| Author: | Cruz Gonzalez, Pablo |
| Title: | Transcranial direct current stimulation as an adjunct to cognitive training for older adults with mild cognitive impairment |
| Advisors: | Fong, Kenneth (RS) |
| Degree: | Ph.D. |
| Year: | 2021 |
| Subject: | Magnetic brain stimulation Mental illness -- Treatment Nervous system -- Diseases -- Treatment Hong Kong Polytechnic University -- Dissertations |
| Department: | Department of Rehabilitation Sciences |
| Pages: | 321 pages : color illustrations |
| Language: | English |
| Abstract: | General background: Transcranial direct-current stimulation (tDCS), a kind of non-invasive brain stimulation (NIBS), delivers direct current to the brain and acts as a neuromodulator that can facilitate cognitive improvement. tDCS is increasingly used as a type of non-pharmacological therapy (NPT) in cases of mild cognitive impairment (MCI) and dementia. Cognitive training (CT), which falls under the umbrella of cognitive rehabilitation (CR), is a form of NPT and consists of repeated guided practice, in a structured manner, of tasks associated with specific cognitive domains. There is mixed evidence for the effectiveness of CT in enhancing cognitive function in persons with MCI (PwMCI). CT is based on the principle that repetitive and structured practice of a task-specific domain with active therapist involvement will lead to changes in the neural processes that underlie the cognitive task, and in turn, transfer the skills to the respective cognitive domain. These benefits may also be generalized beyond the targeted cognitive domain, and as a result, CT could also improve daily living skills through the amelioration of cognitive functioning. As CT strengthens neural circuits during practice, these could be targeted by tDCS to increase the likelihood of transmission across neurons and thus alter behavior. Concurrent CT and tDCS may therefore produce synergistic effects that are superior to those of the administration of CT alone. This thesis accordingly aimed: 1) to evaluate the literature in order to determine the potential efficacy of tDCS in improving cognitive outcomes in persons with dementia (PwD) and PwMCI; 2) to examine whether older adults with MCI would gain more cognitive benefit from receiving CT alone rather than receiving CT coupled with tDCS along three different dimensions (domain-specific cognitive outcomes, task-specific outcomes of CT, and everyday functioning outcomes); and 3) to provide physiological evidence using electroencephalography (EEG) to study brain responses to the interventions. This was a three-phase research project. Phase 1 consisted of a systematic review and meta-analysis, while Phase 2 was a pilot study. Phase 3 was a randomized controlled trial (RCT). The structure of the current abstract is accordingly composed of three mini-abstracts corresponding to the four studies carried out in the three phases in order to achieve the above aims. 1) Systematic review and meta-analyses (Phase 1) Objective: To answer the following research question: Can tDCS serve as a clinical intervention to improve cognitive functions of PwMCI and PwD? Methods: A systematic review was conducted of studies published up to November 2017 involving tDCS in cases of MCI and dementia. Studies were ranked according to the level of evidence (Oxford Center for Evidence-Based Medicine) and assessed for methodological quality (Risk of Bias Tool in the Cochrane Handbook for Systematic Reviews of Interventions). Data was extracted on all protocol variables to establish a reference framework for clinical interventions. Different modalities, tDCS alone or combined with CT, compared with sham tDCS were examined for both short- and long-term effects. Four randomized control trials with memory outcomes were pooled using the fixed-effect model for the meta-analysis. Results: Twelve studies with 195 PwD and four studies with 53 PwMCI met the inclusion criteria. Eleven articles were ranked as level 1b. The results of the meta-analysis on the pooled effects of memory indicated a statistically significant medium effect size of 0.39 (p = 0.04) for immediate effects. This improvement was not maintained in the long term 0.15 (p = 0.44). Conclusion: Short term memory in PwD is improved by tDCS, which also seems to have a mild positive effect on memory and language in PwMCI. However, there is no conclusive advantage of coupling tDCS with CT. More rigorous evidence is needed to establish whether tDCS can serve as an evidence-based intervention for both populations. 2) Pilot study (Phase 2) Objective: The aim of this pilot study was to investigate whether the application of anodal tDCS over the left dorsolateral prefrontal cortex (DLPFC) could boost the effects of a cognitive stimulation (CS) program using a tablet in five older adults with MCI. Methods: A single-subject study of A-B-C-A design was used. After the baseline with the administration of CS (phase A), a sham treatment with CS was applied (phase B). Following the withdrawal of sham treatment, tDCS was introduced in combination with CS (phase C). Finally, phase A was replicated a second time. Results: A significant effect of tDCS was observed for processing speed, selective attention, and planning ability in terms of task performance and completion time. Conclusion: In PwMCI, tDCS appears to have a positive impact on some cognitive components of CS. Further study on the long-term effects of tDCS and generalization of power to daily activities is warranted. 3) Main study (Phase 3) Objective: To investigate whether the receiving tDCS combined with CT would be superior to receiving CT alone on domain- and task-specific cognition and everyday functioning in older adults with MCI. To explore the offline effects of multisession tDCS in combination with CT in older adults with MCI could influence the spectral analysis of absolute power relative to sham tDCS paired with CT and CT alone by means of resting EEG. Methods: This double-blind, sham-controlled randomized trial included 67 older adults with MCI assigned to one of three groups: 1) tDCS combined with CT (tDCS+CT), 2) sham tDCS combined with CT (sham tDCS+CT) and 3) CT alone. Nine sessions of computerized CT based on executive function were administered to the three groups for three weeks. In addition, tDCS and sham tDCS was delivered to the left DLPFC in the tDCS+CT and sham tDCS+CT during CT, respectively. Standardized cognitive assessments were carried out at baseline, post-intervention, and at six-weeks follow-up (FU). Participants' performance in the CT tasks was rated in every session. The Rivermead Behavioural Memory Test-3 was administered to assess transfer effects in everyday memory. Neurophysiological responses were assessed in sixteen cases to study the offline effects of tDCS using EEG at baseline and at post-intervention. Results: Improvements in global cognition and everyday memory (p < 0.017) were found within the three groups after the intervention and at FU with larger effect sizes noted in the tDCS+CT group (d > 0.94). However, there were no significant differences between groups. Regarding the CT outcomes, significant differences among groups were observed in favour of the tDCS+CT group with decreased completion and reaction times of working memory and attention activities (p < 0.017). A significant interaction effect (time x intervention) in channel 1LB (left prefrontal cortex) for absolute power of the theta band was evidenced (p = 0.047). Post-hoc comparisons revealed that this change was statistically significant in the tDCS+CT group (p = 0.047) Conclusions: Computerized CT with or without tDCS may be useful to promote global cognitive functioning and everyday memory in older adults with MCI. The significance of this study fosters insights into a new approach of using CT coupled with tDCS could provide a superior non-pharmacological benefit as compared to CT in the absence of tDCS for older adults with MCI. The combination of tDCS and CT did not produce a superior effect on domain specific outcomes as compared to sham tDCS+CT or CT alone, but did provide comparatively larger effect sizes and improve the processing speed of task-specific outcomes. Computerized CT of executive function appears to produce robust transfer effects of enhanced everyday memory, yet concurrent tDCS provides no superior transfer effect. Some sections of the mini abstracts have been previously published by the author of this thesis as a scientific manuscript which are cited accordingly in the general introduction of Chapter 4, 5, 6 and 7. |
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| Access: | open access |
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