Cross-modal Neuromodulation to Improve Balance and Cognition in Older Adults With Glaucoma: A Randomized Trial of Cerebellar Transcranial Electrical Stimulation

Cross-modal Neuromodulation to Improve Balance and Cognition in Older Adults With Glaucoma: A Randomized Trial of Cerebellar Transcranial Electrical Stimulation

The goal of this clinical trial is to use different tES techniques to constantly stimulate the cerebellum in older glaucoma patients. The main questions aim to answer :

1. If the different types of tES targeting the cerebellum can modulate glaucoma patients' balance function and visual-cognitive function?
2. Which tES techniques among the two types can benefit most?

Participants will be required to receive the stimulation 15 times (3 sessions, 5 continuous days/session, 1-week interval between each session), and complete the balance and visual-cognitive function outcome measurements before and after each session.

Previous research on tES has primarily focused on the effects of different brain cortex stimulation on balance and visual cognitive functions in healthy adults. However, there is a scarcity of research examining the combined effects of these techniques on the cerebellum in visually impaired adults, especially those with glaucoma. Given the cerebellum's crucial role in maintaining balance and cognitive function in glaucoma patients, as evidenced by the latest research, it is essential to determine whether non-invasive cerebellar stimulation can simultaneously improve balance and visual cognitive functions in these patients. Meanwhile, most previous studies only focused on the short-term effects of stimulation, while potential long-term benefits remained unexplored. Our study aims to investigate the long-term effects of two types of tES stimulation on the cerebellum in adults with glaucoma. This research not only aims to fill existing gaps in the literature but also has the potential to develop new intervention strategies to improve functioning in older adults, ultimately enhancing their quality of life.

This study employs a within-subject, sham-controlled, cross-over design. The participants will receive constant tDCS, tACS, and sham stimulation in counterbalanced order. The participants will have three sessions (each session will include five consecutive training sessions) with outcome measurements at six time points. These assessments consist of a baseline test (T1), a test after completing the first session (T2), a test after the first interval week (T3), a test after completing the second session (T4), a test after the second interval week (T5), and a test after completing the third session (T6). The total time will be five weeks.

The outcome measurements will include dynamic balance tests: narrow path walking test and miniBEST test; static balance test: Sensory Organization Test; and two visual cognitive function tests: Reaction Time Test and the Useful Field of View test.

For statistical analysis, IBM SPSS Statistics version 23.0 will be utilized. The Shapiro-Wilk test will be employed to assess the normality of the data distribution. For skewed numerical data, the appropriate transformations will be used to make the data meet the normality assumption. The differences in baseline performance among tACS, tDCS, and sham stimulation were analyzed using repeated-measures ANOVA. To compare the differences between changes in primary and secondary outcomes among baseline and post-intervention time points, the repeated-measures ANOVA will be performed with interventions (tACS, tDCS, and sham) as a within-group factor. Changes in the values will be calculated by subtracting baseline values from the post-intervention values. Paired t-statistics will be obtained to compare the changes in outcome data (subtract baseline from post-intervention) between the interventions (tACS versus tDCS, tACS versus sham, and tDCS versus sham). Post-hoc pairwise comparisons will be performed using Bonferroni corrections. The level of statistical significance is set at p < 0.05.

Inclusion Criteria:

• Age over 55 years old;
• Diagnosis of primary open-angle or normal-tension glaucoma with relative scotoma in both eyes;
• Humphrey Field Analyzer visual field loss (mean deviation of ≤- 6 dB) using the 24-2 testing protocol for both eyes;
• Best-corrected distance visual acuity of 6/12 (equivalent to 0.3 logMAR) or better;
• Cognitive functional score of 22 or above in the Montreal Cognitive Assessment -Hong Kong version (HK-MoCA).
• Only the right-handed population will be recruited (screening by the Edinburgh Handedness Inventory).

Exclusion Criteria:

• Have musculoskeletal disorders or neurological diseases that can affect the balance or nervous system.
• Ocular diseases other than glaucoma (e.g., age-related macular degeneration, diabetic retinopathy, moderate to severe cataract) or severe hearing impairment (to ensure that participants can hear the instructions clearly during assessments and training)
• Have any contraindications for tES