Promoting Adaptive Neuroplasticity in Mild Cognitive Impairment

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. Memory 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. MCI provides a window for interventions that target memory functioning. The proposed study focuses specifically on a groundbreaking combination of mnemonic rehabilitation and non-invasive brain stimulation. The main idea is that brain stimulation can enhance functioning in the specific brain regions/networks, thereby increasing the patients' ability to benefit from different types of memory rehabilitation. This will be a randomized, double-blind study (active vs. fake brain stimulation), that provides multiple treatment session. Outcome will be examined using both laboratory-based and real-world memory testing as well as brain imaging. 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.

Enrollment and interactions/interventions are temporarily paused due to COVID-19 and are expected to resume in the future. This is not a suspension of IRB approval. The proposed study focuses specifically on a groundbreaking combination of mnemonic rehabilitation and non-invasive brain stimulation. The main idea is that brain stimulation can enhance functioning in the specific brain regions/networks, thereby increasing the patients' ability to benefit from memory rehabilitation. This will be a randomized, double-blind study (active vs. fake brain stimulation), that provides multiple treatment session. Outcome will be examined using both laboratory-based and real-world memory testing as well as brain imaging. 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. The general purpose of this study is to examine the effects of two types of treatments for memory impairment in those with mild cognitive impairment (MCI). One form of treatment is cognitive rehabilitation, which involves teaching new ways to learn and remember information. The second form of treatment uses a type of electrical brain stimulation called transcranial direct current stimulation (tDCS) to increase activity in certain brain areas that may be involved with memory. We will use brain imaging to see whether these treatments changed how individuals learn and remember information. We will also use cognitive tests and questionnaires to examine whether memory (and related abilities) changed because of treatment.

Aging, Alzheimer's Disease/Dementia, Cognitive Disorders, Imaging, Magnetic Resonance Imaging (MRI), Neurology, Physical Medicine & Rehabilitation, transcranial direct current stimulation

Raw number of face-name pairs correctly recalled with a maximum of 15 points; higher values are better at each time point. Change at post-session 5 (day 5 after baseline)) calculated relative to baseline performance (positive differences indicate improvement; negative values indicate decline).

Performance measured using deviation from target position (in centimeters). Higher values indicate worse performance. Change at post-session 5 (day 5 after baseline) calculated relative to baseline performance (positive differences indicate decline; negative values indicate improvement).

Changes in task related blood oxygen dependent signal (BOLD) activation for the face-name (novel post > novel pre) contrast in the left inferior frontal gyrus (pars triangularis, pars orbitalis, pars opercularis). Data are preliminary betaweights for the above noted contrast. Positive values reflect increased BOLD signal while negative values represent reduced BOLD signal. Not all participants were able to complete fMRI, which explains sample size discrepancies with other outcome measures.

Performance on the Ecological Memory Simulations- Medical Instructions subtest. Raw points where higher values reflect better performance at each time point (0-15 possible points at each time point). Reported values reflect change from baseline (i.e., post-session day 5 vs. baseline) where positive values represent improvement and negative values represent decline.

Changes on the Multifactorial Memory Questionnaire - strategy subscale. Raw points where higher values reflect better performance at each time point (0-76 possible points at each time point). Reported values reflect change from baseline (i.e., post-session day 5 vs. baseline) where positive values represent improvement and negative values represent decline.

Performance on Ecological Memory Simulations routes subtest (serial order). Higher values indicate better performance at each time point (0-9 possible points at each time point). Change from baseline is reported (post-session day 5 vs. baseline) so higher values indicate better recall while negative values indicate decline.

Planned analyses to examine patient specific characteristics that affect treatment efficacy and would be vital for clinical translation at the individual patient level. Effect of level of cognitive functioning, measured via neuropsychological test performance at baseline, will be evaluated on magnitude of change at post-treatment and 3 month follow-up. Scores range from -3 to +3 standard deviations.

Finite element model based measurement of electric field in the targeted brain regions (Values range from 0 to no theoretical upper limit with higher values reflecting more electrical current; most values will be under 0.5 V/m)

Magnetic Resonance Imaging based measure of brain volume (in percent of intracranial volume; higher values reflect larger brain size)

Inclusion Criteria: General inclusion criteria (all patients): All medications stable for approximately 2-3 months; No history of severe mental illness; No current untreated alcohol or substance abuse/dependence; English as native and preferred language; MRI-compatible if taking part in fMRI studies Able to give informed consent. MCI Inclusion Criteria: - Diagnosis of amnestic MCI based on criteria set forth by Petersen (2004). Additionally, other potential causes of cognitive deficit ruled out by the referring physician Exclusion Criteria: History of neurological disease or injury History of severe mental illness Current untreated alcohol or substance abuse Other conditions may exclude; please discuss with contact