Transcutaneous Stimulation to Improve Cognitive Functions

• ¹ Sidney Kimmel Medical College (SKMC), United States
• ² Temple University, United States
• ³ Jefferson University Hospitals, Thomas Jefferson University, Neurology, United States
• ⁴ Jefferson Hospital for Neuroscience, United States

Transcutaneous stimulation involves the non-invasive application of low dose electrical current across the skin in order to modulate the peripheral and central nervous system. Transcranial Direct Current Stimulation (tDCS) specifically involves current applied to the scalp with the goal of modulating nerves in the scalp itself and activity within the brain. Data from sham-controlled, randomized trials indicates that tDCS can improve working memory in healthy older adults [1], visual episodic memory in adults with mild vascular dementia [2], auditory episodic memory in adults with traumatic brain injury [3]. Case studies of tDCS in adults with Alzheimer’s disease, suggests an improvement in episodic memory [4-6]. The purpose of this study is to quantify the effects of transcranial stimulation to improve cognitive functions in adults with chronic neurocognitive conditions, such as early Alzheimer’s disease. We propose to implement a sham-controlled, randomized trial that recruit participants to perform motor tasks with tDCS (active or sham) treatment. tDCS will be provided using the Halo Neurostimulation system as shown in Figure 1. This study will be approved by the Institutional Review Board at Jefferson Hospital and all participants will be give informed consents. In this study, the amyloid status of patients with mild cognitive impairment will be taken into account. Amyloid status refers to the results of an amyloid positron emission tomography scan. Patients with both positive and negative amyloid studies will be included in this study. By having this objective imaging data, we hope to innovate in this field because we can investigate if amyloid status were a factor in how tDCS might affect the brain. The major issue in most studies of cognition and tDCS is that the laboratory tasks might not generalize to daily function. In this study, we will use naturalistic tasks. Specifically, one arm of the study involves a virtual kitchen computer game with food ingredients and the participants are instructed to make a meal (breakfast or lunch). tDCS will be applied while the participant were engaged in this task and were receiving coaching by the research assistant. We also have a study arm that is performed at home simultaneous with the evidence-based Skills2Care home occupational therapy intervention that already explicitly focuses on day-to-day function of adults with neurological impairment [7]. Tasks may include meal preparation, oral hygiene, and medication management. tDCS will be applied while the participant were engaged in this task and were receiving coaching by a certified occupational therapist. Skills2Care and Virtual kitchen rate of completion will be the measurement of the outcomes in this study. We hypothesize that active tDCS will be more effective than sham on enhancing meal preparation skill and Skills2Care tasks completion, and that the effect will be significantly greater in amyloid negative patients than amyloid positive patients. There will be four groups of participants in this randomized study, namely “tDCS stimulated with positive amyloid status,” “tDCS stimulated with negative amyloid status,” “tDCS sham exposed participants with positive amyloid status,” “tDCS sham exposed participants with negative amyloid status”. The task completion rate of tDCS stimulated and tDCS sham exposed participants in each study arm will be compared first, as shown in Figure 2. A student t-test will be performed on these two groups. A successful outcome will be achieved if the two populations are significantly different from each other (p<0.05). Only if a successful outcome is achieved, we will then proceed to compare “tDCS stimulated with positive amyloid status” and “tDCS stimulated with negative amyloid status” via a student t-test. Secondary measurement of outcomes will be the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), which was developed for identifying and characterizing cognitive decline in the older adult [8]. Another measurement will be Alzheimer's disease assessment scale-cognitive subscale (ADAS-Cog), which is commonly used to measure participants’ cognition in research studies [9]. The Clinical Dementia Rating, which has been shown to be effective in characterizing a patient's level of dementia, will be another measurement in this study [10].The statistical analysis of this measurement will follow the process as described above and as shown in Figure 2. While there are tDCS studies of improving working memory by doing abstract tasks, we are not aware of any tDCS studies explicitly focusing on daily living performed at home [2-6, 11]. Our innovations in this study include that we are using more naturalistic tasks in the training and as the measurement of tDCS outcomes. Numerous groups have investigated tDCS to help patients with cognitive impairment, Alzheimer’s disease, stroke and traumatic brain injury [2-6], but there has not been any device has received FDA-approval and become part of standard of care for patient with cognitive decline. The data from this study will add to the current understanding of tDCS effects on cognitive improvement, especially improvement on naturalistic tasks performance. More importantly, this study will support our ultimate goal of designing a portable, lightweight medical device that patients can use in coordination with rehabilitation, and independently at home, to improve cognitive function.