The aging US population threatens to overwhelm our healthcare infrastructure, especially since the rate of Alzheimer's disease (AD) alone is expected to triple in the coming decades. This problem is compounded in the VA Healthcare System, where over 40 percent of veterans are age 65 or older compared to 13 percent within the general population. Memory deficits are characteristic of AD and cause functional impairment, reduced quality of life, increased caregiver burnout, and eventual institutionalization. The diagnosis of mild cognitive impairment (MCI) identifies those with memory deficits but who remain relatively independent in everyday life. Because these patients are at substantially increased risk of converting to AD, MCI provides a window within which interventions could maximize memory functioning and prolong independence. The proposed study focuses specifically on a groundbreaking combination of mnemonic strategy training and non- invasive brain stimulation. Mnemonic strategies are cognitive tools that help patients work around memory deficits. Our preliminary data suggest that mnemonic strategies are effective for improving memory but that (1) not all patients benefit from training and (2) patients have difficulty generalizing them to new information. We have used functional magnetic resonance imaging (fMRI) in these earlier studies to identify the neural correlates of strategy use, which suggest that the left ventrolateral prefrontal cortex is one such vital region. Transcranial direct current stimulation (tDCS) is a form of non-invasive brain stimulation that is used to enhance neuroplasticity and improve the efficacy of behavioral training techniques (e.g., motor rehabilitation after stroke). Thus, the central premise of the proposed study is that tDCS can enhance functioning in the ventrolateral prefrontal cortex, thereby inducing adaptive neuroplastic change and increasing the efficacy of mnemonic strategy training in patients with MCI. In this randomized, double-blind study, participants will complete 5 consecutive treatment sessions in which they receive either active or sham tDCS over the targeted brain region in combination with mnemonic strategy training. Patients will undergo both laboratory-based and real-world memory testing to examine strategy generalization as well as fMRI scanning before and after training. Persistence of memory test and fMRI improvements will be examined at a 3-month follow-up. The use of fMRI will provide critical information about the mechanisms of action, especially whether the targeted brain region (vlPFC) does, in fact, mediate behavioral improvement. It is expected that, relative to the sham group, the active tDCS group will demonstrate persistent improvement in ecologically-based measures of memory as well as increased activation within the ventrolateral prefrontal cortex. We will also examine the relationship between increased brain activation and generalized effects on other cognitive processes mediated by the targeted brain region. This first-of-its-kind study has the potential to meaningfully translate more basic science findings into neuroanatomically targeted and functionally meaningful treatments for our aging population.

Public Health Relevance

Memory deficits characterize an early stage of Alzheimer's disease called mild cognitive impairment (MCI). Existing treatments have little effect on these memory deficits. This study will use non-invasive electrical brain stimulation in an attempt to improve the effects of cognitive rehabilitation of memory in MCI patients by targeting specific brain regions. This approach may ultimately provide additional treatment options for delaying cognitive decline and improving quality of life in MCI patients.

National Institute of Health (NIH)
Veterans Affairs (VA)
Non-HHS Research Projects (I01)
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Veterans Health Administration
Ann Arbor
United States
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