Multifocal transcranial current stimulation for cognitive and motor dysfunction in dementia

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PROJECT SUMMARY: In older adults with mild dementia, disruption in the ability to complete instrumental activities of daily living stems not only from memory deficits, but also from executive dysfunction which also impacts gait and balance. There is thus an urgent need to develop safe, multi-component interventions designed to maximize functional capacity in this vulnerable population by simultaneously targeting memory, executive function, and the complex control of gait and balance. It is now well-established that memory and executive-motor deficits arise from altered function within specific and spatially distinct brain networks, and, that different forms of transcranial current stimulation can target these networks to provide symptomatic relief to this population. Parallel lines of preliminary evidence specifically suggest that 1) transcranial alternating current stimulation targeting the left angular gyrus (tACS) at gamma frequency can improve episodic and autobiographical memory; and 2) transcranial direct current stimulation (tDCS) targeting the left dorsolateral prefrontal cortex can improve executive function and gait performance, especially when older adults are walking while performing additional cognitive tasks (i.e., dual tasking). At the same time, important technological advances have recently enabled researchers to: study and optimize multi-channel stimulation montages (i.e., electrode placement and current parameters) based upon individualized modeling of generated cortical electric fields; target more than one brain network at the same time within the same montage; implement active-sham protocols that facilitate double-blinding and control of the potential effects of peripheral stimulation; and safely deliver interventions to participants within their own homes via remotely-supervised, caregiver-led administration of stimulation. Building upon these preliminary studies and advances, we propose to conduct a phase II, randomized, sham- controlled, double-blinded, parallel-arm trial to assess the separate and combined effects of tACS targeting the left angular gyrus at gamma frequency and tDCS targeting the left dorsolateral prefrontal cortex on memory, executive function, dual task gait, and instrumental activities of daily living in ambulatory older adults with mild dementia (Specific Aim 1). Within this trial, we will also determine how much of the clinical effects of intervention on memory on the one hand, and executive function and dual task gait performance on the other hand, depend upon the amount of the electric field induced respectively in the left angular gyrus and the left dorsolateral prefrontal cortex, as assessed by individualized e-field high-resolution modelling (Specific Aim 2). This project is expected to demonstrate that tACS and tDCS can be combined into one single intervention to optimize the functional impact of a home-based intervention for older adults suffering from mild dementia. It will also provide insights into the specificity of mapping between brain networks and symptoms, and offer critical foundation to enable personalized optimization of stimulation interventions within future trials.