3 weeks. In contrast, the control group listened to an acoustically comparable audio file lacking gamma-frequency modulation. Cognitive performance was assessed using computerized versions of the Corsi block-tapping test, the Wisconsin card sorting test (WCST), and the digit span test. In addition, resting-state quantitative electroencephalography (QEEG) was conducted to evaluate frontal lobe gamma-band activity under both eyes-open and eyes-closed conditions. Results: Statistical analysis revealed that gamma-band auditory stimulation resulted in a significant enhancement of visuospatial working memory (P=0.001, Cohen’s d=1.42) and cognitive flexibility (P=0.028, Cohen’s d=0.78), alongside marked increases in both absolute and relative gamma power in the frontal cortex under eyes-closed conditions (P<0.01). Conclusion: These findings suggest that auditory stimulation at 40 Hz selectively modulates neural circuits associated with executive and spatial cognitive functions and may serve as a viable non-invasive adjunctive intervention in early-stage AD. Highlights 40 Hz stimulation improved visuospatial working memory (P=0.001, d=1.42). Cognitive flexibility significantly increased after intervention (P=0.028). Frontal gamma power rose under eyes-closed condition (P<0.01). Relative and absolute gamma activity significantly enhanced post-stimulation. Plain Language Summary Alzheimer’s disease (AD) is a condition that gradually damages memory, thinking, and the ability to carry out everyday tasks. It affects millions of people worldwide, and current treatments can only slow symptoms rather than stop the disease. Because of this, researchers are searching for safe, non-invasive ways to support brain function in people with early-stage Alzheimer’s. In this study, we explored whether a specific type of sound stimulation could help improve thinking abilities. The human brain naturally produces rhythmic electrical activity. One pattern, called “gamma” activity (around 40 cycles per second), is linked to memory and attention. Previous research has shown that this type of brain activity is reduced in people with Alzheimer’s disease. We recruited 30 individuals with early-stage Alzheimer’s and divided them into two groups. One group listened to specially designed audio tones that gently stimulated the brain at 40 Hz over three weeks. The other group listened to similar sounds without this specific pattern. We then measured their memory, problem-solving skills, and brain activity. Participants who received the 40 Hz sound stimulation showed clear improvements in visual working memory and mental flexibility. We also observed increased activity in the frontal areas of the brain, which are important for planning and decision-making. These findings suggest that simple auditory stimulation may help strengthen brain function in early AD. Because this approach is non-invasive and relatively easy to deliver, it may offer a promising additional tool to support patients and their families.