Multi-domain amnestic mild cognitive impairment (aMCI) is a preclinical stage of Alzheimer?s disease that is characterized by declines in attention and working memory, which can negatively impact quality of life. As the population of older adults continues to grow, it becomes more imperative to understand what measures may be taken in order to minimize the concomitant growth of the aMCI and Alzheimer?s disease populations. We have recently demonstrated that transcranial alternating current stimulation (tACS), a painless and well- tolerated form of non-invasive brain stimulation, enhances divided attention abilities in a paradigm that also challenges sustained attention and working memory processes. Given that divided attention, sustained attention and working memory are all detrimentally affected in multi-domain aMCI, the use of tACS to remediate these declines may prove to be an important new therapeutic approach. However, additional research is necessary to understand the efficacy of tACS as a therapeutic for aMCI. This project represents the first attempt to assess efficacy of tACS as a therapeutic in aMCI by implementing a double-blinded, placebo- controlled tACS study. Older adults (aged 60-80 years) with multi-domain aMCI will participate in an experiment that requires six in-lab sessions on separate days. During the first session, participants will be given tests of working memory and sustained attention to evaluate baseline performance. During sessions 2-4, tACS will be applied while participants are engaged in a divided attention paradigm that invokes the use of both sustained attention and working memory. Sessions 5 and 6 will be one day and one month later, respectively, and participants will be presented the same paradigm from sessions 2-4 to assess tACS-related effects on divided attention, as well as the same cognitive tests from session 1 to assess tACS effects on sustained attention and working memory performance in non-divided attention tasks. During all six sessions, electroencephalography data will be collected to characterize the neuroplastic changes associated with tACS- related alterations in these cognitive functions. Participants will be randomly assigned to receive either verum stimulation or control stimulation. It is hypothesized that only the verum stimulation group will exhibit improvements in the divided attention task as well as in non-divided attention tasks that assess sustained attention and working memory abilities. Furthermore, these hypothesized gains in cognition are expected to be retained at the one-month follow-up and all performance improvements are expected to occur with corresponding changes in neural activity akin to healthy young adults. Together, this research will provide an important contribution toward understanding the potential of tACS as a therapeutic for aMCI, help elucidate the neuroplastic changes associated with remediating cognitive declines, and set the stage for future longitudinal research to assess the efficacy of this approach as a preventative measure against dementia from Alzheimer?s disease.

Public Health Relevance

The overall goal of the proposed research is to remediate cognitive declines in adults with amnestic mild cognitive impairment (aMCI) through non-invasive brain stimulation. In healthy adults, we have recently used non-invasive brain stimulation to enhance divided attention performance in a paradigm that invokes the use of sustained attention and working memory. Therefore, it is hypothesized that non-invasive brain stimulation will not only improve divided attention ability in adults with aMCI, but result in improved performance in other (non- divided attention) tasks that utilize sustained attention and working memory processes, which are known to be deficient in this population.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Exploratory/Developmental Grants (R21)
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Nursing and Related Clinical Sciences Study Section (NRCS)
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Luo, Yuan
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University of California San Francisco
Schools of Medicine
San Francisco
United States
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