Augmenting Cognitive Training in Older Adults: COVID Admin Supplement

ABSTRACT:This randomized clinical trial will test whether transcranial direct current stimulation (tDCS) of frontal cortices enhancesneurocognitive and functional outcomes achieved from cognitive training in older adults experiencing age-relatedcognitive decline. Change in well-validated measures of neurocognitive function and everyday abilities will serve asoutcome measures. Functional and structural neuroimaging biomarkers of neural plasticity and learning (fMRI, GABAMRS, etc.) will measure intervention-associated alterations in specific brain regions impacted by cognitive aging. tDCSis a noninvasive brain stimulation method that facilitates neural plasticity and learning. Accordingly, when used as anadjunctive intervention, tDCS may augment cognitive training effects. This study will leverage existing multisite clinicaltrial infrastructure at McKnight Brain Institutes located in two of the states with the largest representation of older adultsin the United States: University of Florida, University of Miami, and University of Arizona. Adults over the age of 65represent the fastest growing group in the US population. As such, age-related cognitive decline represents a majorconcern for public health. Recent research suggests that cognitive training in older adults can improve cognitiveperformance, with effects lasting up to 10 years. However, effects are typically limited to the tasks trained, with littletransfer to other cognitive abilities or everyday skills. Effects may also be reduced in people with Alzheimer'sdisease risk factors. A two-phase multisite randomized clinical trial will examine the individual and combined impactof pairing cognitive training with transcranial direct current stimulation (tDCS) in older adults experiencing age-relatedcognitive decline (n = 360; 120 per site). Participants will consist of elderly men and women 65-90 years of age withevidence of age-related cognitive decline, but not MCI or Alzheimer's disease (MoCA≥25). We will compare changesin cognitive and brain function resulting from CT and CT combined with tDCS using a comprehensive neurocognitive,clinical, and multimodal neuroimaging assessment of brain structure, function, and metabolic state. Functionalmagnetic resonance imaging (fMRI) will be used to assess brain response during working memory, attention, andmemory encoding; the active cognitive abilities trained by CT. Proton magnetic resonance spectroscopy (MRS) willassess markers of neural plasticity, GABA concentrations, and cerebral metabolism. We hypothesize that: 1) tDCSwill enhance neurocognitive function, brain function, and functional outcomes from CT; 2) Effects of tDCS on CT willbe maintained up to 12 months following training, and 3) Neuroimaging biomarkers of cerebral metabolism, neuralplasticity (GABA concentrations) and functional brain response (fMRI) during resting vs. active cognitive tasks willpredict individual response to tDCS, with certain Alzheimer's risk factors (e.g., APOE4 genotype, family history ofAlzheimer's disease) predicting poorer cognitive and functional outcome. To date, no studies havecomprehensively examined combined CT and tDCS intervention in the elderly. This study will provide definitive insightinto the value of combating cognitive decline in a rapidly aging US population using tDCS with cognitive training.