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

The Hong Kong Polytechnic University36 enrolled

Overview

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.

Interventions

transcranial electrial stimulationOTHER

This intervention is uniquely designed to enhance balance function in patients with glaucoma using non-invasive cerebellar Transcranial Electrical Stimulation (tES), encompassing both transcranial Direct Current Stimulation (tDCS) and transcranial Alternating Current Stimulation (tACS). Glaucoma-induced visual field loss disrupts the visual feedback critical for postural control, forcing patients to rely heavily on sensory re-weighting (integrating vestibular and proprioceptive inputs). The cerebellum is the central hub for this multi-sensory integration and motor adaptation. By modulating cerebellar excitability and neural oscillations, this intervention aims to facilitate sensory re-weighting, optimize vestibular-ocular/spinal reflexes, and ultimately improve dynamic and static balance.

Eligibility

Sex: ALLMin age: 55 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Dynamic Balance Performance-The dual task Narrow Path Walking Test

The Narrow Path Walking Test (NPWT) is a modified version of the Time Up and Go Test (TUGT) that assesses dynamic balance function during gait in a more challenging environment. In the TUGT, subjects stand up from a 46 cm-tall chair, walk 3 m at their normal walking speed, bypass an obstacle, return, and sit down. NPWT requires participants to perform the same procedure as the TUGT. In NPWT, a 40 x 300 cm green mat with 24% Michelson contrast against the walking path to create a challenging environment, dividing the path into two 20 cm-wide narrow pathways to test mediolateral dynamic balance. The NPWT time will be measured. To add difficulty, the dual task of the serial subtraction will be added in the walking procedure.To achieve stable performance, each test will be repeated 3 times, and the results will be averaged to ensure consistency. The recording parameters for NPWT will include trial time, mistakes, cognitive performance, and dual-task cost.

Time frame: The outcome will be assessed 6 times: before and after each stimulation session (tDCS, tACS, Sham session ) (each session length = 5 consecutive days). Therefore, there will be tDCS-pre, tDCS-post; tACS-pre, tACS-post; Sham-pre, Sham-post.

Secondary Outcomes

Balance performance - Mini-BESTest

The Mini-BESTest will be utilized to assess participants' balance through a series of 14 tasks that encompass both static and dynamic balance challenges, including activities such as sit-to-stand, walking with head turns, standing on one leg, and Time up and Go with a dual task. Each task is scored on a scale from 0 to 2, with higher scores reflecting superior balance abilities. To provide a comprehensive evaluation, we will include variations in task difficulty, enabling us to analyze how different levels of complexity influence balance performance. The total score from the Mini-BESTest will be examined to gauge participants' balance proficiency and to identify any improvements resulting from the intervention. All tasks will be administered in a standardized sequence, ensuring a systematic and reliable approach to balance assessment for all participants.

Sensory Organization Test

The SOT provides a quantitative assessment of an individual's ability to utilize specific sensory cues to maintain stability during quiet stance. The protocol consists of six standardized conditions designed to systematically disrupt or isolate sensory information: (1) eyes open, firm surface; (2) eyes closed, firm surface; (3) sway-referenced vision, firm surface; (4) eyes open, sway-referenced surface; (5) eyes closed, sway-referenced surface; and (6) sway-referenced vision and surface. During the assessment, participants will be instructed to stand still with their feet shoulder-width apart for 20 seconds per trial. The primary outcome measures include the Composite Equilibrium Score, representing a weighted average of postural stability across all conditions, and Sensory Analysis Ratios, which are calculated to pinpoint specific impairments in the visual, somatosensory, and vestibular systems.

Visual cognitive function-Useful Field of View test

The UFOV test will include three conditions: 1. Stimulus Identification: A central target will be displayed on the screen for 60 frames, before being masked by a 'white noise' screen. The display duration will be adjusted using a 3-up/1-down adaptive staircase procedure to determine the threshold, with testing concluding after eight reversals or seventy-two total trials. 2. Divided Attention: Both a central and a peripheral target will be displayed simultaneously, the latter appearing randomly at one of eight meridian locations (0°, 45°, 90°, 135°, 180°, 225°, 270°, 315°, 360°) at 20° from the center. The presentation duration will be adjusted using the algorithm as in test 1 to reach a threshold. 3. Selective Attention: This condition will include a central target, a peripheral target, and additional peripheral distractors. The distractors will subtend the same visual angle as the peripheral target. Apart from the introduction of distractors, the procedure is the same as for test 2.

Visual cognitive function-reaction time test

The total Reaction Time Test will be divided into two parts. The first part will involve a simple reaction assessment, utilizing Python software to create the stimulus. Participants will be instructed to respond to a stimulus shown in the center of the screen. The second part of the test will involve a choice reaction test, in which four squares will be arranged horizontally on the screen. The stimulus will appear randomly in one of the squares, and the participants will be guided to react to the position as quickly as possible. For the first part, the corresponding time to the stimulus will be recorded. For the second part, the reaction time to the stimulus and the task accuracy will be recorded. Each part will be repeated 3 times to get the average score.