The moderating effects of sex, age, and education on the outcome of combined cognitive training and transcranial electrical stimulation in older adults

Abstract

Computerized cognitive training (CCT) has been shown to improve cognition in older adults via targeted exercises for single or multiple cognitive domains. Combining CCT with non-invasive brain stimulation is thought to be even more effective due to synergistic effects in the targeted brain areas and networks. However, little is known about the moderating effects of sex, age, and education on cognitive outcomes. Here, we investigated these factors in a randomized, double-blind study in which we administered CCT either combined with transcranial direct (tDCS), alternating (tACS) current stimulation or sham stimulation. 59 healthy older participants (mean age 71.7 ± 6.1) received either tDCS (2 mA), tACS (5 Hz), or sham stimulation over the left dorsolateral prefrontal cortex during the first 20 min of a CCT (10 sessions, 50 min, twice weekly). Before and after the complete cognitive intervention, a neuropsychological assessment was performed, and the test scores were summarized in a composite score. Our results showed a significant three-way interaction between age, years of education, and stimulation technique (F_(6,52) = 5.53, p = 0.007), indicating that the oldest participants with more years of education particularly benefitted from tDCS compared to the sham group, while in the tACS group the youngest participants with less years of education benefit more from the stimulation. These results emphasize the importance of further investigating and taking into account sex, age, and education as moderating factors in the development of individualized stimulation protocols.

Clinical trial registration: ClinicalTrials.gov, identifier NCT03475446.

Keywords: age; cognitive training; education; older adults; sex; tACS; tDCS.

Figure 1

CONSORT flowchart.

Figure 2

Study design. Participants underwent the pre-assessment (neuropsychological test battery and questionnaires) within 6 weeks before the intervention and completed the post-assessment within 2 weeks after the end of the intervention. During each of the 10 sessions, the CCT was combined with either tDCS, tACS, or sham stimulation during the first 20 min of the trainings. After a 10 min break and removal of the stimulation electrodes, they continued the cognitive training with two further tasks targeting one of three cognitive domains (inhibition, spatial working memory, processing speed).

Figure 3

(A) Significant three-way interaction between age, years of education, and stimulation on composite score differences. There is a positive tDCS effect in oldest adults while in youngest adults tACS might have some beneficial effects. (B) There was a trend (p = 0.9) for a significant interaction between sex, age and stimulation on composite score differences. TDCS might be beneficial in oldest males, while tACS seems to support the efficacy of the cognitive training in youngest females.