BASELINE COGNITIVE AND ELECTROPHYSIOLOGICAL MARKERS PREDICT THETA–GAMM TACS OUTCOMES FOR WORKING MEMORY ENHANCEMENT IN SUBJECTIVE AND OBJECTIVE COGNITIVE DECLINE

Introduction: Response to neuromodulation in subjective cognitive decline (SCD) and mild cognitive impairment (MCI) is heterogeneous; identifying markers that anticipate responders would optimize candidate selection and enable more precise, individualized treatments.
Objective: To evaluate whether neuropsychological and behavioral measures at pretreatment predict response to multisession theta–gamma transcranial alternate current stimulation (TG-tACS) for working memory (WM) enhancement.
Methods: Twenty-nine older adults (21 women; 50–85 years) with SCD/MCI underwent a pretreatment comprehensive neuropsychological assessment, and EEG (task-related individual theta peak) and behavioral data (d’) were recorded during a visual match-to-sample WM task. The intervention consisted of two blocks of 8 consecutive sessions of real TG-tACS or sham (2 blocks, counterbalanced order). Analysis: Based on the intervention outcomes, participants were classified as “good” or “poor” responders. Subsequently, one-way ANOVAs were applied to compare pretreatment measures between both groups; significant variables were evaluated using ROC curves.
Results: The comparisons between “good” and “poor” responders showed significant group differences in low-load d′ (p = 0.048), high-load d′ (p = 0.030), individual theta peak (p = 0.024), educational level (0.016) and immediate free recall (p = 0.005). The individual ROC curves showed moderate sensitivity and specificity values between 72% and 79%. The combination of these variables reached high sensitivity = 90%, and specificity = 88% values.
Conclusion: Baseline neuropsychological and task-related markers allow accurate prediction of response to theta–gamma tACS, enabling efficient clinical identification of suitable candidates for this intervention.