Transcranial direct current stimulation interventions for cognition in older adults

Abstract

The population of older adults is rapidly growing worldwide, thereby increasing the prevalence of age-related health difficulties. One of the most concerning of these is age-related cognitive decline, referring to the gradual reduction of cognitive abilities with ageing, in the absence of neurodegenerative disease. These changes are typically more pronounced in executive functions and episodic memory, and can have a marked impact on an individuals’ functional independence. Consequently, there is widespread interest in developing interventions aimed at ameliorating this process. Non-invasive brain stimulation approaches such as transcranial Direct Current Stimulation (tDCS) have received increasing attention as a potential treatment for age-related cognitive decline. Indeed, tDCS has shown promise of generalised and sustainable cognitive benefits in healthy younger adults. Work in older adults remains less clear, however, likely contributed to by variability in protocols and methodological limitations. This thesis aimed to address these issues with: 1) the largest experimental study of its kind to date and the first to be published as a Registered Report on the effects of a combined cognitive training and tDCS protocol on cognitive functions in healthy older adults, and; 2) a comprehensive systematic review and meta-analysis synthesising previous work on the effects of tDCS interventions on cognitive function in healthy older adults.The experimental study is outlined in chapter 2. Here, 131 healthy older adults were recruited using a Bayesian sampling approach, which ensured that the study had sufficient power to address key research questions. Participants received five sessions of either decision-making training and anodal tDCS (2mA, 20 minutes) to the left PFC on consecutive days previously shown to enhance executive function in young adults, or one of three control protocols. They completed a comprehensive cognitive assessment immediately before their first session, one day after their last session and at one and three-month follow-up. This included tasks assessing executive functions, memory and processing speed and questionnaires on everyday functioning that were completed by the participant and a significant other. Finally, COMT and BDNF genetic polymorphisms were obtained from saliva samples to determine their influence on response to intervention and baseline performance. Contrary to hypotheses, left PFC tDCS did not enhance training benefits on the decision-making task, improve performance on untrained tasks (transfer) or benefit everyday function at any of the post-intervention time points. Strong evidence for the null hypothesis via Bayesian analyses was observed. However, exploratory task- and genetic-based individual difference analyses hinted at the possibility of transfer to working memory and episodic memory at one and three-month follow-up assessment, respectively, but require further investigation via confirmatory research. Overall, this study suggested that training and tDCS with the current parameters is unlikely to confer short or long term cognitive benefits to healthy older adults.In chapter 3 the systematic review and meta-analysis on previous studies investigating the effects of tDCS on cognitive function in healthy older adults is presented. 32 studies were selected according to the PRISMA guidelines. Studies employed various protocols with respect to stimulation duration and intensity, number of sessions, presence of concurrent training task and whether they employed online/offline stimulation. Targeted cognitive domains included episodic memory, working memory, executive functions and language and there was substantial variability in the timing of assessments, which were grouped into “short-term” and “follow-up” assessments for the purpose of our analyses. In addition, subgroup analyses and meta-regression were used to characterise the influence of stimulation parameters on outcomes.Random effects meta-analyses revealed a small beneficial effect of tDCS on cognitive function at short-term and long-term assessment. For the most part there was no significant influence of specific stimulation parameters on outcomes, but there was a difference between studies with and without concurrent training at follow-up, such that studies which administered stimulation alone produced greater benefits than those with concurrent training. There was likely publication bias within the literature, suggesting that the beneficial effects of tDCS may be inflated. But, the finding of even a small beneficial effect was considered promising given the lack of optimisation work in this population.Taken together, tDCS seems to offer at least modest benefits to cognitive function in healthy older adults, but is less likely to enhance cognitive training benefits or produce transfer to untrained tasks. This contrasts work in healthy young adults, and might reflect a combination of neural changes experienced in ageing such as increased atrophy and decreased functional specialisation. Both studies discussed the role of individual differences in response to tDCS and highlighted the importance of designing protocols specifically for older adults. Indeed, future studies should be focussed on optimising tDCS protocols by directly comparing the effects of different parameters in older adults. Despite its promise, tDCS requires extensive work in well-powered, rigorously controlled studies with a commitment to open science practices before it can be rolled out as an intervention for cognitive decline in ageing.