Increased Variability in Response to Transcranial Electrical Stimulation in Older Compared to Young Adults: A Systematic Review and Meta-Analysis

Abstract

Background: Aging is associated with a decline in cognitive and motor functions, affecting daily activities and quality of life. Combining transcranial electrical stimulation (tES) with behavioral training may be a promising intervention against this decline. However, individual response variability may obscure group-level effects and mislead conclusions about tES efficacy. Quantifying this variability is crucial for accurately assessing stimulation effects and understanding individual response factors, like age. Yet, no study has quantitatively compared tES variability across age groups. This systematic review and meta-analysis examine age-related variability in cognitive and motor responses to tES.Methods: Following PRISMA guidelines, we searched PubMed and Cochrane for studies directly comparing young and older adults under similar experimental conditions. Across 25 studies comprising 498 older adults (mean ± SD age: 67 ± 5 years) and 493 young adults (mean ± SD age: 24 ± 3 years) receiving transcranial direct current (tDCS) or alternating current stimulation (tACS), we quantified behavioral variability using the log-transformed coefficient of variation ratio (lnCVR).Results: Results revealed substantially higher response variability in older compared to young adults during active tES (22%, lnCVRactive = -0.24 [-0.40, -0.08], p = 0.003), but not during sham conditions (lnCVRsham = -0.16 [-0.36, 0.03], p = 0.11).Conclusion: These findings provide the first quantitative evidence that advanced age increases behavioral tES response variability, highlighting the need to develop personalized tES approaches to optimize their therapeutic efficacy in older populations.

Note:
Funding declaration: The project was funded by the Deutsche Forschungsmeinschaft (DFG, project number: 497919823, AN 1103/4-1 to DA and Research Unit 5429/1, project number: 467143400, FL 379/34-1, FL 379/35-1 to AF, ME 3161/5-1, ME 3161/6-1 to MM, AN 1103/5-1 to DA, and project number: 539593253, AN 1103/6-1 to DA). CTLL is a PhD fellow funded by the “Deutscher Akademischer Austauschdienst” (DAAD), German Academic Exchange Service, scholarship: 91828451).

Conflict of Interests: The authors declare no conflicts of interest.

Keywords: Aging, Variability, stimulation effect, Transcranial electrical stimulation (tES), transcranial direct current stimulation (tDCS), transcranial alternating current stimulation (tACS), Meta-analysis